Cardiovascular Disease: Comprehensive Analysis
Cardiovascular disease is rarely caused by a single frailty. Rather, it is a multifaceted failure that includes physical, psychological, and genetic weaknesses. Since cardiovascular disease remains the number one killer in Western societies, there is more published scientific information about its prevention and treatment than exists for other diseases. Overlooking just one risk factor, such as elevated levels of C-reactive protein, fibrinogen, or homocysteine, could lead to the development or worsening of the heart and/or vascular disease. The Cardiovascular Disease protocol is the most comprehensive chapter in this book; we urge persons concerned with the disease to study the chapter carefully. This comprehensive analysis of cardiovascular disease could be a book in and of itself. If you prefer to review a more succinct version, refer to the protocol entitled Cardiovascular Disease: Overview.
At least 68 million people in the United States suffer from some form of heart disease, with an estimated 1.1 million Americans annually experiencing an acute myocardial infarction (MI or heart attack). According to current statistics released from the American Heart Association, cardiovascular disease accounts for about 950,000 deaths annually (about 41% of total mortality from all causes); coronary heart disease accounts for 460,000 of those deaths. In fact, one person dies every 33 seconds from heart disease, culminating in about 2600 deaths every single day. Additionally, the scope of this insidious health problem is worldwide. Globally, cardiovascular disease accounts for almost 50% of all deaths (GSDL 2002).
Researchers reporting in the American Journal of Critical Care further unsettled the scientific community when they declared that 50% of patients with coronary artery disease do not have any of the traditional risk factors (Futterman et al. 1998). In fact, 50% of all individuals 50 years or younger who die from heart disease succumb without any established signs of heart disease. Does this mean that traditional risk factors are no longer valid? The intent of this material is to answer that question by providing a comprehensive review of contemporary and novel risk factors that contribute to cardiovascular disease and a complete dialogue regarding treatment options available to patients.
| Traditional Risk and Predictive Factors |
- Earlobe creases
- Thyroid disease
- Deranged lipids
- Inherited weaknesses
- Gender susceptibility
- Sedentary lifestyle
- Gum disease
- Iron overload
Male-pattern baldness is a subject of interest in regard to the incidence of coronary heart disease (CHD). The Department of Medicine at Harvard Medical School and Brigham and Women's Hospital conducted an 11-year study involving 22,071 male physicians to determine the relationship between baldness and CHD (Lotufo et al. 2000). The study evaluated the following patterns of hair growth: no hair loss, frontal baldness only, and frontal baldness with mild, moderate, or severe vertex balding. (Vertex refers to the top of the head.) The Harvard study concluded that the risk of CHD increased progressively throughout the different groups, with vertex balding showing the greatest association. Vertex baldness appears to be a valid marker for an increased risk of coronary heart disease, particularly when clustered with other factors such as hypertension or hypercholesterolemia (high cholesterol).
About 1973, the association between diagonal earlobe creases and the threat of an eventual heart attack was made. Chronic circulatory problems allow the vascular bed in the earlobe to collapse and the telltale earlobe crease to appear. More than 30 studies have been recorded in medical literature, with one involving 264 patients from a university-based coronary care unit or a catheterization laboratory who were followed for 10 years. Researchers concluded that after adjusting for other risk factors, the presence of a unilateral earlobe crease was associated with a 33% increase in the risk of a heart attack; the risk increased to 77% when the earlobe crease appeared bilaterally (Elliott et al. 1996).
Diagonal earlobe creases, appearing at a 45° downward angle toward the shoulder, are a better predictor of sudden death from a heart attack than age, smoking, obesity, elevated cholesterol levels, or a sedentary lifestyle, particularly before the age of 80. The predictive value of the diagonal earlobe crease does not apply to Asians, Native Americans, or children with Beckwith's syndrome (a heredity disorder associated with neonatal hypoglycemia and hyperinsulinism) (Elliott 1983). While earlobe creases do not prove heart disease, the Mayo Clinic announced that out of 121 patients, the earlobe crease plus symptoms of heart attack (i.e., chest pain) meant a heart attack about 90% of the time. Similar symptoms, but without the earlobe crease, terminated in a noncoronary diagnosis 90% of the time (Pearson et al. 1982).
Kentucky and Tennessee have not only the highest rates of heart disease deaths, but also the highest rates of cigarette smoking. Prolonged exposure to cigarette smoke, either direct or secondhand, increases the risk of dying from a heart attack or complications arising from atherosclerosis by three- to fivefold. Much of the ill-omened health effects related to smoking occur due to an increase in free-radical activity. Unfortunately, as the population of free radicals increases, vitamin C (a powerful antioxidant) decreases in the smoker.
The following reactions define the hardship cigarette smoking imposes upon the cardiovascular system: increased heart rate (one cigarette can increase the heart rate 20-25 beats a minute); disrupted circulation to the legs and feet (it takes 6 hours for the circulation to return to normal after just one cigarette); an increased need for oxygen; insulin resistance; hypertension; and higher levels of adrenaline. Note: Smoking doubles the blood levels of adrenaline. This results in vasoconstriction and platelet aggregation, increasing the risk of both heart attacks and strokes.
Earl Mindell, R.Ph., Ph.D., warns that smokers have higher levels of fibrinogen (Mindell 1998). Fibrinogen is necessary for the proper clotting of blood, but abnormally high levels of fibrinogen can cause blood clots to form spontaneously. It is judged that smoking accounts for half of the vascular risks attributable to fibrinogen.
Cigarettes contain toxic substances (there are 4000 poisons in tobacco), some of which inactivate vitamin B6, a nutrient extremely important in homocysteine control. Homocysteine management is typically difficult in smokers (consult Newer Risk Factors in this protocol for a complete discussion regarding homocysteine; the Therapeutic Section of this protocol outlines a detailed strategy to reduce homocysteine levels).
The Lancet added to the concerns surrounding smokers when it reported that men with the lowest serum albumin levels have the highest rate of death from various causes, including heart disease (Schatz et al. 2001). Smoking lowers this predictive protein (Mindell 1998).
Data published in the Journal of the American Medical Association (JAMA), indicate that the critical phase of cardiovascular disease is significantly accelerated in smokers. The critical phase is marked by 60% coverage of arterial surfaces with atheromatous materials. Although the ages were hypothetically assigned, a smoker with normal blood pressure and cholesterol levels reaches the critical phase 10 years earlier than the nonsmoker and 20 years earlier if the smoker is also hypertensive (Grundy 1986).
It is estimated that each cigarette steals 8 minutes of life from a smoker. This means that an individual smoking one pack a day loses a month of life each year. Two packs clip 12-16 years off the life expectancy of a lifetime smoker (Goldberg 1999).
However, it is important for a smoker to realize that the body has an immense capacity for restoration. Within 24 hours of being tobacco-free, the chance of heart attack decreases. Within 48 hours, nerve endings start to regroup and breathing becomes noticeably improved. Within 2-3 months, circulation improves and walking becomes easier. Lung capacity increases up to 30% and energy levels rebound. After 1 year, the risk of a heart attack is 50% less than the individual still smoking; within 2 years, the risk of heart attack drops to ranges closely rivaling an individual who has never smoked. Another bonus occurs as inflammation is reduced and subsequently C-reactive protein (CRP), a newer cardiovascular risk factor (discussed later in this protocol), decreases.
Although the body is resilient, it is extremely important that the smoker not wait too long to embark upon recovery. For information pertaining to nutrients that offer protection to a smoker, turn to the Bromelain, Coenzyme Q10, Curcumin, Proanthocyanidins, Vitamin C, and Vitamin E subsections in the Therapeutic section of this protocol.
Hypertension, observed more in men and African Americans, is a disorder characterized by blood pressure persistently exceeding 140/90 mmHg. Current research indicates that an optimal blood pressure is below 120/80 mmHg. It is important to note that damage to the vasculature can occur when the blood pressure is moderately but chronically elevated. Some individuals may not realize they are hypertensive because symptoms such as epistaxis (nosebleed), tinnitus, dizziness, headache, blurred vision, and arrhythmias are not always present.
Dr. Charles DeCarli (University of Kansas) found that men who had even mildly elevated blood pressure 25 years earlier now have abnormal brain signals and suffer from vascular disease and strokes more often than men who had normal blood pressure in midlife. "Take care of risk factors when you're young or they'll come back to haunt you," warns DeCarli.
The Archives of Internal Medicine reported the results of the most comprehensive study to date, evaluating 10,874 Chicago men (ages 18-39 from 1967-1973) concerning the long-term effects of high blood pressure. About 62% of those studied had either high-normal blood pressure (systolic pressure 130-139 and diastolic pressure 85-89) or Stage I hypertension (systolic pressure 140-159 and diastolic pressure 90-99).
Individuals with a high-normal blood pressure had a 34% increased risk of dying from coronary heart disease and those with Stage I hypertension a 50% higher risk. Life expectancy was shortened by 2.2 years for men with high-normal blood pressure and by 4.1 years for those with Stage I hypertension. Dr. David A. Meyerson (Johns Hopkins cardiologist and spokesman for the American Heart Association) said the Chicago study affirms the need for a population-wide effort for health promotion by lifestyle modification; the commitment should begin early in life and continue lifelong. Since the lifetime risk for hypertension among middle-aged and elderly individuals is 90%, corrective intervention (at an earlier age) could relieve a huge public health burden (Miura et al. 2001; Vasan et al. 2002).
Findings in the New England Journal of Medicine (exploring the role of moderately elevated blood pressure as a forerunner of heart disease) concurred with the results gathered from the Chicago hypertension trial (Vasan 2001). The parameters describing moderately elevated blood pressure were identical in both trials, that is, a systolic pressure of 130-139, a diastolic blood pressure of 85-89, or both. The researchers tracked 6859 participants, noting a stepwise increase in cardiovascular events among persons with higher base line blood pressure. Thus, the results of various credible studies demonstrate that high-normal blood pressure should not be taken lightly; a regime to counter even a slight rise in blood pressure (exceeding optimal-normal levels) should be regarded as essential to reducing cardiovascular risk.
Diastolic or Systolic: Which Poses the
For decades it was thought that the diastolic (the lower blood pressure) was the most critical measurement when diagnosing hypertension and assessing blood pressure-induced vascular damage. The journal Hypertension renounced this theory, reporting that systolic pressure is the crucial assessment, not the diastolic, as previously considered (Izzo et al. 2000). (Systolic pressure represents the maximum force exerted by the heart against the blood vessels during the heart's pumping phase.) The difference between the systolic and diastolic blood pressure is referred to as pulse pressure; if the number chronically exceeds 60, advanced atherosclerosis is usually present.
Types of Hypertension
While most cases of high blood pressure are classed as essential or primary hypertension (meaning no known cause can be found for the elevation), it is a misnomer to imply that unfounded hypertension is innocent. Any sustained elevation of blood pressure can affect the intima (innermost structure) of small blood vessels, the brain, the retina, the kidneys, and the heart.
Secondary hypertension is frequently linked to primary diseases, such as renal, pulmonary, endocrine, and vascular diseases. Malignant hypertension, the most lethal form, is characterized by severely elevated blood pressure that commonly damages major organs and the vascular system. Many patients with this condition exhibit signs of hypokalemia (inadequate levels of potassium in the bloodstream), alkalosis (blood pH >7.45), and excessive aldosterone secretion (a hormone that conserves water and sodium and increases potassium excretion).
How Does Hypertension Inflict Damage?
Hypertension increases the risk of cardiovascular disease by affecting the performance of arteries. Normally, arteries expand and contract effortlessly with each heartbeat. With sustained hypertension, the arterial walls become thickened, inelastic, and resistant to blood flow. This process injures arterial linings and accelerates plaque formation. Nonfunctional blocked vessels are unable to expand to accommodate the flow of blood, and the left ventricle is forced to pick up the slack. The endless exertion proves too much, and the ventricle may become distended and hypertrophied. In exhaustion, the pump eventually fails. The health of the left ventricle is an extremely important assessment when evaluating the worthiness of the heart.
Arterial damage is invitational to spasms occurring in the walls of the arteries. The spasm further impedes the flow of blood, adding additional challenge to the ailing heart as it works to move the blood against the backflow. A lack of egress and the heart's aggressive action can cause a weakened area in the arterial wall to balloon, forming an aneurysm. The rupture of the artery can result in massive internal bleeding and death. An aneurysm or stroke, angina pectoris, and myocardial infarction are even more likely to occur if the individual has high cholesterol and/or elevated blood pressure.
Watch Serum Creatinine Levels
Serum creatinine levels in hypertensive patients are an extremely important marker, and unfortunately one frequently ignored. Creatinine is highly reliable in predicting cardiac outcome in individuals with high blood pressure. Researchers analyzed data from a massive study, involving 14 U.S. medical schools and 10,940 subjects. It was determined that 50% of hypertensive individuals with creatinine levels of 2.5 mg/dL (or greater) die within 8 years. According to Dr. Neil B. Shulman (principal investigator) cardiac deaths begin to spiral when creatinine levels reach 1.7 mg/dL, with fatalities mounting as creatinine increases. Although high levels of creatinine frequently reflect kidney impairment, most individuals with high creatinine die as a result of a heart attack or stroke, not renal disease (Shulman 1989).
Syndrome X and Hypertension
Syndrome X, one of the newer cardiac risk factors, may best explain why some individuals are not protected from heart disease when hypertension is treated independently. Excesses of insulin, a hallmark of Syndrome X, makes the sympathetic nervous system dominant and results in the release of catecholamines, that is, dopamine, epinephrine, and norepinephrine, which contribute to hypertension by diminishing blood vessel diameter. Hyperinsulinemia also encourages the retention of salt and water, a process that increases blood volume and blood pressure. About 50% of hypertensive patients are insulin resistant and should be treated for hyperinsulinemia (excess blood insulin) primarily rather than focusing on a symptom of the syndrome, that is, high blood pressure. Gerald Reaven (professor emeritus (active) of medicine at Stanford University) states that it is vital that every healthy-heart program address the hypertension-Syndrome X association or little success in shielding hypertensive patients from a heart attack can be expected (Reaven 2000).
Blood Pressure Medication:
Patients are searching for alternatives to hypertension medications in light of the information gathered from an 8-year study involving 117,534 people. Half of the individuals were given antihypertensive drugs and the other half a placebo. The number of deaths at the end of the 8-year study was about the same in each group; however, the side effects of the drugs eroded the equality of the results. Additional information regarding compliance/response rates among hypertensive patients using drugs to reduce blood pressure may be found in the British Medical Journal (Nuesch et al. 2001).
If an antihypertensive drug therapy is used, Cozaar or Hyzaar (angiotensin II antagonists) appear to be safer and more effective than short-acting calcium channel blockers. It should be noted that beta-blockers and diuretics (antihypertensive treatments) have been associated with an increased risk of developing diabetes by impairing insulin sensitivity. However, benefits have been obtained using alpha-1-blockers (antihypertensive vasorelaxants) in regard to increasing insulin sensitivity (Lithell 1996). Unfortunately, the National Heart, Lung, and Blood Institute stopped one phase of a large hypertension study because alpha-blockers were found less effective (even dangerous) compared to more traditional drugs in reducing the incidence of cardiovascular events. The troublesome results surfaced after gathering statistics from the ALLHAT (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) study (ALLHAT 2000).
During the course of the ALLHAT study, it was found that subjects taking doxazosin (Cardoxan, Carduran, and Dosan) had a 25% higher risk of death from coronary heart disease, as well as nonfatal myocardial infarction, peripheral artery disease, stroke, angina, and congestive heart failure. The high numbers of cardiovascular events could chiefly be explained by a doubled risk for congestive heart failure. The other significant finding was that doxazosin was less effective (by an average of 3 mmHg) in controlling systolic blood pressure compared to other drugs evaluated. The researchers surmised that while this discovery may explain the higher risk for angina (16%) and stroke (19%), it could not fully account for the doubling of congestive heart failure (IHP Information for Health Professionals 2000).
The HOPE Project
On March 11, 2000 , a satellite symposium of the American College of Cardiology Scientific Session was held during which several speakers discussed the results of the Heart Outcomes Prevention Evaluation (HOPE) study. The study represented a 6-year undertaking, assessing the value of ramipril (an angiotensin-converting enzyme, or ACE inhibitor) in the prevention and management of cardiovascular disease (Anon. 1993; Hall et al. 1997; Doctors' Guide 1999). Ramipril, a generic of the drug Altace, is principally used in the treatment of high blood pressure, but its benefits appear far-reaching. During the study, researchers also sought to determine whether vitamin E was more effective than a placebo in preventing major cardiovascular outcomes (see the comments regarding the unfavorable review of vitamin E).
| A brief explanation of the renin-angiotensin system: |
| The juxtaglomerular cells in the kidneys stimulate renin secretion when either blood volume or serum sodium decreases. Renin (an enzyme) participates in the conversion of angiotensinogen to angiotensin I, which is rapidly hydrolyzed to form the active compound angiotensin II. The vasoconstrictive action of angiotensin II decreases the glomerular filtration rate; the concomitant action of aldosterone, a mineralocorticoid hormone produced by the adrenal cortex, promotes sodium retention, causing blood volume and sodium reabsorption to increase. Agents that inhibit the angiotensin-converting enzyme decrease sodium and water retention, reduce blood pressure, improve cardiac output, and typically decrease heart size. |
Some 9500 people from 270 hospitals in 19 countries participated in the HOPE study. Included in the trial were those with evidence of coronary artery disease, stroke or peripheral vascular disease, and high-risk patients with diabetes. Subjects were randomized to one of four treatments: ramipril alone, vitamin E alone, ramipril and vitamin E, or neither.
Dr. Salim Yusuf, Ph.D. (professor of medicine and director of the division of cardiology, McMaster University ), reported that ramipril reduced the risk of new heart attacks, strokes, and mortality by 20-25%. Diabetic complications, heart failures, and the need for coronary revascularization (reestablishing blood flow through surgical means) were significantly reduced as well. Dr. Yusuf reported on another phase of the HOPE study, that is, documenting the worth of vitamin E as a cardioprotector, announcing that no advantage was observed with supplementation.
As frequently occurs when trial results are overwhelmingly in favor of one treatment over others, the study was halted. The ramipril-treated group received such an obvious benefit it was deemed unethical to withhold the drug from the control group. In fact, Dr. Victor Dzau, M.D. (professor of theory and practice of medicine at Harvard Medical School ), suggests that it might be helpful (in certain cases) to use ACE inhibitors to reduce risks of potentially costly medical problems even in the absence of hypertension.
According to Dr. Bertram Pitt (professor of internal medicine at the University of Michigan ) the HOPE study confirms that the activation of the renin-angiotensin system impacts the risk of a heart attack through various pathways. For example, when angiotensin II is elevated, it affects the transport of cholesterol into the vessel wall and its oxidation, as well as increasing cytokines, inflammatory proteins. This begins a cycle that involves high levels of low density lipoproteins (LDLs), increasing angiotensin II, which, in turn, increases the oxidation of LDL cholesterol.
In addition, Dr. Dzau explains that within unstable atherosclerotic plaque a great deal of inflammation has been observed, and inflammatory cells produce angiotensin II. This situation is complicated by the fact that angiotensin II also leads to inflammation. The result is a sequence that constantly increases angiotensin production and inflammation, events invitational to atherosclerosis and ischemic events. The power of ACE inhibitors (such as ramipril) to prevent cardiovascular disease is partially explained by their ability to interrupt these cycles.
Of tremendous interest was the finding that patients with diabetes experienced a reduction in diabetic neuropathy and the progression of the diabetic process while using ramipril. Over the 4.5 years of the HOPE study, the number of patients who developed new diabetes in the ramipril group was one-third that of the placebo group. If the ramipril-diabetes advantage can be confirmed, it would indicate that the renin-angiotensin system is also involved in the pathogenesis of diabetes. Bolstering the hypothesis, Captopril (another ACE inhibitor) also resulted in improved insulin sensitivity.
A remarkable finding was that the benefit derived from ramipril was independent of blood pressure modulation. A reduction of only 3 systolic points and 1.8 diastolic points from a mean baseline of 138/76 was observed. Nonetheless, a clear reduction in unwanted outcomes, that is, cardiovascular deaths, myocardial infarctions, and strokes occurred in all blood pressure categories. Dr. Yusuf speculates that 2 million people a year could be spared a major cardiovascular event if ramipril were widely used.
Researchers were impressed with the absence of side effects during the course of the trial. However, if a patient has hyperch lo r lemia (an excess of chloride in the blood) or renal dysfunction, the physician should be very careful about administering any ACE inhibitor. If ramipril is to be used, 10 mg a day appears to be the optimal dosage. Hypertensive patients should start at a lower dose, such as 2.5 mg, and gradually increase. It is uncertain whether all ACE inhibitors are equal to ramipril in delivering cardioprotection; the ACE inhibitor Quinapril failed in reducing ischemic events, but researchers question whether the dosage was more in error than the drug.
Comments regarding the unfavorable review of vitamin E
Dr. Richard Passwater, a long-time vitamin E devotee, explains that the length of time in which vitamin E is used determines its cardiovascular defense. Dr. Passwater showed (1977) that taking 400 IU of vitamin E daily for 10 years or more dramatically reduced the occurrence of heart disease prior to 80 years of age. Also, the type and blend of vitamin E administered can alter outcome. The Life Extension Foundation has long advocated a complex of alpha-tocopherol (80%) with gamma-tocopherol (20%) for optimal protection.
In contrast to the HOPE study, The Lancet reported the benefit of administering 800 IU a day of alpha-tocopherol (vitamin E) to individuals with preexisting cardiovascular disease and on hemodialysis (Boaz et al. 2000). Increased oxidative stress (imposed through dialysis) appears to increase cardiovascular mortality. A total of 15 (16%) of the 97 patients assigned to vitamin E and 33 (33%) of the 99 patients assigned to placebo had a primary endpoint. Five (5.1%) patients assigned to vitamin E and 17 (17.2%) patients assigned to placebo had myocardial infarctions.
A new Israeli study showed the incidence of a fatal heart attack was 43% lower in a vitamin E supplemented group compared to a placebo group. Despite the reduced death rate from heart disease in the vitamin E group, both vitamin E and placebo groups had approximately the same overall risk of dying during the course of the trial. The increase in noncardiac deaths (which included deaths from a car accident, surgery, and complications following kidney transplantation) appears to be a distortion of statistics (Austin 2002).
While bewildering to the consumer, varying dosages and blends of vitamin E applied to diverse populations often result in dissimilar conclusions. Turn to the Vitamin E subsection in the Therapeutic section to read about Dr. Passwater's study, as well as current documentation supporting supplementation to protect against cardiovascular disease.
The Therapeutic section also highlights numerous suggestions to treat hypertension, including alpha-lipoic acid, L-arginine, calcium, coenzyme Q10, essential fatty acids, garlic, hawthorn, magnesium, olive leaf extract, policosanol, potassium, taurine, and vitamin C. Natural ACE inhibitors are green tea, garlic, hawthorn, olive leaf, taurine, proanthocyanidins, angelica, and ginkgo biloba. To read about the influence other conditions have on hypertension, consult the following sections in this protocol: Smoking, Obesity, Stress, Genetics, Fibrinolytic Activity, Homocysteine, Syndrome X, Chelation Therapy, and Does Sodium Restriction Lower Blood Pressure?
Excessive body weight is a risk factor in so many diseases that obesity itself is now regarded as a disease. In the United States , 104.4 million adults are overweight, and 42.5 million are obese. Considering these alarming numbers, it is prudent to wonder when a troublesome weight problem is no longer just an annoyance but a significant risk for heart disease. Measuring body mass index (BMI) has helped physicians and patients answer this question.
During the American Heart Association's 71st Scientific Session (in 1998), the guidelines for assessing the risks imposed by obesity (as measured by BMI) were reported. This study was based on data from the Framingham Heart Study and the Third National Health and Nutrition Examination Survey (Edelsberg et al. 1998). The results follow in Figure 2.
The pattern of the fat distribution is another important prognosticator of host vulnerability. For example, android obesity or male-pattern obesity is characterized by central abdominal obesity. Android obesity, that is, apple-shaped bodies, are historically associated with an increased risk of hypertension, diabetes, hyperinsulinism, cardiovascular disease, and premature death. Conversely, fat distribution confined primarily to the hips and thighs--that is, gynoid or pear-shaped obesity--is more likely to be regarded as benign and is common in females (Sardesai 1998).
| The Risk of Heart Disease in Obese Individuals |
| MEN || WOMEN |
| Not obese |
(BMI 22.5) = 35% risk
| Not obese |
(BMI 22.5) = 25% risk
| Mildly obese |
(BMI 27.5) = 38% risk
| Mildly obese |
(BMI 27.5) = 29% risk
| Moderately obese |
(BMI 32.5) = 42% risk
| Moderately obese |
(BMI 32.5) = 32% risk
| Severely obese |
(BMI 37.5) = 46% risk
| Severely obese |
(BMI 37.5) = 37% risk
BMI may be calculated as follows:
- Convert weight in pounds to kilograms by dividing total weight by 2.2.
- Determine height and convert to inches.
- Convert height in inches to meters. 1 meter equals 39.37 inches. (Height in inches 4 39.37 = height in meters.)
- Square the height in meters by multiplying it by itself.
|Divide weight in kilograms by height in meters squared. |
| This calculation can be done by a weight loss physician or over the phone by calling (800) 226-2370. |
The Risks of Obesity: The Benefits of Weight Loss
Research has clarified the reasons that fatness increases cardiovascular risks. Obesity forces the heart into intensive labor because useless pounds must be serviced in the same fashion as valuable tissues and organs. The risk of diabetes and hypertension increases almost 3 times in obese individuals. For example, a weight gain of 10% can increase systolic blood pressure by 6.5 mmHg and fasting blood glucose by 2 mg/dL. Blood cholesterol levels typically increase by about 12 mg/dL for each 10% of weight gained and HDL levels decrease (Family Practice Notebook 2000). Even a 5- to 10-pound weight loss can provide significant health benefits such as lowered blood pressure or improved blood glucose control in the diabetic (Chandler 2002). Other factors increasing cardiovascular risk, such as excessive fibrinogen, elevated C-reactive protein, and insulin resistance, often share a common denominator, that is, obesity.
A 10- to 15-pound weight loss can also lessen the risk and progression of Syndrome X. As weight drops, tissues become more insulin sensitive, amending a primary identifiable trait in Syndrome X. Although not all obese individuals develop Syndrome X, the more overweight one is, the greater the risk of developing the syndrome and the clusters of disease factors surrounding it (a discussion of Syndrome X as an antecedent to cardiovascular disease may be found in the section devoted to Newer Cardiovascular Risk Factors).
Overeating in the absence of obesity poses a cardiac risk, as well. Reports from patients indicated that unusually heavy meals were often consumed during a 26-hour period preceding a myocardial infarction (Lopez-Jimenez et al. 2000).
Leptin in Obesity and Heart Disease
Leptin, a hormone produced by fat cells, increases with obesity and appears to play a role in the vascular complications associated with overweight conditions. The discovery of leptin (in the last decade) raised hopes that it could be used as a drug to treat obesity. However, most obese people were later found to have elevated levels of the hormone, making leptin injections inappropriate. However, assessing leptin levels has emerged as a means of screening for heart disease.
The journal Circulation showed that men with established heart disease had blood leptin levels 16% higher than men considered heart healthy. Every 30% increase in leptin increased the risk of a heart attack or a vascular event 25% (Wallace et al. 2001). The association between leptin and heart disease was observed regardless of BMI, suggesting that leptin is a reliable marker for the amount of fat in the body. Body composition (the comparative proportions of protein, fat, water, and mineral components in the body) may thus be a better indicator of risk for heart disease than overall obesity.
The levels of leptin, structurally a cytokine, rise in tandem with C-reactive protein (CRP), a marker of blood vessel inflammation and itself a significant heart risk. These findings imply that body fat influences CRP levels (Mercola 2002a) in addition to a myriad of other health problems.
JAMA recently reported that leptin has a stimulatory effect on platelet aggregation (Nakata et al. 1999; Bodary et al. 2002). The identification of a functional leptin receptor (OB-Rb) on platelets suggests a signaling mechanism between fat cells and platelets. To test the hypothesis, researchers examined mice deficient in leptin or the leptin receptor after a laboratory-induced vascular injury. Leptin-deficient mice had a prolonged time to occlusion, whereas leptin-deficient mice administered the hormone demonstrated a significant reduction in the time to occlusive thrombosis. Since leptin levels correlate well with adiposity, strategies aimed at weight reduction should remain the first line of defense. Lastly, exercise training in Type II diabetic subjects also reduced serum leptin levels independent of changes in body fat mass, insulin, or glucocorticoids (Ishii et al. 2001).
It is apparent that individuals need to establish a sensible approach to eating, that is, a program that can be comfortably maintained long term, void of either binges or periods of starvation. To lose weight only to regain it poses many health risks. For example, a decrease in HDL cholesterol is often reported in women who chronically cycle their weight from highs to lows (Olson 2000). Weight cyclers typically have 7% lower HDL cholesterol than noncyclers (Olson et al. 2000). To read about dietary supplements that may assist in weight loss, see the subsections relating to L-Carnitine, Chromium, CLA, and nutrients that lower serum insulin levels in the Therapeutic section of this protocol.
The degenerative process that accompanies diabetes significantly affects the heart. Atherosclerosis tends to develop early, progress rapidly, and be more virulent in the diabetic. Data released from the Framingham Study showed a 2.4-fold increase in congestive heart failure in diabetic men and a 5.1-fold increase in diabetic women over the course of the 18-year study (Fein et al. 1994).
Diabetics are particularly susceptible to silent myocardial infarctions, that is, an asymptomatic attack that interrupts the blood flow to coronary arteries. More than 80% of people with diabetes die as a consequence of cardiovascular diseases, especially heart attacks (Whitney et al. 1998). High homocysteine levels also play a significant role in diabetes-induced cardiovascular disease. In fact, hyperhomocysteinemia is considered a reliable predictor of mortality among diabetic patients.
Typically, Type II diabetes develops because of a lack of insulin sensitivity at the cellular level. As a result, the bloodstream becomes overloaded with nonfunctional insulin and a glut of glucose. The reason for this is that as glucose is increasingly unable to be used for energy metabolism and accumulates in the blood, the pancreas secretes more insulin in a futile attempt to restore normal glycemic control. After an extended period of excess insulin secretion, the pancreas may lose its ability to produce insulin, and the Type II diabetic may then become insulin dependent. When insulin loses its sensitivity or receptivity, its metabolic disposition changes, and insulin becomes more of an adversary than an advocate within the host.
Much of the stress of diabetes is due to a constant state of flux, that is, moving from hyperglycemia to hypoglycemia in a relatively short period of time. Nondiabetics are spared glycemic-induced stress. For example, most healthy individuals maintain postabsorptive blood glucose levels of 90-100 mg/dL. Even after fasting or overeating, blood glucose levels seldom fluctuate lower than 60 mg/dL or over 160 mg/dL (Pike et al. 1984). It has been suggested that evolutionary success requires a staunch defense of the range of blood sugar, since exceeding the limits at either end produces dire circumstances. An unstable diabetic lacks the homeostatic mechanisms that provide for intricate glucose balance, and as a result the heart and circulatory system suffer.
Chronic hyperglycemia causes monocytes and adhesion molecules to bind to vessel walls. In turn, cholesterol and other lipids are more easily deposited. Lipids become disorganized, with more of the LDL cholesterol and less of the beneficial HDL cholesterol appearing in the bloodstream (Reaven 2000). As the volume of urine produced increases, life-saving minerals are often excreted with urine. Without adequate mineral representation, the heart can be forced into fatal arrhythmias. Hypertension, abnormal coagulation, and obesity multiply the health concerns that frequently plague diabetic patients.
During hypoglycemia, the ability of the nervous system to function decreases, but the breakdown of fats increases. In this situation, fat assumes the role of a glucose surrogate. Necessary as this mechanism is, it is not without a disadvantage. Substitute pathways are not always well regulated, and excess fats not used as an energy source may accumulate, contributing to the atherogenic process.
The symptoms of hypoglycemia can mimic a heart attack, that is, dizziness, fatigue, sweating, shakiness, lightheadedness, palpitations, and in some cases, unconsciousness. Normal brain function requires 6 grams of glucose an hour, which can be delivered only if arterial blood contains over 50 mg/dL of glucose (Pike et al. 1984). Although hypoglycemia is not a heart attack, the stress imposed upon the heart can be significant.
To learn more about the impact that Obesity, Stress, Gender, and a Sedentary Lifestyle have upon diabetes, consult those subsections in the Traditional Risk Factors section of this protocol; other relative information may be found in the Fibrinolytic Activity and Syndrome X subsections of Newer Risk Factors (also in this protocol). For natural suggestions to benefit a diabetic, read about Alpha-Lipoic Acid, L-Carnitine, Chromium, DHEA, Essential Fatty Acids, Fiber, Garlic, Magnesium, Olive Leaf Extract, Selenium, Vitamin A, Gamma-Tocopherol, Vitamin K, and Zinc in the Therapeutic section of this protocol. The Diabetes protocol in this book should be thoroughly studied by individuals with unstable blood glucose levels.
HYPERCHOLESTEROLEMIA AND DERANGED LIPID PROFILES
Too much cholesterol is not good, but too little may not be good either. The American Heart Association announced in 1999 (at the annual Stroke Conference) that people with cholesterol levels less than 180 mg/dL doubled their risk of hemorrhagic stroke compared to those with cholesterol levels of 230 mg/dL; however, the risk of a stroke escalated as cholesterol levels exceeded 230 mg/dL. It is estimated that high cholesterol levels account for about 10-15% of ischemic strokes; low cholesterol may be a contributing factor in nearly 7% of hemorrhagic strokes. The National Cholesterol Education Program announced that cholesterol levels of approximately 200 mg/dL appear ideal for stroke prevention (CNN 1999; Mercola 1999).
Nonetheless, opinions are still divided as to the magnitude of the hypocholesterolemic risk. Until the quandary has been fully resolved, there are reasons to be cautious about severely reducing dietary fat and serum cholesterol. Recall that in foods, triglycerides carry the fat-soluble vitamins (including vitamin K, an extremely important nutrient in normal blood coagulation) (Whitney et al. 1998). In addition, some researchers believe that hypocholesterolemia weakens cerebral arterial walls, making breakage under pressure more likely (Hama 2001). (About 20% of all strokes result from cerebral hemorrhages.) Various studies indicate that very low levels of cholesterol may also increase the risk of death due to cancer, particularly leukemia and lung cancer (Zyada et al. 1990; Telega et al. 2000).
Cholesterol is so important that the body produces from 800-1500 mg each day to provide for the following metabolic processes:
- Cholesterol is present in every cell in the body, strengthening cell walls and assisting in the exchange of nutrients and waste materials across membranes.
- The central nervous system, composed of the brain and spinal cord, contains nearly one-fourth of the body's store of cholesterol. As much as 50% of myelin (the insulating sheath on many nerve fibers) is cholesterol. Cholesterol is essential for the conduction of nerve impulses.
- Bile acids, formed from cholesterol, are vital for proper fat digestion.
- Cholesterol is the precursor of adrenal and reproductive steroid hormones.
- Surface cholesterol makes the skin resistant to chemicals and disease organisms, hindering entry through pores. Cholesterol stored in the skin assists in converting sunlight to vitamin D.
Although high concentrations of total serum cholesterol are related to mortality in individuals younger than 65 years, clinical trials have failed (until recently) to look at large numbers of individuals (> 70 years of age) to assess their response to higher cholesterol levels. According to data published in The Lancet, the risk imposed by hypercholesterolemia decreases with age (Weverling-Rijnsburger et al. 1997; Schatz et al. 2001). In fact, hypocholesterolemia (low cholesterol levels) appears associated with higher death rates among elderly people, due to mortality from cancer and infection. Therefore, administering a hypocholesterolemic drug to senior subjects may actually increase their risk of succumbing through other forms of degenerative disease.
Dr. Steven Whiting, dean of the Institute of Nutritional Science , explains how cholesterol can change from an essential sterol to an atheromatous material. Free radicals and hypertension can damage the inside of an artery, causing a small rupture or tear to occur. The body recognizes the problem and attempts to handle it with the materials available. Fibrin, a stringy, insoluble protein, is the first material laid down at a wound sight. Fibrin does what it must: seal or coat the damaged area in the artery. Unfortunately, fibrin can grasp other bloodstream infiltrates in its web-like structure, that is, collagen proteins and minerals that have precipitated out of solution. According to Dr. Whiting, a significant bump in the arterial pathway may have developed and then along comes cholesterol. Cholesterol appears to add the final coat to the plaque, building up in the artery (Whiting 1989).
Optimal Ranges of Blood Lipids
When levels of HDL (high density lipoproteins, also known as good cholesterol) are elevated, cardiovascular disease is reduced. The HDL2 subfraction is even more correlated with cardiac protection and longevity than total HDL cholesterol (Sardesai 1998). Typically, low triglyceride/LDL levels and high HDL levels place an individual in a better position cardiovascularly. HDL levels are considered desirable in a range of 50-70 mg/dL.
Total cholesterol for most individuals appears best managed between 180-200 mg/dL. The "how low can you go" logic is not wise when setting relevant cholesterol goals, considering the many functions assigned to cholesterol and the unsettled questions surrounding the safety of very low cholesterol levels.
The risk factors for heart disease are often calculated by dividing total cholesterol by HDL. Assessment of the HDL-total cholesterol ratio is not standardized, but according to Health and Wellness (Sixth Edition), a value of 4.5 places the individual at an average risk; a ratio above 4.5 indicates an increased risk; and a ratio below 4.5 means a decreased likelihood of developing heart disease (Edlin et al. 1999).
Most laboratories use a reference range of 90-130 mg/dL for LDL cholesterol, but LDL appears optimal at 100 mg/dL or lower. Dr. Henry Ginsberg ( Columbia University ) estimates that reducing LDL cholesterol 7% may translate into a 15-20% reduction in risk of coronary heart disease (Ginsberg et al. 1998). Note: LDL cholesterol is not measured directly; levels are calculated using the following formula:
LDL = total cholesterol - HDL - (triglycerides 4 5).
Cholesterol tests indicating acceptable levels may convey a false sense of security. Current research indicates that standard cholesterol tests miss 50% of people at risk for heart attacks, due to the inability to detect abnormally small cholesterol particles. Note: Syndrome X is characterized by abnormal lipoprotein metabolism, showing smaller, denser LDL particles. To read more about Syndrome X, please consult the Newer Risk Factors section in this protocol.
LDL pattern B is the smallest and most susceptible to oxidation of all forms of cholesterol. Both LDL pattern B and lipoprotein(a) increase the risk of heart attack threefold; neither can be detected by standard cholesterol tests. Without the detection of the smaller cholesterol subsets and the appropriate treatment, plaque buildup progresses twice as fast. Trapped LDL or lipoprotein(a) over time forms plaque with a fibrous cap. Unstable plaque can rupture, which causes the blood to clot, increasing the risk of sudden heart attacks or strokes. Laboratories providing total screening, that is, testing for normal and abnormal-sized lipoproteins, should be used for evaluations.
Triglyceride levels are usually regarded within a normal range at 30-199 mg/dL, but researchers have found that patients with clinical coronary heart disease were less likely to experience new events if tri-glyceride levels were below 101 mg/dL (Kreisberg et al. 2000). Most clinicians believe that triglycerides are best maintained below 101 mg/dL in all subsets of the population. Perhaps J.M. Gaziano ( Harvard Medical School ) led the most startling study in regard to the risks imposed by deranged blood lipids. The subjects with the highest ratio of triglycerides to HDL had a 16-fold greater incidence of coronary events compared to those with the lowest ratio (Gazinao et al. 1997).
Triglyceride levels rarely rise unless one has insulin resistance or hyperinsulinemia, conditions often modifiable by controlling carbohydrates in the diet. According to the data reported in Atherosclerosis, elevated triglyceride levels usually modulate when less food is consumed, particularly foods causing a rise in blood sugar levels, that is, bakery products, pastas, and foods with added sugar (Stavenow et al. 1999; Atkins 2002). Note: Other areas in this protocol relating to hyperlipidemia are heredity, sedentary lifestyle, gum disease, hypothyroidism, hemochromatosis, fibrinogen, Lp(a), homocysteine, Syndrome X, and C-reactive protein. Read about natural lipid-reducing agents such as artichoke extract, L-carnitine, chromium, conjugated linoleic acid, curcumin, DHEA, essential fatty acids, fiber, garlic, ginger, grapefruit pectin, gugulipid, hawthorn, niacin, pantethine, policosanol, poly-enylphosphatidylcholine, and tocotrienols in the Therapeutic section of this protocol.
More than one-quarter of a million heart episodes occur annually--that is, palpitations, angina, arrhythmias, and heart attack--as a result of a stressful experience. This is particularly evidenced when an ailing heart struggling to keep pace with circulatory demands is forced to deal with an emotional provocation. The journal Circulation reported that an individual who is prone to anger is about 3 times more likely to have a heart attack or sudden cardiac death than someone who is the least prone to anger (Williams et al. 2000).
The journal Life Sciences offers an explanation for stress-related cardiovascular events. Higher levels of homocysteine are associated with feelings of aggression and rage in both men and women (Stoney et al. 2000). Individuals may be spurred into erratic behavior by metabolic processes gone awry. The modulation of homocysteine levels may allow a more docile individual to emerge, less cardiac risk prone from two perspectives (less homocysteine = less violent behavior and less cardiac disease). A comprehensive review of homocysteine appears in the section devoted to Newer Risk Factors. Vitamins and minerals to maintain healthy homocysteine levels are presented in the Therapeutic section.
Type A individuals are also at a greater cardiovascular risk because their lives are dominated by self-imposed stress. Work expectations are driven by an unrelenting desire to achieve. An exaggerated sense of time urgency prompts accelerated locomotion and faster decision-making. Cynicism, hostility, and impatience snuff out many personal relationships and deny the heart a much needed rest from disharmony.
Under stress, the sympathetic nervous system is alerted and the release of adrenaline increases; ultimately, one's breathing, heartbeat, and blood pressure also increase. Cardiac patients are often prescribed beta-adrenergic blocking agents to calm the sympathetic nervous system, a gesture that asks a drug to succeed where attempts at lifestyle changes may have failed.
Type D behavior, another variant having heart disease linkage, was described in The Lancet (Denollet et al. 1996). Withheld and denied emotions, that is, refusing to cry even when weeping is justified and a lack of social connectedness (traits common to a type D personality), appear contributory to heart disease and stroke.
During periods of mental or emotional arousal, a silent ischemic attack (a decreased supply of oxygenated blood) can occur. Although asymptomatic, severe heart damage may result. Unlike an angina attack, which is usually prompted by physical exertion, more than three-fourths of silent ischemic attacks are caused by mental arousal. There is also a definite link between the hardening of the carotid artery and higher levels of stress (Barnett 1997).
A recent study of 2800 men and women over 55 years of age showed that even minor depression can increase cardiac mortality 60%, while major depression may actually triple the rate of cardiac-related deaths (Pennix et al. 2001). There is also convincing evidence that depression significantly increases the risk of mortality following a heart attack or coronary bypass surgery (Baker et al. 2001).
Researchers explain the relationship between mindset and mortality, pointing out that stress response to depression appears to trigger chronically high cortisol levels, a hormone secreted by the adrenal glands (Pennix et al. 1999a). Hormonal imbalances, in turn, can alter insulin resistance and increase blood pressure, magnifying the risks imposed by a heart attack or bypass surgery.
A study conducted at Duke University ( Durham , NC ) showed that men with established heart disease who underwent 4 months of stress management (1.5 hours weekly) experienced a significant reduction in clinical cardiovascular events. The advantage was observed at the conclusion of counseling and throughout 5 years of assessment, suggesting both economic as well as clinical benefit (Blumenthal et al. 2002).
Stress protracts to so many traditional risk factors that emotions may be the dominant issue in coronary health. Note the following risk factors that share stress as their common bond.
- Stress can destroy sound eating habits by the uncaring selection of inappropriate foodstuffs, eating hurriedly, or eating not because of hunger but as a respite from a dismal situation. Stress is a strong contributor to obesity, a factor in cardiovascular disease.
- Stress increases blood pressure. In studies involving 3000 Caucasians with depression and anxiety (ages 23-64), these individuals were found to have twice the risk of developing hypertension. The odds worsened for African Americans, with the risk factor for hypertension increasing more than 3 times during periods of unresolved stress. Even the companionship of a pet has been shown to reduce stress and subsequently blood pressure (Alexander et al. 1996; Beck et al. 1996).
- Stress makes blood glucose levels more difficult to control (Challem et al. 2000). Diabetes, a long-established risk to heart health, has been termed a disease fueled by emotions.
- Alternative Medical News reports that stress increases blood cholesterol levels. Students preparing for exams, Indianapolis 500 drivers (following the race), and accountants after the April 15 deadline show higher cholesterol levels (Alternative Medical News staff 1995).
Scientific testing has advanced genetic screening far beyond compiling an oral history of ancestral successes and failures. Instead, geneticists are looking for mutated genes that may be expressing themselves as contributors to coronary artery disease. For example, 50% of suppressed HDL cholesterol can be linked to genetic factors. A gene (ABC1), when mutated, appears responsible for increasing the risk of heart disease by lowering levels of HDL cholesterol. Michael Hayden (professor of medical genetics at the University of British Columbia) reports that people with defects in ABC1 have just as much risk for heart disease because of too little HDL as individuals with high levels of LDL cholesterol (Cosgrove 1999).
Assessing Apo-E Status
The apoE4 variant of apoprotein E is the most well-defined genetic trait affecting poor LDL levels. According to Ronald Krauss, M.D., a double allele (referred to as a double E4 genotype) is associated with high blood cholesterol and an increased prevalence of cardiovascular disease (American Heart Association 1998).
The apoE4 allele is very saturated fat sensitive, suggesting dietary manipulation may be an advantage to those with this genetic fault. In 90% or more of the population, modest dietary cholesterol has very little impact upon LDL cholesterol levels (Bland 2001). However, moderate dietary cholesterol intake in apoE4 individuals can lead to significant increases in plasma LDL levels. Jeff Bland, Ph.D., challenges that public health recommendations do not address genotypes that alter dietary guidelines. Recommendations to universally avoid cholesterol-rich foods prevent some who are not cholesterol sensitive from eating a food that is a "pretty good food," such as an egg.
There are three main alleles or variants of the apoE gene: E2, E3, and E4. Every individual inherits two of these alleles: one from each parent. Research has shown that each allele affects cholesterol metabolism differently. Smoking appears to increase the risk of coronary heart disease in men of all genotypes but particularly in men carrying the E4 allele. Researchers hypothesize that the genetic-coronary link may be due to increased oxidation of LDL cholesterol among smokers with this genotype. Compared to individuals who carry two neutral E3 alleles, those who carry at least one E4 allele tend to produce significantly more LDL cholesterol as well as more total cholesterol; those who have at least one E2 allele typically produce less LDL cholesterol (Humphries et al. 2001; Wang et al. 2001).
Establishing an apoE genotype in menopausal women sheds light on the complex issues of estrogen replacement therapy (ERT) as a cardioprotector. For example, women with the apoE-2 genotype (and using ERT) appeared to benefit the most from the lipid-altering effects of hormones compared to other genotypes. Menopausal women with the apoE-2 genotype (and not using ERT) have the lowest levels of protective HDL cholesterol. If on ERT, apoE-2 carriers have the highest HDL levels of all genotypes. This study suggests that the apoE-2 genotype may predispose a woman's body to produce more protective HDL cholesterol in response to ERT than those of other types (Heikkinen et al. 1999).
The study also showed that women with the apoE-3 genotype (and using ERT) had the highest levels of triglycerides. It appears women with the apoE-3 genotype are more sensitive to the triglyceride-raising effects of hormone therapy. A previous placebo-controlled study of over 150 postmenopausal Finnish women found that LDL cholesterol levels in women with the apoE-4 genotype respond less favorably to ERT (Heikkinen et al. 1999).
Studies that fail to consider genotype may explain the wide disparity in results regarding lipid levels and cardiovascular risk in postmenopausal women receiving HRT. With recent advances in genetic testing, another important piece of the puzzle is now available to help physicians predict how hormone replacement therapy will impact each woman's cardiovascular health (Kardia et al. 1999; von Muhlen et al. 2002).
Homocysteine: The Genetic Link
Compiling a family history of cardiovascular health is a common medical assessment, looking particularly at the early onset of disease. Because of an increasing awareness of the risks imposed by newer risk factors, homocysteine is being factored into the genetic equation. With a gene frequency between one in 70 and one in 200, elevated blood levels of homocysteine may be more common than previously thought (Berwanger et al. 1995). Canadian researchers estimate the inherited amino acid disorder (homocysteinemia) is present in approximately 20% of coronary artery disease patients (Superko et al. 1995).
There are multiple mechanisms involved in the pathogenesis of hyperhomocysteinemia, including not only heterozygosity, but dietary factors as well (Kardaras et al. 1995). Note: Heterozygous refers to inheriting a gene for a characteristic from one parent and the alternative gene from the other parent. The offspring of a heterozygous carrier (of a genetic disorder) has a 50% chance of inheriting the gene associated with the trait. In support of the genetic theory of hyperhomocysteinemia, epidemiological evidence has shown homocysteine levels to be 45% lower in Westernized adult black South Africans than in age-matched white adults, revealing racial genetic differences in homocysteine metabolism (Vermaak et al. 1991).
About one-half of individuals with hyperhomocysteinemia respond favorably to higher doses of vitamin B6 due to an inborn cystathionine-B-synthase deficiency; others have a mutation in the methylenetetrahydrofolate reductase gene (MTHFR), which controls the ability to convert folic acid into 5-methyl tetra-hydrofolate, an active contributor in the methyl donation pathway of the folate cycle (James et al. 1999). The disruption of this cycle represents the domino effect, that is, when one system fails to perform, others downstream are affected as well. In this case, homocysteine clearance is disrupted and hyperhomo-cysteinemia, a powerful endangerment to cardiac health, results. The genetic flaw is correctable by administering 5-methyltetrahydrofolate supplements (the active form of folate) to bypass the metabolic block (Bland 2000a).
Additional Inheritable Risks for Degenerative Disease
- In 1991, researchers identified the gene responsible for hemochromatosis, a predominantly genetic disease reflecting abnormal iron retention despite eating an ordinary diet. Small numbers of individuals with hemochromatosis acquire the condition through chronic iron supplementation or blood transfusions, but the genetic form is most common. To learn more about hemochromatosis (a significant threat to heart health), consult the Iron Overload section.
- The journal Arteriosclerosis, Thrombosis and Vascular Biology reported that carotid plaque was significantly more common in both men and women whose parents died prematurely of coronary heart disease (CHD) than in subjects with no familial history of early cardiac death (Zureik et al. 1999).
- Lp(a) is frequently cited in medical literature as an important inheritable cardiac risk factor for individuals without other apparent signs of heart disease. Approximately 50% of children whose parents have elevated Lp(a) will also have similar Lp(a) derangements (Superko 1996). Although Lp(a) levels are influenced by heredity, this marker is often modifiable by targeted nutritional intervention.
- Genetic factors can influence obesity and fat distribution. Laval University (Quebec, Canada) determined that pairs of identical twins, overfed by the same amount of calories, showed a similarity with respect to body weight and percentage of fat, with about 3 times more variance among pairs than within pairs. After adjustment for the gains in fat mass, the within-pair similarity was particularly evident with respect to the changes in regional fat distribution and amount of abdominal visceral fat, with about 6 times as much variance among pairs as within pairs. Researchers concluded that the tendency to store energy as either fat or lean tissue is influenced by genetic factors (Bouchard et al. 1990).
- A condition known as Dunnigan-type familial partial lipodystrophy (FPLD) bears striking similarities to Syndrome X. The gene mutation responsible for FPLD causes weight gain in the abdomen as well as the face and chest. Affected individuals have high insulin levels, high blood pressure, high triglycerides, and low levels of HDL cholesterol. A recent study confirmed that individuals with FPLD have 6 times the risk of coronary heart disease compared to noncarrier relatives in a control group, that is, 34.8% versus 5.9% at any age and 26.1% versus 0% before the age of 55. The average age of developing heart disease was 46.5 years in individuals with FPLD, with the risk being greater among women than in men. Four of 14 women (about 28%) with FPLD underwent bypass surgery before the age of 55. In contrast, hospitalization data from the general Canadian population in 1996 indicated that one woman in 7350 had been hospitalized between the ages of 35-54 for coronary bypass artery surgery (Canadian Institute for Health Information, http://www.cihi.ca; Hegele 2001; Today's News 2001).
At one time, cardiovascular disease was considered to be predominantly a disease affecting men, not women. Statistics do not support this logic. Studies have demonstrated that heart disease is the number one killer for both men and women. Of the 1.1 million heart attacks reported annually, about 500,000 occur among women.
The Framingham Study reported findings involving 5209 participants, 2873 of whom were women (Framingham Heart Study 1998). Results of the study follow:
- In both men and women, coronary heart disease has exceeded that of other cardiovascular illnesses, such as stroke or congestive heart failure.
- While coronary events occurred twice as often in men, with advancing age the incidence of heart disease in women approaches that seen in men. Menopause appears to be the interval associated with a significant rise in coronary events, as well as a shift to more serious manifestations of the disease.
- The New England Journal of Medicine reported that hormone replacement therapy (HRT) in menopausal women with angiographic-determined heart disease did not lower the progression of the disease (Nabulsi 1993; Herrington et al. 2000). New guidelines issued by the American Heart Association agreed that women with cardiovascular disease should not be given HRT for the sole purpose of preventing future heart attacks. In fact, HRT raised the risk of recurrent attack and death during the first year of usage and thereafter lowered it only slightly (Mosca et al. 2001). Although estrogen replacement therapy may be helpful in lowering refractory lipoprotein(a) and high fibrinogen levels, it increases C-reactive protein levels, making its benefit uncertain (please read the previous section on Heredity and Assessing ApoE Status for extremely valuable information regarding HRT in postmenopausal women).
- Coronary heart disease manifests itself differently in men and women. In women, angina was the most common initial symptom, whereas in men, myocardial infarction was the most frequent first coronary symptom.
- High triglycerides were more predictive of eventual heart disease in women than in men. In fact, high triglycerides threaten the outcome in diabetic women undergoing bypass surgery (Sprecher et al. 2000). Elevations in C-reactive protein (CRP) are the single strongest predictor of future vascular risk, according to the Women's Health Study. Women with the highest levels of CRP in their blood had a fivefold increased risk of future cardiovascular disease and a sevenfold increase in the likelihood of a heart attack compared to those with low levels.
- When a heart attack was the first coronary event, nearly half were unrecognized in women, compared to only a third undetected in men.
- Only 56% of women experiencing a heart attack can expect to live another year, compared to 73% of male victims. Women under 50 years of age are twice as likely to succumb following the attack compared to similarly afflicted men. Statistics change with age, with men and women between the ages of 60-69 showing similar survival patterns (Mukamal et al. 2001): 27% of men who have a heart attack will likely have a second attack within 6 years compared to 31% of women.
- Diabetes is a particularly strong coronary risk factor in women.
- The New England Journal of Medicine reported that the risk of myocardial infarction increased among women who used second generation oral contraception, that is, levonorgestrel. Although inconclusive, early trials indicate third generation oral contraceptives, that is, desogestrel or gestodene, may carry a lesser risk (Tanis et al. 2001).
- Many studies have demonstrated that men who are physically active tend to live longer, illustrating a clear exercise-response curve, with greater activity more effective than moderate. The New England Journal of Medicine recently reported similar findings for women. Both walking and vigorous exercise are associated with substantial reductions in the incidence of cardiovascular events among postmenopausal women; prolonged sitting is predictive of increased cardiovascular risk (Manson et al. 2002).
Scientists believe that a properly planned exercise program may be the single greatest preventive measure against cardiovascular disease. However, it is extremely important that the individual and the activity be properly matched. Even among apparently fit persons, intense but sporadic exercise actually increases the risk of a fatal heart attack. A singles tennis match in an unprepared participant increases the risk of a heart attack sixfold.
The exercise level need not be unpleasantly aggressive to be beneficial. In the past, it was thought that an individual using exercise as a cardiovascular protective should select an activity that produced a state of breathlessness and participate in the action several times a week. It has now been determined that cardiovascular strengthening can be obtained from low intensity activity such as walking for 30 minutes a day. In fact, Dr. Shah Ebrahim, a British cardiologist, states that sexually active men, that is, those engaging in sex 3-4 times a week, reduce their risk of either a stroke or a heart attack by half. Some researchers question whether the mild to moderate energy expended during intercourse is the perk favoring a healthier cardiovascular system or if it is the mindset that drives the sexual act.
The New England Journal of Medicine reported findings relating to the impact of exercise upon 180 postmenopausal women (45-64 years) and 197 men (30-64 years) (Stefanick et al. 1998). The participants were divided into four groups: diet plus exercise, diet alone, exercise alone, and controls. LDL cholesterol levels in the diet-plus-exercise group were significantly reduced compared to the three remaining groups. It is also possible that exercise will alter the size of LDL particles. (Recall that abnormally small LDL particles are highly susceptible to oxidation and elude standard testing processes, misrepresenting the end results.)
Exercise reduces blood pressure and heart rate by influencing sympathetic neural and hormonal activity. As epinephrine (adrenaline) and norepinephrine levels are decreased, one's blood pressure and heart rate subsequently decrease (Katona et al. 1982; Duncan et al. 1985; Smith et al. 1989).
The statistics support that a regular exercise program reduces the risk of stroke, not only by lowering blood pressure, but also by increasing peripheral circulation and oxygen delivery. These findings were confirmed in a 10-year study, involving 14,101 Norwegian women (50-101 years of age). The results showed that the risk of dying from stroke declined as physical activity increased; the most active women had approximately 50% lower risk of death from stroke across all age groups (Ellekjaer et al. 2000).
Excessive fibrinogen, a risk factor for cardiovascular disease, is impacted by exercise. A study showed that exercise of moderate intensity increases fibrinolytic activity by increasing tissue plasminogen activators. (Tissue plasminogen activators break down fibrinogen, decreasing the risk of blood clot formation.) The substantiation of this process occurred when 14 sedentary men (average age 35) and 12 physically active men (average age 35) participated in exercise sessions in the morning and evening at 50% maximal oxygen consumption. The results of the study indicated that moderate-intensity exercise increased the activity of tissue plasminogen activators in both physically active and sedentary men, particularly during evening exercise. C-reactive protein, another of the newer risk factors for cardiovascular disease, also appears lowered by exercise (Szymanski et al. 1994; Ford 2002).
A sedentary lifestyle encourages weight gain and worsens Syndrome X, a condition of insulin resistance and compensatory hyperinsulinemia (insulin excess). Conversely, physical fitness increases cellular glucose responsiveness and decreases the amount of insulin secreted after a carbohydrate load (Challem et al. 2000). Exercise makes the vasculature less prone to damage when insulin levels are unstable. The vulnerabilities associated with Syndrome X, that is, diabetes, hypertension, hypertriglyceridemia, and suppressed HDL levels are often modifiable by exercise-induced weight loss.
If cardiovascular disease has manifested, a monitored exercise program can assist in recovery. Exercise helps in building a new network of blood vessels, naturally bypassing those impaired. The conclusion regarding exercise is that it is never too late to reap the benefits from a properly structured program. However, according to the Framingham Heart Study, only recent physical activity makes a significant difference (Sherman et al. 1999). Exercise undertaken earlier in life showed no sustained cardioprotection.
Beneficial as physical activity is, even low-intensity exercise can be a harbinger of free radicals; over -exercising can generate enough free radicals to damage the DNA in white blood cells. The remedy is to provide the system with adequate amounts of antioxidants before engaging in physical activity. Also, sweating during exercise can drastically deplete minerals. This phenomenon likely contributes to the numbers of sudden deaths occurring among athletes and joggers. Lost body fluids and minerals should be replaced immediately.
Researchers are examining the role of gum disease in the genesis and progression of heart disease. The inflammatory process, observed in the lining of atherosclerotic blood vessels, appears to be paralleling chronic inflammation observed in periodontal disease. The findings reported in the American Journal of Epidemiology showed that fibrinogen and C-reactive protein (coagulability and inflammatory markers) are increased in individuals with periodontal disease (Wu et al. 2000). Dr. Wu and colleagues at State University of New York reported that gum disease might also be related to hypercholesterolemia, although a weaker link is found between elevated cholesterol and gum disease than for the elevations in CRP and fibrinogen.
Bleeding, red, swollen gums are depictive of gingivitis, a condition of inflammation and bone deterioration promulgated by bacteria. The American Academy of Periodontology recently launched a media story showing that people with periodontal disease are 200-300% more likely to experience a heart attack than those with healthy gums. Allowing for multiple cardiac risk factors, the researchers concluded that gum disease was a greater risk for cardiovascular disease than hypertension (Genco 1997).
A pilot study (involving 38 heart attack patients matched to a comparable group of 38 people without known heart disease) showed a dramatic correlation between periodontal disease, CRP, and cardiac health: 85% of cardiac patients presented with gum disease compared to only 29% in the control group. Not only did the heart attack patients with periodontal disease have higher levels of CRP than those without gum disease, the CRP levels were directly related to the severity of the oral condition (Medscape Wire 2000) (to read about the risks imposed by high levels of CRP, please turn to the Newer Risk Factors section appearing in this protocol).
Should the gums be pulling away from the teeth and appear red, swollen, or tender, seek immediate dental care. Other red flags are gums that bleed while brushing, bad breath, or a discharge of pus. Turn to the Calcium, Coenzyme Q10, and Vitamin C subsections in the Therapeutic section to learn about maintaining healthy gum tissue and avoiding periodontal disease.
(HYPO- AND HYPERTHYROIDISM)
Seldom considered but often the source of disease, the thyroid gland (a member of the endocrine system) should be evaluated in all cardiac patients. A healthy thyroid gland benefits the heart by modulating basal metabolic rate, improving one's mindset, lowering cholesterol and homocysteine levels, and regulating one's heartbeat and circulation. As the following dialog will exemplify, disease states are common when either over- or underperformance of an organ occurs.
Researchers became keenly aware of the importance of a healthy thyroid gland after assessing the homocysteine and cholesterol levels in 7000 individuals from the general U.S. population (Morris et al. 2001). After subdividing test participants into two groups (those with hypothyroidism and those with normal thyroid function), researchers realized that about two-thirds of those diagnosed with hypothyroidism had cholesterol levels nearly 4 times higher than normal. Those who tested positive for hypothyroidism were more likely to be white, female, and "slightly older." Interestingly, an increase in plasma thyroxine concentrations (an iodine-containing hormone secreted by the thyroid gland with the chief function of increasing the rate of cell metabolism) typically precedes reductions in plasma cholesterol levels.
Approximately 50% of individuals thyroid-impaired also had high homocysteine levels compared to only 18% with a healthy gland. Researchers determined that about 90% of hypothyroid subjects in the U.S. population are either hyperhomocysteinemic or hypercholesterolemic; in contrast, only 31% of individuals with normal thyroid function have similar physical complaints (Morris et al. 2001).
The age groups affected by poor thyroid performance and cardiovascular disease are widespread. For example, clinicians examining a group of heart attack victims younger than 40 years of age found two common abnormalities: (1) elevations in serum cholesterol levels and (2) reductions in basal metabolic rate.
A 5-year study involving 347 patients (reported in the Journal of the American Geriatric Society) evaluated the effects of thyroid therapy upon atherosclerosis in a subset of the population 54.7-64.5 years old (Wren 1968): 132 of the individuals had experienced heart attacks, strokes, angina pectoris, or disruption in peripheral circulation; the remaining 215 participants were asymptomatic but were considered high risks because of the presence of electrocardiographic abnormalities, hypertension, diabetes, or hypercholesterolemia.
Only 9% of the patients (31 of the total 347) tested positive for hypothyroid conditions. Nonetheless, all were treated with thyroid extract, and substantial clinical improvements occurred in a number of the patients. Of the 132 symptomatic patients, 29 of 41 with angina reported benefits that included increased exercise tolerance, decreased frequency and severity of attacks, and less need for nitroglycerin. Mean cholesterol levels fell by about 22%. During the 5-year study, 11 patients died, less than half of the expected rate based on United States Life Tables (Barnes 1976).
How might poor thyroid function contribute to arteriosclerotic vascular disease, that is, the hardening of the arteries? Researchers speculate that hypothyroidism may slow or decrease the metabolic breakdown of fats such as cholesterol. In addition, a dysfunctional thyroid gland may also impair kidney function and interfere with the activity of a gene (methylenetetrahydrofolate reductase) that the body depends on to process (remethylate) homocysteine.
Also, if the body fails to convert thyroxine (T4) to tri -iodothyronine (T3), the body's most potent thyroid hormone, T3 becomes less available in the bloodstream, while levels of reverse T3 (rT3), an inactive metabolite of T3, tend to build up (Shanoudy et al. 2001). A low T3-rT3 ratio is associated with a lesser ability of the left ventricle to pump blood and is highly predictive of poorer short-term outcome in patients with severe chronic heart failure.
In 1998, the American College of Physicians established guidelines for maintaining thyroid health, recommending routine assessment of thyroid simulating hormone (TSH) levels in all women over 50 years of age; women ages 35 and older should be evaluated every 5 years.
In addition, a positive test for the thyroid peroxidase antibody (TPOAb) can be an important early warning sign of emerging dysfunction (Stockigt 2002). Having either high TSH or a positive TPOAb raises the risk of progressing to overt hypothyroidism eightfold; having both increases the risk 40-fold. Note: Hypothyroidism affects more women than men, but the risk increases with age for both men and women. In addition, women are about 5-10 times more prone to hyperthyroidism than men.
The attempts to improve cardiovascular performance without factoring in the possibility of a poorly functioning thyroid gland diminish the chances of success. Conversely, remarkable improvements can be expected if hypothyroidism exists and is treated as the primary condition provoking lipid or vascular derangements.
Hyperthyroidism (an overactive thyroid gland) is also an endangerment to cardiac health, forcing blood vessels into a chronic state of prolonged excitability. Italian researchers measured vascular function (before and after treatment for hyperthyroidism) and compared it to a control group with a healthy thyroid gland. Researchers found that excess levels of thyroid hormones had a strong negative impact on the function of the endothelium (the inner lining of blood vessel walls), resulting in up -regulation of blood flow through the circulatory route (Napoli et al. 2001).
Compared to individuals with normal thyroid function, hyperthyroid patients produce significantly higher levels of nitric oxide, leading to increased blood flow and dilation of blood vessels in a resting state. Hyperthyroid patients, typically, show an exaggerated vascular reaction to the cardiac effects of acetylcholine (a neurotransmitter) and norepinephrine (a stress hormone synthesized by the adrenal medulla). Patients with overt hyperthyroidism as well as those with subclinical disease who were given echocardiograms showed that a supercharged thyroid gland caused the cardiovascular system to show clear signs of parasympathetic withdrawal (Petretta et al. 2001). Excitory instructions directed to the endothelium explain why even subclinical thyroid dysfunction is an independent risk factor for heart disease. Endo-thelium, stimulated by over-reactive thyroid messages, is implicated in both congestive heart failure as well as heart attacks.
In the early stages of hyperthyroidism (when TSH levels are high, but thyroid hormone levels are still normal), the heart may already be losing its ability to calm itself. Over time, chronic excitability (leading to increased blood circulation and heart rate) overworks the heart and literally wears it out. Interestingly, when following treatment to resolve hyperthyroidism, the vascular mechanics return to normal.
Illustrative of the value of a healthy thyroid gland, the National Health and Nutrition Examination Survey showed that once the thyroid falters in its performance, the heart may not be far behind (Rodriguez 2001). The need for a thyroid evaluation is thus impossible to overstate. Identifying and treating hypo- or hyperthyroidism can improve both the quality and duration of life.
IRON OVERLOAD (HEMOCHROMATOSIS)
The research to determine the effects of iron excess on cardiovascular health has had mixed findings. The Annals of Epidemiology reported that no association between iron levels and mortality from cardiovascular disease was found in data collected from NHANES II and the National Death Index (Sempos et al. 2000). Reports published in two respected journals (Journal of the American Heart Association and American Journal of Epidemiology) chronicled an opposing view, showing that free iron corresponds to a greater risk of fatal heart attacks and strokes by encouraging free-radical production (Kiechl et al. 1997; Klipstein-Grobusch et al. 1999).
Just as the iron in your car can rust, the iron in your body is susceptible to rust, or oxidation, a process that damages tissues and blood vessel walls. Several studies have found that iron is most damaging to the heart if LDL cholesterol levels are also high. This occurs as free iron oxidizes LDL cholesterol, increasing the damage imposed upon the heart and vascular system.
Hemochromatosis not only increases the oxidation process, but also reduces antioxidants, including glutathione (Young et al. 1994). As glutathione is depleted, free radicals (attacking in the cerebral region) can increase stroke progression. Stroke patients with high blood ferritin (a measurement of the total iron stored in the body) experienced greater post -stroke trauma, that is, increased lethargy, aphasia, and unawareness (Davalos et al. 2000).
An iron overload further complicates a cardiovascular outcome by contributing to an irregular heartbeat, heart attacks, and heart failure. Every 1% rise in blood iron increases the risk of heart disease 4% (Whitney et al. 1998). Interestingly, iron-induced cardiac irregularities can affect both young and senior subjects, even anemic patients.
Dr. Hidehiro Matsuoka ( Kurume Medical School in Japan ) says iron somehow interferes with nitric oxide, a chemical that relaxes blood vessel walls, allowing the blood to flow more freely. As iron levels increase, malondialdehyde (a marker reflecting oxidation and impaired endothelial function) also increases. Individuals with hemochromatosis who were appropriately treated had lower levels of malon-dialdehyde, and their blood vessels performed with greater normalcy (Tzonou et al. 1998; Fox 2002).
Patients with an iron overload are frequently advised to avoid foods rich in vitamin C or vitamin C supplements because of the iron enhancing factors associated with ascorbic acid. Some (with hemochromatosis) can use 500 mg of buffered vitamin C, taken 3 times a day between meals, without difficulty. Cast-iron cookware and iron-fortified foodstuffs should be avoided, and meats and alcohol should be restricted. On the other hand, coffee or tea consumed with meals assists in blocking iron absorption from foods. Fruits (nonascorbic acid varieties) and vegetables are excellent dietary choices for individuals with an iron overload. Simply withdrawing iron-fortified foods from the diet can prompt dramatic changes in iron levels.
Dispersed throughout the Therapeutic section are supplemental suggestions to reduce iron overload, such as calcium, fiber, garlic, magnesium, vitamin E, and green tea, but individuals wishing to protect themselves from iron buildup may also want to consider a blood donation. Some individuals donate the blood to themselves to ensure a healthy future supply, but this course is only valuable if the individual is not anemic. Should anemia coexist with hemochromatosis, drugs in the form of iron chelators may be prescribed.
Optimal iron levels appear to be <100 mcg/dL, although the standard reference range is up to 180 mg/dL. Tests such as total iron binding capacity, serum iron, and a DNA test called HLA-H, along with family history, are other excellent screening tools for hemochromatosis.
Comment: Adequate amounts of iron are absolutely essential to good health, but using iron supplements or iron fortified foods is not recommended for men or postmenopausal women, unless diagnosed with an iron deficiency. It is judged that approximately one of every 200 people actually has iron overload disease. Read the sections devoted to Heredity and Chelation Therapy in this protocol to learn more about hemochromatosis.
NEWER RISK FACTORS
In the last 25 years, the incidence of coronary fatalities has decreased 33%. This is due largely to avoiding the traditional risk factors. Dr. Paul M. Ridker, M.D., M.P.H. (director of cardiovascular research at Brigham and Women's Hospital in Boston , MA ), speculates that an auxiliary list of newer predictive factors may significantly increase the numbers benefiting from 21st century diagnostics and treatment (Ridker 1999a) (see Figure 3).
| Newer Predictive Factors |
| Fibrinogen (a marker for blood coagulability and inflammation) |
|Fibrinolytic Activity (the regulation of fibrinogen concentrations) |
|Lipoprotein(a) (a marker for impaired fibrinolysis and plaque buildup) |
|Homocysteine (a marker for hypercoagulability and vascular assault) |
|Syndrome X (a condition of insulin resistance and hyperinsulinemia) |
|C-Reactive Protein (CRP) (an inflammatory marker) |
Fibrinogen is a blood protein that plays a critical role in normal and abnormal clot formation, a mechanism referred to as coagulation. A process of checks and balances, an interaction between clotting factors and naturally occurring anticoagulants, normally results in healthy levels of fibrinogen and normal coagulation. If fibrinogen levels increase above normal, however, a blood clot becomes a threat; if fibrinogen levels decrease below normal, a hemorrhage can result. Although the reference range used by most laboratories is 150-460 mg/dL, it is crucial to keep serum fibrinogen under 300 mg/dL, a level considered safe.
The coagulation of blood depends upon a number of proteins found in plasma, called clotting factors. Normally, clotting factors are inactive, but following injury, they become activated. Exposed collagen or chemicals released from injured tissues initiate a series of chemical reactions that result in the production of prothrombin activators. Prothrombin activators convert prothrombin to thrombin, which, in turn, converts fibrinogen to fibrin (a network of protein fibers that can trap blood cells, bloodstream infiltrates, and platelets). The risks multiply as materials become trapped in the tangle. An atheromatous tumor (capable of continued growth) can result in full occlusion (Whiting 1989; Seeley et al. 1991; Kohler et al. 2000).
Fibrin may stimulate cell proliferation by providing a scaffold along which cells migrate and by binding fibronectin, which stimulates cell migration and adhesion. Fibrinogen thus encourages monocyte adhesion and smooth muscle proliferation, further occluding the vessel. In advanced plaque, fibrin may also be involved in the tight binding of LDL and the accumulation of lipids (Smith 1986; Koenig 1999a).
Vascular closure represents only one facet of the risk: plaque is highly susceptible to breakage and clot formation. About 700,000 heart attacks and stroke deaths occur in the United States each year as a result of a blood clot obstructing the delivery of blood to the heart or brain. Reports in the New England Journal of Medicine showed that those with high levels of fibrinogen were more than twice as likely to die of a heart attack, but the risk of a stroke increases as well (Wilhelmsen et al. 1984; Packard et al. 2000).
A cohort of the large scale EUROSTROKE project (215 cases and 521 controls) showed that fibrinogen was a powerful predictor of stroke, both fatal and nonfatal events. After dividing subjects into four quartiles based on fibrinogen levels, researchers found that the risk of stroke increased nearly 50% for each ascending quartile. Fibrinogen increased the risk of stroke independent of smoking status, but the odds ratio worsened with higher systolic blood pressure. For example, the fibrinogen risk increased from 1.21 among those with a systolic pressure below 120 mmHg to 1.99 among subjects with a systolic pressure of 160 mmHg or above (Bots 2002).
Fibrinogen also promotes the negative activity of platelets by encouraging platelet aggregation (Koenig 1999b). In addition, German researchers determined that fibrinogen deposition at the vessel wall promotes platelet adhesion during ischemia (Massberg et al. 1999). Platelets, the smallest of blood elements, are absolutely essential in sealing vascular injuries, whether caused by a knife wound or hypertension. According to Dr. James Braly, M.D., as long as the interior of the vessel is smooth, platelets are not summoned into service; however, if trauma is detected, platelets rush to the site, forming a plug to repair the wound. Once activated, platelets do more than provide the materials for vascular repair. They also release serotonin (a vasoconstrictor) and the powerful platelet aggregator thromboxane A2, further adding to the risk of a thrombus (Braly 1985; Smith 1986; Ernst et al. 1993).
Aortic stenosis is the abnormal narrowing of the valve between the left ventricle and the aorta. The narrowing, or stenosis, is often associated with calcification, a process that may involve fibrinogen (Levenson et al. 1997). Fibrinogen appears to have an attraction for calcium; as fibrinogen and calcium unite, the valvular diameter becomes smaller.
The Life Extension Foundation was the first research group to recognize the importance of assessing fibrinogen as an independent risk factor for cardiovascular disease. A study reported in the Journal of the American College of Cardiology corroborated the Foundation's position on fibrinogen, when nearly 400 male physicians participated in the Physicians' Health Study (Ma et al. 1999). The blood fibrinogen levels of 199 subjects, who experienced heart attacks during the study period, were compared with those of 199 control subjects who did not suffer heart attacks. Individuals having heart attacks had significantly higher fibrinogen levels compared to those physicians with healthy fibrinogen levels. Several studies have shown a stronger association between cardiovascular deaths and fibrinogen levels than for cholesterol.
For example, a study involving 3043 patients with angina pectoris (who underwent coronary angiography and were followed for 2 years) concluded that higher baseline levels of fibrinogen were predictive of a heart attack and likelihood of sudden cardiac death. In contrast, coronary risk was low among patients with low fibrinogen concentrations despite increased serum cholesterol levels (Thompson 1995). A similar study showed that fibrinogen was directly associated with the presence of myocardial infarction and an independent short-term predictor of mortality (Acevedo et al. 2002; Bots et al. 2002; GSDL 2002).
Various factors influence plasma fibrinogen levels:
- Increased winter cardiovascular mortality is related to a cold weather increase in fibrinogen. The exposure to cold increased fibrinogen 23-38% over baseline (Woodhouse et al. 1997; Horan et al. 2001).
- Smokers and depressed individuals have higher levels of fibrinogen (Mindell 1998; Castilla et al. 2002).
- Estrogen replacement therapy appears to attenuate normal age-related increases in fibrinogen (Stefanick et al. 1995; el-Swefy et al. 2002).
Unfortunately, pharmaceutical drugs have not been of significant value in reducing fibrinogen levels. The initial data suggested that Bezafibrate (a European drug) reduced fibrinogen levels in patients with established coronary heart disease. However, the Bezafibrate Infarction Prevention Study yielded disappointing results, with no significant evidence of efficacy in lowering fibrinogen (Behar 1999).
Anticoagulant therapy usually becomes the treatment of choice to reduce fibrin. Warfarin (Coumadin) and heparin are often prescribed, but it is difficult to administer enough of an anticoagulant to lessen the risk of a blood clot without increasing the risk of a hemorrhage. Dispersed throughout the Therapeutic section are products with fibrinolytic and antiplatelet aggregating activity, such as aspirin, bromelain, curcumin, essential fatty acids, garlic, ginger, ginkgo biloba, green tea, gugulipid, niacin, pantethine, policosanol, proanthocyanidins, vitamin A, beta-carotene, vitamin C, and vitamin E. A novel drug approach to reduce excess fibrinogen is to take 400 mg of pentoxifylline twice daily.
To read about other factors affecting fibrinogen, consult the Obesity, Sedentary Lifestyle, Gum Disease, Fibrinolytic Activity, and Link Between Infection and Inflammation in Heart Disease sections in this protocol.
Balance between tissue plasminogen activators (t-PA) and plasminogen inhibitors (PAI-1) controls activity in the fibrinolytic system. If the fibrinolytic process is faulty, individuals can be classed as either hemorrhage or thrombosis prone. Generally, increased PAI-1 concentrations reflect impairment of the fibrinolytic process, with a reduction in plasmin formation and an accumulation of fibrin, platelets, minerals, and lipids. This model can predispose recurrent thrombosis. Recent data from animal and human studies indicate that PAI-1 is preferentially produced in visceral adipose tissue, a finding that explains the hypercoagulability associated with obesity. In patients with PAI-1 deficiencies, a hemorrhage may be a concern (Reilly et al. 1991; Farrehi et al. 1998; Kohler et al. 2000; Ridker 2000).
The New England Journal of Medicine reported that anomalies occurring in t-PA and PAI-1 are likely to be critical factors underlying hyperinsulinemia in ischemic heart disease (Despres et al. 1996; Ridker 2000). Barry Sears, Ph.D., believes scientific evidence has rightly exposed hyperinsulinemia as an indicator of an eventual heart attack (Sears 1995). Hyperinsulinemia bestows some of its coronary damage by increasing the risk of hypertension (twofold), hypertriglyceridemia (three- to fourfold), Type II diabetes (five- to sixfold), and by diminishing HDL levels.
The research suggests that peripheral factors influence the clotting of blood. For example, The Lancet reported that air travel increases the risk of venous thrombosis by increasing prothrombin factors (Scurr et al. 2000). Note: Venous thrombosis is a condition characterized by a blood clot in a noninflamed vessel. Pain, swelling, and inflammation may follow if the vein is significantly occluded.
Although blood clots loom as one of the dominant factors in cardiovascular disease, the selection of supplements that favor fibrinolysis and discourage platelet aggregation should be done sensibly. It is possible that the cumulative value of nutrients that oppose blood clot formation could overcorrect a condition, particularly if used in concert with prescribed blood thinners. Note: For information regarding asymptomatic patients taking warfarin, please consult the Vitamin K subsection in the Therapeutic section of this protocol.
The peak time for the most damaging of heart attacks appears to be between 6 a.m. and noon . The reason why is of deep concern to the medical community. Some theorize that facing the challenges and urgencies of a new day could be activating the sympathetic nervous system. Was the "fight or flight" mentality too much stimulus for a cardiac prone individual? Note: UCLA researchers speculate that if the sympathetic nervous system is involved in the circadian pattern of sudden death, this involvement reflects exaggerated morning end organ responsiveness to norepinephrine (an adrenal medulla adrenergic hormone), not higher morning sympathetic outflow (Middlekauff et al. 1995).
Japanese researchers took the question further and measured serum lipids and clotting factors in two groups of men: those who suffered a heart attack during the 6-hour morning "peak period" and those who had a heart attack at other times during the day or night (Fujino et al. 2001). Morning heart attack victims were found to have significantly higher levels of Lp(a), the only distinguishable factor compared to the other group. There was also a tendency toward hypercoagulation, increasing the risk for developing a life-threatening thrombus or clot. The conclusion of the Japanese study was that increases in Lp(a) appear to be influencing coagulation factors involved in the occurrence of morning heart attacks.
The physical character of Lp(a) adds to its complexities. For example, Lp(a) is a distinctive serum lipoprotein composed of an apoB-containing lipoprotein structure (virtually identical to LDL cholesterol) attached by a single disulfide bond to a long carbohydrate-rich protein, apolipoprotein(a):
LDL + apo(a) = Lp(a).
Comment: apo(a) is remarkably similar to plasminogen, an inactive precursor of plasmin (also called fibrinolysin), an agent capable of dissolving fibrin (McClean et al. 1987; Hajjar et al. 1989; Harpel et al. 1989; Ridker 2000).
Because apo(a) is highly homogenous (having a likeness in form) with plasminogen, it has been hypothesized that Lp(a) competes for plasminogen that binds to fibrin and endothelial cell surfaces, thus inhibiting fibrinolysis. Experimental work indicates that Lp(a) modulates fibrinolysis, inhibits plasminogen binding to fibrin, and may also inhibit t-Pa, a clot-dissolving substance produced naturally by cells in the walls of blood vessels. The end result is a greater risk of blood clot formation, and thus heart attack and stroke (Loscalzo et al. 1990; Ridker 2000; Caplice et al. 2001).
Complicating the atherosclerotic-Lp(a) mechanism, apo(a) has a sticky "velcro" nature, causing it to easily tie up in blood vessels. As apo(a) participates in vascular repair, its adhesiveness provides an ideal trap for LDL, VLDL, and other bloodstream infiltrates, for example, calcium. In layered fashion, circulating materials mount the debris, promoting the growth of an atheromatous tumor. As plaque accumulates, greater amounts of Lp(a) are observed at the site of the occlusion.
It should be noted that plaque formation is an essential response to vascular injury. When a blood vessel has been damaged, repair is paramount. If benign materials, such as vitamin C, are available to protect the vessel from injury and to participate in vascular repair, the need for Lp(a) is moot. Without adequate amounts of vitamin C, Lp(a) becomes indispensable (Rath 1993).
There is a vast difference between the materials used to repair vascular injuries. For example, vitamin C repairs the wound, leaving the vessel wall smooth, but stronger; Lp(a) repairs the injury, leaving residual trappings, a sticky compress, capable of continued growth. Although Lp(a) has an important function in the body, Matthias Rath, M.D., considers Lp(a) 10 times more dangerous than LDL cholesterol.
The risk of a major cardiovascular event nearly tripled among middle-aged men (participating in a Lp(a)/heart study) whose Lp(a) levels fell within the highest 20% of the study group compared to those with lower levels (von Echardstein et al. 2001). The risks escalate even higher if Lp(a) coexists with high LDL cholesterol, low HDL cholesterol, and hypertension.
Elevated Lp(a), above 30 mg/dL, has been noted in 20% of all thromboembolism patients compared to 7% of healthy controls (von Depka et al. 2000). Lp(a) may prove to be one of the most predictive of the risk factors for strokes, re -stenosis (recurrent narrowing of a vessel), or heart attack following either coronary bypass surgery or angioplasty. Recent studies also incriminated Lp(a) in angina pectoris, citing accumulations of Lp(a) in the plaque of unstable angina patients. Comment: According to the American Heart Association, the lesions on artery walls contain substances that may interact with Lp(a), leading to the buildup of fatty deposits (American Heart Association 2002).
Aortic stenosis, the narrowing of the valve separating the left ventricle from the aorta, is often described as a calcification process. Lp(a) appears to play a role in this process; as Lp(a) is deposited on the aortic valve, it creates a binding site for calcium (Shavelle et al. 2002). Researchers at the University of Washington (Seattle) hypothesized that HMG CoA reductase inhibitors (statins) might slow aortic calcification: 28 patients receiving statin therapy for approximately 2.6 years had a 62-63% lower rate of aortic valve calcium accumulation; 44-49% fewer statin patients experienced definite progression of the disease process (Shavelle 2002) (please consult the section devoted to valvular disease for an in-depth discussion regarding aortic stenosis).
The reference interval for Lp(a) is 0-30 mg/dL. Reference ranges are valuable only as generic markers. Depending upon the test, risk may be significantly increased as values reach upper or lower limits of normal. Various reputable cardiologists strive for an Lp(a) less than 10 mg/dL among patients (Sinatra 2002). Read about essential fatty acids, L-lysine, L-proline, niacin, vitamin A, and vitamin C (nutrients that assist in maintaining healthy Lp(a) levels) in the Therapeutic section of this material.
Introduction to Homocysteine
For a discussion relating to detoxification mechanisms and nutrients to reduce homocysteine levels, consult the Homocysteine Lowering Nutrients and Elimination Pathways subsections in the Therapeutic Section of this protocol.
Although the dangers imposed by hyperhomocysteinemia are not a new discovery, most of the medical community has until recently ignored homocysteine as a cardiovascular risk. Decades ago, Kilmer McCully, M.D., pioneered the homocysteine/cardiovascular hypothesis; the Life Extension Foundation focused upon the dangers of homocysteine and outlined a vitamin protocol to reduce hyperhomocysteinemia in an article released in November 1981 (Anti-Aging News pp. 85-86). Eric Braverman, M.D., joined the crusade, describing homocysteine as a substance that is worse than cholesterol (Braverman 1987).
Homocysteine is regarded as more dangerous than cholesterol because homocysteine damages the artery and then oxidizes cholesterol before cholesterol infiltrates the vessel. Craig Cooney, Ph.D., says that homocysteine is now widely recognized by scientists as the single greatest biochemical risk factor for heart disease, estimating that homocysteine may be a participant in 90% of cardiovascular problems.
Although homocysteine's role in atherosclerosis and atherothrombosis is confirmed, it should be noted that most naturally occurring substances have purpose in physiology. The American Academy of Family Physicians explains that homocysteine is typically changed into other amino acids for use in the body's normal functions (American Family Physician 1997). For example, homocysteine is an intermediate product of methionine metabolism. Two pathways detoxify homocysteine, the remethylation pathway (which regenerates methionine) and the trans -sulfuration pathway (which degrades homocysteine into cysteine and then to taurine). The amino acids cysteine and taurine are important nutrients for cardiac health, hepatic detoxification, cholesterol excretion, bile salt formation, and glutathione production. Because homocysteine is located at a critical metabolic crossroad, it either directly or indirectly impacts the metabolism of all methyl - and sulfur groups occurring in the body (Miller et al. 1997).
In addition, a select group of researchers contend that the residuals (metabolites) of homocysteine appear to support adrenal gland function and contribute to neurotransmitter synthesis and the regeneration of bones and cartilage. If their undocumented speculations prove valid, it should be strongly emphasized that homocysteine must be detoxified in order for its byproducts to offer any biological advantage. If disposal systems (remethylation and trans -sulfuration) are nonfunctional, allowing homocysteine to accumulate, the results can be deadly. Remethylation and trans -sulfuration are discussed in detail in the Therapeutic section of this protocol, under the subsections Homocysteine Lowering Nutrients and Elimination Pathways.
The Hazards of Hyperhomocysteinemia
Experiments show that if homocysteine accumulates in the cell, all methylation reactions are inhibited. Because methylation is used for so many body processes (apart from homocysteine metabolism), if this system becomes dysfunctional, essential pathways are foiled. For example, methylation is fundamental to maintaining healthy DNA, lessening the possibility of mutations and strand breaks. Since DNA strand breaks have been detected in the biopsies of diseased cardiac tissue, it is suspected that strand breaks fuel the progression of heart disease. In addition, DNA strand breaks are associated with accelerated aging and a greater cancer risk (Domagala et al. 1998; Seki et al. 1998).
If homocysteine is not detoxified and begins to accumulate, plaque builds up in the endothelial cells lining the arteries through various mechanisms. For example, homocysteine speeds the oxidation of cholesterol, which then becomes bound to small, dense LDL particles. Macrophages then take up the particles to become foam cells in plaque. The earliest detectable lesion of atherosclerosis is the fatty streak (consisting of lipid-laden foam cells that are macrophages that have migrated as monocytes from the circulation into the subendothelial layer of the intima) that later become fibrous plaque (Naruszewicz et al. 1994; Cranton et al. 2001). Dr. Kilmer McCully, a crusader for the homocysteine theory of heart disease, says that homocysteine plays a key role in every pathophysiological process that leads to arteriosclerotic plaque (McCully 1996).
A heart attack or stroke is more likely to occur as homocysteine promotes coagulation factors, favoring clot formation (Magott 1998). The European Journal of Clinical Investigation reported that 40% of all stroke victims have elevated homocysteine levels compared to only 6% of controls (Brattstrom et al. 1992). Other studies chronicled similar findings: the elevations in homocysteine in 16 of 38 patients with cerebrovascular disease (42%), seven of 25 with peripheral vascular disease (28%), and 18 of 60 with coronary vascular disease (30%) but in none of the 27 normal subjects (Clarke et al. 1991).
In addition to causing cardiovascular disease by increasing the incidence of blood clots, hyperhomocysteinemia triggers atherosclerosis by encouraging smooth muscle cell proliferation, intimal-medial wall thickness, thromboxane A2 activity, lipid abnormalities, and the binding of Lp(a) to fibrin (Magott 1998; Sandrick 2000).
Vascular integrity is compromised as homocysteine blocks production of nitric oxide in the cells of blood vessel walls, causing vessels to become less pliable and even more susceptible to plaque buildup (Boger et al. 2000; Holton 2001). Scientists explain that vessels lose their expansion capacities as homocysteine reduces nitric oxide's availability (Tawakol et al. 2002). Homocysteine significantly hampers coronary microvascular circulation by impairing dilation functions.
Drs. Allen Miller and Gregory Kelly explain that homocysteine facilitates the generation of hydrogen peroxide. By creating oxidative damage to LDL cholesterol and endothelial cell membranes, hydrogen peroxide can then promote injury to vascular endothelium (Starkebaum et al. 1986; Stamler et al. 1993; Miller et al. 1997). Nitric oxide (also known as endothelium-derived relaxing factor) normally protects endothelial cells from damage by reacting with homocyst eine, forming S-nitrosohomocysteine, which inhibits hydrogen peroxide formation. However, as homocysteine levels increase, this protective mechanism can become overloaded, allowing damage to the endothelial cells to occur (Stamler et al. 1992, 1993, 1996).
Genes are also involved in homocysteine attack. This has a significant impact upon the cardiovascular system, as homocysteine activates genes in blood vessels, encouraging the coagulation process and the proliferation of smooth muscles (Outinen et al. 1999).
Since homocysteine wields such a powerful cardiovascular blow from so many different directions, it is estimated that a 3-unit increase in homocysteine equates to a 35% increase in heart attack risk (Verhoef et al. 1996). The risk becomes even greater if hyperhomocysteinemia occurs with other risk factors. For example, a hypertensive woman with elevated homocysteine levels has a 25-fold increased risk of vascular disease.
Other homocysteine/disease associations are:
- High concentrations of homocysteine and low levels of folate and vitamin B6 are associated with an increased risk of extracranial carotid-artery stenosis, particularly in the elderly (Selhub et al. 1995).
- Higher levels of homocysteine predispose deep venous thrombosis (den Heijer et al. 1996).
- The link between hyperhomocysteinemia-hypercholesterolemia and hypothyroidism is clearly drawn in the section devoted to Thyroid Disease appearing in this protocol.
- Plasma homocysteine levels predictably increase with elevations in creatinine. As chronic renal failure occurs, hyperhomocysteinemia is frequently observed (Wilcken et al. 1979; Chauveau et al. 1993).
- Homocysteine metabolism is impaired in patients with Type II diabetes. Intramuscular injections of 1000 mcg of methylcobalamin (a homocysteine-lowering nutrient) once a day for 3 weeks reduced elevations of plasma homocysteine in diabetic test subjects (Araki et al. 1993).
- While the focus of this protocol is upon cardiovascular disease, it should be noted that individuals suffering with Alzheimer's disease, depression, eye problems, liver damage, Crohn's disease, ulcerative colitis, irritable bowel disease, pernicious anemia, and Parkinson's disease often present with elevated homocysteine levels (Refsum et al. 1991; Savage et al. 1994; Mayer et al. 1996; Cattaneo et al. 1998; Clarke et al. 1998; Romagnuolo et al. 2001; Duan et al. 2002).
- A large-scale prospective study of 4700 Norwegian men and women (65-67 years of age) showed that for each 5-millimol/L increase in plasma homocysteine levels, the number of deaths from all causes jumped 49%. This included a 50% increase in cardiovascular deaths, a 26% increase in cancer mortality, and a 104% increase in noncancer and noncardiovascular fatalities (Vollset et al. 2001).
Chronically high levels of homocysteine normally affect 30-40% of healthy elderly people. But in older individuals with severe illnesses, the prevalence of hyperhomocysteinemia may almost double. Based on a random testing of 600 hospitalized elderly patients (ages 65-102 years), researchers found evidence of hyperhomocysteinemia in over 60% of those with serious chronic conditions): 70% presented with vascular disease and 63% presented with cognitive impairment (Ventura et al. 2001). Impaired kidney function, the use of drugs (particularly diuretics), and malnutrition were suspected as causes of age-related hyperhomocysteinemia. Of the senior population in the United States , 67% have one or more vitamin levels within 15% of the lower recommended range, suggesting the need for review of reference values in elderly people.
While cholesterol does not normally pose a cardiac risk until levels exceed 240 mg/dL, some researchers consider homocysteine so capricious that even so-called normal levels may contribute to heart disease. Homocysteine levels should be kept as low as possible, below 7 micromol/L of blood plasma. Laboratories usually regard levels up to 15 micromol/L as normal, but epidemiological data reveal that homocysteine levels above 6.3 reflect a steep, progressive increase in the risk of a heart attack (Robinson et al. 1995). Although the incidence of hypertension, thrombotic stroke, peripheral vascular disease (gangrene), blood vessel toxicity, and the risk of heart attack escalate as homocysteine levels increase, homocysteine levels are not routinely evaluated in a cardiovascular work-up.
The Therapeutic section and the sections Homocysteine Lowering Nutrients and Elimination Pathways detail a program to assist in managing hyperhomocysteinemia. Note: Because of homocysteine's role in the metabolism of sulfur and methyl groups, elevated levels of homocysteine would be expected to negatively impact the biosynthesis of SAMe, carnitine, chondroitin sulfate, coenzyme Q10, creatine, cysteine, dimethylglycine, glucosamine sulfate, glutathione, melatonin, pantethine, phosphatidylcholine, and taurine. Many of these substances are profiled in the Therapeutic section for their cardioprotection and restorative qualities. The short supply of these agents could severely disable cardiac performance (Miller 1997).
For the past 20 years, eclectic physicians have judged Syndrome X to be a powerful indicator of an eventual heart attack. For clarity, let it be understood that a syndrome represents clusters of symptoms. In Syndrome X, the symptoms are an inability to fully metabolize carbohydrates; hypertriglyceridemia; reduced HDL levels; smaller, denser LDL particles; increased blood pressure; visceral adiposity; disrupted coagulation factors; insulin resistance; hyperinsulinemia; and, often, increased levels of uric acid. Note: For years, high uric acid levels have been associated with cardiovascular disease, but the relationship was poorly understood. Dr. Gerald Reaven unraveled the link when he determined that elevations in uric acid are often prompted by Syndrome X, a forerunner to heart disease (Fang et al. 2000).
Until hyperinsulinemia is diagnosed and a therapeutic course is charted, the arteries are under severe attack and the risk of a blood clot increases. Lesions, or wounds and injuries, damage the arteries; the attempts at vascular repair corrode the vasculature with atheromatous material, blockading and closing off vital circulatory routes. The population of sticky platelets increases along with the production of free radicals. Lipogenesis (the production and accumulation of fat in arterial tissue) encourages smooth muscles in the vasculature to proliferate. Along with excessive amounts of fibrinogen (a plasma protein that encourages the clotting of blood), PAI-1 is induced, further increasing the likelihood of a blood clot. HMG-CoA reductase, the rate-limiting enzyme involved in hepatic cholesterol production, appears to be simulated in both diabetic and nondiabetic animal studies amidst high levels of insulin (Dietschy et al. 1974).
Syndrome X interferes with glucose delivery, a consequence initiated by insulin's nonresponsiveness at the receptor site on the cell. Normally, ordinary levels of insulin will escort glucose into the cell, leaving a bloodstream favoring neither hyper- or hypoglycemia. In Syndrome X, the receptor turns a cold shoulder to the hormone, and insulin is no longer able to deposit its cargo; as a result, glucose loads up in the bloodstream. The pancreas is aware of the problem and attempts to resolve it by discharging more and more insulin. The logic appears to be that since normal levels of insulin cannot get the job done, perhaps greater and greater amounts of circulating insulin will be able to drive glucose, the principal metabolic fuel, into our 100 trillion cells.
In most cases of Type II diabetes, the problem is insulin resistance and inadequate compensatory insulin; in Syndrome X, insulin resistance and excessive amounts of insulin are the hallmarks. The vast difference between the two conditions is that in Syndrome X, the pancreas does not falter in its effort to pump out insulin (Reaven 2000). It sounds as if the host has won, but the following reasons discredit this logic.
- The pancreas can tire in its endless effort to supply compensatory insulin, and insulin-dependent diabetes will result.
- Hormones are powerful substances with an equally meaningful purpose. When insulin is not used for its intended functions, insulin builds up in the bloodstream, and from various perspectives, the risk of heart disease increases.
For example, the Quebec Cardiovascular Study found that individuals with elevated levels of triglycerides and LDL cholesterol, plus low HDL cholesterol, had 4.4 times the risk of heart disease compared to men with none of the risk factors. But the risk soars to 20-fold for men with a triad of elevated fasting insulin, apolipoprotein B, and small, dense LDL particles. According to Dr. Benoit Lamarche ( Laval University ), hyperinsulinemia should not be overlooked as an independent risk factor for ischemic heart disease. His case-controlled study of 91 patients and 105 controls found fasting insulin levels 18% higher in cases than controls. For each 30% increase in insulin concentration, there was a 70% increase in the risk of ischemic heart disease over 5 years (Despres et al. 1996; Physician's Weekly 1998b).
Insulin growth factor-1 (IGF-1), a hormone that increases the body's sensitivity to insulin and promotes clearance of glucose and toxic metabolites, appears critical to surviving the crisis and aftermath of a heart attack (Conti et al. 2001). Lower levels of IGF-1 during the early phase of a myocardial infarction are associated with poorer clinical outcomes, arrhythmias, ischemia, and death.
Italian researchers measured IGF-1 levels in the blood of patients within 24 hours of the onset of heart attack symptoms. IGF-1 (a hormone that enhances the elasticity of blood vessels, strengthens heartbeat, and increases blood flow) was about 5 times lower compared to healthy controls (47 ng/mL versus 189 ng/mL). The transient reduction of IGF-1 during the early phase of infarction appears to cause an acute worsening of insulin resistance.
A decline in IGF-1 is also linked to poorer prognosis following a heart attack. Of the 23 patients evaluated regarding IGF-1 levels (postinfarction), 12 experienced adverse clinical events in the 90-day follow-up period. The two individuals with the lowest IGF-1 levels died from the heart attack or its complications. Negative end results were attributed to reduced insulin sensitivity, glucose clearance, fat metabolism, and cardiac function. Interestingly, infusing IGF-1 into rats (programmed to develop metabolic syndrome) alleviated hyperphagia (overeating), obesity, hyperinsulinemia, hyperleptinemia (excesses of a hormone frequently found in the bloodstream of overweight, cardiac-prone individuals), and hypertension (Vickers et al. 2001).
The IGF-1 system is regulated by various stimuli, including hormones, growth factors, and nutritional status (Fu et al. 2001). For example, IGF-1 increased when protein foods were emphasized in the diet, in combination with adequate levels of vitamin D and calcium (Rizzoli et al. 2001).
Unfortunately, many physicians fail to consider insulin resistance as a forerunner to Type II diabetes and cardiovascular disease. A fasting blood glucose level above 115 mg/dL, triglycerides above 160 mg/dL, low HDL cholesterol, blood pressure persistently over 140/90 mmHg, total cholesterol above 240 mg/dL, and 10-15 pounds of extra weight are important evaluations regarding the likelihood of insulin resistance (Challem et al. 2000). A normal 2-hour postprandial glucose is generally between 70-139 mg/dL. If fasting or 2-hour postprandial insulin levels are measured, a normal range is 6-35 mcIU/mL. The Life Extension Foundation believes that fasting insulin levels over 5 mcIU/mL may be a cause for concern, and respected physicians and scientists are aligning with this projection.
Even if these tests are run, physicians often err in properly assessing the cumulative values of multiple irregularities. The signs are all there, but a failure to connect the dots can lead to a treatment that never addresses the source of the ill health. Syndrome X is largely a nutritional disease that is manageable with dietary corrections, reducing carbohydrates such as sweets, pastas, and breads and instating good fats in carbohydrates' place (consult the section entitled Essential Fatty Acids in this protocol for a discussion regarding good and bad fats).
The Harvard University School of Public Health announced that women between the ages of 38-63 increased their risk of heart attack by about 40% if their diet contained quantities of carbohydrates, particularly refined carbohydrates (Liu et al. 2000). It has been determined that the type of food selected and the quantity consumed determine how much insulin must be supplied.
Dr. Gerald Reaven believes an appropriate breakdown of the food groups should be about 45% of calories from carbohydrates, 40% from fat, and 15% from protein. Substituting appropriate fats for carbohydrates quiets an insulin release from the pancreas, and a primary step in Syndrome X has been averted. Dr. Reaven cautions that current dietary recommendations, that is, replacing fats with carbohydrates, may be fine for some individuals, but it is a grievous, even fatal, suggestion for those who are insulin resistant (Reaven et al. 2000). Note: Nutritionists reviewing the concept of macronutrient fractions stress the importance of selecting healthy foods to supply requirements. Eating ad libitum from unwise food choices, but within acceptable percentages, could still render the diet unhealthy from many perspectives.
To read more about Syndrome X, consult the sections entitled Hypertension, Obesity, Sedentary Lifestyle, Fibrinolytic Activity, and Beta-Blockers. Also, the Therapeutic section has supplemental recommendations to assist in controlling Syndrome X, including alpha-lipoic acid, conjugated linoleic acid, DHEA, essential fatty acids, magnesium, vitamin A, and vitamin C.
C-Reactive Protein (CRP)
CRP is a marker for systemic inflammation that rises several hundredfold in response to acute tissue injury but stays relatively stable in the absence of inflammation. CRP appears in the serum before the erythrocyte sedimentation rate begins to rise, often within 24-48 hours of the onset of inflammation. Elevated CRP levels can indicate the presence of chronic low-grade inflammation, with linkage to blood vessel damage and vascular disease (Pasceri et al. 2000). High levels of CRP appear to alert mark inflammatory processes that have the potential to disrupt fatty plaque buildup inside blood vessels, causing a critical rupture; the end result is a blood clot.
When CRP levels are factored in as a cardiovascular risk, along with hypertension, diabetes, elevated cholesterol, family history, and BMI, there is significant improvement in predicting cardiac health compared with models that exclude CRP testing. Ten prospective studies (six in the United States and four in Europe ) have consistently shown that hs-CRP is a powerful predictor of a future first coronary event in apparently healthy men and women. ("hs" refers to high sensitivity testing, the only method able to discriminate the subtle differences in CRP in a range that accurately predicts coronary risk.)
As new as CRP is to many as a risk factor in coronary artery disease, Rudolf Virchow, a German pathologist (1821-1902), hypothesized that inflammation was the causative factor in the atherogenic process. Decades later, scientists confirmed that increased monocytes (white blood cells critical in early plaque development) and macrophages (mononuclear phagocytic cells capable of scavenging and ingesting dead tissue and degenerated cells) are present, particularly at points of plaque rupture. It appears that CRP and several other inflammatory markers may be elevated many years prior to a coronary event.
However, data from the University of Texas Health Sciences Center indicate that CRP is more than a measurable antecedent preceding a cardiac problem. CRP, along with the cooperative efforts of an unidentified serum factor, acts directly upon the blood vessels to activate adhesion molecules in endothelial cells: the intercellular adhesion molecule (ICAM-1) and the vascular cell adhesion molecule (VCAM-1). VCAM-1 appears to be an early molecular marker of lesion-prone areas as a response to experimental hypercholesterolemia. In humans, ICAM-1 and VCAM-I expression is increased in the endothelium of atherosclerotic plaque. Researchers concluded that CRP appears intricately involved in the inflammatory process, thus proving to be a potential target for the treatment of atherosclerosis (Pasceri et al. 2000; Biomedical Science 2001; Alvaro et al. 2002).
The journal Circulation reports that CRP appears able to affect the activity of LDL cholesterol (increasing atherogenesis). The cycle begins as stranded LDL is taken up by macrophages; macrophages, gorged with fats contained in blood, become bloated and develop into foam cells. When foam cells have reached their maximum load, they explode, discharging their fatty contents into the blood vessel wall at the site of injury. The presence of added fat signals the need for more macrophages to clean up the mess. They stuff themselves, explode, and the cycle starts anew. Since native LDL does not induce foam cell formation, CRP appears to ready LDL for uptake by the macrophages, initiating the sequence (Braley 1985; Zwaka et al. 2001).
In the Physicians' Health Study, middle-aged men deemed healthy at baseline were evaluated over an 8-year period in regard to CRP levels and a cardiovascular event. This study showed that those in the highest quartile of hs-CRP had a twofold higher risk of (future) stroke, a threefold higher risk of (future) heart attack, and a fourfold higher risk of (future) peripheral vascular disease (Rifai et al. 2001a, 2001b). Stroke patients with the highest CRP levels were nearly 2.4 times more likely to die within the next year compared to patients with the lowest levels (DiNapoli et al. 2001). Another of hs-CRP's strengths is its ability to detect at-risk patients with normal cholesterol levels.
The risk of stroke, according to data reported in the New England Journal of Medicine, decreased among those using statin drugs (White et al. 2000). The Cholesterol and Recurrent Events Trial concluded that pravastatin (administered long term) appears to be doing more than reducing cholesterol, perhaps acting as an anti-inflammatory. Another study (also published in the New England Journal of Medicine) reported that pravastatin reduced CRP levels after both 12- and 24-weeks' administration, independent of LDL cholesterol levels. It appears statin therapy may prevent coronary events among individuals with relatively low lipid levels but with elevated levels of CRP (Ridker et al. 2001). Conversely, some drugs, including hormone replacement therapy, actually increase CRP levels and the inflammatory response.
Researchers hypothesized in the Journal of the American College of Cardiology that the cytomegalovirus (CMV) (herpes-type viruses) may stimulate an inflammatory response, reflected by elevated CRP levels. The journal Circulation reported that older people who have IgG antibodies to the herpes simplex-I virus experienced a twofold increase in the risk of a myocardial infarction or coronary heart disease death. Since the relationship between CMV and coronary heart disease is not observed in all people, researchers consider the ability of individuals to control CMV inflammatory activities, the variable in the progression to a myocardial infarction (Zhu et al. 1999; Siscovick et al. 2000).
The infectious process in heart disease is chronicled in numerous studies, but the microorganisms involved remain of interest. Subsequently, a group of researchers from Johannes Gutenberg University (in Mainz , Germany ) evaluated 572 heart patients. They tested for antibodies in the bloodstream that would show that the immune system had at some stage been exposed to a variety of different viruses and bacteria. These included herpes simplex-1 and -2, which cause cold sores and genital herpes; Epstein-Barr virus, which causes mononucleosis, chlamydia, and flu virus; and Helicobacteria pylori, which causes stomach ulcers. Then they looked at the patients again 3 years later to see how many had survived. The death rate was 3.1% in patients who tested positive for only a few of the viruses or bacteria, 9.8% for those with four or five, and 15% in those positive for six to eight. Among those who had the most advanced artery hardening, 20% of those exposed to between six and eight infections had died, compared to 7% of those with three or fewer (BBC 2002b).
Japanese researchers concentrated upon finding a method to distinguish between bacterial and viral infection by measuring inflammatory markers, among them C-reactive protein (CRP). They found that during the acute stage of bacterial infections, CRP levels were moderately or highly increased, whereas in viral infections, CRP levels were normal or slightly increased. The researchers propose that the measurement of CRP (among various inflammatory markers) during the acute phase of illness, that is, within 5 days of onset, is of value to determine whether the infection is caused by a bacteria or virus (Sasaki et al. 2002). For an opposing view regarding the association between viruses and CRP levels, please consult the section entitled Link Between Infections and Inflammation in Heart Disease in this protocol.
Figure 4 shows the risk factors associated with CRP (data extracted from publications authored by Dr. Paul Ridker). It is important to note that risk factors vary according to individual publications and may change with future publications.
| Risk Factors Associated with CRP |
| || RELATIVE RISK FOR:1 |
| MEN || Future MI || Future Stroke |
| CRP (mg/L) || (heart attack) || |
| >2.11 1.15-2.10 0.56-1.14 <0.55 || 2.9 2.6 1.7 1.0 || 1.9 1.9 1.7 1.0 |
| || RELATIVE RISK FOR: |
|WOMEN || Future MI || Future Stroke |
| CRP (mg/L) || |
|>7.3 ||5.5 ||5.5 |
|3.8-7.3 ||3.5 ||3.5 |
|1.5-3.7 ||2.7 ||2.7 |
|<1.5 ||1.0 ||1.0 |
1 Relative risk is the ratio of the chance of a disease developing
among members of a population exposed to a factor compared to
a similar population not exposed to the factor.
|Ridker et. al. (1998); Ridker et. al. (1997). |
Current research indicates that persistent CRP elevation, lasting longer than 96 hours following a successful coronary stent implantation, is predictive of prolonged inflammation leading to re-stenosis (Gottsauner-Wolf et al. 2000). Patients who developed re -stenosis within the first 6 months had increases in CRP levels for up to 96 hours following the procedure, although their baseline CRP had been normal. Patients without re -stenosis displayed an increased CRP level that was sustained for no longer than 48 hours and subsequently decreased. Higher CRP levels appear predictive of less satisfactory end results, following angioplasty and stent procedures.
Although many of the newer risk factors are not yet standardized, some laboratories are using a CRP reference range of 0.24-1.69 mg/L. Recent medical events resulting in tissue injury, infections, or inflammation may increase CRP levels and, if not factored into clinical interpretations, can distort results.
To read more about factors affecting CRP levels, consult the sections referring to Smoking, Obesity, Sedentary Lifestyle, Gender, Gum Disease, and The Link Between Infections and Inflammation in Heart Disease. Improved glycemic control and normalizing blood pressure may also assist in reducing inflammation and (subsequently) CRP levels.
CRP appears responsive to aspirin, DHEA, fish oil, pravastatin, vitamin C, vitamin E, and vitamin K supplementation (consult the Therapeutic Section to learn more about natural products). As research continues, it may be found that many other nutrients and herbs known for their anti-inflammatory properties are equally valuable in maintaining healthy CRP levels. Note: CRP appears to reduce levels of vitamins A, C, and E, as well as carotenoids, zinc, and selenium. Individuals with elevations in CRP may wish to emphasize these nutrients for their contribution to cardiac health.
THE LINK BETWEEN INFECTIONS AND
INFLAMMATION IN HEART DISEASE
Infections are of particular interest because of the increasing attention paid to the role of inflammation in heart disease, according to David S. Siscovick, M.D., professor of medicine and epidemiology at the University of Washington . The data incriminate the infectious process in various phases known to contribute to heart disease. For example, current research suggests that infection may be an important determinant of fibrinogen levels, offering one possible explanation for the association between chronic or acute infection and vascular events (Woodhouse et al. 1997). Many researchers class inflammation as worse than cholesterol at triggering heart attacks. Note: Men with hypercholesterolemia and inflammation have a significantly higher risk of cardiovascular death (2.4) compared to those with only high cholesterol levels (1.4) (Engstrom et al. 2002).
Dr. Paul Ridker ( Boston 's Brigham and Women's Hospital) recently explained that everyone reaching middle age has some degree of fat buildup, that is, plaque in the vasculature. New evidence suggests the plaque becomes threatening if weakened by inflammation, which makes the buildup squishy and fragile. Even a small lump can burst, promoting the formation of a clot that in turn chokes off blood flow and causes a heart attack. Thus, reducing the inflammatory process is of equal importance to lipid monitoring in controlling the dangers of plaque (Associated Press 2002).
Researchers observed that mortality from ischemic heart disease markedly increases during the flu season, particularly among the elderly. One reason for this appears to be that patients with influenza A, a flu virus, tend to have much higher levels of CRP. Researchers at Rochester General Hospital and Rochester School of Medicine and Dentistry showed that CRP increased 370% during infection and that old age magnified the increase (Falsey et al. 2001; Horan et al. 2001).
A higher white blood cell count, common when the body is fighting off infection, is associated with an increased coronary risk by diminishing blood flow to the heart muscle and encouraging blood clot formation. The higher the white blood cell count, the greater the patient's risk of death from a heart attack or of developing congestive heart failure (Barron et al. 2000).
In fact, angina pectoris appears less a prognosticator of a forthcoming heart attack than a febrile (flu-like, feverish) infection prior to the attack. Peter Ammann, M.D. ( Switzerland ), stated that he has observed significantly higher numbers of myocardial infarctions among patients with febrile conditions, mainly of the upper airways, within 2 weeks prior to infarction (Ammann et al. 2000; Healthlink 2000).
Bacteria appear to gain entry into the heart via immune cells, most likely activated in the process of clearing infections from the respiratory passages. The bacteria most suspected of initiating coronary problems are Chlamydia pneumoniae, Pasteurella aerogenes, Enterococcus endocarditis, Staphylococcus aureus, Enterococcus faecalis, Candida albicans, and Viridan streptococcus. (Some researchers add H. pylori, a bacteria associated with duodenal ulcers, peptic ulcers, and chronic gastritis, to the list.)
Tissue specimens from patients who had undergone a carotid endarterectomy showed high levels of C. pneumoniae in 11 of 17 cases (64%). The American Heart Association also reported that C. pneumoniae was found in the infected arteries of autopsied cardiac patients. Dr. Tatu Juvonen ( Oulu University Hospital in Finland ) explains that C. pneumoniae is a specific microbial antigen that causes inflammation and atherosclerotic cells to proliferate (Mosorin et al. 2000; Vink et al. 2001).
An alternative to this dismal situation may be antibiotic therapy, controlling the inflammatory process attacking the vessel wall. An American study of more than 16,000 British patients showed that people treated with two types of antibiotics had a significantly reduced risk of heart attack. Those treated with tetracyclines were at 30% less risk than patients not given antibiotics, while those who took quinolones (antimicrobials) had a 55% reduced risk. It appears antibiotics may act in the same fashion as anti-inflammatory drugs, reducing inflammation in the arteries (BBC News 1999, 2002a).
Inflammation appears to be an independent risk factor that may explain cardiovascular disease in the presence of normal cholesterol, blood pressure, and coronary arteries. MINC patients, individuals experiencing a myocardial infarction with normal coronary arteries, should be at lower risk for a cardiac event because they most often have normal electrocardiograms, higher HDL levels, and no significant impairment in LDL cholesterol. Dr. Ammann believes the trigger may be systemic inflammation or specific infective agents, advancing a benign complaint to a life-threatening condition. Interestingly, migraine headaches have also been observed as forerunners to a heart attack in otherwise healthy individuals (Ammann et al. 2000; HealthLink 2000).
IS ATRIAL FIBRILLATION PREDICTIVE OF CARDIAC MORTALITY?
Atrial fibrillation, a condition shared by over 2 million Americans, occurs when the atria, the upper chambers of the heart, beat faster than the lower two chambers, the ventricles. Many problems can cause atrial fibrillation, including a leaky heart valve, hypertension, obesity, stimulants (including caffeine and alcohol), medications (such as sumatriptan, a headache drug), and thyroid disorders. Dr. Robert Atkins, M.D., adds that patients should be evaluated for heavy metal intoxication and mycoplasmal infections, factors also capable of provoking atrial fibrillation.
Although not immediately life-threatening, atrial fibrillation may cause up to a 30% reduction in cardiac output, resulting in shortness of breath, fatigue, and reduced exercise capacity. In fact, the American Heart Association no longer regards atrial fibrillation as a benign disorder. About 75,000 strokes related to atrial fibrillation occur each year in the United States . Up to 23% of such patients die, and 44% experience significant neurologic deficits. (The mortality rate from other causes of stroke is about 8%.) Nonetheless, Dr. H.J. Crijns (University Hospital Gröningen, the Netherlands), declares that even patients with heart failure should not be in greater danger because of atrial fibrillation if the condition is well managed (Kennedy 1999; Alpert 2000; Crijns et al. 2000).
Blood thinners are often prescribed for atrial fibrillation, but a program based in natural medicine is also helpful. While full correction of the chaotic rhythm associated with atrial fibrillation is often difficult to achieve, nutritional supplements can lessen the risk of a blood clot. Dr. William Campbell Douglass, M.D., states that vitamin E (800 IU daily), cod liver oil capsules (4 daily), olive oil (1 tbsp daily), and bromelain (about 750 mg 3 times a day on an empty stomach) have similar action to Coumadin and aspirin, thinning the blood and reducing the risk of a thrombotic event (Douglass 1996). Other heart nutrients such as CoQ10, hawthorn, carnitine, taurine, magnesium, and ginkgo biloba are also important. To read more about the supplements recommended for atrial fibrillation, please consult the Therapeutic section of this protocol. Also refer to the Thrombosis Prevention protocol in this book.
An estimated 4 million Americans have recurring cardiac arrhythmias. Arrhythmia is any change in the normal sequence of electrical impulses in the heart that results in an abnormal rhythm. The heart might skip a beat, beat irregularly, beat very slowly, or beat very fast. The symptoms of a more serious arrhythmia and benign palpitations are very similar. An arrhythmia might be brief and harmless or it might be associated with cardiac disease. Therefore, arrhythmia should always be addressed by a qualified physician because the end result can be quite dissimilar (although not representative of the norm, some types of arrhythmias can be extremely dangerous or even fatal). The major types of cardiac arrhythmias are:
- Tachycardia (a heart rate in excess of 100 beats per minute). A reduction in parasympathetic tone or an increase in sympathetic stimulation will increase the frequency of heartbeats. An elevation in body temperature or a toxic condition can also result in tachycardia. The abnormally fast heart rhythm of tachycardia can prove dangerous because the racing rhythm interferes with the heart’s ability to contract properly (Seeley et al. 1991; Ozdemir et al. 2003).
- Bradycardia (the ventricles beat at a rate less than 60 beats per minute). Bradycardia, even as low as 50 beats per minute, can be normal in athletes and in individuals who lead a physically active lifestyle (AHA 2002; NASPE 2002). In these people, regular exercise maximizes the ability of the heart to pump blood efficiently, so fewer heart contractions are required to supply the body's needs. In other cases, bradycardia can be caused by excessive vagus nerve stimulation (vagus stimulation is principally responsible for parasympathetic control over the heart) (Merck Manuals 2003a). In addition, a dysfunctional sinoatrial node (SA; specialized heart tissue that controls heartbeat), as well as hypothyroidism, severe liver disase, hypothermia, and typhoid fever can result in bradycardia. Medications including propranolol (Inderal), atenolol (Tenormin), metoprolol (Toprol-XL), sotalol (Betapace), verapamil (Calan, Isoptin, Verelan), and diltiazem (Cardizem, Dilacor-XR) can slow the heart rate to bradycardia status (IH/HMS 2002; Stein 2003). In some instances, the weak pace may indicate the heart is not beating well enough to ensure adequate blood flow. Note:When the parasympathetic nervous system is active, the heart rate tends to be slower; conversely, the heart rate is accelerated when the sympathetic nervous system is active.
- Sinus Arrhythmia (a normal increase in heart rate that occurs during inspiration, the act of drawing air into the lungs). On inspiration, there is a decrease in vagal tone (parsympathetic stimulation) and an increase in sympathetic tone. This produces an increase in heart rate. Conversely, on expiration there is an increase in vagal tone and a decrease in sympathetic tone, resulting in a decrease in sinus rate. Sinus arrhythmia (occurring most often in young healthy people) does not result in symptoms and is generally classified as benign (Michaels 1995; MHI 1999).
- Paroxysmal Atrial Tachycardia (a sudden increase in heart rate to 160–200 beats per minute that can last for only a few seconds or for several hours). Paroxysmal atrial tachycardia starts with a premature P wave that is superimposed on the T wave. The series of early beats in the atria is responsible for the accelerated heart rate. Paroxysmal atrial tachycardia (the most common form of arrhythmia is children) is not regarded as a disease and is seldom life-threatening. The episodes are usually more unpleasant than they are dangerous and the prognosis is generally good. Note:The P wave results from depolarization of the atrial myocardium and precedes the onset of atrial contractions (atrial contraction begins at about the middle of the P wave); the T wave represents repolariztion of the ventricles (Seeley et al. 1991).
- Atrial Flutter (the atria beat more often than the ventricles). This means that the atria have a shorter time to push all of their blood into the ventricles and the ventricles may not fill with sufficient blood. Depending upon how fast the atria are beating, the body may not receive enough oxygen-rich blood. The faster the atria beat, the more difficult it is for the body to receive ample oxygen. Atrial flutter is subdivided into two types: typical and atypical. Typical atrial flutter has a very characteristic electrocardiogram (ECG) pattern and is caused by localized reentry with impulse pathways occupying large portions of the right atrial wall. Because the circuit is fixed and accessible, typical atrial flutter can often be treated by destroying a portion of the circuit during a procedure known as ablation. Conversely, atypical atrial flutter exhibits a more variable ECG pattern and more than one circuit may be responsible. Atypical atrial flutter behaves much more like atrial fibrillation (pounding heart rate or pulse, shortness of breath, or dizziness) than does typical atrial flutter. Thyroid disorders, heart valve disease, coronary artery disease, and heart failure as well as a swelling or irritation near the heart are possibilties that can provoke atrial flutter. If a fast atrial flutter goes untreated, the body could become oxygen deprived. As a result, a heart attack or fluid accumulation in the lungs are possible consequences. The sooner treatment is begun, the better the chances are of avoiding serious cardiac or respiratory endangerments (Seeley et al. 1991; PDR 1997).
- Atrial Fibrillation (the two small upper chambers of the heart, the atria, quiver instead of beating effectively). Because blood is not completely pumped out of the atria, blood may pool and clot. If a piece of a blood clot in the atria leaves the heart and becomes lodged in an artery in the brain, a stroke results. It is estimated that about 15% of strokes occur in individuals experiencing atrial fibrillation. An individual with atrial fibrillation does not always have blockages in the arteries (coronary arteries) that serve the heart muscle or other serious heart problems, but the odds favor a cardiac association. Chronic hypertension (high blood pressure); abnormalities of the heart valves (thin tissue flaps that keep blood flowing in one direction through the heart); and abnormalities of the heart's pumping function are causes of atrial fibrillation. About one third of individuals with atrial fibrillation have no structural heart disease and no identifiable cause for their heart rhythm problem. In these instances, atrial fibrillation may be due to (1) microscopic abnormalities of the muscle of the atria; (2) abnormalities within individual heart cells; (3) abnormal electrical properties of groups of heart cells; and (4) exposure to heart stimulants such as alcohol, caffeine, or too much thyroid hormone (Seeley et al. 1991; MC 2003).
- Ventricular Tachycardia (a rapid heart beat initiated within the ventricles and characterized by three or more consecutive premature ventricular beats known as ectopic beats). Ventricular tachycardia (occurring in approximately 2 out of 10,000 individuals) is a potentially lethal arrhythmia that can cause the heart to become unable to pump adequate amounts of blood throughout the body. The heart rate might be between 160–240 beats per minute. Ventricular tachycardia can occur spontaneously or it can develop as a complication of a heart attack, cardiomyopathy, mitral valve prolapse, and myocarditis or after heart surgery. It may also be a result of scar tissue formed following an earlier heart attack or an undesired effect of anti-arrhythmic drugs. Disrupted blood chemistries (a low potassium level), pH (acid/base) changes, or insufficient oxygenation can trigger ventricular tachycardia. Re -entry (re-stimulation of the electrical conductive pathway from a single initial stimulus) may also be a mechanism in ventricular tachycardia. Sustained ventricular tachycardia is dangerous because it can worsen until it becomes ventricular fibrillation ; —a form of cardiac arrest (Seeley et al.1991; Illustrated Health Encyclopedia 2002; Merck Manual s 2003b).
- Ventricular Fibrillation (a pulseless arrhythmia with irregular and chaotic electrical activity and ventricular contractions in which the heart immediately loses its ability to function as a pump). Sudden loss of cardiac output with subsequent tissue hypoperfusion (a process that intensifies anaerobic metabolism and instigates the formation of lactic acid which further deteriorates the systolic performance of the myocardium) creates global tissue ischemia. The brain and myocardium (the middle layer of the heart, consisting of cardiac muscle) are most susceptible to injury. Without immediate emergency treatment (an electric shock to restore normal rhythm), an individual loses consciousness within seconds and dies within minutes. Ventricular fibrillation is the primary cause of sudden cardiac death (Seeley et al. 1991; Kazzi et al. 2001).
Symptoms of more serious arrhythmias and symptoms of benign palpitations can be very similar. Palpitations are often described as a sensation in the chest and throat that the heart is flopping or pounding, seeming to beat harder and faster than usual, or beating irregularly. Some individuals experiencing palpitations report feeling faint, dizzy, or out of breath. When no medical or cardiac cause can be found, lifestyle events such as exercise, stress, or fear or using tobacco, caffeine, alcohol, cough and cold remedies, or diet pills might be determined to be the cause of the arrhythmia. Palpitations that recur, become sustained or uncomfortable, or are associated with other symptoms require further investigation (Hendrickson 2001; DeRoin 2003; NHLBI 2003).
However, most individuals who experience heart palpitations have some type of cardiac arrhythmia. Virtually any arrhythmia can cause palpitations. The most common cardiac causes of palpitations are premature atrial complexes, premature ventricular complexes, episodes of atrial fibrillation, and episodes of supraventricular tachycardia. In some cases, palpitations are caused by a more dangerous arrhythmia such as ventricular tachycardia. Because life-threatening arrhythmias are usually seen in individuals with underlying heart disease, it is especially important to identify the cause of palpitations in individuals who have fundamental heart disease. The same recommendation applies to palpitations in individuals who have significant risk factors for heart disease: family history, tobacco habits, high cholesterol, excess weight, or sedentary lifestyle (Fogoros 2003).
The Cardiac Cycle
Dysfunction in the heart's electrical conduction system can make the heart beat too fast, too slow, or at an uneven rate. The cardiac cycle (the period from the beginning of one heartbeat to the beginning of the next) is the sequence of events that occurs when the heart beats. This cycle is regulated by specialized cardiac muscle cells in the wall of the heart that form the conduction system of the heart. The heart beats normally when an electrical impulse from the SA node (sinoatrial node) moves uninterrupted in a set pattern throughout the heart. The normal flow of an electrical impulse is:
SA node → right atrium → AV node (atrioventricular node) → atrioventricular bundles → bundle branches → special conducting fibers (His-Purkinje system) → ventricles
The SA node, which functions as the pacemaker of the heart, is located in the upper wall of the right atrium and initiates contractions of the heart. Action potentials originate in the SA node and spread over the right and left atria causing them to contract. A second area of the heart called the atrioventricular node (AV node) is located in the lower portion of the right atrium. When action potentials reach the AV node, they spread slowly through the AV node and into a bundle of specialized cardiac muscle called the bundle of His or atrioventricular bundle. The slow rate of action potential conduction in the AV node allows the atria to complete their contraction before action potentenials are delivered to the ventricles.
After the action potentials pass through the AV node, they are transmitted rapidly through the atrioventricular bundle, which projects through the connective tissue separating the atria from the ventricles, to two branches of conduction tissue called the left and right bundle branches. At the tips of the left and right bundle branches, the conducting tissue branches further to many small bundles of Purkinje fibers. The Purkinje fibers rapidly deliver action potentials to all the cardiac muscle of the ventricles. As long as this exact route is followed, the heart pumps and beats regularly (a normal heart rate, or number of contractions, is about 70–80 beats per minute) (Seeley et al. 1991; AHA 2002; NHLBI 2003).
Arrhythmia may also result from an abnormal impulse rate in the SA node or when a condition called “heart block” exists. In heart block, electrical signals are delayed, partially conducted, or completely interrupted (NHLBI 2003).
Another common cause of arrhythmia is damage to the heart's "wiring" resulting from decreased blood flow from clogged coronary arteries or from heart muscle that died as a result of a heart attack (myocardial infarction). Other factors affecting heart rhythm are ingested toxins, congenital heart arrhythmia, anemia, thyroid conditions, hypoglycemia, mitral valve prolapse, and high blood pressure (DeRoin 2003; THI 2003). These underlying factors must also be treated to correct the arrhythmia.
Diagnostic tools used in arrhythmia are an electrocardiogram (ECG); intracardiac electrophysiology study (EPS, a study that involves placing wire electrodes within the heart to determine the characteristics of heart arrhythmias); and tilt table examinations (tilt table study is mainly used in diagnosing vasovagal syncope, a classic fainting episode). Once serious arrhythmia is diagnosed, it might be treated with drugs; an implantable device that sends electrical shocks or impulses to restore normal heart rhythm, i.e., an implantable cardioverter defibrillator (ICD) or pacemaker; or surgery that can remove misfiring heart tissue (radiofrequency and surgical ablation) or create a new electrical pathway (maze surgery) (ACC 2002; DeRoin 2003; NHLBI 2003).
Frequently used anti-arrhythmic drugs are anticoagulants (warfarin); sodium channel blockers (class I); beta-blockers (class II); potassium channel blockers (class III); calcium channel blockers (class IV); and digitalis (Chaudhry et al. 2000; ACC 2002). Almost all medications have side effects including the antiarrhythmic drugs. One side effect is a potentially life-threatening pro-arrhythmia (meaning the drug itself causes arrhythmia). Because studies show that anti-arrhythmics have no mortality benefit and can even increase mortality, patient benefit vs. risk must be considered before using anti-arrhythmics (Brendorp et al. 2002; Sanguinetti et al. 2003; Yamreudeewong et al. 2003). Overall there is still no ideal anti-arrhythmic agent and drug selection remains highly individualized (Tsikouris et al. 2001).
Arrhythmia and Myocardial Infarction
Patients are monitored very closely in a coronary intensive care unit immediately following a myocardial infarction (MI) because this is a time period when life-threatening dysrhythmias can develop. Life-saving thrombolytic treatment that is used to open a clogged coronary artery (“clot busters”) can also cause an increased risk of dysrhythmia. Successfully opening an artery results in a sudden influx of blood (reperfusion) into the blood-starved area of the heart. Reperfusion has the potential to cause a fatal arrhythmia. In part, the culprit is thought to be a free-radical reaction. Therefore, reducing the free-radical burden on the heart offers potentially helpful benefits. In a post-MI setting, studies have demonstrated the importance of cardio -protective treatment.
Compared to placebo, when coenzyme Q10 (120 mg daily) was given to patients with acute MI, there was significant reduction in total arrhythmias and symptoms of angina pectoris. There was also better left ventricular function. Total cardiac events, including cardiac deaths and nonfatal infarction, were also significantly reduced in the CoQ10 group compared to the placebo group (15.0% vs. 30.9%) (Singh et al. 1998). Subsequent studies demonstrated that CoQ10 significantly reduced serum lipoprotein(a) and decreased oxidative stress overall. After 1 year of follow-up, even subjects receiving optimal lipid-lowering therapy (lovastatin) had a significant reduction in total and low-density lipoprotein (LDL) cholesterol compared to baseline levels. Fatigue was found to be more common in the placebo group which did not receive CoQ10 (Singh et al. 1999, 2003).
Omega-3 fatty acids (fish oil) given within 18 hours to patients with acute MI also demonstrated protective benefits, and after 1 year of follow-up, total cardiac events were significantly reduced (including nonfatal infarctions, cardiac deaths, total cardiac arrhythmias, left ventricular enlargement, and angina pectoris) (Singh et al. 1997). Other benefits provided by omega-3 fatty acids were reduced rates of heart attacks; reduced susceptibility to sudden death from ventricular arrhythmia; and reduced inflammation and lowered serum triglycerides (O’Keefe et al. 2000; De Caterina et al. 2003; Lee et al. 2003). Lee et al. (2003) concluded that “the use of omega-3 fatty acids should be considered as part of a comprehensive secondary prevention strategy post-myocardial infarction.” Flaxseed, perilla, and fish oils are sources of omega-3 fatty acids. Perilla oil works well (Ezaki et al. 1999); does not have an unpleasant taste; and does not cause the gastrointestinal side effects which limit the use of fish oil for some. Note:Because EPA/DHA can interfere with blood clotting, individuals with any type of hemorrhagic disease related to excessive bleeding should consult their physician before supplementing with fatty acids. In addition, individuals taking anticoagulant drugs such as Coumadin should inform their physician that they are taking EPA/DHA supplements. The dose of anticoagulant medication they are taking might require adjustment based on template bleeding time tests.
Ensuring that the heart gets enough blood and protecting it from free radical reactions are essential. Natural medicine offers tremendous possibilities for individuals with arrhythmia, but it is important to remember that no treatment should be undertaken without the guidance of a cardiologist or physician trained in natural medicine as well as the approval of your personal cardiologist or physician. In particular, close professional medical supervision is essential with larger doses. Pregnant women should never take any supplement without consulting their personal physician. Additionally, persons with cardiac arrhythmias should avoid caffeine, heavy alcohol intake, and saturated fats. Chelation therapy might also be an option.
The Therapeutic Section of this protocol includes discussions of numerous supplements that offer protective and supportive benefits for individuals with arrhythmias: acetyl-L-carnitine, alpha lipoic acid, angelica, bugleweed, coenzyme Q10, fish oil, garlic, Ginkgo biloba, hawthorn, magnesium, olive leaf extract, perilla and flaxseed oil, potassium, selenium, taurine, thiamine, and vitamin E.
WARNING: Some supplements are regarded as pro-arrhythmic in susceptible individuals (e.g., Ma Huang and excessive dosages of supplemental choline). Additionally, before supplementing with the nicotinic acid form of vitamin B 3, cardiac patients with arrhythmias should consult with a physician (NASPE 2003; NTC website).
CONGESTIVE HEART FAILURE
Congestive heart failure (CHF) reflects the heart's inability to pump sufficient amounts of oxygenated blood to supply the body's needs. It does not mean the heart has ceased to work, but rather that the heart's pumping mechanism is performing inadequately. Conditions that damage the heart, such as a heart attack, ischemic heart disease (a lack of oxygen in tissue cells), cardiomyopathy (fibrous tissue partially replaces heart muscle and blood no longer moves efficiently), alcohol abuse, rheumatic fever, arrhythmias, pericarditis (inflammation of the thin sac covering the heart), or drug toxicity can result in CHF. Symptoms of CHF are fluid retention, fatigue, weakness, and unjustified dyspnea (shortness of breath after slight exertion). In some cases, liver and kidney function are also disrupted.
CHF occurs when the heart fails to adequately pump blood through the largest organ of the human body, 65,000 miles of blood vessels (the vascular system). This breakdown causes increased pressure in the circulatory system, allowing fluid to escape from the bloodstream and accumulate in tissues and organs. More than 100 years ago, CHF would have been diagnosed as dropsy, an abnormal accumulation of a clear watery fluid in a body tissue or cavity. Dropsy was the most common of all forms of heart problems until the current epidemic of coronary diseases.
The heart is a two-sided instrument, having a right and left atrium and a right and left ventricle. The atria of the heart receive blood from veins and function as reservoirs before the blood enters the ventricles. The ventricles are the major pumping chambers of the heart, ejecting blood into the arteries and forcing it throughout the vascular system.
Just as there are two sides to the heart, there are two types of heart failure (right-sided and left-sided). The right side of the heart has the job of moving the blood through the pulmonary blood supply to the lungs, where it picks up oxygen. If the failure occurs on the right side of the heart, it means the right side is not keeping pace with the left side and the blood accumulates in the vessels leading to the heart. Excess fluid (as peripheral edema) occurs in the lower legs, ankles, and feet (Atkins 1988).
In left-sided failure, the ventricle that normally pumps blood from the lungs through the aorta to the body lags in its effort compared to the right ventricle. Blood accumulates in the veins leading from the lungs, and the lungs become congested. Terms such as pulmonary edema or fluid in the lungs usually mean the left side of the heart is failing, allowing the congestion. The patient may experience shortness of breath (most evidenced upon exertion) or paroxysmal nocturnal dyspnea (shortness of breath occurring after several hours of sleep). Often, left-sided and right-sided failures coexist, meaning the patient may experience both at the same time. Acute pulmonary edema can be fatal.
Traditional medicine treats CHF with diuretics and inotropic drugs that increase the contractility of the heart. If overweight, a weight-loss program will probably be recommended, as well as an individualized exercise regime. Abstinence from tobacco, either direct or secondhand, is essential. Experimental studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) can lead to the development of congestive heart failure when given to susceptible individuals. Researchers feel that there have been few epidemiological investigations equal to the importance of this finding (Page et al. 2000).
The Archives of Internal Medicine clarified the risks, reporting that NSAIDs appear to cause fluid retention and an increase in blood pressure in patients with prevalent heart failure. Patients who have had congestive heart failure, angina, heart attacks, bypass surgery, or angioplasty with stent placement should seriously consider safer alternatives. This warning is not restricted to prescription NSAIDs but to over-the-counter anti-inflammatory drugs as well (Feenstra et al. 2002).
Dispersed throughout the Therapeutic section of this protocol are numerous supplemental suggestions to benefit the patient with CHF. (Read about alpha-lipoic acid, L-arginine, L-carnitine, coenzyme Q10, hawthorn, vitamin B6, selenium, taurine, and thiamine.) Diet also plays an important role. For example, carbohydrate restriction exerts a diuretic effect, prompting an immediate loss of salt and water. Removing water accumulations from saturated tissue is of great advantage to individuals with high blood pressure and congestive heart failure.
The purpose of heart valves is uncomplicated. Valves simply route the blood in a forward direction, preventing its backward flow. Functioning properly, valves are control devices, opening and closing with each beat of the heart, warranting a healthy lap around the circulatory system. But valves can be damaged by rheumatic fever, infections, injuries, tumors, and calcification, hampering their ability to direct the blood supply.
Some valves, once injured, pose more serious health hazards than others. Those include the mitral, aortic, and the tricuspid valves and are the focus of this section of the protocol. Note: This material was collected in part from the ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease (Bonow et al. 1998).
The mitral valve, or bicuspid valve, is located between the left atrium and the left ventricle. (The mitral valve is the only valve with two rather than three cusps.) The mitral valve allows oxygenated blood to flow from the left atrium into the left ventricle but prevents blood from flowing back into the atrium. As blood is forced against the valve, it closes the two cusps, allowing a smooth trajectory from the ventricle to the aorta.
Mitral Valve Prolapse
Mitral valve prolapse (MVP), or floppy valve syndrome, is a slight deformity in the valve separating the left atrium from the left ventricle, a condition that affects 5-10% of the population. During MVP, one or both of the cusps protrude back into the left atrium, causing the floppy valve appearance.
Mitral valve prolapse is fairly benign in most patients, but about 1-10% of MVP patients have serious problems such as chest pain, arrhythmias, and leakage of the valve, leading to congestive heart disease. Coenzyme Q10 and magnesium (detailed in the Therapeutic section of this protocol) are of significant advantage to individuals with MVP.
Mitral Valve Regurgitation
Mitral regurgitation, the backflow of blood from the left ventricle into the left atrium, occurs because the valve is too leaky. The mitral valve can become regurgitant for many reasons, including the aging process, rheumatic valvular disease, endocarditis, chest trauma, or a previous heart attack. Mild but chronic regurgitation does little to alter the overall cardiac health of the patient, but if the condition is moderate to severe, the left ventricle and left atrium can enlarge because of the increased volume of blood. The enlargement of the left atrium can cause symptoms of fatigue, pulmonary edema, atrial fibrillation, and atrial thrombi. The enlargement of the left ventricle can lead to congestive heart failure.
The leakage can be repaired by surgery and/or insertion of a metal ring around the valve to assist in holding the valve in shape. If surgical replacement is elected, the diseased valve is cut out and replaced with a prosthetic heart valve.
Knowing when to perform the surgery is critical. The consequences of waiting too long may negate any surgical advantage because of enlargement and damage to the left ventricle. Leakiness occurring in a damaged valve can actually make the job of the left ventricle easier. The effort expended by the left ventricle when the valve is leaking is less than when the valve is repaired. The weakened left ventricle may not be strong enough to keep pace with the efficiency of the repaired or artificial valve. Therefore, the first sign of left ventricular impairment may be the best clue that it is time to consider surgery.
Mitral Valve Stenosis
Mitral stenosis occurs when the mitral valve is too tight, and the blood cannot flow easily from the left atrium to the left ventricle. To compensate, the left atrium will enlarge to develop the extra pressure to push the blood into the ventricle. As pressure in the left atrium increases, blood pools in pulmonary vessels. The excess blood then seeps out into the air spaces of the lungs and shortness of breath results.
If the condition is mild, there is a minimal effect on the overall health of the person. However, some patients experience significant symptoms such as fatigue, dyspnea, orthopnea (requires sitting or standing to breathe comfortably), and cyanosis (a bluish discoloration of the skin and mucous membranes). Mitral valve stenosis can lead to atrial fibrillation, which if not well managed increases the risk of stroke. People who have the combination of atrial fibrillation and mitral stenosis have a high rate of stroke, on the order of 5% per year.
Therapeutic options include balloon valvuloplasty (a procedure in which one or more balloons are placed across a narrowed valve and inflated to decrease the severity of stenosis), mitral commissurotomy (a procedure to increase the size of the opening by separating adherent, thickened leaflets), or replacement with a prosthetic valve. The two methods of repair are not permanent; the valve will become stenotic in about 5-15 years. A mechanical prosthetic valve requires chronic anticoagulation therapy.
The tricuspid valve has three main cusps and is situated between the right atrium and the right ventricle of the heart. The right atrium receives blood returning from the body and pushes the blood into the right ventricle. As the right and left ventricles relax (during the diastolic phase of the heartbeat), the tricuspid valve opens, allowing blood to enter the ventricle. During the systolic phase of the heartbeat, both blood-filled ventricles contract, pumping out their contents while the tricuspid and mitral valves close to prevent any backflow.
Tricuspid regurgitation is a condition in which the tricuspid valve becomes leaky, allowing blood to flow backward from the right ventricle into the right atrium. It can occur by itself or in combination with a disease process that elevates right ventricular pressure.
When tricuspid regurgitation occurs by itself, perhaps due to subacute bacterial endocarditis, regurgitation does not pose much of a problem. But when tricuspid regurgitation occurs in union with mitral stenosis or lung disease, fatigue, abdominal discomfort, nausea, and swelling of the legs and feet result. If surgery is scheduled to correct another cardiac problem, the tricuspid valve should be evaluated for surgical repair at that time. Otherwise, medical treatment includes a low-salt diet, diuretics, and digoxin.
Tricuspid stenosis is a condition in which the tricuspid valve is too tight. Symptoms of tricuspid stenosis closely parallel those of tricuspid regurgitation, that is, nausea, fatigue, abdominal discomfort, and swelling of the legs and feet. Patients are frequently advised to follow a low-sodium diet and to use diuretics; if atrial fibrillation develops, digitalis may be prescribed. Balloon valvuloplasty or valve replacement is usually recommended if medical treatment proves ineffective. Because the risk of thrombus on the valve is higher in the tricuspid position than in the mitral position, bioprosthetic valves are better than mechanical valves, despite their limitations.
The aortic valve, composed of three semilunar cusps, is located between the left ventricle and the aorta. The aortic valve prevents blood from flowing back into the left ventricle from the aorta.
Aortic stenosis is a condition in which the aortic valve is too tight. This means that the opening through which blood must flow is too small; consequently, the left ventricle must generate higher pressure to maintain normal blood flow. It usually takes decades for the condition to fully develop. Not until the aortic valve area has narrowed to about one-fourth of its normal size do circulatory problems become significant.
The most common cause of aortic stenosis in adults is a degenerative calcification process that immobilizes the aortic valve cusps. The calcification process can either decrease worthiness of the valve or result in total fusion. Studies implicate a chronic inflammatory process in calcium buildup, leading to aortic valvular stenosis. Therefore, long-term anti-inflammatory therapy may be beneficial.
The degree of closure does not always correlate to symptoms. Thus, aortic valve replacement is usually reserved for patients experiencing symptoms, rather than those with narrowing who are asymptomatic. Eventually, angina, syncope (fainting), and heart failure may develop. After the onset of symptoms, the average survival is usually less than 2-3 years.
Fifty-one asymptomatic patients with severe aortic stenosis were followed for an average of 17 months. During this period, two patients died (with cardiac symptoms preceding their deaths). Other studies have shown similar survival trends among asymptomatic patients. (Sudden death occasionally occurs in the absence of symptoms, but the numbers are small, less than 1% per year.)
Once symptoms have become apparent, surgery becomes the patient's best option. Not all experts agree on when to do valve replacement surgery in asymptomatic patients with aortic stenosis. The rationale for early surgery is that the first symptom of aortic stenosis can be sudden death.
In theory, the aortic valve can be replaced in almost all patients, even octogenarians, who are otherwise in good health. Insertion of a prosthetic aortic valve is associated with low perioperative morbidity and mortality; complications arise at the rate of at least 2-3% a year, with death due directly to the prosthesis at about 1% a year. Symptomatic but inoperable patients are usually prescribed digitalis, diuretics, and an ACE (angiotensin converting enzyme) inhibitor.
Aortic regurgitation occurs when the blood flows from the aorta back into the left ventricle. Some of the blood that should be flowing to the body from the heart flows back into the left ventricle. As a result, the left ventricle has to pump harder to move the blood though the circulatory route and back to the heart. A few of the factors provoking aortic regurgitation include congenital deformities, calcification, rheumatic fever, infective endocarditis, systemic hypertension, and anorexic drugs.
Acute aortic regurgitation is a medical emergency. During acute, severe aortic regurgitation, the left ventricle does not have time to make the necessary adjustments to accommodate the backflow and, as a result, forward stroke volume decreases. Tachycardia (a heartbeat over 100 beats a minute) occurs as a compensatory mechanism, but the effort is usually not equal to the task. Pulmonary edema and/or cardiogenic shock, a condition of critically low cardiac output, can result. (About 80% of events involving cardiogenic shock are fatal.)
Conversely, in chronic aortic regurgitation, a number of compensatory adjustments occur, rendering aortic regurgitation less dangerous. In fact, the majority of patients remain asymptomatic through this compensated phase, which may last for decades. With time, the left ventricle progressively enlarges and depressed myocardial contractility increases. This can progress to the extent that the full benefits of surgical correction, that is, recovery of left ventricular function and improved survival, are no longer possible.
The results of several studies, involving 490 asymptomatic patients with chronic aortic regurgitation who were followed for an average of 6.4 years, give a brief history regarding the developmental patterns of the condition.
- The rate of progression to symptoms and/or left ventricle dysfunction averaged 4.3% a year. (As the left ventricle goes, so goes the heart.)
- Sudden death occurred in six of the 490 patients (an average mortality rate of < 0.2% a year).
Are Artificial Valves as Good as
The replacement of diseased natural heart valves with artificial valve can be life-saving, but the replacement valves are never considered as good as healthy natural ones. There are two general types of valves: mechanical and bioprosthetic (usually taken from pigs). The mechanical valves last longer but require the patient to take anticoagulants. The bioprosthetic valves do not require long-term anticoagulation therapy, but they frequently must be replaced after about 10 years in adults. Their replacement comes quicker in children and persons on kidney dialysis. The major risk of prosthetic heart valves is stroke. Those taking anti-coagulants reduce the incidence of stroke, but the risk is not totally eliminated.
The following natural products may be of value to patients with valvular disease. The herbs profiled have one or more chemicals that convey the biological property delineated and are subsequently not equal in therapeutic strengths (Duke Database). Researchers state that carnitine may provide independent benefit in ischemia when used as monotherapy, or additional benefit when used in combination with conventional beta-blockers or calcium antagonists (Jackson 2001). To learn more about the following supplements, please consult the Therapeutic section.
- Vasodilators. Angelica, garlic, ginger, ginkgo biloba, hawthorn, magnesium, niacin, and olive leaf
- ACE inhibitors. Angelica, garlic, ginger, ginkgo biloba, grape seed, green tea, hawthorn, olive leaf, procyanidins, and taurine
- Calcium blocking properties. Angelica, garlic, ginger, ginkgo biloba, grape seed, green tea, hawthorne , magnesium, and olive leaf
- Digitalis-like activity. Bugleweed and taurine
- Diuretic activity. Angelica, bugleweed, curcumin, garlic, ginger, grape seed, green tea, hawthorn, olive leaf, taurine, vitamin B6, vitamin C, and vitamin E
- Anti-inflammatories. Angelica, bromelain, bugleweed, chondroitin, curcumin, DHEA, EFAs, garlic, ginger, ginkgo biloba, grape seed, green tea, hawthorn, olive leaf, and vitamin C
- Beta-blocking activity. Grape seed, green tea, hawthorn, magnesium, and taurine
The following therapeutics are arranged alphabetically and not by order of importance, providing greater accessibility to readers.
Alpha-Lipoic Acid (a.k.a. Thiotic Acid)—beneficial in preventing and treating Syndrome X, has antioxidant and antidiabetic activity, protects LDL cholesterol against oxidation, lowers total cholesterol, is beneficial in congestive heart failure and strokes, inhibits protein glycation, and stabilizes arrhythmias
Some researchers credit alpha-lipoic acid with being the principal supplement for preventing and reversing Syndrome X. Lipoic acid earned this reputation by increasing the burning of glucose. The mitochondria (the powerhouse of the cell) are one of the benefactors of enhanced glucose utilization, via the Krebs's cycle, a process that utilizes glucose, amino acids, and fatty acids to yield high energy. Many of the B vitamins assist in maximizing production from the Krebs's cycle, but perhaps none is as efficient as lipoic acid (Challem et al. 2000).
Note: Free radicals are produced as a byproduct of the energy generated during the Krebs's cycle. Alpha-lipoic acid appears to quench free radicals that are not contained during the reactions.
As glucose is provided to fuel the Krebs's cycle, blood glucose and insulin levels decrease and simultaneously another perk occurs: insulin sensitivity increases. Lipoic acid resulted in a 50% increase in insulin-stimulated glucose disposal and a significant improvement in insulin sensitivity compared to a nonsupplemented placebo group. Blood glucose levels often drop 23-45% in lipoic acid-treated diabetic animals. The journal Hypertension also reported alpha-lipoic acid, a thiol compound known to increase tissue cysteine and glutathione levels, reduced systolic blood pressure in spontaneously hypertensive rats (Jacob 1995, 1996, 1997; Vasdev et al. 2000).
Lipoic acid is of value in treating diabetic and nondiabetic subjects with congestive heart failure. Researchers from Beijing University added that lipoic acid, because of its free-radical scavenging effects, is able to protect the myocardium from free-radical damage and subsequently decrease the incidence of malignant arrhythmias (Gao et al. 1991). Antioxidants are extremely important in cardiac health, for the heart is one of the most susceptible of all organs to free-radical damage. (There are three times more free radicals produced in aging hearts compared to young hearts.)
Alpha-lipoic acid is, in fact, regarded as the universal antioxidant because it enhances the activity of other antioxidants. It acts like a big brother in regard to vitamin E, coenzyme Q10, and vitamin C, assisting in recycling these important antioxidants for continued service. Lipoic acid's antioxidant qualities appear greater than vitamin E's because vitamin E works only in the fatty parts of cells, whereas lipoic acid works in both watery and fatty portions (Challem et al. 2000).
Stroke deaths dropped from 78% to 26% in lipoic acid animal studies conducted by Lester Packer. The journal Stroke confirmed that alpha-lipoic acid reduced stroke infarct volume and free-radical activity, inhibited platelet-leukocyte activation and adhesion, and increased cerebral blood flow (Clark et al. 2001).
Lipoic acid reduced the formation of glycosylated end products (AGEs) (Jain et al. 1998). Glycation occurs when proteins react with sugar to form AGEs. This process increases the risk of cardiovascular disease by oxidizing LDL cholesterol and rendering blood vessels tough and inflexible. This gradually affects the left ventricle, reducing its ability to pump oxygen-rich blood into the circulation. Stiffness occurring in the myocardium increases diastolic pressure, and arterial rigidity increases systolic pressure. Also, glycosylated cholesterol-carrying proteins are no longer capable of binding to receptors on liver cells to signal the cessation of cholesterol manufacturing. A healthy cholesterol-carrying protein halts the copious supply of cholesterol. Without this binding process, cholesterol continues to be pumped out. Lipoic acid interrupts all of these processes at the starting point, by inhibiting glycation.
Note: Although a normal byproduct of oxidative metabolism, free radicals in excess are considered germane to the onset of vascular disease. When out of control, these highly unstable electrons can cause extensive damage to lipid membranes, organelles, and DNA itself. But most all of nature is two-pronged, having a good side as well as a bad. For example, free radicals participate in many positive reactions, including mitochondrial respiration, prostaglandin synthesis, platelet activation, and leukocyte-phagocytosis, (the engulfing and destruction of microorganisms and cellular debris). It is thus extremely important to supply sufficient nutrient cofactors to support endogenous antioxidant enzyme systems (such as superoxide dismutase, catalase, and glutathione peroxidase) but to retain enough free-radical oxidative activity to carry on essential life processes (Sinatra 2001).
Some researchers believe 50-250 mg a day (in concert with other antioxidants) may be sufficient to protect against Syndrome X. Most Life Extension members have been taking between 250-500 mg a day of alpha-lipoic acid. If the patient has unstable blood glucose levels, higher doses of lipoic acid will be required. German practitioners frequently use 600 mg daily as adjunctive therapy in coronary artery disease and 600-1800 mg of alpha-lipoic acid to improve insulin sensitivity and diabetic conditions. Higher doses should be administered with the help of a qualified physician who can adjust insulin requirements as indicated. Note: Dr. Lester Packer, in The Antioxidant Miracle, recommends taking biotin supplements with alpha-lipoic acid when the daily intake exceeds 100 mg. Alpha-lipoic acid may compete with biotin and interfere with biotin's activities in the body.
Reader's guide to lipoic acid food sources
Liver, yeast, spinach, broccoli, potatoes, and red meat.
Angelica (Angelica archangelica)—an anti -anginal, anti-inflammatory calcium antagonist,
ACE inhibitor, and diuretic
Angelica, a member of the carrot family, contains 15 compounds considered to be calcium channel blockers. One of the calcium antagonists in angelica is, in fact, more potent than verapamil (Calan, Isoptin), a popular calcium channel blocker prescribed for angina, atrial fibrillation, and spasms occurring in the blood vessels (Duke 1997).
James Duke, Ph.D. (botanist), comments that it is well known that vegetarians have a low incidence of heart disease. Usually their low-fat diet gets the credit, but Dr. Duke speculates that it may be because they eat lots of plants from the carrot family, such as carrots, celery, fennel, parsley, and parsnips, which (like angelica) contain compounds with calcium channel blocking activity. Calcium channel blockers (whether natural or pharmaceutical) are powerful anti-anginals.
Angelica bestows its cardiac advantage through various pathways. For example, angelica not only reduces the incidence of angina attacks, but also regulates an erratic heartbeat. It has diuretic properties, making it of value in the treatment of congestive heart failure and hypertension. Chemicals contained in angelica exhibit another mechanism to reduce blood pressure, that is, the inhibition of ACE, the angiotensin-converting enzyme (Duke Database 1992).
Inflammation, one of the newer risk factors for heart disease, is also reduced by angelica (read about the inflammation-heart disease connection in the sections dedicated to Newer Risk Factors). A suggested angelica dosage is 15-30 drops 1-3 times a day.
Comments: How many milligrams (mg) of herb are in a drop of extract? According to Herb Pharm, a respected name in the herbal industry, the milligrams represented by 1 milliliter of extract (about 30-40 drops) from a dried herb are given by the herb-to-menstruum ratio (menstruum is a solvent—a liquid that dissolves a solid). This number varies for extracts made from fresh herbs due to the increased yield of these extracts. Liquid extracts are more assimilable than powdered herbs so the weights are not comparable. If trying to follow a recommendation, the form of the recommendation (powdered herb, liquid extract, etc.) needs to be considered. Quality and quantity are separate issues and even liquid extracts cannot be accurately compared on a mg-to-mg basis. Many factors determine the quality of an herbal extract, including the makeup of the menstruum, extraction technique, and raw herb quality. The following is only an approximate calculation, but it may be helpful:
1 mL is equal to about 33 drops of many extracts
1 mL of a 1:4 ratio contains extractives from gram of herb (0.25 gram = 250 mg)
The strength ratio does not directly address quality. Quality is dependent on other factors such as the quality of the herb, the plant part used, special handling, the extraction process and technique, as well as storage. Always follow dosage instructions (and caveats) appearing on the label.
L-Arginine—dilates blood vessels, reduces blood pressure, replicates the activity of nitroglycerine, and is needed to produce nitric oxide
L-arginine, along with a properly planned exercise program, assists in amending abnormalities occurring in blood vessels. Individuals with congestive heart failure often have blood vessels that fail to dilate in response to certain drugs, a sign that the inner blood vessel wall, or endothelium, is compromised.
A study reported in the American College of Cardiology concluded that treatment with L-arginine produced a fourfold increase in blood vessel dilation from 2.2-8.8% (Hambrecht et al. 2000). Regular forearm exercises increased the dilation response by the same amount, but the combination of L-arginine and exercise training resulted in an improvement from 2.9-12%. Doses of 5.6-12.6 grams of arginine increased blood flow to the extremities 29%; the distance walked on a treadmill in 6 minutes increased 8% (Rector et al. 1996).
Much of L-arginine's effectiveness comes by way of increasing nitric oxide, a blood vessel dilator and clot buster produced in endothelial cells by the enzyme nitric oxide synthase (Brunini et al. 2002). Nitric oxide counteracts the vasoconstriction and platelet-aggregating effects of the stress hormone adrenaline (epinephrine) and assists in maintaining vascular elasticity. Nitric oxide (the endothelial relaxing factor) is needed for expansion and contraction of the arterial system (Rohdewald 1999). L-arginine increases nitric oxide, but hypertension, hyperhomocysteinemia, diabetes, and smoking decrease it.
Because of arginine's vasodilating properties, it is frequently used as a treatment for angina pain and hypertension. Researchers at the University of Southern California ( Los Angeles ) speculate that a defect in nitric oxide production may be a possible mechanism of hypertensive disease (Campese et al. 1997). Some cardiologists, in fact, recommend L-arginine over nitroglycerine, since the two substances appear to replicate a similar vascular function: the ability to relax smooth muscles and dilate blood vessels.
In their current book, The Arginine Solution, Drs. Robert Fried and Woodson C. Merrell note that as people age and develop disorders such as hypertension, hypercholesterolemia, and atherosclerosis, their ability to make sufficient amounts of nitric oxide from arginine is impaired, contributing to a decline in their cardiovascular health. Drs. Fried and Merrell contend that increasing arginine intake addresses various cardiovascular risks associated with decreased nitric oxide synthesis, often improving symptomatic and clinical evaluations (Fried et al. 1999). A suggested dosage is 2 grams before bedtime. Arginine caveat: Individuals who have frequent herpes outbreaks may find arginine-rich foodstuffs or supplementation contraindicated.
Reader's guide to arginine food sources
Most protein foods and carob, chocolate, nuts, seeds, beans, oats, peanuts, and wheat and wheat germ.
Artichoke Extract—reduces cholesterol and triglycerides
Artichoke (Cynara scolymus), a delicious table vegetable, has a reputation that extends beyond culinary enhancement. It has long been used to improve digestive and liver complaints, but more recently artichoke has become popular as a hypolipidemic. Studies have shown that the more lipid correction needed, the greater artichoke's cholesterol-lowering effects. Caffeoylquinic acids and flavonoids, constituents of artichoke, appear to deliver much of the plant's positive effects.
In a multicenter, placebo-controlled, randomized trial, 143 patients with initial cholesterol levels greater than 280 mg/dL took either a placebo or 450 mg of artichoke dry extract 4 times a day. After 6 weeks, those taking the artichoke extract showed an 18.5% reduction in cholesterol compared to a 5.6% reduction in the placebo group. LDL-cholesterol decreased 22.9% among those taking the artichoke extract and 6.3% in the placebo group. The LDL/HDL ratio showed a decrease of 20.2% among the artichoke users (Englisch et al. 2000). Another short-term study (6 weeks) showed that artichoke reduced triglycerides from 214.97 mg/dL to 188.07 mg/dL (Fintelmann 1996a, 1996b). There were no drug related adverse events during the course of these studies, indicating an excellent tolerability.
Artichoke reduces cholesterol by decreasing the synthesis of cholesterol in the liver and increasing the conversion of cholesterol to bile acids. (Cholesterol is a building block for bile acids.) According to Michael Murray, N.D., cholesterol levels are sometimes high because of the impaired conversion of cholesterol to bile acids. Thus, low bile acid levels send a powerful signal to the liver to provide more cholesterol. Artichoke extract intercepts this signal, and the liver complies with less cholesterol production ( Murray 1998b).
The flavonoid luteolin appears to be pivotal in the hypocholesterolemic effects of artichoke. Statin drugs reduce cholesterol by competitively inhibiting the binding of HMG-CoA reductase. Tocotrienols also degrade this enzyme. Artichoke research has found no direct inhibition of HMG-CoA reductase. Other enzymatic steps occurring later in the biosynthesis of cholesterol appear unaffected. It seems luteolin inhibits cholesterol below the level of HMG-CoA reductase and therefore spares coenzyme Q10 synthesis. Recall that the cholesterol cascade begins with acetyl-CoA being converted to HMG-CoA. HMG-CoA reductase reduces HMG-CoA to mevalonic acid. Mevalonic acid participates in several steps that reduce it to squalene. Squalene is then converted to cholesterol (Murray 1998b; Sardesai 1998).
A suggested dosage is 1 capsule 3 times a day, containing 300 mg of artichoke standardized to contain 13-18% caffeoylquinic acid. Note: The American Journal of Clinical Nutrition recently reported that chlorogenic acid, a component of black tea and coffee, could increase homocysteine levels (Olthof et al. 2001). Chlorogenic acid also appears in artichoke and would therefore be contraindicated in refractory hyperhomocysteinemia. Lastly, individuals with gallstones or biliary tract obstruction should not use artichoke.
Aspirin—reduces C-reactive protein (CRP), platelet aggregation, and cardiac inflammation
Aspirin has been used for over a century to relieve pain; research suggests that it may play an equally important role in heart health. A study involving 51,085 participants showed a total of 2284 cardiovascular endpoints occurring during an aspirin trial. The risk of a first nonfatal heart attack was reduced 32% among aspirin users compared to nonusers. The researchers concluded that aspirin therapy could prevent a third of myocardial infarctions occurring in apparently healthy individuals (Hebert et al. 2000). JAMA also reported that aspirin usage was associated with reduced all-cause mortality, particularly among older subjects with known coronary artery disease and impaired exercise capacity (Gum et al. 2001).
Three studies looked at the incidence of stroke subtypes among aspirin users. A 1.69-fold increase in the risk of hemorrhagic stroke occurred among aspirin users, but no increase in ischemic strokes was noted. Secondary prevention trials, evaluated by Drs. Patricia R. Hebert ( Yale University ) and Charles Hennekens ( University of Miami ) indicated that aspirin therapy administered to 10,000 persons would prevent about 67 myocardial infarctions and cause approximately 11 hemorrhagic strokes. In November 2001, the New England Journal of Medicine published that over a 2-year period, no difference was found between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage (Hebert et al. 2000; Mohr et al. 2001).
The drug disposition of aspirin is persuasive when applied to a cardiovascular model. For example, low-dose aspirin (81 mg) appears to provide partial protection against abnormal blood clot formation, having a 2-day lasting effect on blood platelets. Platelets become less sticky and the risk of a heart attack and transient ischemic attacks (TIAs) is subsequently reduced.
Aspirin exerts some of its cardioprotection by inhibiting the enzyme cyclooxygenase, a trigger in the inflammatory process (Newmark et al. 2000). One molecule of aspirin will destroy the cyclooxygenase enzyme for 4-6 hours (read the sections devoted to C-Reactive Protein and The Link Between Infections and Inflammation in Heart Disease to learn how the inflammatory process advances cardiac disease).
Aspirin appears to lower C-reactive protein (CRP). In the Physician's Health Study, participants were randomly assigned at baseline to receive 323 mg of aspirin on alternate days and were then followed through first myocardial infarction. The study showed that low dose aspirin reduced heart attack risk by about 44% compared to the control group; the risk was 55% lower than that of placebo-treated men with high CRP levels. The results of this study suggest that in addition to aspirin's antagonism toward platelet clumping, it may also attenuate thrombosis through anti-inflammatory mechanisms (Physicians Weekly 1998a).
Aspirin significantly cut the death rate from cardiac disease among 2368 noninsulin-dependent diabetic patients with coronary artery disease. (The aspirin benefit was greater among diabetic patients than nondiabetics.) Diabetic patients using aspirin had a 10.9% mortality risk from cardiac diseases, while diabetics not using aspirin had a 15.9% risk (Harpaz et al. 1998).
The aspirin advantage extended to include carotid endarterectomy patients. Individuals using low-dose aspirin (81-325 mg a day) reduced the risk of myocardial infarction, stroke, and death for a 30-day to 3-month interval following surgery. Individuals taking 650-1300 mg were not similarly protected, illustrating that the dose can alter the end response (Taylor et al. 1999).
Current information indicates that aspirin can also reduce the level of heart damage during a heart attack. When taking aspirin because one believes they are experiencing an acute heart attack, the aspirin should be chewed rather than swallowed and is best taken within 30 minutes of the onset of symptoms.
In conclusion, the Antithrombotic Trialists' Collaboration (representing a review of 287 studies involving 135,000 patients) announced that over 40,000 lives are lost worldwide every year because aspirin is underused. According to the report, aspirin (or other antiplatelet drugs) is protective in most patients at increased risk of occlusive vascular events, including those with acute myocardial infarction or ischemic stroke, unstable or stable angina, previous myocardial infarction, cerebral ischemia, peripheral arterial disease, or atrial fibrillation (Antithrombotic Trialists' Collaboration 2002).
Aspirin (75-150 mg a day) appears to be an effective antiplatelet regimen for long-term usage, but in acute settings, an initial loading dose of at least 150 mg may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances (Antithrombotic Trialists' Collaboration 2002). Note: The New England Journal of Medicine recently published that warfarin, in combination with aspirin or given alone, was superior to aspirin alone in reducing the incidence of composite events following an acute myocardial infarction. Warfarin was, however, associated with a higher risk of bleeding (Hurlen et al. 2002).
The American College of Chest Physicians suggests that all people over 50 years of age, with one cardiac risk factor and no condition that would negate treatment, consider aspirin therapy. The cautionary includes those individuals who have increased prothrombin time, disturbed gastric mucosa, or hypertension. As acclaimed as low-dose aspirin is, studies have shown that aspirin does not appear comprehensive enough to prevent a heart attack if fibrinogen levels are excessively high. It should also be noted that a concomitant administration of ibuprofen (but not rofecoxib, acetaminophen, or diclofenac) antagonizes the platelet inhibition activity induced by aspirin. Thus, treatment with ibuprofen in patients with increased cardiovascular risk may limit the cardioprotective effects of aspirin (Catella-Lawson et al. 2001).
Bromelain—is an anti-inflammatory, reduces fibrinogen, lessens risk of blood clots, is beneficial in atrial fibrillation, is hypotensive, relieves angina, and is basic to smokers
Bromelain, derived from pineapple (Ananas comusus), is regarded as a natural anti-inflammatory, acting as a protein-digesting enzyme. Since the revelation that inflammation may be causal to cardiovascular disease, bromelain has attained new stature. Proteolytic enzymes work directly on the inflammation, neutralizing and removing damaged cell tissue. The digesting nature of bromelain suggests that it can also reduce atherosclerotic plaque accumulating in arteries.
Bromelain lowers blood pressure, breaks down fibrinogen, and relieves angina. It opposes platelet aggregation and is helpful in thrombophlebitis. Many of bromelain's qualities make it particularly valuable to smokers and patients with atrial fibrillation (Murray 1995c; Duke 1997).
A suggested bromelain dosage is 1/8-1/4 teaspoon taken between meals to relieve inflammation. The strength of enzymes is often expressed as milk-clotting units (MCU) and gelatin-digestive units (GDU) per gram. One level teaspoon of Life Extension Bromelain Powder (2.9 grams) has enzymatic strength of 3500 MCU or 2000 GDU. Bromelain tablets (500 mg) are also available. Typically, bromelain is used 3 times a day.
Bugleweed (Lycopus virginicus)—is a diuretic and has a digitalis mentality
Bugleweed has a reputation that dates to folk medicine. Historically, herbalists used bugleweed to regulate the heart and improve circulation. Bugleweed's repute is enduring, for practitioners still use the herb to stabilize a rapid or irregular heart rhythm, whether the problem is functional or organic.
Bugleweed is beneficial in the treatment of hypertension and congestive heart failure, ridding water from edematous tissues and organs. It has been called a natural digitalis, milder but with some of the same characteristics as the drug. Bugleweed does not accumulate and is therefore considered nontoxic (Santillo 1990; Ritchason 1995). A suggested dosage is 30-40 drops in a little water 2-4 times a day. (For an explanation regarding milligrams per drop, turn to Angelica, appearing alphabetically in this section.)
Calcium—is a hypotensive mineral and an anti-arrhythmic, supports healthy bones around gum tissue, and reduces iron overload
Minerals, although usually not considered as focal, are in many ways more important to survival than vitamins. One can live longer with a vitamin deficiency than with a mineral shortage (Whiting 1989). For example, a deficiency of calcium, magnesium, or potassium can force the heart into fatal cardiac arrhythmias. In addition, inadequate mineral intake appears to have a correlation with hypertension. Hypertensive individuals may be unwittingly contributing to the problem by consuming about 18% less dietary calcium than normotensives.
Researchers at the Oregon Health Sciences found that supplemental dietary calcium lowers blood pressure, whereas restricted-calcium diets tend to elevate blood pressure (Geri Clark in Woman's Day). According to research from the Indiana University School of Medicine, a unifying theory showing how calcium reduces blood pressure is not available. A membrane stabilizing effect, natriuresis (the excretion of greater than normal amounts of sodium in the urine), and calcium's ability to control regulatory processes are mechanisms debated (Luft et al. 1990). However, epidemiologic findings suggest that there is a threshold for the protective effect of calcium, below which the risk of hypertension increases at a greater rate. The set point of this threshold may be about 700-800 mg a day, but other variants, such as metabolic type, absorption rates, and genetics may modify this dosage (McCarron et al. 1991).
Calcium is not a universal resolvent for hypertension (Meese et al. 1987). In some cases, clinicians report no significant hypotensive effect in dosages as high as 2.5 grams a day. Patients wishing to try calcium should not withdraw blood pressure medication abruptly but use the drug in combination with calcium over a 3- to 6-month assessment period. During this interval, watchful monitoring may allow a gradual reduction in medication.
According to information published in the journal Stroke, low dietary calcium intake poses a significant risk for women in regard to heart disease and stroke. Researchers analyzed the dietary intake of 85,764 women, compiled from the Nurses' Health Study. After an adjustment for risk factors associated with cardiovascular disease, calcium intake was significantly related to the risk of stroke. Women with the lowest calcium intake (especially from dairy sources) had the greatest risk of heart problems, perhaps because of higher cholesterol levels and a tendency for blood cells to clump. The increase in risk was limited to the lowest quintile of intake; intakes of calcium greater than 600 mg a day did not appear to reduce risk of stroke further (Iso et al. 1999).
Calcium is also of advantage in reducing iron overload. The American Journal of Clinical Nutrition stated that 300 mg of elemental calcium, taken with a meal, reduced the amount of iron absorbed from food by 40% (Hallberg et al. 1998). Amounts larger than 300 mg did not further inhibit iron absorption. Since some individuals become tolerant to calcium-induced iron absorption blockage, it is important to have blood tests periodically to evaluate sustained effectiveness. Calcium is also important in periodontal disease by supporting healthy bone around gums (Balch, et al. 1997).
Calcium citrate is a good choice considering absorption, but calcium citrate malate acid is about 30% better absorbed than calcium citrate. Calcium bis-glycinate was shown to absorb 180% better than calcium citrate and 21% better than calcium citrate malate. A suggested dosage is 1000 mg of elemental calcium a day.
Reader's guide to food sources of calcium.
Milk and dairy products are frequently criticized, particularly those that are homogenized. During homogenization, an enzyme appearing in milk (xanthine oxidase) is broken down to a smaller size. The enzyme's altered state allows entry into the bloodstream and a reaction to occur on arterial walls. As a protective gesture, atheromatous materials are laid down at the site of contact. In addition, milk is often challenged as a worthy source of calcium. Its high phosphorous content and magnesium shortfall are thought to impede calcium absorption. Dark green vegetables, salmon (with bones), sardines, most nuts and seeds (especially sesame seeds), blackstrap molasses, root vegetables, and liver are considered to be safer, surer sources of calcium.
The interrelationship of factors acting on absorption
The importance of providing an environment conducive to nutrient utilization cannot be overstated. For example, in an alkaline medium, calcium forms insoluble, nonabsorbable calcium phosphate. Conversely, hydrochloric acid lowers the pH of the digestive tract, providing a favorable milieu for absorption.
Nutrients also play a role, either supporting or opposing absorption. For example, the amino acid lysine (found in milk products, eggs, meat, fish, and fowl) enhances calcium absorption. Other calcium enhancers include vitamin D, vitamin A, vitamin C, and magnesium.
Diets high in sugar alter calcium uptake; coffee, alcoholic beverages, and phosphorous-rich soft drinks also promote increased calcium excretion. Oxalic acid (found in almonds, beet greens, cashews, chard, cocoa, rhubarb, soybeans, and spinach) retards calcium absorption by binding with calcium in the intestines, producing insoluble, nonabsorbable salts. (Oxalic acid is problematic only if the diet is persistently structured around these foodstuffs.) Calcium and tetracycline form an insoluble complex that impairs both mineral and drug absorption.
L-Carnitine—is an energizer and hypolipidemic, aids weight loss, improves circulation, increases exercise tolerance, and is beneficial treatment in angina, diabetes, congestive heart failure, and cardiac arrhythmias
Robert Crayhon, nutritionist and author, considers carnitine the single most important nutrient in regard to cardiac health. Carnitine, a coenzyme similar to the family of B vitamins, is essential for the burning and transport of long-chain fatty acids, the fuel for cardiac energy. Up to 70% of energy produced by muscles comes from the burning of fats. To expect the normal functioning of heart muscles, the transport of carnitine into tissues is critical (Crayhon 1998).
Lysine and cofactors yield about 25% of the carnitine the body needs for optimal performance. The remaining 75% can come from the diet, if dietary selections are made with a slant toward carnitine-rich protein foods, especially mutton, lamb, and beef. Interestingly, protein foods, those frequently shunned on a heart-healthy diet, raise HDL cholesterol and increase carnitine levels (Crayhon 1998).
Carnitine is often effective in reducing the incidence of cardiac arrhythmias and angina attacks. According to statistics, patients receiving L-carnitine experienced fewer premature ventricular contractions at rest and improved cardiac output (Cacciatore et al. 1991). But if oxygen levels decrease, carnitine also decreases, and the patient may be in jeopardy from two perspectives.
Patients with stable angina, who were evaluated by means of a stress test, were able to exercise longer before abnormalities were detected while on 900 mg of orally administered L-carnitine (Kamikawa et al. 1984). Individuals acting as controls in the study and receiving a placebo experienced distress at 6.4 minutes into the test, while individuals receiving carnitine supplementation extended the period of symptom-free exercise to 8.8 minutes. Researchers also state that carnitine may provide independent benefit in ischemia, when used as monotherapy, or additional benefit when used in combination with conventional beta-blockers or calcium antagonists (Jackson 2001). Although research indicates carnitine may be an effective adjunctive therapy, never discontinue cardiac medications without the consent of your physician.
Carnitine, administered to individuals displaying heart trauma, substantially lessened coronary damage and the risk of occlusion. Arterial plugs were less likely to form as carnitine modulated lipids, with less of the objectionable and more of the beneficial fats produced. After 4 months of carnitine therapy, total cholesterol levels were reduced by about 20%, triglycerides were reduced 28%, and HDL increased 12%. Triglycerides and HDL were more responsive to carnitine supplementation if the diet contained no more than 40% of calories from carbohydrates (Pola et al. 1980, 1983; Murray 1996b).
Carnitine is of value in treating congestive heart failure. A group of 60 men and women (ages 48-73) were selected for a carnitine heart study, having failed conventional treatment. Thirty of the patients were given LPC (L-propionylcarnitine, 500 mg 3 times a day for 180 days), along with their drug regime. At 30 days into the trial, the patients were evaluated for improvement in exercise tolerance and left-ventricular ejection fraction. Compared to controls, both parameters showed significant recovery at the 1-month interval, but improvement was even more pronounced at the 90- and 180-day marks. Exercise tolerance improved 16.4% at 30 days, 22.9% at 90 days, and 25.9% at 180 days; left-ventricular ejection fraction progressively increased 8.4%, 11.6%, and 13.6% throughout the course of the trial (Cacciatore et al. 1991; Mancini et al. 1992; Murray 1996d). Note: L-carnitine has been approved by the FDA, under the name Carnitor, as a therapy for congestive heart failure.
Glycosylated hemoglobin, HbA1c (a hemoglobin molecule chemically linked to glucose), is a test used to evaluate glucose levels over the previous 6-8 weeks. The test measures glycosylation of hemoglobin in the red cells over their lifetime of 90-120 days. HbA1c, for a nondiabetic, is normal at 4-6%; for a diabetic, the goal is to maintain HbA1c less than 7% (7% is an average of 150 mg/dL of glucose). It appears carnitine may have the potential to assist in stabilizing blood glucose levels, so that peaks and valleys are less troublesome to diabetic patients. Carnitine accomplishes this by increasing glucose disposal and improving insulin sensitivity (DeGaetano et al. 1999; Mingrone et al. 1999). A report published in JAMA showed that a significant financial savings ($685-$950 annually) accrued to diabetes within 1 year of improved HbA1c levels (Wagner et al. 2001).
Individuals who are at increased cardiac risk because of obesity may find value in carnitine supplementation. Carnitine, especially when combined with omega-3 fatty acids and a decrease in carbohydrate consumption, promotes weight loss. If used for obesity, begin with 500 mg and gradually increase dosage to 2 grams a day. If an individual is morbidly overweight, larger doses, up to 4 grams a day, may be required (Crayhon 1998). Hypothyroidism, a contributing factor to both obesity and coronary artery disease, frequently parallels carnitine deficiencies.
Some practitioners report better cardiac management when using L-carnitine fumarate, a less hygroscopic and more bioavailable form of the vitamin-like nutrient. Others prefer LPC (L-propionylcarnitine) for the treatment of angina. Acetyl-L-carnitine is touted because of its ability to energize, a result of extremely efficient utilization. Because of the energizing effects of acetyl-L-carnitine, Robert Crayhon, author of The Carnitine Miracle, suggests it be taken no later than 3 p.m. to preserve a restful night's sleep.
As with most supplements, dosage is subjective. Some individuals notice increased energy with 1 gram of L-carnitine or 500 mg of acetyl-L-carnitine a day. Clinical studies frequently use from 1500-3000 mg daily. Because increased energy production begets a greater generation of free radicals, carnitine should always be used with an antioxidant program.
Carnosine—is an antioxidant, protects against strokes, and reduces AGEs
In January 2001, the Life Extension Foundation hailed carnosine as a substance capable of slowing many of the processes involved in aging, including cardiovascular degeneration. Carnosine, a combination of the amino acids alanine and histidine, accomplishes this in part by playing a dual role in regard to proteins. For example, it yields a protective effect through antioxidant activity and also participates in the repair or removal of damaged proteins. By quenching the destructive potential of the deadly hydroxyl radical and impacting protein degradation that occurs as a result of collagen crosslinking (glycation), carnosine offers significant protection against vascular disease.
Glycation is a reaction that occurs when proteins react with glucose. A series of reactions follow (including the oxidation process), terminating in the formation of an advanced glycosylated end product (AGEs), a protein the body cannot break down. These processes decrease vascular tone and resiliency and are factors that influence the progression of cardiovascular disease and hypertension. Glycated proteins produce 50-fold more free radicals than nonglycated proteins; carnosine may be the most effective antiglycating agent known (Durany et al. 1999).
Russian scientists set out to determine the effect of carnosine upon rats programmed to develop strokes. The first experiment focused upon carnosine as a revitalizer in hypoxic animals (those exposed to low oxygen levels). When oxygen-deprived animals were revitalized with normal levels of oxygen, the carnosine treated rats were able to stand after 4.3 minutes, as compared to 6.3 minutes in the untreated group (Boldyrev 1997).
In the second study, a stroke was simulated in the animals by arterial occlusion. The scientists found that carnosine acts as a neuroprotector in the ischemic brain. Rats treated with carnosine displayed more normal electrocardiograms, less lactate accumulation (a common measure of the severity of injury), and better cerebral blood flow (Stvolinsky et al. 1999).
A suggested dosage is 1000-1500 mg daily. By taking at least 1000 mg a day of supplemental carnosine, the enzyme carnosinase (an enzyme that degrades carnosine) is overwhelmed, thus making the carnosine available in the body. Carnosine should not be used during pregnancy or lactation.
Chondroitin Sulfate—is an anti-inflammatory and antioxidant and inhibits LDL oxidation
Chondroitin sulfate (CS) is extremely popular in relieving the sore joints of osteoarthritis. In 1968, Dr. Lester Morrison began a 6-year study to determine its value as a cardio -protector. Dr. Morrison divided 120 patients with coronary heart disease into two groups. Lifestyles were not altered during the test period, that is, all participants continued with their prescribed medication and appropriately designed diets. One group also took 1500 mg a day of CS for 4 years, and then 750 mg for another 18 months. After 6 years, four people in the CS group had died, compared to 13 in the nontreated group. Most impressive was the finding that only six people in the CS-treated group had acute cardiac incidents over the 6-year period, while 42 patients in the group that did not receive CS had acute events (Morrison et al. 1969; Morrison et al 1973; Anderson 2002).
Dr. Morrison speculates that the decrease in cardiovascular deaths could be staggering if CS were routinely used by larger numbers of the population. Although further research is needed, it appears CS delivers its cardiovascular protection though anti-inflammatory and antioxidant pathways. A suggested daily dose is one to three 400-mg tablets.
Chromium—modulates blood glucose levels, lowers cholesterol, and is helpful in weight management
Of the 16 minerals currently deemed essential, none plays a more important role in blood glucose control than chromium. However, the benefits of chromium, a trace mineral, are not limited to modulating errant blood glucose levels. Obesity, coronary heart disease, hypertension, and hyperlipidemia often have a common denominator: insulin insensitivity, a condition worsened by a chromium deficiency. It is estimated that 90% of Americans consume less than the recommended amount of chromium each day, a shortfall that may eventually terminate in some form of ill health. (Note: No recommended dietary allowance (RDA) has been established for chromium, but the ESADDI (estimated safe and adequate daily dietary intake) is 50-200 mcg.)
A group of 180 people with Type II diabetes participated in a study to determine the worth of chromium picolinate (CrP) supplementation in controlling unstable blood glucose levels. The individuals were divided into the following three groups: (1) received only a placebo, (2) received 200 mcg daily of CrP, or (3) received 1000 mcg daily of CrP. Perhaps the finding of greatest interest was the decrease in hemoglobin A1c levels after 4 months (thus signifying increased glycemic control). Hemoglobin A1c dropped from greater than 9% pretreatment to less than 7% in the 1000-mcg-a-day treatment group. Chief Researcher Richard Anderson said: "Nearly all of participants no longer had the classic signs of diabetes. Blood sugar and insulin levels became normal. Most important, the gold standard diagnostic measure of diabetes, blood levels of hemoglobin A1c, sank to normal." This would be considered an optimal response with any diabetes drug regimen (Anderson et al. 1997). Note: The beneficial effects of chromium in individuals with diabetes were observed at levels higher than the upper limit of the ESADDI.
Research is conflicting regarding weight loss with chromium supplementation. While some studies renounce its value, a current study showed that 600 mcg of niacin-bound chromium given to "modestly dieting-exercising African-American women" caused a significant loss of fat and sparing of muscle compared to a placebo group (Crawford et al. 1999). Michael Murray, N.D., reported that individuals using 400 mcg of chromium picolinate for 2 1/2 months lost 4.6 pounds and added 1.1 pounds of muscle, for a total weight loss of 3.5 pounds ( Murray 1996).
Typically, chromium decreases total cholesterol and triglycerides 10% and increases HDL 2%. These changes are most observed if initial body chromium levels are very low ( Murray 1996). For most individuals, 200-400 mcg of chromium (divided throughout the day) is adequate; higher (supervised) doses may be required if used for Type II diabetes (turn to Niacin in this section to read about the boost chromium gives niacin, requiring lesser amounts of vitamin B3 to manage blood lipids).
Reader's guide to chromium food sources, enhancers, and antagonists
Brewer's yeast, whole grains, mushrooms, corn and corn oil, dairy products, potatoes, and dried beans are examples of chromium food sources; selenium, vitamin E, and essential amino acids enhance its absorption; iron opposes it.
Coenzyme Q10—lessens the incidence of angina attacks, arrhythmias, cardiomyopathy, congestive heart failure, heart valve irregularities, hypertension, mitral valve prolapse, and periodontal disease; protects LDL cholesterol against oxidation; increases exercise tolerance; burns unwanted fat; supports healthy cholesterol and triglyceride levels; and is beneficial to smokers
Coenzyme Q10 (CoQ10) can be synthesized in the body, but individuals with periodontal disease, hypertension, or cardiovascular diseases are frequently deficient. Heart tissue biopsies in patients with various heart diseases showed a CoQ10 deficiency in 50-75% of cases. A significant finding is that cholesterol-lowering medications (as statin drugs) reduce CoQ10 levels. A CoQ10 deficiency of 25% is associated with illness and a deficit of 75% is associated with death in animals (Bliznakov et al. 1988; Hattersley 1994).
The heart strengthening benefits of CoQ10 make it of significant value in the treatment of congestive heart failure (CHF). Depending upon the degree of cardiac impairment, CoQ10 can be used independently or added to traditional medicine.
Administering CoQ10 (50-150 mg daily) for 90 days to 2664 patients with CHF resulted in the following symptomatic and clinical improvements: cyanosis (bluish skin color), 78.1%; edema, 78.6%; pulmonary crackle, 77.8%; dyspnea, 52.7%; palpitations, 75.4%; sweating, 79.8%; arrhythmia, 63.4%; and vertigo, 73.1%. Fifty-four percent of the patients observed a concurrent improvement in several symptoms, which could be interpreted as an improvement in quality of life (Baggio et al. 1994). A 1-year study involving 640 individuals with CHF showed that patients using CoQ10 were healthier and required less hospitalization (Morisco et al. 1993).
The ejection fraction (how fully the heart pumps the blood out), end diastolic volume index (the adequacy of the heart to fill with blood), cardiac index (the amount of blood pumped out, considering body size), stroke volume (amount of blood pumped out on each beat of the heart), and cardiac output (the amount of blood pumped out per minute) all improved while using CoQ10 (Judy et al. 1984; Murray 1996). The improvement observed in left ventricular function may prove valuable in preventing left ventricular depression following coronary artery bypass and valvular surgery.
The effects of oral treatment with CoQ10 (120 mg a day) were compared for 28 days in 73 (intervention group A) and 71 (placebo group B) patients with acute myocardial infarction. Following treatment, angina pectoris (9.5% versus 28.1%), total arrhythmias (9.5% versus 25.3%), and poor left ventricular function (8.2% versus 22.5%) were significantly reduced in the CoQ10 group compared to the placebo group. Total cardiac events, including cardiac deaths and nonfatal infarctions, were also significantly reduced in the CoQ10 group compared with the placebo group (15% versus 30.9%) (Singh et al. 1998; Niibori et al. 1999).
Mitral valve prolapse is a common condition associated with a heart murmur. It is often asymptomatic but can produce chest pain, arrhythmia, or leakage of the valve, leading to congestive heart disease. Children with mitral valve prolapse received CoQ10 (2 mg/kg a day) for 8 weeks while eight received a placebo. This dosage proved highly effective in returning heart function to normal in seven of the eight children; none of the placebo-treated patients improved. However, relapse was common among those who stopped taking the medication within 12-17 months but rarely occurred in those who took CoQ10 for 19 months or more. (Oda et al. 1984; Murray 1996b).
The following examples exemplify the breadth of CoQ10's credits:
- CoQ10 therapy is associated with a mean 25.4% increase in exercise duration and a 14.3% increase in workload (Sacher et al. 1997).
- The frequency of angina attacks, a squeezing or pressure-like pain in the chest, usually provoked by exercise, decreases by about 53% during CoQ10 supplementation ( Murray 1995).
- CoQ10 has been reported to lower Lp(a), a powerful predictor of cardiac health (Singh et al. 1999; Health Concerns 2002). To read more about Lp(a), consult the section (in this protocol) dedicated to Newer Risk Factors.
- CoQ10 inhibits oxidation of LDL cholesterol. CoQ10 accomplishes this by attaching to LDL particles circulating in the bloodstream. Were there more riders (CoQ10) than carriers (LDL) the oxidation of LDL cholesterol would be less worrisome (Thomas et al. 1995; LEF 2000).
- CoQ10's antioxidant activities extend to protect the cells and lungs of smokers. By aiding oxygen delivery, reducing platelet aggregation, and hampering free-radical activity, the brain and heart have significantly greater protection. In addition, current data provide direct evidence for an interactive effect between exogenously administered vitamin E and CoQ10 in terms of uptake and retention, and for a sparing effect of CoQ10 on vitamin E. Vitamin E, in turn, plays a pivotal role in determining tissue retention of exogenous CoQ10 (Ibrahim et al. 2000).
- Hypertensive patients demonstrated a significant improvement while supplementing with CoQ10. Before treatment with CoQ10, most patients were taking from 1-5 cardiac medications. During the study, overall medication requirements dropped considerably: 43% stopped between 1-3 drugs. Typically, diastolic and systolic blood pressures drop by about 10% with CoQ10 therapy (Langsjoen et al. 1994; Lam 2001).
- Periodontal disease, a risk factor regarding heart health, responds to CoQ10 supplementation. Gingival pocket depth, swelling, bleeding, redness, pain, exudates, and looseness of teeth were significantly improved using 50 mg of CoQ10 a day (Wilkinson et al. 1977; Murray 1996). The herbs goldenseal and echinacea should accompany CoQ10 supplementation to further reduce oral infection.
- For the dieter, CoQ10 is good news ( Murray 1996). Together with a well-planned diet and exercise program, CoQ10 assists in shedding unwanted pounds.
- CoQ10's ability to energize the heart is perhaps its chief attribute. The heart is one of the most metabolically active organs in the body, pumping approximately 2000 gallons of blood through 65,000 miles of blood vessels, beating 100,000 times each day (American Heart Association 2002). According to Decker Weiss, N.M.D., the heart requires large amounts of uninterrupted energy to fuel this unbelievable performance. The mitochondria (supplying 95% of the body's total energy requirement) are represented in large numbers (up to 2000 per heart cell).
- In addition to energy supply, CoQ10 is an important defense system in tissues and muscles, particularly those having large numbers of mitochondria. As the mitochondria produce energy to fuel cellular functions, a plethora of free radicals results (Treatment and Research Newsletter 1998). Heart cells have more CoQ10 than any other cells, a supply critical to ATP production, cardiac function, and free-radical protection (Guyton et al. 1996; Porth et al. 1998).
Despite the large body of clinical evidence demonstrating CoQ10 efficacy, it is tragic that the majority of cardiac physicians still disregard its potential. A suggested dosage is 30-400 mg a day, depending upon the degree of cardiac support required. (Use CoQ10 in divided doses with meals containing fat; use larger doses under physician supervision.)
Reader's guide to CoQ10 food sources
Beef, mackerel, salmon, sardines, peanuts, and spinach.
Conjugated Linoleic Acid (CLA)—aids in fat loss, reduces cholesterol and triglycerides, and assists in the utilization of beneficial fats
Some researchers regard the principal causal factor of obesity to be CLA deficiency. CLA can be obtained from dietary choices such as turkey, lamb, beef, and some fatty dairy products, but the current trend away from meats and fats has caused levels of CLA to drop meaningfully (Ip et al, 1994).
CLA appears reliable in reducing body fat, while preserving lean body tissue. CLA accomplishes this by increasing the basal metabolic rate and impacting the distribution of fat, especially abdominal obesity. (Recall that apple-shaped bodies are considered vulnerable in regard to heart disease.) A Norwegian human study found that CLA-supplemented subjects lost up to 20% of their body fat in 3 months without changing their diet, while the control subjects on an average gained a slight amount of body fat during the same period (Health-N-Energy 2000).
CLA displays hypolipidemic properties as well as the ability to reduce arachidonic acid levels, an initiator of inflammatory leukotrienes (Liu 1998). (Leukotrienes are considered 1000 times more reactive than histamine.)
Researchers set out to determine the effects of CLA on the establishment and progression of experimentally induced atherosclerosis in rabbits. To establish atherosclerosis, New Zealand white rabbits were fed a diet containing 0.1-0.2% of cholesterol for 90 days. Some groups were fed the atherogenic diet and CLA. For effects on progression of atherosclerosis, rabbits with established atherosclerosis were also included in the study. At dietary levels as low as 0.1%, CLA inhibited atherogenesis; at dietary levels of 1%, CLA caused substantial (30%) regression of established atherosclerosis. This is the first example of substantial regression of atherosclerosis being caused by diet alone (Kritchevsky et al. 2000).
Some question whether linoleic acid and CLA accomplish the same tasks. Although the two acids are related, they appear to oppose one another on factors that influence cardiac performance. While the linoleic acid cascade has a greater tendency to stimulate fat formation, CLA inhibits it. Cholesterol is more likely to be oxidized by various factors working off the linoleic cascade, whereas CLA appears to stabilize cholesterol.
Laboratory animals, supplemented with CLA for 36 weeks at a dose 50 times higher than the suggested upper range for human consumption, completed the study without signs of toxicity. A suggested dosage is three to four 1000-mg capsules taken early in the day.
Curcumin—is anti-inflammatory and hypocholesterolemic, inhibits platelet aggregation, and is protective to smokers
Curcumin, not to be mistaken for the herb cumin, is the yellow pigment of turmeric (Curcuma longa) found in mustard and curry powder. Curcumin has gained popularity because of its antioxidant and antiplatelet aggregating qualities. Curcumin's ability to control platelet aggregation appears directly related to thromboxane inhibition (a promoter of aggregation) and an increase in prostacyclin activity, an inhibitor of aggregation (Srivastava et al. 1985; Toda et al. 1985).
Curcumin is such a powerful antioxidant (comparable to vitamins C and E) that it is considered protective to smokers, lessening free-radical attack and cellular damage. Yet, its cardioprotection extends to reducing blood lipid levels, particularly cholesterol. Rats fed 0.1% curcumin, along with a cholesterol diet, had about one-half of the blood cholesterol as rats fed equal amounts of cholesterol but without curcumin (Rao et al. 1970).
Curcumin also possesses potent anti-inflammatory activity. It is, in fact, comparable to cortisone and phenylbutazone in acute inflammatory conditions and about one-half as effective in chronic models. As curcumin reduces inflammation (a more recently established risk factor for cardiovascular disease), fibrinolysis is promoted and leukotriene formation inhibited (Arora et al. 1971; Chandra et al. 1972; Murray 1994).
A recommended dosage is 900 mg 1-2 times a day.
anti-inflammatory and anti -lipidemic, increases hormonal levels, and is beneficial in diabetes and Syndrome X
Low levels of DHEA, a steroid normally freely expressed in the human body, are associated with inflammation and heart disease in men. DHEA delivers much of its protection by acting as a prohormone, meaning it can bolster lagging estrogenic or androgenic hormones. In fact, DHEA's value as an anti -lipidemic appears due in part to its ability to increase estrogen and testosterone levels. Studies show that DHEA reduced by 50% the expected atherosclerotic buildup in rabbits fed a high-cholesterol diet. In men, DHEA lowered total cholesterol and bad low-density-lipoprotein cholesterol better than and more safely than the drugs clofibrate and gemfibrozil (Smith 1998) (read about testosterone as a cardio -protector later in this protocol).
Other anti -atherogenic properties of DHEA include inhibiting the activity of fibroblasts (cells that proliferate at the site of chronic inflammation), encouraging proinflammatory cytokine production. An imbalance of the cytokine network appears to be involved in the development and progression of congestive heart failure (CHF) (Yang et al. 2001). The greater the cardiac debility, the more pronounced the imbalance. Note: A cytokine imbalance refers to a shift toward greater levels of inflammatory cytokines combined with inadequately raised or decreased levels of anti-inflammatory cytokines.
Pro -inflammatory cytokines interleukin-1b (IL-1b), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) typically rise with age. High levels of TNF-alpha are destructive to the heart muscle, while excesses of IL-6 are associated with fibrinogen production and the instability of atheromatous plaque (di Minno et al. 1992; Ikeda et al. 2001; Lindmark et al. 2001). As DHEA suppresses the activity of IL-6 and TNF-alpha, inflammation and the risk of clot formation significantly decrease (Kipper-Galperin et al. 1999; Kaiser 2001).
Japanese researchers suggest screening for pro-inflammatory cytokines and using the appropriate anti-inflammatory treatment to reduce the risk of heart disease (Ikeda et al. 2001). By contrast, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) actually increases the likelihood of CHF. The use of NSAIDs (other than low-dose aspirin) in the previous week was associated with a doubling of the odds of a hospital admission with CHF. The use of NSAIDs by patients with a history of heart disease was associated with an odds ratio of 10.5 for first admission with heart failure, compared with 1.6 in those without such a history (Page et al. 2000).
Improved glucose control among diabetic rats supplemented with DHEA indicates it may be of value to patients with diabetes and Syndrome X. Research shows that serum DHEA levels fall when serum insulin levels rise (Lukaczer 2000). Reducing carbohydrates to less than 40 grams a day (lessening the incidence of an insulin surge) resulted in a 34% increase in DHEA. Scientists thus speculate that DHEA might be the missing link in the insulin resistance/hyperinsulinemia epidemic. Insulin appears to deliver its blow to DHEA by inhibiting production and stimulating clearance (Nestler et al. 1992).
DHEA, by incorporating into HDL and LDL cholesterol, protects against oxidation. With age, cholesterol-bound DHEA becomes scarce, and compared to younger people with adequate levels of DHEA, oxidation spirals. Another hindrance to antioxidant defense occurs as superoxide dismutase (a powerful antioxidant) becomes lethargic as DHEA levels dwindle (Bednarek-Tupikowska et al. 2000). Japanese researchers also showed that DHEA prevented aggression from increasing during times of mental stress, significantly reducing levels of norepinephrine, a hormone synthesized by the adrenal medulla (Sawazaki et al. 1999).
The Massachusetts Male Aging Study determined that in a sample analysis of 1167 men, those with serum DHEA-S (DHEA-sulfate) in the lowest quartile at baseline (< 1.6 mcg/mL) were significantly more likely to incur ischemic heart disease (Feldman et al. 2001). Most studies show DHEA supplementation to be of value in regard to the cardiac health of men, but the Rancho Bernardo Study found DHEA-S levels were not significantly associated with cardiovascular mortality in women (Khaw 1996).
A suggested DHEA dosage is 15-75 mg, taken early in the day (50 mg represents a typical daily dose). Blood tests are valuable 3-6 weeks into therapy to assist in assigning appropriate dosages. (Optimal DHEA levels for men are between 400-560 mcg/dL; for women, the range is considered ideal at 350-430 mcg/dL.) It has been suggested that antioxidants such as green tea, vitamin E, and N-acetyl-cysteine should accompany DHEA supplementation. Yet, the threat of potentiating free-radical activity in the liver appears roused only at much higher doses than are needed to provide the desired effects.
Because DHEA invigorates hormonal systems, DHEA is not recommended for men with prostate cancer or for women with estrogen-dependent cancer without physician approval. (Recall that DHEA can be converted into testosterone and estrogen.) Before starting DHEA therapy, men should know their serum PSA (prostate specific antigen) level and should have passed a digital rectal examination. DHEA does not cause prostate cancer, but since DHEA can cause an increase in testosterone levels, the presence of an undetected cancer should be ruled out before initiating the therapy.
Essential Fatty Acids—inhibits platelet clumping; has antispasmodic activity; improves HDL-LDL ratio; lessens risk of second heart attack, stroke, and re -stenosis following angioplasty; inhibits cardiac arrhythmias; is hypotensive; reduces fibrinogen, Lp(a), C-reactive protein (CRP), total cholesterol, and homocysteine; improves insulin sensitivity; and is beneficial to dieters
The current mania regarding low fat diets is contributing to deficiencies and imbalances of the essential fatty acids linoleic acid and alpha-linolenic acid. The body cannot synthesize these fats and is dependent upon the diet for their supply.
Some individuals support the premise that fats do little more than make you fat and that they can be eliminated without upsetting metabolic processes. In truth, fats initiate the transmission of vital messages, in part by programming activity in the omega-6 and omega-3 fatty acid cascades. Instructions received by prostaglandins (hormone-like substances produced from fatty acids) encourage some prostaglandins to oppose and others to neutralize, a process that holds the entire family in check. Prostaglandins are found in virtually all cell membranes and control most metabolic functions. Vital as they are, when out of balance, they can prove the undoing of the host. For example, PGE2 is generally regarded as a less desirable (even destructive) prostaglandin. (Although PGE2 can provoke an inflammatory response, the body does need some PGE2 to maintain the mucosal integrity of the intestinal wall.) On the other hand, PGE1 and PGE3 are good prostaglandins, meaning they decrease the likelihood of platelets clumping and dilate blood vessels, while exerting anti-inflammatory activity (Braly 1985).
Standard American Diet
The standard American diet is high in saturated fats and arachidonic acid but frequently is deficient in alpha-linolenic acid, an omega-3 fatty acid. Many Americans have an omega-6-omega-3 ratio of about 20-30:1. Clarifying our departure from primitive diets, ancient kinsmen maintained a ratio nearer 1:1. A more realistic ratio, according to Joseph Pizzorno, N.D., may be nearer 2:1 (Simopoulos 1999; Pizzorno 2001).
Dr. James Braley, M.D., cautions that a dietary departure from the omega-3 fatty acids can lead to an overproduction of PGE2, a pro-inflammatory, platelet-aggregating prostaglandin. For this reason, diet and supplementation should most often favor the lagging omega-3 fatty acids. When the omega-3s are emphasized, arachidonic acid, the precursor to PGE2, is reduced (Braly 1985).
Illustrative of the importance of having more good prostaglandins than bad, some researchers estimate that 30% or more of heart attacks occur as a result of smooth muscles in the walls of the coronary arteries going into spasm, causing disruption of oxygen supply to the heart. If oxygen cutoff is not long lasting, a renewed delivery of oxygen begins and the spasm ceases. PGE1 dilates the blood vessels, making them less prone to spasm; conversely, PGE2 constricts blood vessels. Compounding the problem, PGE2 is often released during heart spasm, further constricting the blood vessels (Braly 1985).
Figure 5 illustrates the omega-6 and omega-3 cascades and the enzymes delta-6- and delta-5-desaturase (rate controlling enzymes) that spur sequential movement through the series. Recall that from arachidonic acid, the parent of PGE2, leukotrienes are formed.
A functional delta-6-desaturase enzyme appears to be crucial to blood pressure management. An example of this occurred when two trial groups, selected from 25 nonobese participants with mild to moderate hypertension, were given either linoleic acid (sunflower oil) and alpha-linolenic acid (linseed oil) or their reduced forms, GLA (360 mg a day) and EPA (180 mg a day). The first group was delta-6-desaturase dependent; the second group was not. After 8-12 weeks, the group receiving the GLA and EPA had reduced their blood pressure by about 10%. Those in the first group, who lacked the activity of delta-6-desaturase, experienced no significant hypotensive benefit. This observation may indicate that the defective desaturation of the essential fatty acids by the enzyme delta-6-desaturase plays an important role in the etiology of essential hypertension (Venter et al. 1988).
Diabetes, hypercholesterolemia, and nutritional deficiencies (zinc, vitamin B6, and magnesium) can inhibit delta-6-desaturase activity. At Comprehensive Cancer Care 2001, Joseph Pizzorno, N.D., prominent educator and cofounder of Bastyr University, cited obesity, viral assaults, stress, aging, alcohol, smoking, and trans fats as additional factors retarding the efficacy of delta-6-desaturase (Pizzorno 2001). Individuals with a sluggish delta-6-desaturase enzyme (about 10-20% of the population) should use the fatty acid appearing downstream from the enzyme. (Figure 5 illustrates this sequence.)
Modulates Lipids, but so Much More
Typically, both men and women observe an increase in HDL2, the most beneficial of the HDL subtypes, after 6 months of omega-3 fatty acid supplementation. The protective role of total HDL against coronary artery disease appears primarily mediated through the HDL2 fraction (Bakogianni et al. 2001). During the course of a recent study, HDL2 cholesterol rose 24% among those eating a daily omega-3-rich fish meal and adhering to a restricted calorie diet. Those who did not lose weight nonetheless experienced a 21% rise in HDL2 cholesterol on the fish diet (Diets 2000). Recall that individuals achieving longevity frequently display elevations in HDL2b cholesterol, suggesting better cardiac function.
A number of studies have shown the protective value of fish consumption in regard to averting coronary heart disease and the incidence of sudden cardiac death. For example, a recent study reported data collected from the Physicians' Health Study involving more than 22,000 men followed over a 17-year time frame. Researchers tested the blood of 94 male study volunteers who experienced an episode of sudden cardiac death (but in whom there was no prior history of heart disease) against 184 matched control study participants who did not experience a cardiac event.
On an average, men who died suddenly had lower levels of omega-3 fatty acids. Among the men with the highest levels of omega-3 fatty acids in the blood, there was a 72% reduction in the risk of sudden cardiac death when compared to the men with the lowest levels of these substances in their blood (Albert et al. 2002; Wascher 2002). Recall that 50% of people who die suddenly of cardiac causes have no signs or symptoms of heart disease; poor omega-3 representation may explain this worrisome statistic.
JAMA reported that women receive a similar cardiac advantage when eating fish or using omega-3 fatty acids (Hu et al. 2002). During 16 years of follow-up, there were 1513 incident cases of coronary heart disease (484 deaths and 1029 nonfatal myocardial infarctions) among 84,688 women (ages 34-59) participating in the Nurses' Health Study. Those who ate fish once a week had a 30% lower risk of heart attack or death compared to those who never ate fish. Interestingly, eating fish 5 times a week was only slightly more beneficial, decreasing risk to 34%. JAMA also cited a 40-50% reduction in strokes among middle-aged women who did not use aspirin but regularly included fish in their diet (Iso et al. 2001a).
A meta-analysis (a method of evaluating statistical data based on results of several independent studies) showed that omega-3 fatty acids reduce the incidence of fatal heart attacks, even in patients with established coronary heart disease (Bucher et al. 2002). Obviously, there are mechanisms released through fatty acid consumption that go beyond regulating cholesterol and triglycerides.
- Dr. Kilmer McCully, pioneer of the homocysteine-heart disease theory, determined that fish oil lowers homocysteine levels. Clinicians and researchers now affirm his work (Culp 2000).
- English researchers reported that fish oil decreased fibrinogen, addressing a major pathological process leading to thrombotic occlusion. A 7-year MAXEPA study concluded without indication of adverse side effects (Saynor et al. 1992).
- Omega-3 fatty acids have been shown to lower Lp(a) (Herrmann et al. 1995; Shinozaki et al. 1996). Note: Cardiologists confess that (in some cases) Lp(a) can be difficult to reduce. A targeted intervention program often includes fish oil (1400 mg EPA and DHA), vitamin C (2-6 grams daily), CoQ10 (60-120 mg daily), L-lysine (1000-3000 mg daily), L-proline (500-1000 mg daily), and niacin. See the Niacin subsection of this section for details regarding dosing instructions and caveats.
- Dr. Robert Atkins, a complementary physician with a background in cardiology, believes that fatty acids are natural defibrillators, lessening the incidence of cardiac arrhythmias and atrial fibrillation. Several years ago, the Life Extension Foundation reported that omega-3 fatty acids reduced the risk of second heart attack and stroke by inhibiting cardiac arrhythmias, maintaining cardiac energy output, and reducing thrombosis.
- DHA reduced 24-hour blood pressure (5.8 mmHg systolic and 3.3 mmHg diastolic) and daytime/ambulatory blood pressure (3.5 mmHg systolic and 2.0 mmHg diastolic) (Mori et al. 1999). For every absolute 1% increase in blood alpha-linolenic acid, systolic and diastolic blood pressure typically drop by about 5 mmHg.
- DHA lowered norepinephrine, a gesture that may protect the cardiovascular system by reducing vasoconstriction and blood pressure (Sawazaki et al. 1999).
- Data suggest that C-reactive protein (CRP) levels can be kept in check by frequent consumption of fish or fish oils. For example, 269 patients underwent angiography for suspected coronary artery disease. The subjects were also evaluated regarding CRP levels and fish consumption. In addition, EPA and DHA levels were assayed in granulocytes (a type of white blood cell). The researchers found that patients with one or more coronary arteries blocked (50% or more) had significantly higher CRP levels in their blood than patients with no significant blockages. They also observed that high CRP levels correlated with low levels of DHA in granulocytes. The level of DHA in granulocytes in turn was closely related to fish consumption. The researchers concluded that DHA has an anti-inflammatory effect that results in lower CRP levels and that fish consumption may decrease the risk of coronary artery disease (Madsen et al. 2001; International Health News, http://www.oilofpisces.com/atherosclerosis.html)
- After angioplasty, 194 patients were randomly assigned to receive either 4.5 grams a day of fish oil (3150 mg of EPA and 1350 mg of DHA for 6 months) or instructions to eat a low fat (25% of total calories), low cholesterol diet (100 mg a day) without fish oil. At the end of the trial, 36% of those not receiving the fish oil showed signs of re -stenosis (closure of previously opened arteries). The rate of re-stenosis in the fish oil group was about 19%. The study suggests, as do other trials, that high-dose fish oil supplements may reduce the frequency of re-stenosis following successful coronary angioplasty. Nonetheless, Mark Milner, M.D., the lead researcher, said his preference for supplying omega-3 fatty acids is fish consumption, not fish oil. Milner cited concern for (potentially) hypocoagulative blood states as the mitigating factor (Milner et al. 1989).
- The omega-3 fatty acids in fish oil help to balance the omega-6 fatty acids normally abundantly supplied in Western diets. When these two groups of fatty acids are out of balance, the body releases chemicals that promote inflammation. People appear to produce more inflammatory chemicals when experiencing psychological stress. With a fatty acid imbalance, the inflammatory response to stress appears to be amplified (Maes et al. 2000).
Information presented at the International Symposium on Gamma-Linolenic Acid, San Diego (April 2000), showed that GLA (an omega-6 fatty acid) lowered blood pressure in animal studies. According to French researcher Jean Pierre Poisson, "Usually in pharmaceutical therapies we see about a 10% reduction. In our case we saw blood pressure drop 6-16%." Future research on humans is still needed, but Poisson concluded: "It appears GLA is a very potent blood-pressure-reducing nutrient" (Engler et al. 1998; Bioriginal Food and Science 2001).
A Texas researcher reported that GLA mitigates the growth of atherosclerotic plaque in the arterial walls of animals. The research holds promise that GLA supplementation (borage oil and evening primrose oil) may be equally important in halting the atherosclerotic process in humans (Nigam 1999).
Balance: Always the Key
The need for balance regarding dietary fats is clearly evidenced in a report appearing in the journal Circulation. Researchers found that low levels of animal fat and protein increased the risk of hemorrhagic stroke in hypertensive women 370% over women eating more dietary fat. The researchers also noted that individuals with a very low intake of saturated fat may develop structural impairment of the arteries. Although saturated fats have been maligned for years, it now appears that some saturated fats, that is, a balance among the family of fats is required for healthy arteries and a reduced risk of hemorrhagic stroke (Iso et al. 2001b).
Technology can transform a benign fat into a dangerous food product. This occurs when fats are exposed to the hydrogenation process, saturating the oil with hydrogen to improve stability, taste, and odor. Heating oils at temperatures above 300°F has the same effect.
Hydrogenation turns liquid oils, such as corn, soybean, sunflower, sesame, and cotton, into a semisolid shortening or margarine. (The harder the fat, the more trans fats it contains.) This process changes a cis (a beneficial fat) to a nonfunctional form (a trans fat) that can no longer participate in prostaglandin production.
Hydrogenated fats deliver a serious blow by reducing activity in the omega-6 and omega-3 cascades (probably by inhibiting the enzymes delta-6-desaturase and delta-5-desaturase). This suggests that the consumption of partially hydrogenated vegetable oils may have an adverse impact upon the relative distribution of the final end products of the essential acids in terms of prostaglandin concentrations. Also, as trans fatty acids increase in the diet (replacing cis unsaturated fatty acids), LDL cholesterol is (typically) raised, but the beneficial HDL cholesterol is decreased. Trans fatty acids also increase Lp(a) levels relative to other fatty acids (Mensink et al. 1990, 1992; Zock et al. 1996).
A study involving 600 men (ages 64-87), determined that every 2% increase in trans fatty acids increased the risk of developing coronary heart disease 25% over the next 10 years (Oomen el al. 2001). The influence of different types of fats can also be observed in the progression of diabetes. For example, the risk of diabetes was not increased among 84,204 women whose intake of fats came chiefly from nuts, seeds, and avocados, but a 2% increase in calories from trans fatty acids raised the risk of diabetes by about 39%. Conversely, a 5% increase in calories from polyunsaturated fats lowered the risk of diabetes 37% (Salmeron et al. 2001; Mercola 2001b).
In 1993, doctors at Harvard Medical School found that women who ate 4 or more tsp of margarine a day had a 50% greater risk of developing heart disease compared to women who ate margarine only rarely (Harvard School of Public Health 2002). Although the amount of trans fatty acids appearing in margarine and shortening has been reduced in the United States , these damaging fats are still found in many other foods such as bakery items and fast food products. Trans fats become a major part of American diets when the 30 pounds of French fries consumed per capita are factored into dietary analysis. Trans fats often hide on dietary labels as partially hydrogenated fats. Learn to read labels and avoid trans fats.
Growing public awareness regarding the dangers imposed by trans fats has prompted a reduction in their consumption. An example of the benefits of eliminating trans fatty acids from the diet comes by way of a study released from The Netherlands. An average 2.4% drop in trans fatty acid consumption prompted a 23% decrease in coronary deaths and saved, it is speculated, about 4600 lives (Oomen et al. 2001; Reuters Health 2001).
Beneficial to Those on Diets
Studies have shown that genetically obese people profit from essential fatty acid supplementation. The weight loss in these individuals is gradual, but reliable, even among those considered intractably obese.
Evening primrose oil, rich in gamma-linolenic acid, appears to stimulate brown fat cells by producing PGE1. Brown fat is of particular advantage in maintaining a desirable weight because it uses extra calories to provide heat, preventing the deposit of unsightly white fat (Braly 1985).
Individual differences in amounts of brown fat have been theorized to account for the ability (or inability) to maintain a desirable weight. Brown fat is found primarily attached to large blood vessels in the thoracic cavity, along certain ribs, the nape of the neck, armpits, and between and below the shoulder blades. Without sufficient amounts of brown fat, calories are not burned and as a result, overweight individuals may actually gain weight on fewer calories. As a weight-deterrent, essential fatty acids most benefit those who are more than 20% overweight (Braly 1985).
Essential Fatty Acids and Syndrome X and Diabetes
Omega-3 fatty acids help maintain flexible cell membranes (Igal et al. 1997). This is important, for healthy membranes contain large numbers of insulin receptors, increasing the surface areas available for insulin binding. This is extremely important in diabetes and Syndrome X.
The Iowa Women's Health Study examined the relationship between dietary fatty acids and Type II diabetes in a cohort of over 35,000 nondiabetic women (ages 55-69). The study showed that women with the highest intake of vegetable fat had a 22% lower risk of developing diabetes during the 11-year follow-up. Substituting polyunsaturated fats for saturated fats reduced the incidence of diabetes by an average of 16%, regardless of fiber intake, magnesium levels, obesity, physical exercise, or smoking status (Meyer et al. 2001; LEF 2001).
Researchers (reporting in JAMA) showed that 120 nondiabetic, hypercholesterolemic men receiving sim -vastatin (20 mg a day for 12 weeks) reduced their total cholesterol 20.8%; LDL cholesterol 29.7%; triglycerides 13.6%; and apolipoprotein B 22.4%. A 13% increase in insulin levels and a 14% increase in insulin resistance, along with a loss of antioxidants (alpha-tocopherol dropped 16.2%, beta-carotene plummeted 19.5%, and CoQ10 fell 22%), minimized the cardioprotective effects of simvastatin. Consuming a modified Mediterranean diet (containing at least 4 grams a day of omega-3 fatty acids) potentiated the cholesterol-lowering effects of simvastatin and counteracted the rise in insulin levels. In addition, beta-carotene and CoQ10 levels were protected (Jula et al. 2002).
What Are the Good Fats?
Individuals wishing to increase their consumption of beneficial fish and marine life should consider scallops, shrimp, herring, mackerel, sea bass, salmon, cod, sardines, tuna (fresh), whitefish, coldwater halibut, and anchovies, varieties containing varying amounts of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). From the plant kingdom, walnuts, most beans, and according to Joseph Pizzorno, N.D. (Comprehensive Cancer Care 2001), Brussels sprouts and all varieties of squash are also sources of omega-3 fatty acids (Pizzorno 2001).
Poultry Science reported that three omega-3 enriched eggs provide about the same amount of n-3 PUFAs as one meal containing fish. Researchers found that the 3 eggs a day did not significantly increase total cholesterol or LDL in most subjects. Typically, plasma triglycerides as well as platelet aggregation decrease. LDL particle size tended to shift toward a less atherogenic dimension, appearing less small and dense (Lewis et al. 2000).
Olive oil, an omega-9 fatty acid (a monounsaturated fat), is an excellent choice for both salads and cooking. However, it is extremely difficult to purchase oils in an ideal state, if shopping from a supermarket; a better choice appears to be extra virgin olive oil in a lightproof container. (Refrigerate the oil immediately after purchase.) Other sources of omega-9 fatty acids are almonds, pecans, cashews, filberts, and macadamias. Omega-9 contributes primarily to the structural elements of phosphatides. Phosphatides, in turn, are necessary for cell membrane integrity.
Almond oil is currently reviewed better than canola oil (rape seed) by various practitioners and researchers. Canola oil, belonging to the mustard family, is derived from seeds of a plant considered (by some) to be toxic. Canola oil, when processed, appears to become rancid very quickly and may over time increase the incidence of heart disease. Refrigeration does not appear to retard its oxidation (Fallon 2002). Canola oil proponents still uphold its value, but until more questions are answered regarding its safety, it seems wiser to select the tried and true olive oil.
According to Robert Erdmann, Ph.D., butter, in small amounts, is a better choice than margarine. He added: "Butter may not only be highly nutritious but may be an underexploited form of alternative health therapy" (Erdmann 1990).
Supplemental Omega-6 and Omega-3 Fatty Acids: What to Buy
To introduce the reader to various omega-6 and omega-3 fatty acids, the following examples are given:
- Perilla oil, 1000-mg per capsule, provides 550-620 mg of alpha-linolenic acid, a precursor to EPA and DHA. Use 6 softgels daily.
- Flaxseed oil (1000-mg softgels) provides 520-570 mg per capsule of gamma-linolenic acid. Use 6 softgels a day.
- Super GLA/DHA provides 920 mg of GLA, 1000 mg of DHA, and 400 mg of EPA. Use 6 capsules daily.
- Evening primrose oil is a source of GLA. Use one to two 1300-mg softgels daily.
- Borage oil also supplies GLA. A 1300-mg softgel supplies 300 mg of GLA. As a preventive, use 1-2 softgels a day and up to 5 a day as a therapeutic.
N ote: Prothrombin time usually remains within a normal range when using omega-3. As the number of platelets decreases, platelet size typically increases; therefore, there is no overall decrease in platelet mass. The New England Journal of Medicine reported that the blood-thinning functions of fish oil are small compared to aspirin, but other researchers caution that bleeding time could increase to inappropriate levels if baseline platelet activity is impaired or fibrinogen concentrations are low (Katan 1995).
Fiber—is a hypolipidemic and antidiabetic agent, aids in weight loss, and blocks iron absorption
The intake of dietary fiber among people living in Western countries is low (about 17 grams a day in the United States ), according to the Third National Health and Nutrition Examination Survey (NHANES). This is unfortunate, for soluble fiber offers significant protection against a number of risk factors associated with cardiovascular disease. For example, mucilages, guar gum, psyllium powder, oat bran, and pectin reduce cholesterol levels. Guar gum (5 grams with meals), psyllium powder (5 grams before meals), or pectin (10 grams with meals) reduce fasting and postprandial blood glucose, as well as insulin levels, in both healthy and diabetic subjects. If taken with meals, soluble fibers (6-10 grams a day) reduce iron absorption from foods, important to those with hemochromatosis or iron overload (Monnier et al. 1980) (to read about hemochromatosis as a contributor to cardiovascular disease, turn to Iron Overload in the section devoted to Traditional Risk Factors).
Illustrative of the value of fiber, researchers from the Veterans Affairs Medical Center , the University of Kentucky ( Lexington ), and the Procter & Gamble Company ( Cincinnati , OH ) evaluated the effectiveness of psyllium as a hypocholesterolemic and blood glucose modulator. Thirty-four men with Type II diabetes and mild-to-moderate hypercholesterolemia were randomly assigned to receive 5.1 grams of psyllium or a cellulose placebo twice daily for 8 weeks. The psyllium group showed significant improvements in glucose and lipid values compared with the placebo group. Serum total and LDL-cholesterol concentrations were 8.9% and 13.0% lower, respectively, in the psyllium group compared to the placebo group. All-day and post -lunch postprandial glucose concentrations were 11.0% and 19.2% lower in the psyllium group (Anderson et al. 1999). These impressive results occur as fiber binds bile acids, cholesterol, and fats, preventing their absorption. Short-chain fatty acids, products of fiber fermentation in the colon, further inhibit cholesterol synthesis by the liver.
Studies in the New England Journal of Medicine confirmed the value of a high fiber diet in improving glycemic control and reducing hyperinsulinemia and plasma lipid levels in patients with Type II diabetes (Chandalia et al. 2000). In a randomized, 6-week crossover study, 13 patients with Type II diabetes were given diets containing either moderate or high amounts of fiber. The moderate fiber allowance was 24 grams (8 grams of soluble and 16 grams of insoluble), an amount compliant with guidelines established by the ADA . The high-fiber diet consisted of 50 grams of fiber (25 grams soluble and 25 grams insoluble).
During the sixth week of the high-fiber diet (as compared with the sixth week of the ADA diet) the diet supplying 50 grams a day of fiber lowered plasma glucose 10%, insulin concentrations 12%, total cholesterol 6.7%, triglyceride levels 10.2%, VLDL 12.5%, and LDL cholesterol 6.3%. It is speculated that the decrease in triglycerides and VLDL may be due more to improved glycemic control than to a direct relationship with the fiber. There was no significant difference between the two diets in terms of HDL cholesterol levels. Note: The fiber-rich foods included in the study were cantaloupe, grapefruit, raisins, oranges, papayas, lima beans, okra, sweet potatoes, winter squash, zucchini, oat bran, and oatmeal.
Fiber is also of advantage to individuals who wish to lose weight. Bulk tends to render a feeling of fullness, negating the desire to overeat. An overweight individual should consider using bulk fibers stirred into an 8-oz glass of water; drink the mixture about 20 minutes before meals.
Diabetics and those not accustomed to higher levels of fiber should initially use the material cautiously. Fiber can significantly alter insulin or sulfonylurea requirements and some individuals experience gastrointestinal distress until the GI tract becomes better acquainted with the new material. A suggested initial dosage is 1 tsp daily; gradually increase to 1 tsp 3 times daily.
Reader's guide to foods high in fiber
Grains are excellent sources of fiber, but many individuals find the addition of cereal grains problematic due to food sensitivities. Vegetables and fruits (raw and with peel intact) are pleasant fibrous additions to the diet.
Garlic—acts as a hypotensive, decreases fibrinogen, inhibits platelet aggregation, thins the blood, protects against LDL oxidation and arterial wall damage, reduces the incidence of arrhythmias, modestly reduces blood glucose levels, protects against iron overload, and is vasodilating
The consensus surrounding the benefits of garlic as a hypolipidemic is not unified. The Archives of Internal Medicine found garlic powder (900 mg a day for 12 weeks) to be ineffective in lowering blood lipids (Isaacsohn et al. 1998). Researchers concede that variations in preparations could be distorting results as well as gender. For example, women showed favorable effects in terms of coronary heart disease risk factors (i.e., increases in HDL-C and reductions in total cholesterol) using garlic oil, whereas men had small adverse effects. There was a significant difference in the garlic oil effect for glucose, with a reduction seen for men and an increase for women (Zhang et al. 2001).
Interestingly, the American Journal of Natural Medicine reported that 4000 mg of fresh garlic (guaranteeing an allicin content of at least 10,000 mcg or a total allicin yield of 4000 mcg) typically lowers total cholesterol levels 10-12%, triglycerides by about 15%, and LDL 15%, while increasing HDL cholesterol levels 10% (Murray 1995a). Healthy human volunteers given 600 mg a day of a garlic preparation (providing 7.8 mg of allicin for 2 weeks) reduced lipoprotein oxidation 34% compared to controls. It should be noted that garlic could cause a transient elevation in blood lipids, as garlic unseats fats deposited in tissues. With continued garlic supplementation, lipid stores complete the breakdown process and blood cholesterol levels modulate.
While much of the research has focused on improving lipid levels, researchers have isolated hypotensive factors in garlic as well. An analysis of published and unpublished randomized, controlled trials (415 patients) showed that 600-900 mg a day of dried garlic powder may be of clinical value in subjects with mild hypertension (Silagy et al. 1994). Other researchers have noted a 5.5% decrease in systolic blood pressure and a modest reduction in diastolic blood pressure in response to aged garlic extract (Steiner 1996).
Garlic, a sulfur-rich plant from the lily family, exerts its hypotensive nature through the following pathways:
- Supplementation with aged garlic significantly reduced epinephrine, a vasoconstricting hormone released from the adrenal medulla (Steiner et al. 1998).
- Garlic moderately inhibited (both in vivo and in vitro) the activity of ACE, an enzyme that increases blood pressure by catalyzing the conversion of angiotensin I to angiotensin II. This sequence constricts blood vessels, conserves water and sodium ions, and, unless interrupted, results in an increase in blood pressure (Rietz et al. 1993).
- Garlic increases the activity of nitric oxide synthase, an enzyme essential for nitric oxide synthesis (Morihara et al. 2002). Nitric oxide, a relaxing factor, not only reduces blood pressure by acting as a vasodilator, but also lessens platelet aggregation, suppresses smooth muscle proliferation, reduces leukocyte adherence to vessel walls, and has anti -anginal and antispasmodic activity.
- Garlic contains chemicals that act as calcium antagonists, reducing blood pressure and lessening the incidence of arrhythmias (Duke Database 1992).
Garlic exhibits additional cardiovascular protection by thinning the blood and acting as a fibrinolytic. German researchers reported successes in treating ventricular tachycardia and fibrillation with garlic, as well as the duration of arrhythmias (Isensee et al. 1993). Garlic also modestly reduces blood glucose levels, while EDTA-garlic combinations appear to decrease iron stores. Dosage suggestions are 1-2 Kyolic caplets (1000 mg) twice daily with meals or 2-8 capsules of Pure-Gar Caps (900 mg) daily with food. (One Pure-Gar Cap contains 900 mg of garlic bulb powder extract standardized to supply 9 mg of allicin, the highest potency available.)
Ginger—reduces cholesterol, prevents blood clots, is an anti-inflammatory, and has chemical components that are calcium antagonists, vasodilators, and ACE inhibitors
Ginger (Zingiber officinale) is reliable in treating a wide variety of cardiovascular complaints. Among ginger's protective properties is its ability to reduce cholesterol by promoting cholesterol excretion, impairing cholesterol absorption, and encouraging bile secretion and bile acid production. (Bile acid is a steroid acid of bile, produced during the metabolism of cholesterol.) Ginger exerts some of its hypolipidemic effects by stimulating cholesterol-7-alpha-hydroxylase, a rate-limiting enzyme of bile acid synthesis (Srinivasan et al. 1991).
Researchers reported the effects of administering ginger (200 mg/kg orally) to 61 cholesterol-fed rabbits (Bhandari et al. 1998). The marked rise in cholesterol, triglycerides, lipoproteins, and phospholipids (which normally follows 10 weeks of cholesterol feeding) was significantly reduced by ginger. The favorable results obtained from ginger were comparable to the hypolipidemic effects of the drug Lopid, known generically as gemfibrozil.
Various chemicals contained in ginger are calcium antagonists, vasodilators, ACE inhibitors, and diuretics, suggesting additional value in reducing blood pressure and the incidence of arrhythmias (Duke Database 1992).
Ginger reduces the likelihood of a blood clot through the following mechanisms:
- Ginger, ginkgo, olive leaf, and garlic each contain chemicals that inhibit platelet-activating factor, PAF (Duke Database 1992). Adequate amounts of PAF are essential to coagulation and inflammatory processes; excesses are associated with blood clot formation, stroke, and heart disease.
- Thromboxane A-2, a platelet-aggregating factor, is inhibited more by ginger than by either garlic or onions (Srivas 1984).
- Prostacylin, an inhibitor of platelet aggregation, is pressed into service by ginger, a process that further reduces the likelihood of blood clot formation (Backon 1986).
Although all of these effects are similar (blood clot reduction), a study involving healthy volunteers showed no irregularities in blood coagulation among participants receiving 2 grams of ginger a day (McCaleb et al. 2000). Nonetheless, caution is indicated for those individuals with baseline disturbances in platelet numbers or prothrombin time. Furthermore, the activity of prescribed blood thinners may be heightened if used in concert with ginger.
Ginger also appears to protect the heart during periods of inflammation. (Recall that inflammation is considered a trigger in heart disease.) Ginger's anti-inflammatory properties are due to interruption of the prostaglandin-leukotriene cascade, blocking damaging prostaglandins but leaving beneficial prostaglandins unaffected. Ginger root (gingerols) has been shown to inhibit cyclooxygenase pathways, sharing anti-inflammatory traits with other popular COX-2 inhibitors (Newmark et al. 2000; Faloon 2001).
A preventive dose of ginger is one to two 300-mg capsules 1-3 times a day. Interestingly, a researcher recently recommended 10 grams (approximately 1 tsp a day) to reduce platelet aggregation (Bordia et al. 1997). A qualified healthcare practitioner must monitor this dosage. JAMA published an article raising a cautionary flag concerning the risk of cardiovascular events among users of COX-2 inhibitors (such as Celebrex and Vioxx) (Mukherjee et al. 2001). The FDA has also objected to claims and promotional activities by Pharmacia Corporation minimizing the potentially serious risk of bleeding associated with Celebrex (Fort 2001). It is hoped further prospective evaluations will characterize and determine the magnitude of the risks. In the interim, natural COX-2 inhibitors (including ginger) loom as welcome alternatives.
Ginkgo Biloba—improves circulation and memory; reduces platelet aggregation and excesses of fibrinogen; has antioxidant and anti-inflammatory activity; prevents capillary fragility; lessens angina attacks, dyspnea, and intermittent claudication; limits brain damage following stroke; increases insulin secretion; and is a vasodilator
Ginkgo biloba is one of the oldest surviving species on earth. But this ancient herb, renowned for its ability to retard aging, has survived the test of time and is yielding remarkable benefits for millions of Americans and Europeans. Heart, circulatory, and cognitive disorders are the principal reasons individuals rely upon ginkgo. More than 300 clinical and experimental studies have supported the worth of Ginkgo biloba.
- Ginkgo has won favor among the Chinese as a heart tonic by lessening coronary demands for oxygen, thus reducing shortness of breath and chest pain (Duke 1997).
- Ginkgo's antioxidant properties, particularly the flavones, assist in strengthening blood vessel walls and improving tone and elasticity (Joyeuz et al. 1995).
- Ginkgo is a vasodilator, making it useful in lowering blood pressure and treating many forms of heart disease (120 mg a day at bedtime for 3 months reduced systolic blood pressure from 125 mmHg to 118 mmHg and diastolic from 86 mmHg to 68 mmHg) (Kudolo 2000). Some of the chemicals contained in ginkgo are ACE inhibitors, further explaining its hypotensive nature (Duke Database 1992).
- Ginkgo is also an anti-inflammatory, adding additional merit to its cardiac profile (Hopes 2000). Consult the section entitled Link Between Infections and Inflammation in Heart Disease (in this protocol) to understand the value of anti-inflammatories in a comprehensive cardiovascular program.
- Ginkgolide B infusions are comparable to standard anti -arrhythmic drugs in controlling irregular heartbeats (Koltai et al. 1989).
- Patients with chronic cerebral vascular insufficiency typically respond well to ginkgo biloba extract (GBE), reporting improvement in vertigo, headache, ringing in the ears, and memory ( Murray 1995c).
- GBE also significantly improves the supply of blood to the limbs. As resting blood flow and peripheral circulation improve, intermittent claudication, a cramp-like pain in the calves, diminishes. In fact, 40 mg of GBE twice a day is from 10-45% more effective at controlling intermittent claudication than pentoxifylline (Trental) (Duke 1997).
Varro Tyler, Ph.D. (dean and professor emeritus at Purdue University ), profiles ginkgo in his book Herbs of Choice as a treatment for peripheral vascular disease and cerebral circulatory disturbances (Robbers 2000). Ginkgo can, in fact, act as a prophylaxis against strokes by reducing fragility of capillaries and counteracting erythrocyte and platelet hyperaggregability. The nature of platelets is strongly influenced by platelet-activating factor (PAF), which ginkgo inhibits.
The American Academy of Neurology reported that ginkgo reduced the extent of brain damage caused by artificially induced strokes in mice (June-July 2000 edition). Mice receiving low-dose GBE 1 week prior to stroke reduced the area in the brain that was affected by 30%. The journal Stroke concurred that GBE reduced stroke infarct volume but noted the beneficial effect appears to be dose related. In fact, researchers found that higher doses had the potential for increasing the risk of intracerebral hemorrhage. The combined clinical use of GBE with antiplatelet, anticoagulant, and thrombolytic agents could potentially further increase the risk (Clark et al. 2001).
Researchers recently reported a function of ginkgo biloba not frequently credited to the herb, that is, an ability to increase insulin secretion. A study was undertaken to determine the effect of GBE on glucose-stimulated pancreatic beta-cell function in normal glucose-tolerant individuals: 20 participants (14 females and six males, ages 21-57) underwent a 2-hour, 75-gram oral glucose tolerance test before and after ingestion of GBE (120 mg a day at bedtime). During the 3-month evaluation, both fasting plasma insulin and C peptide (a biologically inactive residue of insulin formation) increased. Dr. G.B. Kudolo (principal researcher) believes the changes in the insulin-C peptide response curves are due to increased production and secretion of insulin (Kudolo 2000).
N ote: Herbals that influence glycemic control by increasing insulin secretion would be contraindicated in cases of existing hyperinsulinemia. If insulin production declines to the point that hypoinsulinemia exists, herbs that encourage insulin release would then be appropriate.
High quality GBE is typically standardized to contain a minimum of 24% ginkgo flavone glycosides and 6% terpene lactones. Side effects are rare when using the standardized extract; however, concomitant use with an anticoagulant medication or administering GBE to individuals with prolonged prothrombin time may make ginkgo inappropriate. (Ginkgo is not recommended for pregnant or lactating women.) A dosing suggestion is 120-240 mg a day. (A dose of 120 mg a day assists in reducing excessive fibrinogen levels, i.e., levels greater than 300 mg/dL).
Grapefruit Pectin—is hypocholesterolemic
Grapefruit pectin and other food sources rich in soluble fibers are useful adjuvants in the treatment of hypercholesterolemia. In fact, grapefruit pectin, a stringy white fiber, appears equal to or more effective than most popularly prescribed drugs for lowering cholesterol. Since grapefruit pectin is highly soluble, the pectin is broken down in the small intestine so that 100% of the fiber is utilized.
Illustrative of its potential, guinea pigs administered grapefruit pectin reduced their cholesterol by greater than 40% over a 6-week period (Cerda 1994b). No side effects were noted, a vast departure from the potential risks associated with many prescription drugs.
In addition, researchers found citrus pectin effective in reducing atheromatous plaque. Substantiating its worth, an atherogenic diet was fed to a group of microswine to induce hypercholesterolemia. Plasma cholesterol levels rose rapidly and for 360 days were sustained at levels 6-12 times the norm. Half of the microswine were then fed a diet containing 3% grapefruit pectin; the remaining animals received the original diet. Animals were slaughtered 270 days later, and the extent of atherosclerosis determined. The mean surface area covered by plaque in the aorta was 13.6% in the group not receiving pectin compared to 5.3% in the group receiving pectin. Mean coronary artery narrowing was 45% without pectin and 24% with pectin (Cerda et al. 1994a).
Human trials have also been gratifying. Hypercholesterolemic subjects using no other cholesterol lowering agents and without lifestyle modification significantly lowered total cholesterol and LDL while increasing HDL levels (Cerda et al. 1988). Begin with less than 1 scoop of grapefruit pectin (with meals) and gradually increase until 2-3 scoops are used daily. If using grapefruit pectin tablets, use 1000 mg with meals.
Gugulipid—lowers total cholesterol, LDL, and triglycerides; increases HDL cholesterol; regresses plaque formation; opposes platelet aggregation; and has fibrinolytic activity
Numerous studies have demonstrated that gugulipid is beneficial to about 70% of individuals with disorganized lipid profiles, that is, elevations in LDL and total cholesterol or triglycerides. Human clinical trials showed gugulipid dropped total cholesterol levels by 14-27% in a 4- to 12-week period and reduced triglycerides 22-30%. HDL cholesterol increased in 60% of cases considered gugulipid-responsive. In addition, gugulipid regressed plaque formation, opposed platelet aggregation, and encouraged fibrinolysis. Gugulipid is regarded as nontoxic, with liver and kidney function, blood sugar control, and hematological parameters unaffected during clinical trials (Agarwal et al. 1986; Nityanand et al. 1989; Murray 1995c).
Comparing gugulipid to clofibrate, hypercholesterolemic patients appeared more responsive to gugulipid therapy, while patients with hypertriglyceridemia responded better to clofibrate (Nityanand et al. 1989). A suggested dosage is 500 mg (5% guggulsterone content) 3 times a day.
Hawthorn Berry (Crataegus oxyacantha)—normalizes blood pressure; is beneficial to dieters and those with congestive heart failure; prevents premature ventricular contractions and hypoxia; has diuretic and antioxidant potential; lowers cholesterol; acts as a vasodilator; is an ACE inhibitor, beta-blocker, and anti-inflammatory; increases exercise tolerance; and reduces the incidence of tachycardia and palpitations
Dr. James Duke, botanist, says that when hawthorn is evaluated chemically, it appears that the herb covers most of the cardiovascular bases. For example, it contains a calcium-antagonist (magnesium), ACE inhibitors (procyanidins), and beta-blockers (catechin, epicatechin, and procyanidins), plus numerous diuretics, cholesterol-lowering compounds, anti-inflammatories, and antioxidants (Duke 2000b).
The hawthorn berry is considered a smart herb with adaptogenic qualities in regard to normalizing blood pressure. Hawthorn gains much of its hypotensive and weight management properties through its diuretic action. Also, its ACE inhibiting factors interrupt the renin-angiotensin sequence, resulting in lower blood pressure and improved cardiac output (Duke 2000b). Clinicians compare the effectiveness of hawthorn to Captopril, a drug prescribed for congestive heart failure (CHF) and hypertension that also works by inhibiting ACE. (Hawthorn, although helpful in blood pressure management, should not be regarded as the sole therapeutic for hypertension.)
The bioflavonoid content of hawthorn appears to be responsible for much of the herb's cardiac potential, that is, dilating blood vessels, enhancing vitamin C absorption, and protecting against vascular breaks or leaks. Bioflavonoids are powerful antioxidants that not only protect against free-radical damage, but also increase oxygen delivery and blood flow to the heart. This reduces the effort and stress imposed upon the heart to circulate blood, and as an additional bonus, a reduction in blood pressure usually occurs. The risk of stroke was, in fact, 73% lower among individuals who consumed greater amounts of flavonoid-rich foods compared to individuals who consumed less (Keli et al. 1996; Roanoke Times 1996).
During the Middle Ages, hawthorn was used to treat dropsy, a condition now recognized as CHF. Today, European physicians still use hawthorn to treat early signs of CHF, relying upon the herb to strengthen the heart and the power of cardiac contractions. Drugs that have the ability to power up the heart can cause cardiac irregularities; conversely, it appears hawthorn can energize the heart without prompting arrhythmias. Hawthorn, in fact, has a normalizing effect upon the heartbeat, lessening the incidence of tachycardia (a heart rate greater than 100 beats per minute) and palpitations (Santillo 1990).
Studies confirm the multiplicity of hawthorn's actions:
- Various clinicians report an excellent patient response, treating valvular insufficiency, heart fibrillations, and hypoxia with hawthorn (Santillo 1990; Ritchason 1995; Duke 1997).
- Hawthorn appears to stabilize heart rhythm and increase exercise tolerance (Duke 1997). Problem-free exercise occurs as the heart becomes stronger and less taxed by exertion.
- Hawthorn reduces cholesterol levels and the size of existing atherosclerotic plaque (Wegrowski 1984).
Hawthorn is best used long-term because the active constituents do not produce rapid results. It may take 4-8 weeks for improvement in subjective complaints and increased exercise tolerance. Although it is regarded as gentle and safe for chronic usage, a physician should evaluate the patient's drug list before adding hawthorn to the total package. A dosage suggestion is 250-900 mg daily.
Homocysteine-Lowering Nutrients and Elimination Pathways
Homocysteine, a naturally occurring amino acid, is derived from methionine and produced in small amounts by the body. When homocysteine is not detoxified or reduced through metabolic processes (i.e., remethylation or trans -sulfuration) and begins to accumulate, various biological failures occur. According to some experts, homocysteine is now recognized as the single greatest biochemical risk factor for heart disease (McCully 1996) (for an introduction to homocysteine, consult Newer Risk Factors appearing earlier in this protocol).
The published literature emphasizes that folic acid, vitamin B12, and zinc (nutrient cofactors) and trimethylglycine (a methyl donor) are critical to the remethylation of homocysteine, the most common detoxification pathway. Remethylation occurs as methyl groups are donated to homocysteine to transform it to methionine and S-adenosylmethionine (SAMe) (Porter et al. 1993; Undas et al. 1993; Malinow et al. 1998; Baker-Racine 2002).
SAMe, the chief methyl donor, is crucial to the methylation process. Initially, methionine reacts with ATP to produce SAMe. SAMe is then used for methylation and a byproduct of this reaction, homocysteine, is recycled back to methionine. This cyclic dance continues faultlessly, unless something throws it out of sync.
Too much methionine will disrupt the delicate balance. Flesh foods and dairy products are rich in methionine and require greater amounts of nutrient cofactors to preserve the methylation process. Chronic inflammation, high intensity exercise, and age can also put the brakes on methylation. When this occurs, the cycle is broken, and homocysteine detoxification stagnates. The problem comes full circle, as excessive amounts of homocysteine interfere with the methylation process.
Trimethylglycine (TMG), also called betaine, emerges as one of the most important nutrients to prevent and reverse existing heart disease, in part by supporting remethylation (Baker-Racine 2002). TMG usually causes a substantial lowering of homocysteine, but regular dosing must continue to sustain the improvement. The dosage varies from one to eight 500-mg tablets a day, depending upon the amount needed to maintain healthy levels (below 7 micromol e/L of blood).
Choline, another methyl donor, can act independently (not requiring cofactors) to lower homocysteine levels, but it only influences remethylation in the liver and kidneys through conversion into TMG,, leaving the heart and brain less protected. Methylating factors, as vitamin B12 and folic acid, add additional protection.
The second means of homocysteine disposal is via the trans -sulfuration pathway, a sequence dependent upon vitamin B6. This pathway converts homocysteine to the powerful antioxidants cysteine and glutathione, but a deficiency of the B6-dependent enzyme, cystathione-B-synthase, can hamper this process. An alternative is to take larger doses of vitamin B6, but this course is not without risk. Chronic megadose vitamin B6 supplementation (300-500 mg daily) can result in neurological symptoms that typically fade when the dosage is reduced or discontinued. Careful monitoring to determine the lowest vitamin B6 dose capable of controlling homocysteine levels is essential.
Some individuals lack the enzyme necessary to convert vitamin B6 to its active form (Robinson et al. 1995). In this case, use the biologically active pyridoxal-5-phosphate to control elevations in homocysteine. Note: Vitamin B6 is also a reliable diuretic, making it of particular advantage to patients with high blood pressure and congestive heart failure.
For most individuals, hyperhomocysteinemia is a modifiable cardiovascular risk factor. In fact, about one-half of individuals with hyperhomocysteinemia respond favorably to vitamin B6 supplementation. Researchers selected 421 patients, mildly hyperhomo-cysteinemic, to determine their response to vitamin B6 (250 mg daily). After 6 weeks of vitamin B6 supplementation, 56% of the patients had normal homocysteine levels. Non-normalized homocysteine concentrations were treated with a combination of supplements, vitamin B6 (250 mg daily) and/or folic acid (5 mg daily) and/or TMG (6 grams daily). The more aggressive treatment normalized homocysteine levels in 95% of the remaining cases (Franken et al. 1994).
Another 20% of hyperhomocysteinemic patients have a mutation in the gene, methylenetetrahydrofolate reductase, disrupting the conversion of folic acid to 5-methyltetrahydrofolate, an active contributor in the methyl donation pathway of folate. In this incidence, it is necessary to use 5-methyltetrahydrofolate supplementation to bypass the metabolic block (James et al. 1999; Bland 2000a) (additional information regarding methylenetetrahydrofolate reductase appears in the section devoted to Heredity, one of the traditional risk factors, in this protocol).
A Polish study showed that administering folic acid (5 mg a day), vitamin B6 (300 mg a day), and B12 (1000 microgram a day) over an 8-week period reduced benchmark homocysteine levels by one-half (from 20 micromol/L to 10 micromol/L) and also reduced thrombin, an intermediate in the production of fibrinogen (Undas et al. 1999). Individuals with low folate status, regardless of age or sex, have a 69% greater risk of fatal heart disease compared to individuals with higher levels (greater than 13.6 nanomol/L) (Morrison 1996; Pirisi 2001; Tice et al. 2001). It is theorized that properly administered folate might prevent as many as 13,500-50,000 premature deaths annually (Boushey et al. 1995).
The New England Journal of Medicine reported that a combination of folic acid, vitamin B12, and pyridoxine reduced homocysteine levels and also the necessity for revascularization procedures. (Revascularization refers to restoring adequate blood supply by means of a coronary bypass or angioplasty.) Researchers concluded that this inexpensive nutritional therapy, with minimal side effects, should be considered as adjunctive therapy for all patients undergoing coronary angioplasty (Schnyder et al. 2001).
The American Journal of Clinical Nutrition reported that a chemical component of coffee and black tea (chlorogenic acid) could raise plasma homocysteine levels (Olthof et al. 2001). Another team of researchers targeted unfiltered coffee as being most contributory to hyperhomocysteinemia (Grubben et al. 2000). On the other hand, a diet rich in fruits and vegetables may decrease the risk of heart disease (7-9%) by reducing blood levels of homocysteine. Fresh and unaltered foods have a more reliable nutrient bank and are capable of delivering more homocysteine-lowering vitamins and minerals.
It should be noted that niacin may increase plasma homocysteine levels (from 1-4 micromol/L) in some people (Desouza et al. 2002; Berkeley Heart Lab, http://www.berkeleyheartlab.com/HCP/hcp_frequentlyaskedquestions_4.shtml). Researchers at Pantox Laboratories ( California ) explain that niacin appears to interfere with homocysteine clearance by depleting SAMe. Concurrent TMG supplementation may represent a cost-effective way to prevent niacin-mediated depletion of SAMe and thus avoid hepatotoxicity and possibly other adverse niacin side effects (McCarty 2000).
Administering homocysteine-lowering nutrients is so individualized that testing is essential to determine adequate dosages. To assume that homocysteine is not a threat (because you have the B vitamins in your supplemental protocol) is not a guarantee that the dosage is appropriate to render protection. The following daily supplements (used alone or in combination) have demonstrated homocysteine-lowering effectiveness: 500-9000 mg of TMG, 800-5000 mcg of folic acid, 1000-3000 mcg of vitamin B12, 250-3000 mg of choline, 250-1000 mg of inositol, 30-90 mg of zinc, 100-500 mg of vitamin B6, and 200-800 mg of SAMe. SAMe is of value in lowering homocysteine levels only if folic acid and vitamins B6 and B12 are also present; without nutrient cofactors, SAMe will eventually break down into homocysteine.
Note: Extremely important data were published showing that pretreatment with 800 IU of vitamin E and 1000 mg of C (before an oral methionine load to experimentally produce homocysteine) blocked the damaging effects of hyperhomocysteinemia. Coagulation and circulating adhesion molecule levels significantly increased after methionine ingestion alone but not after methionine ingestion with vitamins (Nappo et al. 1999).
Reader's guide to food sources, enhancers, and antagonists to homocysteine-lowering B vitamins
Medications to treat congestive heart failure commonly result in multiple B vitamin deficiencies, disrupting disposal systems for homocysteine clearance (Sinatra 2001). Also, B vitamins are considered unstable when exposed to the heating process, but the following foods represent the most nutrient-dense choices:
Vitamin B6 appears in most foodstuffs, but the best sources are brewer's yeast, carrots, chicken, eggs, fish, meat, peas, spinach, sunflower seeds, walnuts, and wheat germ.
Complimentary nutrients in regard to vitamin B6 absorption are the full B complex, vitamin C, magnesium, potassium, and zinc. Antidepressants, alcohol, coffee, exercise (to excess), estrogen therapy, and oral contraceptives appear to either increase the need for vitamin B6 or reduce its status. Diuretics and cortisone drugs block its absorption, and theophylline, an oral bronchodilator, antagonizes pyridoxal phosphate synthesis (Ubbink et al. 1996).
Vitamin B12, the most complex of the B vitamins, should be of special interest to vegans who, after chronic abstinence from animal products, can become seriously depleted in this nutrient. However, most vitamin B12 deficiencies occur not because of inadequate dietary consumption, but rather because of poor absorption. The intrinsic factor, a substance secreted by the gastric mucosa, is essential for the absorption of B12, transporting cyan o acobalamin (vitamin B12) across the membranes of the ileum (the distal end of the small intestine).
Animal derivatives, eggs, fish and marine life, beef and pork, and milk and dairy products are good sources of vitamin B12. Nutrients considered B12 enhancers are others of the B complex (especially folic acid and vitamin B6), vitamin C, iron, potassium, sodium, and calcium.
Medications to treat gout, anticoagulant drugs, and potassium supplements may block the absorption of vitamin B12 from the digestive tract (Balch et al. 1997). For optimal B12 utilization, avoid coffee, alcohol, smoking, and laxatives.
Folate-rich foods are liver, wheat germ, legumes, green leafy vegetables, beets, citrus fruits, most fish, pork, and whole grains. Fortification of enriched grain products with folic acid is associated with a substantial improvement in folate status in middle aged and older adults (Jacques et al. 1999).
Folic acid is most efficient when combined with vitamin B12, biotin, pantothenic acid, and vitamin C. According to the Committee on Dietary Allowances, heat and oxidation (occurring during cooking and storage) can destroy as much as half of the folate in foods. Sulfa drugs interfere with the bacteria in the intestines that manufacture folic acid, and Streptomycin totally destroys it. Methotrexate depletes folate, causing a transient elevation in homocysteine, and phenytoin (an antiepileptic drug) interferes with folate metabolism. Lastly, oral contraceptives, alcohol, coffee, and smoking are also considered folic acid antagonists.
Magnesium—reduces blood pressure, is a calcium antagonist, tempers the sympathetic nervous system, is beneficial in arrhythmias and mitral valve prolapse, increases the number and sensitivity of insulin receptors, has antidiabetic properties, encourages the methylation process, prevents toxic buildup of homocysteine, reduces calcium levels, is a vasodilator, and opposes platelet aggregation
Magnesium, a potent vasodilator, may prove to be a better hypotensive in some individuals than calcium (50% of magnesium-depleted patients are hypertensive, a condition often remediable with supplementation).
The British Medical Journal reported that magnesium supplementation lowered blood pressure by a mean of 12/8 mmHg (systolic and diastolic pressures) in 19 of 20 subjects (Dyckner et al. 1983). Magnesium reduces blood vessel contractibility by regulating levels of bradykinin, angiotensin II, prostaglandins, serotonin, epinephrine, norepinephrine, and dopamine; as a result, vessels vasodilate and blood pressure decreases.
Besides being a hypotensive mineral, magnesium is absolutely essential to proper cardiac function, allowing relaxation of the heart and supporting normal heart rhythms. In a study of patients admitted to coronary care units experiencing arrhythmias, 100% had complete resolution when administered IV magnesium over a 5-hour period. Dr. Bart Chernow (a surgeon at Sinai Hospital in Baltimore , MD ) reports that magnesium injections following bypass surgery reduced heart rhythm irregularities 50%, without side effects (Alternative Medical News staff). After 3 months of oral magnesium supplementation, platelet-dependent thrombosis typically is reduced 35% in 75% of patients.
In a study in the American Journal of Clinical Nutrition, researchers from the U.S. Department of Agriculture reported the effects of a magnesium-deficient diet on 22 healthy postmenopausal women ages 47-78. The women all ate the same meals for 6 months as they lived together under close supervision, taking in about 130 mg of dietary magnesium each day. Half the women also took an additional 280 mg of magnesium in supplemental form for 81 days while the other half received a placebo; during the second half of the study period, the groups crossed over to the other treatment category.
The researchers assessed magnesium levels in urine and blood regularly, as well as heartbeat patterns through electrocardiograms. Not surprisingly, serum and urine concentrations of magnesium were lower on the controlled diet, but heart rhythms were also significantly affected by lesser amounts of magnesium. A lack of magnesium provoked the heart into rhythmic abnormalities, as well as more frequent heartbeats. The researchers concluded that the cardiac muscle is more sensitive to magnesium intake than skeletal muscle and that a deficiency has the potential to cause dangerous cardiac irregularities (Klevay et al. 2002).
Calcium channel blockers are popular as anti -arrhythmics and antispasmodics (to read more about calcium channel blockers, consult the sections devoted to Beta-Blockers and Calcium Channel Blockers appearing in this protocol). By relaxing arterial smooth muscles and reducing stress on the myocardium (the thick middle layer of the heart), magnesium delivers many of the effects of a calcium channel blocker (Whitaker 1995b).
Magnesium turns off activity in the sympathetic nervous system. By blocking the release of excitatory hormones (epinephrine and norepinephrine), the "fight or flight" response of the sympathetic nervous system is inhibited (Gonzalez 2000). Although the therapeutic profile of magnesium is similar to a beta-blocker, the drug should not be abruptly stopped and magnesium commenced; without a gradual withdrawal of the drug, a rebound could occur, provoking a heart attack.
In mitral valve prolapse, the valve separating the left atrium from the left ventricle protrudes into the left atrium. Of patients participating in an evaluation, 85% were found to have low magnesium levels, suggesting that a deficiency plays a role in the disturbance (Simoes-Fernandes et al. 1985; Galland et al. 1986; Murray 1996). Numerous studies indicate that magnesium lessens mitral valve prolapse symptoms, palpitations, fatigue, breathing difficulties, and nonanginal chest pains. Others have observed improvement in exercise tolerance and reduced stress within the heart itself (Shechter et al. 2000). Comment: Low magnesium levels also are associated with angina attacks in men. It appears that as magnesium status drops, the frequency of angina attacks increases (Satake et al. 1996).
Too much calcium in the bloodstream may be a forerunner to aortic stenosis (Bonow et al. 1998). Magnesium hinders the absorption of calcium; therefore supplementing with at least 500 mg a day could inhibit the excesses of calcium hardening the cusps of valves (for a comprehensive look at aortic stenosis, consult the section of this protocol dedicated to Valvular Disease).
Magnesium plays an important role in the prevention and treatment of Syndrome X and diabetes. It benefits these conditions by increasing the number and sensitivity of insulin receptors (Waterfall 2000).
In addition, increased homocysteine concentrations cause abnormal metabolism of magnesium in vascular smooth muscles cells, priming these cells for homocysteine-induced atherogenesis, cerebral vaso-spasm, and stroke. Researchers from State University of New York propose that vitamin B6, vitamin B12, and folic acid, together with physiological levels of magnesium, are needed to prevent magnesium depletion and occlusive cerebral vascular diseases induced by homocysteinemia (Li et al. 1999).
Magnesium status is integral in various drug therapies. Recent controlled studies have shown that treatment with magnesium significantly reduced the frequency and complexity of ventricular arrhythmias in digoxin-treated patients with congestive heart failure. In fact, magnesium improved the efficacy of digoxin (digitalis) in slowing the ventricular response in atrial fibrillation. The complex and potentially life-threatening interactions between magnesium and some cardiovascular drugs suggest that magnesium status should be carefully monitored in patients receiving cardiac pharmaceuticals (Crippa et al. 1999).
Unfortunately, the test used by the majority of physicians to measure magnesium levels is worse than useless, according to Dr. Sherry A. Rogers, an environmental medicine specialist. Dr. Rogers refers to this test as "the most dangerous test in medicine" for if it is used, it too often shows misleading normal levels. The assumption that adequate amounts of magnesium exist when, in fact, deficiency states exist may be a fatal mistake. A study in the Journal of the American Medical Association reported that about 90% of practicing physicians never think to check magnesium levels, even in patients who are severely depleted (Whang et al. 1990). Note: Magnesium deficiency is better detected by measuring mono-nuclear blood cell magnesium, as opposed to serum levels.
A dosage suggestion is 500-1500 mg daily of magnesium bound to succinate, citrate, or aspartate. Magnesium oxide, in larger doses, can cause loose stool.
Reader's guide to magnesium-rich foods, enhancers, and antagonists
Magnesium is found in most foods, particularly nuts, whole grains, legumes, brown rice, dark green vegetables, and fish (Balch et al. 1997).
Magnesium enhancers include the B-complex (especially vitamin B6), vitamin C, calcium, essential fatty acids, and essential amino acids. The body's requirement for magnesium increases if using alcohol, taking higher amounts of vitamin D, or if exposed to fluoride, tobacco, or unrelenting stress. Cod liver oil, calcium (excessive intake), and iron decrease magnesium absorption. Diuretics and chronic diarrhea can seriously deplete many minerals, including magnesium.
Niacin (Vitamin B3)—lowers Lp(a), reduces fibrinogen, normalizes blood lipids, and acts as a vasodilator
Nicotinic acid and nicotinamide are types of the vitamin niacin; although related, they are different in their therapeutic delivery. Nicotinamide, often marketed as a superior lipid-lowering version of niacin, actually has little effect in lowering blood lipids (Segrest 2000). It is nicotinic acid that modulates most all lipid parameters, lowering total cholesterol, LDL, VLDL, Lp(a), and triglyceride levels, while increasing HDL cholesterol. Nicotinic acid has, in fact, won favor with the FDA, adding it to a list of other remedials capable of lowering triglycerides.
Because of niacin's broad-spectrum effectiveness against hyperlipidemia, niacin can act independently or in concert with other drugs. Dr. B. Greg Brown (of the University of Washington , Seattle ) reported to the American Heart Association that a combination of a statin drug (which lowers LDL cholesterol) and niacin (which raises HDL cholesterol) brought the progression of atherosclerotic disease to a standstill. According to Brown, a niacin-simvastatin combination resulted in a 70% reduction in heart attacks, strokes, and other disease-related events. According to Brown, "This represents twice the reduction seen with statins alone." Simvastatin (Zocor) plus niacin increased HDL levels 30% over baseline, while Zocor alone increased HDL only 7-10% (Kerr 2000). In addition, nicotinic acid can act independently, accomplishing what no drug can currently do: lower Lp(a); 1500 mg a day of niacin reduced Lp(a) an average of 20%; 3000 mg a day reduced Lp(a) an average of 26% (Berkeley Heart Lab).
Niacin has properties that are the opposite of those of nicotine. Nicotine, a toxic substance in tobacco, is a vasoconstrictor; niacin is a vasodilator. Niacin's vasodilating quality makes it beneficial in the treatment of hypertension and various forms of heart disease.
In 1991 a group of scientists found that small amounts of niacin in combination with chromium, lowered cholesterol levels by an average of 14% and improved the total cholesterol-HDL ratio 7% (Urberg et al. 1987; Cichoke 2001). This finding is valuable since niacin has some significant side effects, making it less justifiable in large doses. Articles appearing in the American Journal of Cardiology and the Journal of Cardiovascular Risk confirmed niacin's hypolipidemic value and also reported that low-dose niacin was effective in reducing plasma fibrinogen levels in subjects with peripheral vascular disease (Philipp et al. 1998; Ma et al. 1999).
If used independently, 1-3 grams of niacin is sometimes required to lower cholesterol levels, a dosage that can cause side effects ranging from nuisance complaints to significant endangerments. Allergic-like reactions, such as itching and flushing, are common, but niacin can also disrupt liver function, causing elevations of liver enzymes.
Other risks associated with niacin:
- Individuals dosing with niacin may experience a rise in uric acid, an increase that can bring on a gout attack (Goldberg 1998). Recall that individuals with Syndrome X often present with higher levels of uric acid.
- Niacin may interfere with folate and homocysteine metabolism and actually increase plasma homocysteine levels (Desouza et al. 2002). Dr. David Blankenhorn was the first to discover the niacin-homocysteine connection at USC in the CLAS study. Niaspan, an extended-release niacin, raised homocysteine levels in some, but not all people; the amount is generally between 1-4 micromol/L and appears to be dose-dependent (Berkeley Heart Lab).
- Niacin may deplete SAMe, a pivotal player in methylation. If niacin does decrease SAMe, a likely consequence would be an elevation of plasma homocysteine (McCarty 2000). Note: Concurrent TMG supplementation may represent a cost-effective way to prevent niacin-mediated depletion of SAMe and thus avoid hepatotoxicity (and possibly other adverse niacin side effects). The lack of sufficient detoxification (due to SAMe depletion) appears to explain many of the adverse effects associated with niacin dosing.
- Niacin can also increase blood glucose levels. In nondiabetic patients, 1500 mg a day of Niaspan (an extended-release niacin) increased fasting blood glucose levels 2.5-11% following a 2-hour glucose load. Using 3000 mg a day of immediate-release niacin, fasting blood glucose increased 4.1% and 11.6% following a 2-hour glucose load. The niacin effect in Type II diabetic patients is currently under investigation (Berkeley Heart Lab). However, it is speculated that individuals predisposed to Type II diabetes may have a poorer response to niacin (in regard to glucose management) compared to individuals without a diabetic inclination.
Considering these negatives, large-dose niacin may be too great a price to pay for the benefits. If a decision is made to use high-dose niacin, some practitioners report that an aspirin taken 30 minutes before the dose markedly reduces some of the lesser side effects, for example, the allergic-like symptoms.
Reader's guide to vitamin B3 sources, enhancers, and antagonists.
Good sources of niacin are lean meats, whole grains, brewer's yeast, peanuts, eggs, poultry, fish, and green, leafy vegetables. Milk; some cheeses, for example, cheddar cheese; bananas; and turkey are good sources of tryptophan (a precursor to niacin) (Braly 1985).
Vitamin B3 enhancers (in regard to absorption) are the B-complex (especially vitamins B1, B2, and B6), vitamin C, magnesium, zinc, protein, and essential fatty acids. Antagonists to niacin absorption are alcohol, coffee, excess sugar, antibiotics, and steroids.
Olive Leaf Extract—according to botanist James Duke, the cardiac properties found in olive leaf extract include antioxidants, anti -aggregates, anti-arrhythmics, anti-inflammatories, cyclooxygenase inhibitors, diuretics, hypotensives, vasodilators, antispasmo d tics, antidiabetics, platelet activating factor inhibitors, weight modulators, antiperiodontics, antihyperlipidemics, and plaque fighters
Olive leaf extract (Olea europaea), although historically regarded as a medicinal for fever and malaria, is also valuable in the treatment of cardiovascular disease. Olive leaf extract has been shown in both laboratory and clinical settings to have antidiabetic, hypotensive, and vasodilating properties (Petkov et al. 1972; Gonzalez et al. 1992; Fehri et al. 1994). Researchers documented that an aqueous extract of olive leaves inhibits ACE, the enzyme that converts angiotensin I to angiotensin II (Duke 1992). The vasoconstricting nature of angiotensin II terminates in an increase in blood pressure, a sequence that olive leaf extract disrupts.
According to Dr. Duke, chemicals contained in O. europaea are regarded as calcium antagonists, diuretics, and anti-inflammatories. In addition, olive leaf protects LDL cholesterol against oxidation and inhibits the production of thromboxane A2 and platelet-activating factor (PAF). These functions discourage vasoconstriction and platelet clumping (Duke 1992; Petroni et al. 1995; Mindell 1998).
Chelation therapy, in conjunction with an aggressive supplemental program that relied heavily upon olive leaf extract, has proved remedial among select senior subjects who have suffered multiple heart attacks and arrhythmias. A suggested dosage is one to two 500-mg olive leaf extract capsules, administered 3 times daily with meals.
Pantethine—reduces cholesterol, discourages platelet clumping, and has antioxidant activity
Pantethine, a biologically active, intermediate form of pantothenic acid (vitamin B5) and a precursor to coenzyme A, is a powerful natural pharmaceutical that reduces cholesterol, increases heart muscle contractility, slows the heart rate, and has antioxidant activity.
Pantethine (300 mg 3 times daily) reduced serum triglycerides 32%, total cholesterol 19%, and LDL cholesterol 21%; HDL cholesterol levels increased 23% (Arsenio et al. 1986, Murray 1996b). Pantethine further reduces cardiovascular risk by inhibiting platelet clumping and the production of the inflammation-producing chemical, thromboxane A2 (CVR, http://www.thewayup.com/products/0012.htm). A dosage suggestion is 300 mg 3 times a day.
Policosanol—is a hypocholesterolemic, protects LDL cholesterol against oxidation, inhibits thromboxane and the proliferation of vascular cells, discourages blood clot formation, inhibits platelet aggregation, and increases exercise tolerance
Policosanol, derived from sugar cane, is a new face on the cholesterol scene in the United States but is a popular hypocholesterolemic in other countries (Mas et al. 1999). The main ingredient in sugar cane is octacos anol, a long-chain fatty alcohol found in the waxy film that covers the leaves and fruit of plants.
Policosanol represents an effective alternative to lowering cholesterol for many people. For example, 10 mg a day of policosanol (over a 6- to 12-week period) lowered LDL cholesterol 20%, reduced total cholesterol 15%, and raised the beneficial HDL cholesterol 7-28%. Doubling the dose (20 mg a day) resulted in the following lipid improvements: LDL cholesterol reduced about 28%, total cholesterol about 20%, and HDL increased by 7-10%. Triglycerides were unaffected. During the course of the trial, participants continued on a low cholesterol diet.
The hypolipidemic effects of policosanol are comparable to many cholesterol-lowering drugs (Prat et al. 1999). The results of a head-to-head study classing popular hypocholester olemic drugs against policosanol follow in Figure 6.
Policosanol also outclassed the drugs in regard to increasing levels of the beneficial HDL cholesterol. Yet, a combination of policosanol and gemfibrozil (Lopid) was more hypocholesterolemic than either used singularly. In fact, policosanol even upgraded the efficiency of bezafibrate, a once touted fibrinogen-lowering drug that yielded disappointing results in the Bezafibrate Infarction Prevention Study (Castano et al. 1998; Behar 1999). Bezafibrate in union with policosanol dramatically reduced LDL and total cholesterol. In addition, policosanol appears to replicate another of the objectives of statin drugs, reducing the proliferation of cells. A telltale sign of a diseased vessel is that the smooth lining of the vessel becomes thickened and overgrown with cells.
When comparing the value of a drug to a natural alternative, the safety factors must be considered. Usually, the ramifications of a nutrient, in contrast to a drug, are not side effects but side benefits. For example, the oxidation of LDL cholesterol (a particularly destructive form of cholesterol that creates chronic inflammation) is inhibited by policosanol. As less inflammation and blood vessel destruction occur, fewer foam cells appear (Noa et al. 1996). Conversely, if the oxidation of LDL is not inhibited, metalloproteinase enzymes are aroused, further damaging the vasculature by interfering with the protective nature of HDL cholesterol.
Policosanol combines well with aspirin to inhibit the formation of clots, with each influencing the activity of different platelets (Arruzazabala et al. 1997; Carbajal et al. 1998). The synergistic approach provides more comprehensive protection against platelet aggregation. Another factor in blood clot formation, thromboxane, is repressed after a couple of weeks of policosanol therapy.
Policosanol users can expect an improvement in exercise tolerance. When patients with heart disease were given 10 mg a day of policosanol, exercise capacity and oxygen uptake increased, but ischemia decreased. The improvement in treadmill-ECG tests confirmed that policosanol benefits heart patients, but healthy, physically active individuals also reported increases in exercise tolerance and strength (Stusser et al. 1998). Policosanol not only improved cardiovascular capacity, but also protected against atherosclerotic lesions (thickened fatty streaks in the vasculature).
Policosanol does not appear to interfere with other heart medications. However, it may potentiate the effects of propranolol, a beta-blocker used to treat hypertension. The 10-mg dose has had more than 2 years of clinical testing with no significant ill effects noted, except some patients reported an unexpected weight loss. Blood tests (after about 2 months of policosanol therapy) will allow the individual to adjust the dose commensurate with need. Some individuals will need only 5-10 mg of policosanol to maintain healthy cholesterol levels; others will require 20 mg a day. Note: Policosanol has undergone as many clinical trials as most drugs.
Polyenylphosphatidylcholine (PPC)—is a hypolipidemic, improves exercise tolerance and apoB/apoA-1 ratio, lessens angina attacks, and increases levels of HDL2b
Phosphatidylcholine, the main component of lecithin (a soy product), has a long history as a preventive in arteriosclerosis, cardiovascular disease, and brain derangements. PPC, a newer, polyunsaturated soy derivative, has shown extraordinary promise in managing hypercholesterolemia. It appears that PPC delivers its value by traversing into cholesterol, where direct modulation of the substance occurs. In a study involving 100 participants, PPC lowered total LDL cholesterol by about 15%, reduced triglycerides 32%, and raised HDL levels by about 10% (Klimov et al. 1995; Jordon 2000).
| Comparison of Policosanol to Classic Drug Therapy |
| CHOLESTEROL-LOWERING AGENT || DOSAGE || LIPOPROTEIN EVALUATED || AMOUNT REDUCED |
| Lovastatin (Mevacor) || 20 mg || LDL Cholesterol || 22% |
| Simvastatin (Zocor) || 10 mg || LDL Cholesterol || 15% |
| Policosanol || 10 mg || LDL Cholesterol || 24% |
PPC significantly increased apolipoprotein A-1 and only slightly increased apolipoprotein B, while decreasing postprandial triglycerides, VLDL, and IDL (Klimov et al. 1995; Zeman et al. 1995). A apoB is a cholesterol particle that is believed to promote heart disease by affecting how cholesterol is transported in arteries and other tissues. It is found not only in LDL cholesterol, but also in VLDL and IDL, other potentially bad cholesterols. On the other hand, apoA-1 is a protective, anti -atherogenic particle found in the highly beneficial HDL cholesterol. Researchers concluded that PPC appeared to be an appropriate supplement for patients with decreased concentrations of HDL cholesterol and plasma apoA-1.
The Lancet recently reported the results of a 5 1/2-year trial (the AMORIS, Apoliprotein-Related Mortality Risk Study) evaluating the cardiovascular health of 175,553 men and women. Although all conventional markers were assessed (triglycerides, total cholesterol, and LDL-HDL cholesterol ratio), persons with the greatest absolute risk of dying from a heart attack tended to have the highest ratios of apoB to apoA-1 (Srinivasan et al. 2001; Walldius et al. 2001; GSDL 2001).
Over the course of the study, 864 men and 359 women died from acute myocardial infarctions. When researchers compared their blood results, the apoB : -apoA-1 ratio was the strongest predictor of fatal heart attacks. Men with the highest apoB and lowest apoA-1 levels were nearly 4 times as likely to experience a deadly heart attack compared to those with a favorable apo ratio. (In women the relative risk was threefold greater.) apoB proved to be a stronger predictor of risk than LDL cholesterol in both sexes.
The study also showed that the apo ratio remained a strong marker in all age groups, including those patients over age 70, a group in which total cholesterol levels are not considered to be accurate risk indicators for heart attack. Assessing apoB : -apoA-1 ratio appears to identify high-risk individuals who have normal-to-low LDL cholesterol, as well as those with diabetes and insulin resistance. Recall that PPC's credits include increasing the desirable apoA-1.
PPC has a positive effect upon HDL levels, particularly the most protective of the HDL family, HDL2b. Individuals attaining longevity often display HDL differentials favoring HDL2b, suggesting that this subfraction renders, among other health benefits, greater cardio -protection. Another of the restorative capacities of PPC is its ability to increase exercise tolerance (Klimov et al. 1995).
Alcohol in moderation appears to prevent atherosclerosis. Heavy drinking has the opposite effect, in part by promoting oxidation of LDL cholesterol. Administering PPC at 2.8 grams/1000 kcal to baboons made alcoholic for experimentation lessened the expected ethanol-induced increase in LDL oxidation (Navder et al. 1999).
Russian researchers compare PPC to niacin in the treatment of angina and hyperlipidemia. While nicotinic acid is a reliable hypocholesterolemic, the clusters of annoying symptoms (flushing and itching) and less benign side effects (liver disruption and GI disturbance) discredit megadose usage in some individuals. Conversely, PPC therapy has no contraindications, side effects, or drug interactions. A suggested dosage is two 900-mg capsules daily.
Potassium—reduces blood pressure, maintains fluid balance, encourages parasympathetic nervous system, and increases insulin sensitivity
Potassium, considered by some to be the major electrolyte, is found almost exclusively in the intracellular fluids of the cell. Sodium is found in the extracellular fluid, but it is equilibrium between potassium and sodium that determines fluid balance and blood pressure regulation. A high potassium-low sodium intake reduces the blood vessel constricting effects of adrenaline, a hormone associated with sympathetic nervous system arousal; the result is lower blood pressure.
Adults (37 in number) with diastolic blood pressure less than 110 mmHg participated in a crossover trial of 32 weeks ' duration to determine the hypotensive nature of minerals. Sixty mmol/day of potassium (about 2.5 grams) reduced systolic pressure by an average of 12 mmHg and decreased diastolic pressure 16 mmHg (Patki et al. 1990; Murray 1996). Comment: Results of the DASH study illustrate the necessity for providing adequate amounts of potassium, magnesium, and calcium to control blood pressure. To read more about the study, please turn to the subsection entitled, Does Sodium Restriction Lower Blood Pressure? in this protocol (Bland 2000b).
Hypertensive individuals over 65 years of age may find particular value in potassium, since medications are not always as effective among senior subjects. Administering 2.5 grams a day of potassium for 4 weeks to 18 untreated elderly hypertensive patients resulted in a systolic drop of 12 mmHg and a diastolic reduction of 7 mmHG. All entered the study with systolic blood pressure greater than 160 mmHg and diastolic pressure greater than 95 mmHg (Fotherby 1992; Murray 1996). The results were impressive considering the brevity of the study and the fact that potassium's value is cumulative, meaning a greater response is generally seen with longer supplementation.
Researchers at the Johns Hopkins University School of Medicine advocate increasing potassium to treat and prevent hypertension. A group of seven medical researchers reviewed 33 randomized, controlled trials involving over 2600 participants. The researchers concluded that increased potassium intake is effective in lowering both systolic and diastolic blood pressure (systolic blood pressure dropped an average of 3.11 mmHg and diastolic was reduced 1.97 mmHg) (Whelton et al. 1997).
The hypotensive nature of potassium benefited a group of rats made stroke-prone for experimentation. The rats were divided into two groups. Only 2% of the potassium-supplemented group experienced a fatal stroke, compared to 83% of the untreated group (Alternative Medical News Staff). Cardiologists report using 400 mg of magnesium, 500-1000 mg of calcium, and 500-1000 mg of potassium to treat patients with arrhythmias (Sinatra 1997).
Several factors influence potassium levels. For example, insulin therapy appears to cause a potassium deficiency. Conversely, a diabetic supplementing with potassium may observe increased insulin secretions and responsiveness, reducing insulin requirements. Physical exertion (producing heavy perspiration) or diarrhea and vomiting (resulting in loss of body fluids) can cause a mineral depletion. Always replace minerals, for if not replaced, heart function can quickly depreciate. Symptoms of potassium deficiency are weakness, fatigue, mental confusion, and heart disturbances ( Murray 1996).
While the results of potassium studies are impressive, it must be noted that though self-poisoning is uncommon, the consequences are often fatal (Colledge 1988). Potassium supplementation in the form of oral potassium tablets is generally not needed if you are on a good anti-aging diet that includes several servings of fruits and vegetables per day (The estimated safe and adequate daily dietary intake of potassium, as set by the Committee on Recommended Daily Allowances, is 1.9 grams to 5.6 grams per day.)
Most individuals can tolerate excesses of potassium, but individuals taking digitalis, potassium-sparing diuretics, and ACE inhibitors, or individuals with diagnosed kidney disease, should never supplement unless physician prescribed. This cautionary is valid for anyone considering therapeutic dosages of potassium. Due to the potential side effects of potassium on cardiac function, the FDA limits the amount of potassium permitted in nutritional supplements to 99 mg per serving.
Recall that many foods offer reliable potassium stores; subsequently, eating from foods delineated in the potassium food source section should be especially important to individuals with hypertension and cardiac irregularities. It becomes increasingly difficult, however, to provide adequate levels of potassium if taking a diuretic. Patients are commonly told to replace potassium by consuming potassium-rich foodstuffs. Yet, if every milligram of potassium in a banana were retained, it would require eating an entire stock of bananas every day to offset the potassium lost during diuretic therapy (Cuneo et al. 1985; Alternative Medical News Staff).
Reader's guide to potassium food sources, enhancers, and antagonists: Potassium is abundant in most food selections, e.g., 1 banana has 440 mg, 1 medium orange (263 mg), 1 medium peach (308 mg), cup of apricots (318 mg), avocado (680 mg), cantaloupe (341 mg), cup cooked lima beans (581 mg), 1 medium potato (782 mg), 1 medium raw tomato (444 mg), 1 stalk of celery (130 mg), 3 ounces of light chicken (350 mg), 3 ounces of cod (345 mg), 3 ounces of flounder (498 mg), and 3 ounces of salmon (378 mg). Asparagus, carrots, spinach, apples, plums, strawberries, watermelon, roast beef, pork, haddock, and tuna are other reliable sources.
Potassium enhancers (regarding absorption) are vitamin B6, calcium, magnesium, and essential fatty acids. Antagonists to potassium include excesses of sodium, sugar, stress, alcohol, and coffee, plus steroids, diuretics, and laxatives.
Proanthocyanidins—are antioxidants, ACE inhibitors, and beneficial to smokers; reduce platelet aggregation, protect endothelium against white blood cell adherence, increase exercise tolerance
Many names aptly describe the flavonoids found in pine bark, grape seed, citrus peel, lemon tree bark, peanuts, and cranberries. The scientific community once referred to this entire family as pycnogenols, a term now considered outdated. Today pycnogenols are recognized by terms such as proanthocyanidins, oligomeric proanthocyanidin complexes (OPCs), or procyanidolic oligomers (PCOs). In the United States , Pycnogenol is a registered trademark for Horphag Ltd. of Switzerland , identifying a PCO derived from French maritime pine trees.
Much discussion as to whether pine bark or grape seed extract delivers the most medicinal advantage still leaves the question unresolved. Dr. Michael Murray states that while both are excellent sources of proanthocyanidins, grape seed extracts are available that contain from 92-95% PCO content; pine bark extracts vary from 80-85%. An overwhelming majority of the published clinical and experimental trials over the past 20 years have been performed using the grape seed extract, not the extract of pine bark ( Murray 1995b).
Peter Rohdewald, Ph.D., reported that nitric oxide (NO) became the molecule of the year in 1993 when, among other functions, it was determined that NO was a powerful vasodilator (Rohdewald 1999). NO is produced in the endothelial cells from arginine, a process controlled by the enzyme, endothelial nitric oxide synthase. Scientists became additionally excited when it was determined that PCOs stimulate endo-thelial nitric oxide synthase, producing more NO. This action counteracts the vasoconstricting effects of the stress hormone adrenaline and also diminishes the threat of platelets clumping.
Studies indicate that PCOs may be an alternative to aspirin. Among 180 post -stroke patients receiving 500 mg a day of aspirin for 2 years, 21% were forced to stop medication because of side effects; more than 41% experienced an increase in bleeding time. John D. Folts ( University of Wisconsin ) reported that flavonoids benefited laboratory monkeys, reducing the incidence of platelet aggregation and blocked arteries with efficiency equal to or greater than aspirin. Adrenaline can completely wipe out the positive effects of aspirin, but it has no degrading effect on flavonoids. PCOs offer neither GI toxicity nor an effect on coagulation, suggesting a better risk-benefit ratio compared to aspirin (Folts 1997; Watson 1999; Duke 2000b).
Research cited in The Lancet showed an inverse relationship between flavonoid intake and the risk of heart attack, that is, the more flavonoids ingested, the less the incidence of heart disease (Hertog et al. 1993). PCOs provide some of the most beneficial classes of plant flavonoids available.
Consider the multiple pathways PCOs employ to protect against heart disease:
- Inhibits ACE (the angiotensin-converting enzyme) (Duke 2000b). This means that the production of angiotensin II (a vasoconstricting compound) is blocked and sodium and water retention decreases. These actions decrease blood pressure and improve cardiac output; a decrease in heart size usually follows.
- Protects the endothelium from leukocyte adherence, a process that lessens the threat of occlusion (Cooke et al. 1997; Rohdewald 1999).
- Increases intracellular vitamin C levels, a function that strengthens capillary and blood vessel walls (Schwitters et al. 1993; Murray 1995b).
- Appears to offer about 50 times more antioxidant protection than vitamin C or vitamin E, an action that assists in shielding LDL cholesterol from the cardiac damaging oxidation process ( Murray 1995b).
- Lowers blood cholesterol levels, even shrinking the size of cholesterol deposits appearing in the arteries of laboratory animals (Wegrowski et al. 1984).
- Increases treadmill endurance (improvement confirmed by electrocardiograms and stress tests) and reduces myocardial ischemia and cardiovascular deterioration (Petry et al. 2001).
- Regarded as beta-adrenergic receptor blockers, reducing sympathetic nervous system activity and the "fight or flight syndrome" (Duke Database 1992).
- Reports from the Institute of Pharmaceutical Chemistry ( Germany ) indicate that PCOs lower platelet aggregation in heavy smokers without increasing the risk of bleeding (Rohdewald 1999). Tests confirm that the platelet aggregation index was reduced to levels closely challenging those found in nonsmokers, in part by inhibiting the synthesis of thromboxane, a compound derived from inflammatory prostaglandins , that increases platelet aggregation (Putter et al. 1999).
For most individuals, 100 mg daily of PCO (grape seed-skin extract) appears adequate. Therapeutic doses are 150-300 mg a day.
Note: While proanthocyanidins do not prolong bleeding time when used independently, if used with anticoagulant drugs, caution is advised.
Selenium—prevents ventricular tachycardia, is a hypolipidemic, and improves diabetic symptoms, congestive heart failure, and cardiomyopathy
Cardiomyopathy is defined as any disease that affects the structure and function of the heart. For example, the heart may become disabled as fibrous tissue partially replaces the heart muscle; the fibrous tissue degrades the heart's performance, and the blood no longer moves efficiently. The World Health Organization recognizes cardiomyopathy as a selenium deficiency. In addition, French researchers showed that chronic heart failure (associated with oxidative stress) appears to be relieved by selenium supplementation. Selenium may play a role in the clinical severity of the disease, rather than in the degree of left ventricular dysfunction (de Lorgeril 2001).
Selenium limited the incidence of ventricular tachycardia—that is, at least three consecutive ventricle complexes with the heart rate more than 100 beats a minute—from 91% in the control group to 36% in the selenium-treated group; irreversible ventricular fibrillation was reduced from 45% in the control group to 0% in the selenium group (Tanguy et al. 1998). Luoma et al. (1984) noted that 97 mcg of selenium a day increased the ratio of HDL : -LDL cholesterol, while inhibiting platelet aggregation. It is reported that a 1% increase in HDL reduces the risk of a heart attack or stroke 4%.
Korpela et al. (1989), in a 6-month double-blind trial involving 81 heart attack patients, found that 100 mcg of selenium reduced the number of cardiovascular events to one nonfatal heart attack, while the group not receiving the selenium suffered four fatal heart attacks and two nonfatal heart attacks. Among men free of stroke at the outset, low serum selenium was associated significantly with stroke mortality, an adjusted relative risk of 3.7 (Virtamo et al. 1985).
Selenium brought blood glucose levels, malondiald ehyde (a breakdown product of peroxidized polyunsaturated lipids), and glutathione concentrations to near control levels in almost all diabetic patients. A suggested dosage is 200-300 mcg daily.
Reader's guide to selenium food sources, enhancers, and antagonists
Quantities found in foods are dependent upon the selenium content of the soil, but typically whole grains, wheat germ, broccoli, onions, tomatoes, Brazil nuts, brewer's yeast, garlic, eggs, and seafood are classed as selenium sources.
Selenium enhancers include most antioxidants and essential fatty acids. Antagonists to selenium absorption are heavy metals (mercury and cadmium), excesses of iron, saturated and trans fats, unresolved stress, and indulgences in alcohol and tobacco.
Taurine—has hypotensive and diuretic activity, tempers the sympathetic nervous system, is beneficial in CHF and arrhythmias, and has digitalis-like mentality
Taurine is the most important and abundant of the amino acids in the heart, surpassing the combined quantity of all the others. Under high stress conditions—hypertension and many forms of heart disease—the need for taurine increases to compensate for either an accompanying impairment of taurine metabolism or increased requirements. Dr. H. Kohaski and colleagues ( Japan ) suggest that entry-level taurine may have been low and, as the stress of hypertension progresses, taurine levels drop even lower (Kahashi 1983; Braverman et al.1987).
Taurine has a diuretic action that benefits hypertensive individuals, as well as patients with congestive heart failure. Taurine elicits much of its diuretic action by preserving potassium and magnesium and by promoting sodium excretion (Atkins 1996b).
Taurine also reduces blood pressure by acting as an antagonist to the blood pressure-increasing effect of angiotensin, a circulating protein that is activated by renin, a hormone secreted by the juxtaglomerular cells in the kidneys in response to a drop in blood pressure (Braverman et al. 1987). When both blood and urine taurine levels decrease, renin is activated and angiotensin is formed. As a result blood vessels vasoconstrict, water and salt are retained, and blood pressure increases. Taurine suppresses renin and breaks the renin-angiotensin feedback loop. Dr. Robert Atkins, a complementary physician with a creditable cardiology background, amplifies the positive results of scientific literature, stating that taurine would be his choice were he selecting a single nutrient to treat hypertension.
Dr. Y. Yamori (a Japanese researcher who established an amino acid-stroke association) studied a strain of rats, genetically susceptible to strokes. Yamori found the rats had a much lower incidence of stroke, dropping from 90% to 20%, if their diet was supplemented with methionine, taurine, and lysine (Yamori et al. 1983; Braverman et al. 1987).
Japanese researchers found that 3 grams of taurine, administered daily to patients with congestive heart failure, was more effective than 30 mg of CoQ10 (Azuma et al. 1992). The Japanese, who use taurine widely in the treatment of various forms of heart disease, found that 4 grams of taurine, given for 4 weeks, brought relief to 19 of 24 patients with congestive heart failure. Taurine appears to act much like the drug digitalis, increasing the contractility of cardiac muscle and the force of the pumping action.
Taurine appears to impact cardiac arrhythmias through various pathways. For example, some forms of cardiac irregularities are helped by taurine because it regulates membrane excitability and scavenges free radicals. In addition, taurine protects potassium levels inside heart cells, which, when imbalanced, can cause electrical instability and cardiac arrhythmias (Braverman 1987; Chahine et al. 1998).
Some types of premature ventricular contractions and arrhythmias respond to taurine because the amino acid tends to dampen activity in the sympathetic nervous system (SNS) and the outpouring of epinephrine. As the SNS is quieted, the heart tends to beat less aggressively and the blood pressure is lowered. Lastly, Lebanese researchers showed that the incidence of ventricular fibrillation and ventricular tachycardia were significantly reduced when taurine therapy was utilized (Braverman 1987; Chahine et al. 1998). A suggested dosage is 1500-4000 mg daily.
Testo sterone—modulates cholesterol levels, dilates blood vessels, improves circulation, lessens angina attacks, and reduces blood pressure
Testosterone, a muscle-building hormone, appears to do far more than promote the development of male secondary sexual characteristics. There are, in fact, many testosterone-receptor sites in the heart that play a role in maintaining heart muscle protein synthesis and strength (Bricout et al. 1994).
If testosterone levels are normal, cholesterol is more easily managed, and blood has an easier route as it flows through dilated vessels. One study showed that circulation to the heart improved 68.8% in patients receiving testosterone therapy (Wu et al. 1993). A testosterone delivery patch applied to men with low testosterone levels increased exercise time on a treadmill and (according to trial participants) increased quality of life. Improved emotional health (important to the heart) and a decrease in the incidence of angina attacks reflect some of the benefits of upgrading testosterone levels (English et al. 2000).
Typically, fibrinogen, triglycerides, and insulin levels are higher if testosterone levels are low (Marin 1995; Kryger 2002). In addition, the elasticity of the coronary arteries diminishes, contributing to the development of arteriosclerosis. Blood pressure increases, but the growth hormone decreases, further weakening the heart muscle. Abdominal fat, the most dangerous form of obesity, increases.
Physicians who check for testosterone deficiencies or testosterone-estrogen imbalances have in some cases been able to discontinue cardiac and hypertension medications. Improved EKGs confirm subjective reports of improvement. Since testosterone testing is noninvasive, the risk-benefit ratio swings heavily in favor of testing. For information about safely increasing testosterone levels, refer to the Male Hormone or Female Hormone Modulation protocols.
Thiamine (Vitamin B1)— is beneficial in some forms of cardiac arrhythmias, palpitations, enlarged heart, elevated venous pressure, and congestive heart disease
Cardiac arrhythmia refers to a deviation from the normal pattern of the heartbeat. Arrhythmias can be caused by a variety of underlying medical conditions that should be addressed by a qualified cardiologist. Arrhythmias are not always clinically significant because rather benign events can spur healthy hearts to enter irregular patterns of beating. Yet, arrhythmias should be taken seriously, and a diagnosis made as to the causative factors provoking the disturbed beat. Stress, electrolyte imbalance, ischemia, hypoxia, ventricular enlargement, occlusions, an insulin rush, or derangement in the autonomic nervous system can drive a heart into irregular rhythms.
Since thiamine has proved correctional for some types of arrhythmias, there appears to be linkage between irregular heartbeats and beriberi, a disease caused by a deficiency of or an inability to assimilate thiamine. Cultures that depended upon rice, a high carbohydrate food, as a dietary mainstay found the milling process, that is, the removal of the brown coat rich in thiamine, to be their undoing. Beriberi swept through the population with epidemic force.
Cardiac arrhythmias may manifest among heavy drinkers as thiamine deficiencies occur, and symptoms of beriberi appear. But, heavy imbibers are not the only individuals susceptible to thiamine deficiency. Infirm individuals, as well as those who are elderly and malnourished, are at particular risk. Long-term diuretic usage can also contribute to a thiamine deficiency through urinary loss. It is not uncommon for heart palpitations, deranged heart rhythms, and elevated venous pressure to occur as patients become thiamine deficient (Whiting 1989). Additional cardiovascular manifestations of wet beriberi are myocardial lesions, sodium and water retention, and biventricular myocardial failure. Typically, clinical improvement occurs quickly following vitamin B1 therapy (Blanc et al. 2000).
In 1995, 30 patients with severe heart failure and taking furosemide (Lasix, a diuretic) were enrolled in a heart study. Although furosemide was unsuccessful in improving their cardiac condition, 200 mg of thiamine (a day) dramatically improved heart function (Shimon et al. 1995). Some patients may experience improvement from 200-250 mg a day; other individuals may require 500-1000 mg daily. (A full spectrum vitamin B supplement should always accompany single B vitamin supplementation.)
Reader's guide to vitamin B1 food sources, enhancers, and antagonists.
Lean pork, wheat germ, and whole grains (particularly brown rice) are considered to be excellent sources of thiamine. Meat, poultry, egg yolk, fish, legumes, peas, sunflower seeds, nuts, and brewer's yeast represent other good thiamine choices.
Vitamin B1 enhancers are all others of the B complex, vitamin C, vitamin E, and manganese. Alcohol, coffee, antacids, and excesses of sugar and refined carbohydrates decrease thiamine absorption.
Tocotrienols—are antioxidants, decrease platelet aggregation, and have act like statin mentality drugs
Tocotrienols have been until recently the lesser known half of vitamin E. A major functional difference between tocotrienols and tocopherols appears to be the ability of tocotrienols to more aptly decrease cholesterol synthesis in the liver. Both tocotrienols and tocopherols appear to be potent antioxidants, with some research demonstrating greater antioxidant protection and less oxidative damage when supplementing with tocotrienols (Serbinova et al. 1991).
Cholesterol lowering statin drugs—Lipitor, Lescol, Mevacor, Pravachol, and Zocor—operate at the level of 3-hydroxy-3 methylglutar o yl coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is a rate-limiting enzyme that participates in cholesterol synthesis. The cholesterol cascade occurs as follows: (1) acetyl-CoA is converted to HMG-CoA, (2) HMG-CoA is reduced to mevalonic acid by the enzyme HMG-CoA reductase, and (3) several steps convert mevalonic acid to squalene and then to cholesterol.
Tocotrienols, particularly gamma and delta, accelerate the degradation of HMG-CoA reductase, altering the functionality of the enzyme responsible for cholesterol synthesis (Parker et al. 1993). The statin drugs, though acting at the level of HMG-CoA reductase, approach the enzyme differently. Statin drugs do not degrade the enzyme but competitively inhibit its binding. The inhibition of the binding mechanism leads to a higher production of HMG-CoA reductase, which may explain the side effects, such as liver toxicity, associated with statin usage.
Studies indicate that roughly 75% of hypercholesterolemic individuals respond favorably to tocotrienol supplementation. The most impressive cholesterol reductions occur when tocotrienol supplements are combined with dietary changes (a high fiber/low fat diet). In a 12-week double-blind trial, those who responded to tocotrienol therapy saw a reduction of approximately 23% in total cholesterol and a 32% reduction in LDL cholesterol using dietary modification plus tocotrienol supplements. Tocotrienols alone yielded a 16% decrease in total cholesterol and a 21% decrease in LDL cholesterol (Quereshi et al. 1993; ACCM 1998). HDL levels do not appear to respond to tocotrienol supplementation, but apo-B, a protein component found in LDL, VLDL, and IDL cholesterol, is lowered. Thromboxanes are also considered toco-trienol responsive (Qureshi et al. 1997).
The Kenneth Jordan Heart Research Foundation ( New Jersey ) reported the results of 50 patients with narrowing of the carotid artery who that were treated with either a placebo or tocotrienols: 25 patients (some with carotid stenosis greater than 49%) received 650 mg of tocotrienols plus tocopherols; a control group of 25 patients, with comparable closure, received a placebo. Each group was evaluated every 6 months for the first year and every year thereafter with ultrasonography. In the placebo group, 15 patients showed worsening of the stenosis, eight remained stable, and two showed some level of improvement. In the tocotrienol plus tocopherol group, three patients showed minor worsening, 12 remained stable, but 10 patients showed regression of stenosis. Participants experienced a simultaneous drop in triglycerides and LDL cholesterol (Papas undated; Tomeo et al. 1995; Watkins et al.1998).
The late Karl Folkers, a pioneer in CoQ10 research, observed that drugs inhibiting HMG-CoA reductase activity cause a simultaneous decrease in CoQ10 levels (Folkers et al. 1990). The reason for this is that the HMG-CoA enzyme also plays a role in CoQ10 synthesis. Individuals using either statin drugs or tocotrienols may wish to increase their intake of CoQ10; a decrease in CoQ10 could negate any benefit garnered from a hypocholesterolemic drug.
According to Andreas M. Papas, Ph.D., appropriate tocotrienol dosages are as follows: 100 IU of mixed tocopherols and 100 IU of tocotrienols if young and healthy and without a family history of heart disease; 200 IU of mixed tocopherols and 200 IU of toco-trienols for young adults with some cardiac risk factors or healthy people up to 50 years of age without risk factors; 400 IU of mixed tocopherols and 400 IU of tocotrienols for people who have a personal or family history of chronic heart disease. The latter dosage includes senior subjects and those under severe stress and eating a poor diet.
Vitamin A and Beta-Carotene—lower fibrinogen levels and heart disease risks and increase insulin sensitivity
Dexter Morris, M.D. ( University of North Carolina ), says that phytochemicals keep your heart healthy. "The 60-80 age group has a much greater risk of heart disease than younger people do. If your diet is rich in fruits and vegetables, you can reduce risk," according to Morris. In a study begun in 1973, researchers kept track of 1883 men ages 35-59 who that had high cholesterol levels. Over the next 20 years, the men who had the highest levels of carotenoids in their blood had 60% fewer heart attacks and deaths (Morris 2001).
Dr. J.E. Manson of the Women's Hospital in Boston reported that those taking 25,000 IU of beta-carotene daily had 22% fewer heart problems and strokes than those taking less than 10,000 IU daily (Friend 1991; Passwater undated). Dr. Monika Eichholzer (scientist at the University of Bern, Switzerland) reported similar findings after tracking 2974 people for 12 years. The relative risk of ischemic heart disease was increased (1.53%) among those lowest in plasma carotene concentrations (Eichholzer et al. 1992).
High vitamin A and beta-carotene serum levels have been reported to reduce fibrinogen levels in humans and animals (Green 1997). Animals fed a vitamin A-deficient diet have an impaired ability to break down fibrinogen, but when injected with vitamin A, they produce tissue plasminogen activators that break down fibrinogen, reducing the risk of clot formation.
Vitamin A is beneficial to individuals with Syndrome X and diabetes. A study involving 52 patients indicated that vitamin A enhanced insulin-mediated glucose disposal (Facchini et al. 1996a). Since beta-carotene must be converted in the body to vitamin A, an adaptation some individuals lack, diabetics may do better using vitamin A rather than beta-carotene.
It should be noted that the protection of beta-carotene is not absolute. In fact, if the individual is consuming greater amounts of alcohol, beta-carotene may actually increase the risk of intracerebral hemorrhage (Leppala et al. 2000). A blend of phytoextracts (alpha-carotene, beta-carotene, lutein, and lycopene) appears to offer more comprehensive cardiac protection than using beta-carotene alone.
For example, individuals participating in the Toulouse study who had higher blood levels of lutein also had a lower incidence of coronary artery disease (Howard et al. 1996). The Los Angeles Atherosclerosis study uncovered a relationship between thickenings in the carotid arteries (an indicator of systemic atherosclerosis) and blood levels of lutein (Dwyer et al. 2001). Participants with the highest blood levels of lutein showed virtually no artery wall thickening, while those with the lowest lutein levels showed increased arterial thickness. In addition, lutein reduces the oxidation of LDL cholesterol, a declaration the Life Extension Foundation first made to members in 1985.
A current Finnish study evaluated 725 middle-aged men free of coronary heart disease and stroke at the study baseline. Men in the lowest quartile of serum levels of lycopene had a 3.3-fold risk of an acute coronary event or stroke compared with other trial participants with higher lycopene levels. In a second study, the same researchers assessed the association between plasma concentrations of lycopene and intima-media thickness (IMT) of the common carotid artery wall in 520 asymptomatic men and women. After adjusting for common cardiovascular risk factors, low plasma levels of lycopene were associated with an 18% increase in IMT in men as compared with men in whom plasma levels were higher than median. In women, the difference did not remain significant after the adjustments (Rissenen et al. 2002).
German researchers reported that plasma levels of alpha-carotene may represent a marker of atherosclerosis in humans. Measuring alpha-carotene levels (among other antioxidants) may be of clinical importance as a practical approach to assess atherogenesis and/or its risk (Kontush et al. 1996).
Some individuals are susceptible to vitamin A toxicity even when the dosage is low. This occurs because of a challenged liver and fewer detoxification mechanisms. Beta-carotene, on the other hand, is generally regarded as nontoxic (to read more about vitamin A toxicity, consult Appendix A). Appropriate dosages for most individuals are 5000 IU of beta-carotene and/or 10,000 IU of vitamin A daily. Several supplements are available that provide the carotenoids alpha-carotene, beta-carotene, lutein, and lycopene.
Reader's guide to vitamin A food sources, enhancers, and agonists.
The richest sources of vitamin A are foods of animal origin, i.e., liver, fish liver oil, milk and milk products, butter, and eggs. Yellow fruits and green and yellow vegetables will also help meet vitamin A requirements.
Enhancers to vitamin A absorption are vitamin C, calcium, magnesium, vitamin E, B complex, choline, and essential fatty acids. Vitamin A antagonists are laxatives and some cholesterol-lowering drugs (Questran). Coffee, alcohol, excess iron supplementation, sugar, tobacco, and mineral oil can also interfere with vitamin A absorption. Food sources of lutein are kale, Brussels sprouts, corn, collards, spinach, and egg yolks. Egg yolks have tiny amounts of lutein—about 0.2 mg a per yolk—because chickens eat corn (Carper 2002). Lycopene is present in tomatoes and several other red fruits.
Vitamin C—lessens risk of stroke and heart attack; strengthens blood vessels; reduces blood pressure, fibrinogen levels, Lp(a), inflammation, and C-reactive protein (CRP); promotes gingival healing; is a reliable antioxidant and diuretic; and is highly beneficial to smokers and those exposed to secondhand smoke
Linus Pauling, a Nobel Prize winner, showed that the body often forms atherosclerotic plaque to repair a wound inflicted upon an artery. When adequate amounts of vitamin C are available, an injured artery is repaired without involving atheromatous materials. In the absence of adequate levels of vitamin C, Lp(a), acting as a surrogate for vitamin C, must participate in the repair. Lp(a) does what it must, but the health of the artery is compromised as plaque is added to the vessel. If ascorbate levels had been adequate, Lp(a) would not have been necessary; without adequate vitamin C, the need for Lp(a) is enormous.
Vitamin C Lowers Lp(a)
Kathie M. Dalessandri, M.S., M.D., was inspired by a report appearing in the Archives of Internal Medicine relating to the ability of vitamin C to lower Lp(a). Dr. Dalessandri, a general surgeon in Point Reyes Station, CA, was displeased with her own Lp(a) levels. She was well aware of the dangers associated with Lp(a), particularly when linked with other risk factors as a family history of heart disease. Dr. Dalessandri (53 years old at the time) was taking hormone replacement therapy and niacin, but the niacin became problematic and had to be discontinued. After reviewing the literature, she decided upon 3 grams a day of both ascorbic acid and L-lysine monohydrochloride as a natural regime against the elevated Lp(a). Dr. Dalessandri reports that her Lp(a) dropped 14 mg/dL, a reduction of 48% after 6 months. She was also pleased that she was able to take vitamin C and lysine without side effects (Dalessandri 2001).
Matthias Rath, M.D., in Eradicating Heart Disease, says that animals do not have heart attacks and strokes because their bodies manufacture vitamin C, a genetic adaptation humans lack. Most mammals produce impressive amounts of vitamin C, the human equivalency of 2000-13,000 mg daily. Under periods of stress the same animal's needs for vitamin C may skyrocket, but the body complies by producing prodigious amounts. Man cannot adapt to stress with the same efficiency as lower animals because of a lack of L-gulonolactone oxidase, an enzyme needed to produce vitamin C from glucose. Dr. Rath states that because of this genetic flaw and inadequate dietary vitamin C, cardiovascular disease can emerge as a form of early scurvy (Rath 1993).
An ascorbic acid deficit contributes to the development of vascular lesions (wounds or injuries) by altering collagen metabolism (Rath 1993). Vitamin C produces many collagen molecules, supporting a strong and elastic blood vessel wall. Over time, arterial collagen must be replenished. If vitamin C is not present in large enough quantities, collagen is not produced, and blood vessels become thin and weak.
Vitamin C levels are lower in patients who have had heart attacks, both fatal and nonfatal events. Randomly selected Finnish men (1605 individuals who were 42-60 years old) entered a study evidencing no signs of preexisting heart disease. Among men with a vitamin C deficiency, 13.2% had a heart attack compared to 3.8% who were not vitamin C deficient. After adjusting for other confounding factors, men who were deficient in vitamin C had 3.5 times more heart attacks than men who were not vitamin C deficient (Nyyssonen et al. 1997).
The most significant report emanated from UCLA, where it was announced that men who took 300-400 mg of vitamin C a day lived 6 years longer than those who received less than 50 mg daily. The study (which evaluated 11,348 participants over a 10-year period) showed that long-term, high vitamin C intake extended average lifespan and reduced mortality from cardiovascular disease 45% (Enstrom et al. 1992; Hansen 2000).
Researchers from the Boston University School of Medicine reported that vitamin C appears effective in lowering mild cases of hypertension. The patients lowered systolic and diastolic blood pressure by about 9% with a daily dose of 500 mg of ascorbic acid (Stauth 2001). The value of vitamin C as a hypotensive nutrient may come by way of its antioxidant activity, possibly by protecting the body's supply of NO, a vasodilator. (Free radicals appear to lower NO levels.) Depriving test animals of antioxidants, such as vitamin C, glutathione, and vitamin E, resulted in oxidative stress and higher blood pressure.
The heart is one of the most vulnerable of all organs to free-radical oxidative stress. Vitamin C can respond to this risk by exerting its antioxidant properties, acting independently, or by prompting the production of other antioxidants. For example, 3 grams of vitamin C increased white blood cell glutathione levels fourfold and plasma glutathione levels eightfold (Jain et al. 1994; Murray 1996b).
Vitamin C is beneficial in reducing fibrinogen levels. In a report published in the journal Atherosclerosis, heart disease patients were given either 1000 or 2000 mg a day of vitamin C to assess its effect on the breakdown of fibrinogen. At 1000 mg a day, there was no significant change in fibrinolytic activity. At 2000 mg of vitamin C a day, fibrinolytic activity increased 62.5% (Bordia 1980).
Inflammation, a newer risk factor for heart disease, is reduced by vitamin C. Each winter (in most countries) there is a 15-30% increase in deaths from cardiovascular and respiratory disease. Researchers in the United Kingdom followed 96 men and women for 1 year to assess the impact of winter stress upon the heart and circulatory system. It appears some of the increase in winter cardiovascular mortality may be related not only to a rise in fibrinogen, but also to an increase in other inflammatory markers, such as C-reactive protein. This cycle may be spurred as winter infections increase and vitamin C intake (because of less availability of fruits and vegetables) decreases. The conclusion of the study was that vitamin C might be able to influence cardiovascular risk and the resulting thrombotic tendency by modulating the inflammatory response to infection (Woodhouse et al. 1997).
Vitamin C appears to lessen the negative effects of many other risk factors, including stress, diseased gums, unhealthy diet, and smoking. Smoking severely depletes the body of vitamin C; vitamin C, on the other hand, destroys free radicals produced in smoke and protects against endothelial dysfunction. Even secondhand smoke breaks down blood antioxidant defenses and accelerates lipid peroxidation, which leads to an accumulation of LDL cholesterol (Tribble et al. 1993). Vitamin C should be a part of an individual's nutritional fortress against the ravages of both firsthand and passive smoke.
A dosage suggestion is 6 grams daily in divided dosages. (A loose stool may result from higher doses of vitamin C. Should this occur simply reduce the dose to a level that is not problematic to the bowel.) Under periods of stress, a great deal more vitamin C can be taken without bowel derangement.
Reader's guide to vitamin C food sources, enhancers, and antagonists.
Vegetables and fresh, uncooked fruits (especially citrus) are vitamin C-rich sources. Raw foods represent excellent choices, having escaped the rigors of processing and preparation.
All vitamins and minerals work synergistically to enhance vitamin C absorption, particularly the bioflavonoids. Alcohol, coffee, sulfa drugs, antibiotics, analgesics, antidepressants, anticoagulants, oral contraceptives, and steroids can drain vitamin C from the body. Smoking seriously depletes vitamin C levels.
Vitamin D—reduces heart disease risk in women
It was reported at the 42nd annual conference on Cardiovascular Disease and Epidemiology Prevention (in Honolulu , HI , on April 23, 2002 ) that women who take vitamin D supplements lowered their risk of death from heart disease by one-third. The finding was an unexpected dividend extracted from an osteoporosis trial to determine the incidence of bone fracture in nearly 10,000 older women. From the trial participants, 4200 women reported taking vitamin D supplements at the onset of the study; another 733 reported a prior history of supplementation. After tracking the women for an average of nearly 11 years, researchers found that the risk of heart disease death was 31% lower in those taking vitamin D at the time of the study (Mercola 2002b).
Recent studies indicate that moderate or severe hypovitaminosis D was present in 66% of patients taking daily vitamin D in amounts less than the recommended dosage for their age; 37% of the patients taking daily vitamin D in excess of the recommended amount for their age were nonetheless still deficient. Thus, experts recommend at least 400 IU of vitamin D a day; if the individual is elderly and not participating in outdoor activities (and sunlight exposure), 800 IU a day is recommended (Thomas et al. 2000).
Vitamin E—prevents plaque formation, protects LDL from oxidation, strengthens blood vessels, reduces blood viscosity and platelet aggregation, is helpful in atrial and ventricular fibrillation, is an antioxidant and antidiabetic nutrient, improves insulin sensitivity, is protective to smokers, reduces C-reactive protein, has diuretic activity, and is beneficial to those with hemochromatosis
Dr. Richard Passwater commented in June 2001 that good research is timeless. The following is an example of an excellent study that should not be lost in the archives. In 1974, Dr. Passwater enrolled 17,894 persons (ages 50-98) in a study to determine the effects of long-term vitamin E supplementation. He found the length of time the individual used vitamin E was more important than the amount of the nutrient used. The trend was especially apparent beyond 9 years of usage. Taking 400 IU of vitamin E daily for 10 years or more strikingly reduced the occurrence of heart disease prior to 80 years of age (Passwater 1977).
An ongoing study involving 87,245 nurses (ages 34-59) and 39,910 male health professionals (ages 40-75) showed a significant relationship between the use of vitamin E supplements and a reduced risk of heart disease (Rimm et al.1993; Stampfer et al. 1993). A study reported in The Lancet may have eclipsed all others, showing that 2002 individuals with documented heart disease (supplemented with 400-800 IU of vitamin E daily) reduced their risk of nonfatal heart attacks 77% (Stephens 1996; Challem 2001).
These dramatic results occur in part because vitamin E prevents white blood cells from adhering to arterial walls. Researchers from the University of Texas Southwestern Medical Center explain that when monocytes are suppressed from bonding to the artery, a primary step in arterial closure has been averted (Devaraj et al. 2000a).
According to researchers at Georgetown University Medical School , vitamin E also renders the blood less sticky and platelets less prone to clump. In animal models of endothelial dysfunction, vitamin E improved the activity of endothelium-derived nitric oxide; this effect was not dependent upon the antioxidant protection of LDL cholesterol. Instead, it appears vitamin E inhibits platelet aggregation through a mechanism that involves protein kinase C inhibition, not its antioxidant activity as previously suspected (Freedman et al. 2001).
French scientists found that alpha-tocopherol supplementation prevented lethal ventricular arrhythmias associated with ischemia and reperfusion. In addition, animals with coronary arteries occluded for experimentation experienced a significant decrease in the ventricular fibrillation threshold; animals similarly occluded, but vitamin E supplemented, realized no decrease in the threshold (Dzhaparidze et al. 1986; Fuenmayor et al. 1989; Sebbag et al. 1994). Comment: Ventricular tachycardia represents at least three consecutive ventricular complexes with a heart rate of more than 100 beats a minute. Ventricular fibrillation is a cardiac arrhythmia marked by rapid, disorganized depolarizations of the ventricular myocardium. Blood pressure falls to zero, resulting in unconsciousness; without defibrillation and resuscitation, death can promptly ensue.
According to Ron Kennedy, M.D., atrial fibrillation is a condition in which the regular pumping function of the atria is replaced by a disorganized, ineffective quivering caused by the chaotic conduction of electrical signals through the upper chambers of the heart. The patient has various corrective options, including anti -arrhythmic drugs, anticoagulants, radio-frequency ablation, a pacemaker, and, according to Dr. Kennedy, high-dose (2000 IU a day) vitamin E. Recall that vitamin E reduces blood viscosity and platelet aggregation. If the patient is receiving anticoagulant therapy and wishes to add vitamin E, close monitoring by a physician is essential to avoid compromising the clotting mechanism (Kennedy 1999).
Researchers from the University of Naples reported encouraging data regarding pharmacological doses (about 900 mg a day) of vitamin E administered to elderly patients with coronary heart disease and insulin resistance. Lower fasting and 2-hour blood glucose levels, reduced plasma insulin and triglyceride concentrations, and an improved HDL : -LDL ratio indicate vitamin E is useful in stabilizing insulin-resistant patients with coronary heart disease (Paolisso et al. 1995).
According to Dr s. Ishwarlal Jialal and Dr. Sridevi Deveraj (University of Texas Southwestern Medical Center at Dallas ), diabetics have increased inflammation and are more prone to cardiovascular disease (Deveraj et al. 2000). It appears that V vitamin E, by decreasing inflammation, may contribute to a reduction in cardiovascular disease in both diabetic and nondiabetic subjects. Vitamin E lowered levels of IL-6 50% ; and 1200 IU of vitamin E reduced C-reactive protein (CRP) 30% (Devaraj et al. 2000b; O'Brien 2001). CRP levels remained constant 2 months postsupplementation. For an in-depth review of CRP, consult the CRP subsection under the sections Newer Risk Factors and The Link Between Infections and Inflammation in Heart Disease, in this protocol.
Vitamin E appears to be decreased in patients with hereditary hemochromatosis or iron overload. Iron loading, in experimental studies, significantly decreases hepatic and plasma vitamin E, a shortage amenable with supplementation. Free-radical index markers increase three- to fivefold in an iron-loaded liver, but supplementation with vitamin E has been shown to reduce levels by about 50% (Brown et al. 1996).
Free radicals activate a gene that encourages overgrowth of smooth muscles in the blood vessel walls, a process that can contribute to closure (Gonzalez-Flecha 2002). Vitamin E, a reliable antioxidant, has the opposite effect, that is, it turns off the gene responsible for smooth muscle proliferation. Vitamin E's antioxidant powers extend to protect the cells and organs (particularly the lungs) from damage caused by smoking.
Vitamin E has (for decades) been credited (for decades) with diuretic activity, stimulating urine excretion ( Davis 1965). This action is of a significant advantage to patients with edematous tissues and elevated blood pressure.
The type and blend of vitamin E used affects the end results. Studies have shown that alpha-tocopherol may not protect as aggressively against coronary heart disease unless it is combined with the gamma-tocopherol form. Both alpha-tocopherol and gamma-tocopherol can decrease platelet aggregation, inhibit blood clot formation, protect LDL cholesterol against oxidation, and increase endogenous SOD production (an enzyme with antioxidant activity); gamma-tocopherol, however, shows greater activity on each function.
Unfortunately, gamma-tocopherol has a couple of factors working against its utilization. For example, gamma-tocopherol can be obtained from foodstuffs, but it is poorly retained, and much of it is excreted in urine after being metabolized by the liver. Furthermore, a protein, referred to as alpha-tocopherol transfer protein, identifies and selectively chooses alpha-tocopherol over other forms of vitamin E. As a result, alpha-tocopherol is found more abundantly in lipids, blood, and body tissues. This scenario does not allow for maximum protection against free-radical attack.
It is strongly recommended that individuals relying upon the cardio -protective effects of vitamin E include (as part of their intake) the gamma-tocopherol form, but the complexing process determines the benefit. A union of alpha-tocopherol (80%) with gamma-tocopherol (20%) appears ideal; too much alpha-tocopherol may oppose the antioxidant qualities of gamma-tocopherol.
In addition, the hypolipidemic value of toco-trienols, the lesser known half of vitamin E, should not be overlooked. The most dramatic cholesterol reduction is seen when tocotrienol supplements are combined with dietary changes (a high-fiber, low-fat diet). In a 12-week, double-blind trial, those who responded to tocotrienol therapy saw a reduction of approximately 23% in total cholesterol and 32% in LDL cholesterol using dietary modification plus toco-trienol supplements. Tocotrienols alone yielded a 16% decrease in total cholesterol and a 21% decrease in LDL cholesterol (Quereshi et al. 1993; ACCM 1998). apo-B, a protein component found in LDL, VLDL, and IDL cholesterol also appears to be tocotrienol responsive (Qureshi et al. 1997).
Tocotrienols degrade the enzyme 3-hydroxy-3-methylgulutaryl coenzyme A reductase, a the rate-limiting enzyme that participates in cholesterol synthesis. Researchers credited this function as being the mechanism delivering tocotrienol's hypolipidemic edge (Qureshi et al. 2001). A team of researchers from Switzerland reported greater hypolipidemic value when using gamma-tocotrienol rather than a mixture of tocotrienols (Raederstorff et al. 2002). To read more about tocotrienols and dosing recommendations, please consult the Tocotrienols subsection appearing earlier in this section.
A suggested dosage of vitamin E is 400-1200 IU a day. Comment: Initially, blood pressure rose in approximately one-third of hypertensive individuals treated with vitamin E (Shute 1976). Therefore, individuals who are hypertensive should use 100 IU a day for 1 month and add 100 IU each month until 400 IU a day is reached (Balch et al. 1997). Because of the reductions in blood glucose levels, diabetic individuals wishing to use vitamin E should begin with low dosages. Gradually increase the dosage, allowing for appropriate insulin or drug adjustments. Lastly, Pracon, Inc., a hospital outcomes analysis firm in Reston , VA , estimated that healthcare expenses could be reduced $7.7 billion annually if the public regularly took vitamin E supplements.
Reader's guide to vitamin E food sources, enhancers, and antagonists.
Vitamin E is found in wheat germ, whole grains (brown rice, cornmeal, oatmeal, and wheat), vegetable oils (soybean, corn, and cottonseed), egg yolk, butter, milk fat, meat (especially liver), dark green leafy vegetables, legumes, nuts, and seeds.
Vitamin E enhancers are vitamin A, B complex vitamins, vitamin C, magnesium, manganese, selenium, inositol, and essential fatty acids. For optimal vitamin E absorption, excessive fat intake should be avoided, as well as birth control pills and the chronic use of mineral oil.
Vitamin K—modulates calcium levels; reduces inflammation, C-reactive protein (CRP), IL-6, the risk of thrombosis, and the progression to valvular stenosis; and has a role in glucose management
As important as calcium is as a hypotensive and antiarrhythmic mineral, it has a detrimental side if it seeps into arteries. Arterial calcification, common to the aging process, is a risk factor leading to the development of heart disease, atherosclerosis, and mitral and aortic valve stenosis. Researchers recently reported the results of a comprehensive study evaluating 2213 individuals over a 10.4-year period in regard to coronary calcium levels. Those with a calcium score in the fourth quartile were 3.7 times more likely to die over the 10 years than were individuals in the first quartile (Buenano et al. 2000).
Harvard Medical School announced that about 25% of adults over 65 years of age have arterial calcification, increasing their risk of severe heart disease 50% (Harvard Heart Letter 1999). However, the Framingham Heart Study determined that the risks imposed by thoracic aortic calcification are not restricted to senior subjects; 35-year-old men with aortic calcification had 7 times the risk of dying of a sudden heart attack (Witteman et al. 1990).
The cumulative results of 8 years of research determined that women with severe kyphosis (increased convexity in the curvature of the thoracic spine) increased their risk of pulmonary death (likely a blood clot) by 2.6 times. Compared with women who were fracture-free, those with one or more vertebral fractures had a 1.23 times greater mortality rate. Mortality increased as the number of fractures increased (Kado et al. 1999).
It was also noted that women with atherosclerotic calcification had 7% less bone mass. Dutch researchers connected the dots and determined that postmenopausal women with calcification in bone tissue and atherosclerotic vessels had diminished vitamin K levels. It was concluded that vitamin K status affects the mineralization process in both bone and atherosclerotic plaque (Jie et al. 1996).
Vitamin K, an underutilized fat-soluble vitamin, overcomes the pathological effects of a calcium imbalance by promoting the deposition of calcium in its primary site (bone) and out of arterial walls.
Note: Because of the number of individuals using anticoagulants, it is important to note that warfarin (Coumadin) caused extensive arterial calcification in laboratory animals (Howe et al. 2000). Humans on long-term warfarin therapy may be at an increased risk for developing arterial calcification due to a drug-induced vitamin K deficiency.
So interrelated is bone loss to cardiovascular disease that measuring bone density has become a predictive factor for cardiovascular health. If bone density deviates one standard from the norm, the risk of stroke increases 3 times (Mitchell 2000). Vitamin K thus emerges as a star player in cardiovascular health, keeping calcium in bones and out of arteries and valves. Note: Be aware that the risks imposed by low bone density have no gender preference. Low bone density is a strong and independent predictor of all-cause and cardiovascular mortality in both men and women (Trivedi et al. 2001).
A group of animals with induced atherosclerosis were given vitamin K (100 mg/kg of body weight), vitamin E (40mg/kg), or a placebo to assess reversal of the atherosclerotic process. At the conclusion of the study, the control group showed aortic calcium of 17.5 microns/mg; those receiving vitamin K had approximately 1 micron/mg of calcium, and vitamin E reduced it even further (Seyama et al. 1999) (for more information relating to valvular calcification, consult the section devoted to Valvular Disease in this protocol).
With age, the levels of IL-6 increase. This creates an imbalance between anti-inflammatory and pro-inflammatory cytokines (Ferrucci et al. 1999). Disproportionate numbers of good and bad cytokines increase inflammation, as well as bone degradation.
IL-6 is germane to this untoward sequence, promoting not only the inflammatory process, but also bone resorption, that is, the loss of substance from the skeletal system (Paule 2001). Vitamin K reduces the levels of IL-6; subsequently, the assault targeted at bone, as well as inflammation (a risk factor for both cardiovascular disease and cancer) is reduced (Reddi et al. 1995). Since C-reactive protein (CRP) is synthesized in response to IL-6, it appears vitamin K may be valuable in reducing elevations in CRP, as well.
Japanese researchers also found that a vitamin K deficiency can mimic the symptoms of diabetes. (The pancreas, which produces insulin, has the second highest levels of vitamin K in the body.) Low levels of vitamin K appear to induce a tendency toward a poor early insulin response and late hyperinsulinemia, following a glucose load in laboratory animals (Sakamoto et al. 1999). Lastly, vitamin K's antioxidant powers are rated (by some) as superior to either vitamin E or coenzyme Q10, other highly respected free-radical fighters (Mukai et al. 1993).
Typically, vitamin K would not be indicated if a patient is on anticoagulant therapy. However, The Lancet reported that asymptomatic patients on warfarin should consider low-dose vitamin K if blood-clotting time, as measured by the international normalized ratio (INR), is 4.5-10.0 (Crowther et al. 2000). Follow-up studies to determine the success of vitamin K therapy (1 mg a per day) showed that 4% of the patients who received vitamin K therapy had bleeding episodes, compared with 17% of those in the placebo group. The conclusion of the study was that low-dose vitamin K, an inexpensive intervention without known toxicity, might prevent a hemorrhage in patients on warfarin therapy.
A suggested vitamin K dosage for patients not on anticoagulant therapy is 10 mg a per day.
Reader's guide to vitamin K food sources and antagonists
Friendly bacteria in the intestines synthesize the majority of vitamin K. However, persistent low-grade levels of intestinal bacteria in the small intestine could hamper vitamin K synthesis. Acidophilus cultures in the form of yogurt or kefir serve not only as a good food source, but also ensure that sufficient friendly intestinal flora are present for vitamin K production.
Green leafy vegetables are vitamin K-rich; other sources include alfalfa, egg yolks, blackstrap molasses, asparagus, Brussels sprouts, cauliflower, oatmeal, and rye. Antibiotics increase the need for vitamin K, and vitamin E (doses greater than 600 IU) antagonizes vitamin K activity.
The calcium paradox
It is important to look at the ways calcium can become an atheromatous material. Most body stores of calcium are found in the bones and teeth, and 1% is found in the bloodstream. This 1% performs so many vital functions, including cardiac health, that the body vigorously defends this minute percentage. If inadequate calcium is available, vitamin D is mobilized in the kidney and rushes to the intestinal wall to pull more calcium into the bloodstream. If inadequate amounts of vitamin D are available, the parathyroid gland delivers a message to bones to release calcium. Because the calcium mass in the bone is so great, it is easy for too much of the mineral to be extracted, overwhelming the amount needed in the blood. After compensating for deficiencies, the excess calcium ties up binds in soft tissues, the lining of arteries, and brain tissue.
Poor calcium regulation also affects arterial plaque, causing it to become harder but more brittle (Harvard Heart Letter 1999). This occurs as calcium deposits in the blood attach to cholesterol deposits on the walls of arteries, making an almost impenetrable union (Shappell 2000). This process further narrows the artery, causing symptoms ranging from fainting spells to sudden death due to abrupt changes in blood pressure (Doss 2001).
It is important to grasp that excesses of calcium (potentiating arterial disease) come essentially from the bone. Furthermore, the results of a test indicating adequate blood calcium levels can be totally misleading, for the supply may have been extracted from the skeletal system. Because secondary pathways, important in maintaining homeostasis, are not well - regulated, it is imperative to maintain adequate calcium levels without summoning the parathyroid gland into service.
Zinc—is important in weight and blood pressure management, regulates glucose and insulin levels, and increases testosterone
Zinc, the second most abundant trace mineral in the body, is important in glucose and insulin management, as well as weight control. Individuals with the lowest dietary intake of zinc showed the greatest prevalence of coronary artery disease, diabetes, and obesity; conversely, as patients made corrections to include more zinc in their dietary program, blood pressure, blood glucose, triglycerides, and central abdominal obesity decreased (Challem et al. 2000).
Zinc is a vital component of insulin, but its worth extends to the cellular receptors, where zinc increases insulin sensitivity. When zinc levels are too low, the pancreas cannot supply enough insulin to control blood glucose levels, and the amount that is produced is less functional (Challem 2000).
However, the emphasis is upon correcting a zinc deficiency, not dosing at will. The journal Diabetes reported that administering large doses of zinc sulfate (220 mg 3 times a day, 90 mg of actual zinc) increased fasting blood glucose levels in Type II diabetic patients from an average of 177 mg/dL to -207 mg/dL (Raz et al. 1989). Glycosylated hemoglobin levels also increased among a group of Type I diabetics receiving 50 mg of zinc a day (Cunningham et al. 1994). Considering these poor statistics, if prediabetic or diabetic, use no more than 35 mg of zinc a day without close blood glucose monitoring.
Zinc assists in controlling weight through various mechanisms. According to Jack Challem (the nutrition reporter), zinc is a copper antagonist (meaning it competes with copper for intestinal absorption). Challem states that this is significant because in test tube and animal experiments, excess copper increases fat (or triglyceride) synthesis from sugar. Zinc supplementation lowers copper levels, so it may decrease the synthesis of triglycerides, which show up as either triglycerides in the bloodstream or fat on the body (Challem 2000).
Lower androgen levels have an adverse effect on lipid metabolism, coagulative function, and insulin sensitivity. For the cardiovascular patient with low testosterone levels, a healthier heart profile may emerge with either testosterone therapy or supplementation to increase androgen levels (Xu et al. 2001). The benefits of zinc as an androgen potentiator were exemplified when 22 men with chronically low testosterone levels were given 50 mg of zinc sulfate daily for 45-50 days to promote fertility. (The 22 had experienced infertility longer than 5 years.) All 22 experienced a significant increase in testosterone levels during zinc therapy. In fact, nine of the 22 wives became pregnant during the study (Netter et al. 1981).
It appears that zinc therapy, although beneficial to most, is not risk-free. Occasionally, emphasizing zinc without copper can lead to copper-deficiency anemia, lower levels of HDL, and higher levels of LDL cholesterol; for some, the lack of balance between the two trace minerals can result in an irregular heartbeat (Klevay 1975). Copper is not risk-free either: it can potentiate free-radical activity.
Epidemiologic and metabolic data are convincing concerning the theory that a zinc-copper imbalance is a major factor in the etiology of coronary heart disease. For this reason, if consuming over 50 mg of zinc daily, 2 mg of copper is recommended several times a week. Since copper is widely distributed in selected foods, such as poultry, organ meats, shellfish, oysters, chocolate, nuts, dried legumes, and cereals, 2 mg a per day can usually be obtained by favoring dietary selections from this list.
Reader's guide to zinc food sources, enhancers, and antagonists.
Zinc content is highest in flesh foods, such as meats, poultry, liver, and oysters. Legumes and whole grain products are also sources of zinc, but larger quantities must be consumed to deliver significant amounts. Other good sources of zinc per kilocalorie ( according to Whitney et al. 1998) are spinach, broccoli, green peas, green beans, tomato juice, plain yogurt, Swiss cheese, tofu, shrimp, and crab.
Vitamins A, B3, B6, and C, as well as calcium, copper, magnesium, essential fatty acids, and essential amino acids enhance zinc absorption. Alcohol, oral contraceptives, excesses of copper and calcium, saturated and trans fats, steroids, obesity, and smoking interfere with zinc utilization. Diarrhea, kidney disease, cirrhosis of the liver, and diabetes can also contribute to a zinc deficiency.
AUXILiARY FACTORS THAT AFFECT CARDIOVASCULAR HEALTH
Anemia—a predictor of death from acute heart attack
Anemia reflects a reduction below normal in the number of red blood cells, hemoglobin level, or hematocrit (a measure of the packed cell volume of red cells in blood). Hematocrit has emerged as an extremely important assessment in targeting individuals at high risk of succumbing to a heart attack (Wu et al. 2001).
Note: A normal hematocrit is between 36-50%; below 36% indicates anemia.
A study reported in the New England Journal of Medicine evaluated 78,974 patients, ages 65 and older, who were hospitalized with acute myocardial infarction. Patients were categorized according to hematocrit upon admission. Researchers considered the prognostic value of hematocrit percentages as well as the impact of blood transfusions on 30-day mortality. Their findings follow:
| Hematocrit Percentages as Predictor of Cardiac Survival |
| Hematocrit 5.0%-24.0% = 78% chance of patient dying within 30 days |
| Hematocrit 24.1%-27.0% = 52% chance of patient dying within 30 days |
| Hematocrit 30.1%-33.0% = 31% chance of patient dying within 30 days |
| Hematocrit >33.1% = No increased risk |
| Reduction in Cardiac Mortality Following Transfusion |
|Note: Transfusion benefits with increased severity of anemia. |
| Patients with hematocrit < 24% reduced mortality 64% with transfusion. |
| Patients with hematocrit 24.1-27% reduced mortality 31%. |
| Patients with hematocrit 27.1-30% reduced mortality 25%. |
It should be emphasized that transfusion therapy is only effective in reducing cardiac mortality among anemic patients; mortality actually increased when transfusions were given to nonanemic patients.
Does Sodium Restriction Lower Blood Pressure?
An evaluation of a hypertensive patient should include measuring plasma renin activity (PRA) to determine if renin is a factor in the pathogenesis of elevated blood pressure. In order to stimulate renin release, the individual is told to follow a diet very low in sodium for 3 days prior to the test. Normal values of adult plasma renin, measured in an upright position and sodium-depleted, are 2.9-10.8 ng/mL an hour.
Renin is an enzyme secreted by the juxtaglomerular apparatus of the kidney in response to many cardiovascular factors, such as a fall in blood pressure, reduced plasma volume, and/or sodium depletion. In an attempt to maintain homeostasis, renin is released, increasing the conversion of angiotensinogen to angiotensin I. Angiotensin I is then converted to angiotensin II, which in turn causes an increase in aldosterone secretion, a sequence that increases peripheral vascular resistance and blood pressure.
Patients with low renin levels respond best to sodium restriction and diuretic therapy. Those with high baseline renin levels will not respond to sodium restriction. According to Jeff Bland, Ph.D., most individuals who have essential hypertension are not salt sensitive. Putting those individuals on a rigorous salt-restricted diet has little impact on their hypertension. Conversely, if an individual is salt sensitive, sodium restriction will have a profound effect upon modulating blood pressure. This is an example of matching an appropriate dietary program with the right genotype (Bland 2000b).
Acknowledging that dietary salt appears to account s for a minor but only a minor segment of increased blood pressure in hypertensive people, it has been proposed that a the larger segment of essential hypertension is caused by enhanced renal sodium retention prompted by hyperinsulinemia. Insulin resistance may also play a role by altering internal sodium and potassium distribution in a direction associated with increased peripheral vascular resistance (Zavaroni et al. 1992; Lukaczer 2000). Researchers were able to demonstrate that blood pressure increased or decreased when lesser or greater amounts of insulin were administered to obese, hypertensive patients (Tedde et al. 1989; Randeree et al. 1992).
The most effective dietary treatment for hypertension appears to be weight loss and a dietary intervention to increase calcium, magnesium, and potassium intake. Results of the Dietary Approaches to Stop Hypertension (DASH) study showed that a diet rich in fruits, vegetables, and low-fat dairy products significantly lowered blood pressure. These foods are excellent sources of potassium, magnesium, and calcium, accounting for the success of the diet. In the study, blood pressure was reduced by 5.6 mmHg and 2.8 mmHg (systolic and diastolic pressures), making dietary intervention comparable to first generation antihypertensives. Weight loss and dietary manipulation appears to control hypertension in nearly one-half of individuals with high blood pressure (Bland 2000a). Can What You Drink Make a Difference?
Endorsing alcohol consumption is difficult considering the number of health risks imposed by drinking. But when considering the health of the heart and vascular system, statistics appear to flip in favor of moderate alcohol consumption. Studies involving atherosclerosis (disease authenticated by cardiac catheterization or autopsy) show less arterial closure among persons who consume moderate amounts of alcohol. A moderate drinker, in fact, decreases the possibility of heart disease by 30-50% (Gaziano 1993; Pearson 1996). This is true for both men and women, particularly imbibers middle-aged or older.
As encouraging as this information is, the line is extremely narrow in regard to the amount of alcohol one can consume and still reap benefits. For example, teetotalers or occasional drinkers lose the alcohol advantage because of inconsistent consumption. Conversely, persons consuming 3 or more drinks a day experience a rapid rise in total morbidity, that is, cardiomyopathy, hypertension, and hyperhomocysteinemia, as well as mortality. The bottom line indicates that nondrinkers, as well as individuals who aggressively imbibe, have a higher risk of succumbing from heart disease than an individual consuming 1-2 drinks a day (Rimm et al. 1996).
It is speculated that about 50% of the protective nature of alcohol is due to alcohol's ability to increase HDL cholesterol (Gordon et al. 1981). An additional edge comes by reducing blood glucose and insulin levels (Facchini et al. 1994). It appears that no advantage is gained from alcohol in regard to lowering either blood pressure or LDL cholesterol levels, but the blood clotting mechanism is altered by alcohol consumption (Renaud et al. 1992; Ridker et al. 1994). It is debatable how alcohol accomplishes this. Perhaps it is by influencing coagulation factors, such as PAI-1, t-PA, and the activity of platelets.
Reports appearing in The Lancet added to the benefits obtained from alcohol, citing the antioxidants found in red wine and dark beer (Maxwell et al. 1994). Antioxidants, regardless of their source, always play heroic roles in heart health. Interestingly, alcohol is still able to convey a cardiovascular advantage, even in light of a poor diet or cigarette smoking.
Is alcohol the utopia we are all searching for? Probably not, considering the dangers imposed by excessive consumption. Persons with a personal or family history of alcoholism and those with hypertriglyceridemia, pancreatitis, liver disease, certain blood disorders, or hypertension, as well as pregnant women, are not candidates for either beginning or continuing to drink alcohol. Those on diets should not forget that alcohol is a significant source of calories as well as carbohydrates. It is also important to recall that drug and alcohol interactions can be fatal. Yet, after acknowledging the negatives, if current consumers of alcohol all abstained from drinking, about 80,000 additional heart deaths would occur annually (Pearson et al. 1994). Although the research is compelling, alcohol should never be considered to be a treatment for either Syndrome X or heart disease.
The pleasure of a cup of green tea is well accepted, but it appears to accomplish far more than satisfy the palate. Published literature confirms the hypolipidemic nature of green tea, reporting decreases in triglycerides and LDL cholesterol, while increasing the beneficial HDL cholesterol. In addition, green tea suppressed the oxidation of LDL cholesterol, further deterring the atherosclerotic process (Chan et al. 1999).
Some researchers liken green tea to aspirin because of similar therapeutic qualities. Information published in Beyond Aspirin (Newmark et al. 2000), states that green tea contains salicylic acid, a naturally occurring COX-2 inhibitor. Green tea, like aspirin, inhibits thromboxane A2; the inhibition of thromboxane A2 lessens the risks of blood clot formation and the dangers imposed by arterial constriction.
Heart attacks and strokes are less likely to occur if neither fibrinogen levels nor the activity of platelet-activating factor (PAF) become excessive. Green tea lowers fibrinogen levels and is a PAF inhibitor. A 4-year study involving 5910 Japanese women (ages 40 and older) showed twice as many strokes among trial participants who used less green tea (less than 5 cups a day) than in those who used more (greater than or equal to 5 cups daily) (Sato et al. 1989).
A cup of green tea appears to be beneficial to hypertensives through various mechanisms. The loss of arterial elasticity (arteriosclerosis) is one cause of high blood pressure. Youthful arteries expand and contract in compliance with the heartbeat to move blood to peripheral sites. Damaged vessels are unable to participate in this ritual. Green tea (by inhibiting thromboxane) reduces arterial constriction and consequently blood pressure is reduced. Also many antihypertensive drugs are ACE inhibitors, meaning angiotensin pathways are disrupted. Without interruption of this feedback loop, blood vessels vasoconstrict, water is retained, and blood pressure increases. Green tea breaks this sequence, acting as a natural (although mild) ACE inhibitor (Duke Database 1992; Faloon 2000).
The 1st International Symposium on Green Tea (September 22, 1989) reported that green tea reduces blood glucose levels. During the ensuing years, the Life Extension Foundation has frequently informed members that green tea reduces the expected glucose and insulin rise after a carbohydrate load. It should also be noted that green tea contains chemicals regarded as beta-adrenergic receptor blockers, anti-inflammatories, diuretics, and calcium antagonists, proving beneficial in arrhythmias and hypertension (Duke Database 1992).
Green tea, an antioxidant, helps remove excess iron from the liver (Carper 2001). Individuals with hemochromatosis should drink several cups or use two to four 300-mg capsules a day. (Each capsule should provide 95% active polyphenols.) Note: Research suggests that decaffeinated green tea has a different therapeutic disposition than that containing caffeine and may be more effective in reducing iron overload. Caffeine drinks are not appropriate for sympathetic dominant individuals and those taking beta-adrenergic drugs.
As similar as green tea and aspirin are in their defensive mechanisms, it would not be wise for an individual, relying on aspirin as a cardio-protective, to depend only on green tea to the exclusion of aspirin.
Nuts: A Heart Food
According to a report published in the American Journal of Clinical Nutrition, one of the most unexpected and novel findings in nutritional epidemiology in the past 5 years has been that nut consumption protects against ischemic heart disease (IHD) (Sabate 1999). Phytonutrients in nuts, such as luteolin (a flavonoid), tocotrienols, fiber, fatty acids, amino acids, and vitamins and minerals, appear to work synergistically to provide heart protection, lower blood pressure, reduce the risk of stroke, and increase longevity. The protective effect of nuts applies to men and women (both black and Caucasian), all age groups, smokers, and sedentary individuals.
Of the tree nuts, walnuts are unique because they are a rich source of linolenic acid. Almonds are a good source of vitamin E and calcium; peanuts provide folate (important in controlling homocysteine) and resveratrol (inhibits blood clots and the inflammatory process). Nuts are also good sources of arginine and fiber (Kris-Etherton 1999).
The Adventist's Health Study reported that individuals who ate nuts 1-4 times a week reduced their risk of acute myocardial infarction 22% (Fraser et al. 1992). Eating nuts more than 5 times a week resulted in a 51% lower cardiac risk compared to individuals who consumed nuts less than 1 time a week. Persons consuming nuts more than 5 times a week reduced their lifetime IHD risk 12%, and men who developed the disease did so 5.6 years later than men who consumed nuts infrequently.
In 1993, the New England Journal of Medicine published results of a walnut study conducted at Loma Linda University . All trial participants conformed to the National Cholesterol Education Program Step 1 Diet, except that 20% of the calories of one diet were derived from walnuts, offset by lesser amounts of fatty foods. Both diets contained identical foods and macronutrients, except for the addition of walnuts in the test diet.
At the conclusion of the study, participants eating the walnut diet had total cholesterol levels 22.4 mg/dL (12.4%) lower and LDL cholesterol levels 18.2 mg/dL (16.3%) lower than those consuming the control diet. Blood pressure was unaffected on either diet. Researchers noted that subjects on the walnut diet, despite increased energy intake, did not gain weight (Sabate et al. 1993). Comment: Nuts, in general, are healthy foods, but select those not roasted at high temperatures in oils of uncertain quality.
The Journal of the American Medical Association recently expanded the potential benefits of higher nut and peanut butter consumption, showing a significantly reduced risk for Type II diabetes among women who regularly include nuts in their diet (Jiang et al. 2002).
Autonomic Balancing: Right Messages, Good Results
The autonomic nervous system, consisting of the parasympathetic (PNS) and the sympathetic divisions (SNS), play major roles in heart function. For example, when the PNS is active, heartbeat, blood pressure, and respiration rate tend to be decreased, as well as the activity of the adrenal glands. Conversely, when the SNS is dominant, the brain alerts the adrenal glands (small organs located on top of the kidneys) to supply adrenaline, the stress hormone. Adrenaline rushes through the bloodstream to all tissues, organs, and glands, heightening their responsiveness. Subsequently, blood pressure, heart rate, blood glucose levels, respiration, and perspiration increase. It is referred to as the "fight or flight" division because a general state of excitement and preparedness is evidenced.
If the individual is healthy, an adrenaline surge is inconsequential. But, if the heart is diseased or damaged, the sympathetic stimuli can be dangerous, even deadly. Type A individuals often live with chronic stimulation of the SNS, a burdening handicap to long-term survival. Note: Interesting data released from the Stanford University School of Medicine showed that insulin-resistant individuals, with compensatory hyperinsulinemia, have a higher nocturnal heart rate, a finding consistent with the possibility that increased heart rates are secondary to insulin-induced sympathetic activity (Facchini et al. 1996b).
Although each of us is born with a propensity toward a sympathetic, parasympathetic, or balanced response from the autonomic nervous system (ANS), Dr. Nicholas Gonzalez (an authority on autonomic balancing) is finding that chemical pollutants and life-style abuses can shift balance and disrupt the natural tendency of the individual. If either division becomes abrasively dominant, the risks imposed upon the heart can be meaningful. For example, if the PNS becomes overly dominant, the risks are as genuine as if the SNS were over -expressed. A heart receiving its instructions from the PNS may become a bit passive, and cardiac output lethargic. Unable to cope with a one-sided response from the ANS, the heart can make fatal errors.
The SNS and PNS are a two-neuron system, meaning that two sets of nerves interconnect in the ganglion. Minerals play an extremely important role in the message sent to organs and glands from the ANS. For example, Dr. Gonzalez explains that magnesium blocks transmission between the two nerves and the ganglion and is regarded as the very best turn-off for sympathetic arousal. On the other hand, calcium arouses activity in the SNS. Potassium, although not a sympathetic toner, acts directly upon the PNS, encouraging increased responsiveness. Exercise quiets the SNS, burning off sympathetic hormones and making stronger parasympathetic expression.
The pH of a parasympathetic dominant tends to be alkaline; the pH of a sympathetic dominant migrates toward acidity. This principle may best explain the benefit some cardiac patients gain when eating a predominantly fruit and vegetable diet, with protein sources limited to smaller amounts of fish and chicken. The alkalinity of a plant-based diet makes the response from the PNS stronger and the activity in the SNS more subdued. Conversely, red meat turns on the SNS and is beneficial to an individual with an overactive parasympathetic response. In fact, Dr. Gonzalez feels a cholesterol level between 210-220 mg/dL is fitting for a parasympathetic because the cholesterol then assumes the nature of a powerful antioxidant.
A cardiac patient should seek counsel with a physician who can determine metabolic type. A physician who can make this determination will also make cohesive choices regarding supplements, diet, and exercise, eliminating conflicting messages being delivered to the heart. Note: Tapes of Dr. Gonzalez's lectures, addressing the ANS in-depth, may be purchased from Conference Recording Service Inc., (800) 647-1110 or at www.conferencerecording.com. Although the lectures focus on treating cancer, the tapes are extremely interesting and informative.
Since over-expression of the adrenergic system (increasing sympathetic activity) can provoke an irregular heartbeat, scientists have searched for drugs that could block its activity. Propranolol became the granddaddy of the family of beta-blockers and is one of the most prescribed drugs in America for arrhythmias, hypertension, and angina pectoris.
Beta-blockers bind to specific receptors on nerve endings in an effort to control blood pressure, anxiety, and arrhythmias occurring before or after a heart attack. The binding process blocks the effects of impulses transmitted by the adrenergic postganglionic fibers of the SNS. As beta-blockers compete with epinephrine (also known as adrenaline) for receptor sites, the excit atory nature of epinephrine is curtailed. Beta-adrenergic receptors are located mainly in the heart, lungs, kidneys, and blood vessels (PDR 1999).
Conventional cardiologists conducting propranolol studies reported satisfaction with beta-blockers, citing fewer second heart attacks among users and a 26% reduction in heart mortality. Many patients were less pleased with beta-blockers, describing clinical depression, erectile dysfunction, and fatigue as compromising factors. Also, beta-blockers have been associated with an increased risk of developing diabetes by impairing insulin sensitivity. Newer beta-blocking drugs such as Toprol are now considered superior to p Propranolol.
Calcium Channel Blockers
The heart is controlled by tiny electrical impulses that regulate the heart, not unlike a pacemaker. Calcium plays a key role in regulating the heart's response to these electrical signals. It flows between the heart cells and surrounding fluid through a sort of chemical turnstile, or calcium channel. The more calcium that gets through the turnstile before the electrical signal is received, the more strongly the heart contracts, an effort that increases the heart's workload. Calcium channel blockers do not totally block movement through the turnstile, but they significantly slows it down. For some, this process lessens the labor required of a damaged heart, signaling it to slow down and take it easy. Because calcium channel blockers dilate the arteries and reduce resistance to blood flow, they are also widely used to control hypertension. The FDA first approved calcium channel blockers in 1982 for the purpose of treating arrhythmias.
While most of the literature (cautiously) supports calcium channel blockers, a few clinicians adamantly oppose their usage. According to Gabe Mirkin, M.D., calcium channel blockers are classified as short-, intermediate-, and long-acting. Older studies showed that short- and intermediate-acting calcium channel blockers might increase the risk of heart attacks; a more recent study showed that longer-acting calcium channel blockers might as well (Estacio et al. 1998). Patients were followed for 67 months, at which time the Drug and Safety Monitoring Committee detected a significant difference in the rate of heart attacks among patients treated with nisoldipine (a long-acting calcium channel blocker) compared with those treated with enalapril (an ACE inhibitor). The termination of nisoldipine treatment was recommended, and patients receiving nisoldipine were switched to enalapril.
Professor Bruce Psaty ( University of Washington ) reported that the risk of a heart attack increased up to 60% among 2655 hypertensive patients taking calcium channel blockers (Psaty et al. 1995). In addition, The Lancet reported that calcium channel blockers, often hailed as an ace in cardiac pharmacology, appear to increase the risk of developing cancer (Pahor et al. 1996). Among 5000 men and women enrolled in a verapamil, diltiazem, and nifedipine study, the risk of cancer increased by about 72% (Atkins 1996c).
Other side effects associated with both calcium channel blockers and beta-blockers are congestive heart failure , (CHF), lightheadedness, fatigue, low blood pressure, shortness of breath, and bradycardia (heartbeat less than 60 beats a minute). Although not enough studies exist to prove that calcium channel blockers cause heart attacks or increase the risk of cancer, the research is strong enough for doctors to use calcium channel blockers with the utmost caution (Mirkin 2002b).
Dispersed throughout the Therapeutic section are a few of the herbs (containing one or more chemicals) considered beta-adrenergic receptor blockers or calcium antagonists. The literature also supports magnesium as a SNS inhibitor as well as a calcium antagonist (Whitaker 1995b; Duke 2000; Gonzalez 2000). Researchers state that carnitine may provide independent benefit in ischemia when used as monotherapy or additional benefit when used in combination with conventional beta-blockers or calcium antagonists (Jackson 2001). Never should drug therapy be stopped and a nutraceutical started without counsel with a qualified physician.
Calcium blocking activity
Angelica, garlic, ginger, ginkgo biloba, grape seed, green tea (Camellia sinensis), hawthorn, magnesium, and olive leaf
Grape seed, green tea, hawthorn, and magnesium
RISK FACTORS ASSOCIATED WITH PRESCRIPTION DRUGS
Many people are unaware that there may be risks associated with taking commonly prescribed prescription medications. In addition, once-daily dosing of certain drugs such as anti-hypertensive agents may not provide 24-hour protection against arterial damage. Individuals who are currently taking any of the medications described in this section are urged to discuss alternative treatment options with their physician.
Nitroglycerin Drugs and Angina
Angina is a sudden intense pain in the chest that is often accompanied by a feeling of suffocation. Angina is caused by a momentary lack of adequate blood supply to the heart muscle. Individuals who have occluded coronary arteries often experience periodic bouts of angina.
Nitroglycerin temporarily dilates blood vessels and reduces workload on the heart. As early as 1879, nitroglycerin was administered to an angina patient (Kipple 1993). Nitroglycerin worked so well that nitroglycerin and other "nitrate" drugs have been used as standard angina therapy ever since. Unfortunately, while these nitrate drugs do provide temporary relief from angina, regular use of nitrate drugs may increase the risk of a future heart attack.
A startling new finding came from a Japanese study that involved 518 patients with suspected coronary artery disease (Murakami et al. 2002). The patients were categorized into groups based on their degree of endothelial dysfunction (a measurement of inner arterial wall damage) and the use of nitrate drugs.
These 518 patients were followed for 45 months to ascertain which patients were more likely to experience major cardiovascular events. As expected, patients with severe endothelial dysfunction had significantly more heart attacks, strokes, bypass surgeries, congestive heart failure, etc. However, the surprising finding was that those who regularly used nitrate drugs were 2.42 times more likely to experience major cardiovascular events. The researchers concluded that the effects of nitrate drugs accelerated atherogenic processes and endothelial dysfunction and that use of nitrate drugs caused future cardiovascular events (Murakami et al. 2002).
Millions of Americans with coronary artery disease have been prescribed nitrate drugs. However, there is now evidence that nitrate drugs actually accelerate arterial wall damage (endothelial dysfunction) and thus contribute to progression of coronary artery disease--the very disorder that the nitrate drugs have been prescribed to alleviate.
Angina patients who rely on nitrate drugs should bring this new information to the attention of their physician. It is important to note that occasional use of a nitrate drug to relieve angina symptoms was not shown to be dangerous in the most recent study. It was the regular use of a nitrate or nitroglycerin drug that increased the risk of heart attack by 2.42 times within a 45-month period (Murakami et al. 2002).
| Commonly Prescribed Nitrate Drugs |
|A 2002 study indicating danger from nitrate drugs referred to regular use rather than occasional use (Murakami et al. 2002). It is highly unlikely that occasional use of a nitrate drug to relieve angina symptoms would cause a problem. However, regular use of a nitrate or nitroglycerin drug more than doubled the risk of heart attack or other pathological vascular event. Commonly prescribed nitrate and nitroglycerin drugs are: |
|Isosorbide Nitro-Dur Transdermal Infusion |
|Isosorbide Dinitrate Nitrolingual Pump Spray |
|Isosorbide Mononitrate Nitrostat tablets |
| Nitroglycerin patches Minitran Transdermal Delivery |
For information about an FDA-approved technique that has been shown to safely reduce angina symptoms, refer to "A Non-Invasive Alternative to Coronary Bypass Surgery" in the May 2003 issue of Life Extension Magazine (pp. 54-60). This article may also be accessed at www.lef.org.
Dietary supplements that have been shown to help protect against endothelial dysfunction include:
- Folic acid (Title et al. 2000a; Woo et al. 2002)
- Vitamin C (Richartz et al. 2001; Pullin et al. 2002)
- Vitamin E (Title et al. 2000b; Raghuveer et al. 2001)
- Arginine (Maxwell et al. 2000; Kawano et al. 2002; Lekakis et al. 2002)
- Taurine (Wang et al. 1996; Fennessy et al. 2003)
- Fish oil (Chin et al. 1994; Morita et al. 2001;
Goodfellow et al. 2000)
It should be pointed out that if left untreated, endothelial dysfunction may become so severe that it will not be possible to reverse it with currently available therapies.
The term endothelial dysfunction is increasingly being described in scientific journals as a significant underlying cause of most forms of cardiovascular disease, including hypertension, atherosclerosis, and congestive heart failure.
Class I Anti-Arrhythmic Drugs Kill Thousands
In the June 1995 issue of Life Extension Magazine, an article exposed the dangers of a class of anti-arrhythmic drugs the FDA had approved to prevent lethal heart arrhythmias (LEF 1995). In this 1995 article, evidence was introduced that the FDA knew of the risks these drugs posed, but had approved them anyway. When the FDA was confronted with accusations that these drugs had been improperly approved, the reply was that the FDA had a theory that these drugs would save the lives of more people by preventing abnormal heartbeats than the drugs would kill by causing abnormal heartbeats. The problem was that the FDA had no evidence that these drugs would save even a single life.
Even after a large study conducted by the National Heart, Lung and Blood Institute showed that anti-arrhythmic drugs had killed large numbers of Americans, the FDA's response was not to remove the drugs, but to merely suggest changes in the labeling of the drugs (CAST 1989; NHLBI. 2002).
True to its word, the FDA did mandate a change in the labeling of at least one of these anti-arrhythmic drugs (Tambocor®). On page 1889 of the year 2003 Physician's Desk Reference, a large warning box appears containing the following statement:
"An excessive mortality or non-fatal cardiac arrest was seen in patients treated with Tambocor compared with that seen in patients assigned to a carefully matched placebo-treated group. This rate was 16/315 (5.1%) for Tambocor and 7/309 (2.3%) for the matched placebo."
What this warning means is that if you take Tambocor (flecainide), your risk of dying or experiencing a heart attack is more than double compared to taking a placebo.
The sordid history of the FDA's approval of Tambocor and other lethal Class I anti-arrhythmic drugs is chronicled in the book Deadly Medicine by Thomas J. Moore (1995).
Are You Taking the Proper Anti-Hypertensive Medication?
The Life Extension Foundation has repeatedly warned persons with high blood pressure (hypertension) to not depend on one-a-day dosing of anti-hypertensive drugs because many of these drugs do not provide complete 24-hour protection. When an anti-hypertensive drug wears off, the patient is vulnerable to having a stroke. One solution to this problem is to take a lower dose of the anti-hypertensive drug twice a day, even though the FDA claims that one-a-day dosing is adequate.
Failure to keep blood pressure at optimal low levels (below 120/85) dramatically increases mortality risk. The United States government states that blood pressure readings as high as 140/90 are acceptable (CDC 2002), but published results of human studies clearly show that maintaining levels below 120/85 confer longevity and protection against heart attack and stroke (Stamler et al. 1993; Stamler 1999).
The best-selling anti-hypertensive drugs in the United States are not necessarily the most effective. Advertising by drug companies and physician "force-of-habit" prescribing often result in hypertensive individuals taking drugs that do not provide optimal blood pressure-lowering effects.
Life Extension long ago recommended a class of anti-hypertension drugs known as angiotensi on II receptor blockers. Some of the first drugs approved in this class w here Cozaar® and Hyzaar® and Life Extension has suggested them as first line therapy. The only drawback to these drugs was that they did not provide consistent one-a-day protection.
A new drug in this class is called Benicar®. A recent study indicated that Benicar may be the first drug to provide true 24-hour blood pressure reduction (Neutel et al. 2002). A typical starting dose of Benicar is 20 mg a day. For patients requiring further reduction in blood pressure, the dose can be increased to 40 mg a day after 2 weeks.
Optimal control of hypertension requires blood pressure checks throughout the day. This is the only way to be certain an anti-hypertensive drug is not wearing off, endangering the arterial system. Even if you take Benicar, it is still critical to verify that it is actually keeping your blood pressure suppressed during an entire 24-hour period.
INVASIVE VERSUS NONINVASIVE TESTING AND HEART PROCEDURES
Facts to Consider Before a Final Decision Is Made
Invasive heart treatment ranks ninth among the top 10 causes of death. Because of the obvious seriousness of any procedure involving the heart, consenting to invasive testing and surgery should be made rationally rather than emotionally. The intent of this protocol is not to steer the patient in regard to cardiac testing and treatment but rather to enlighten the reader concerning both options and risks. Fortunately, researchers have removed many of the uncertainties from the dilemma.
The detection of a heart problem can be made by several noninvasive tests, medical history, physical examination, electrocardiogram, stress tests, blood tests, and an echocardiogram. An echocardiogram provides a graphic outline of the movements of the heart structures, showing the valves and the action of blood flowing through them, the ability of the left ventricle to pump blood, the thickness of the walls of the heart , (considering thickness), and an assessment of the membrane around the heart (the pericardium). It does not show the coronary arteries well enough to determine blood circulation directly to the heart. For this evaluation, the echocardiogram should be combined with a cardiac stress test. This combination will show the workings of the various parts of the heart during stress compared to rest.
The blood tests are valuable because they confirm or refute uncertainties arising from early-stage diagnosis of a heart attack. Creatine kinase (CK), a small fraction of the CK enzyme an isozyme(CK-MB), and troponins are heart damage markers or cardiac enzymes measurable in the blood. CK-MB shows an increase above normal about 6 hours after the onset of a heart attack. It typically reaches its peak level within 9-30 hours and usually returns to normal within 48-72 hours (Cardiac Biomarkers 2000).
Blood tests to measure troponins, specifically troponin T (cTnT) and troponin I (cTnI)--cardiac muscle proteins--have been developed. These proteins control the interaction between actin and myosin, muscle proteins that contract or squeeze the heart muscle. Identifying troponins specific to heart muscle allowed for the development of blood assays that can detect heart muscle injury with great sensitivity and specificity. The normally low level of cTnT and cTnI increases substantially within 4-6 hours of heart muscle damage. Peak levels occur at 14-20 hours, usually returning to normal 5-7 days later (American Heart Association 2000; Cardiac Biomarkers 2000; Sobki et al. 2000).
It is now considered possible to use troponin testing to identify individuals at either low or high risk for a coronary event. Even modestly elevated troponin levels are associated with larger numbers of tiny coronary artery blood clots, complex arterial lesions, and impaired blood flow through the vasculature.
Compared to patients with the lowest levels of troponin T, those with the highest troponin T levels are almost 13 times more likely to die over a 37-month period (Lindahl et al. 2000). The type of troponin blood test used by most clinical laboratories is troponin I. If levels exceed 0.4 ng/mL, antiplatelet and antithrombotic therapy should be considered. Nutrients with an antiplatelet and antithrombotic therapeutic profile are highlighted in the Therapeutic section of this protocol.
Researchers at University of Texas Southwestern Medical Center (Dallas) have discovered another impressive cardiac marker, brain natriuretic peptide (BNP), showing remarkable accuracy in regard to predicting cardiac morbidity and mortality. BNP is a neurohormone synthesized in the muscular wall of the left ventricle of the heart that is released into the circulation in response to ventricular dilation and pressure overload. BNP, a counter -regulatory hormone, promotes excretion of salt by the kidneys and dilates blood vessels.
To determine the predictive value of BNP, 2525 patients were enrolled in a study (half having experienced a heart attack and the other half displaying unstable angina or chest pains). After a 30-day analysis, the researchers found that levels of BNP were higher among patients who died. Also, it was observed that patients with higher BNP were more likely to have a new or recurrent heart attack, develop heart failure, or experience progression of the disease process. Even in patients who had no detectable heart damage from a previous attack, elevated BNP levels identified individuals at high risk of dying or developing life-threatening cardiac complications (de Lemos et al. 2001).
An angiogram, referred to as cardiac catheterization, is a mechanism in which coronary arteries are luminated by injections of dye, a process that aids in diagnosing blocked arteries. A catheter is introduced through an incision into a large vein, usually of an arm or a leg, and threaded through the circulatory system to the heart. As the dye wends its way through the vasculature, blockages are detected by changes in flow rate at points of occlusion. An angiogram is a popular diagnostic tool, but it is not without risks. It is possible that the catheter will damage the artery or loosen a piece of plaque lining the artery wall. The dislodged plaque can block the flow of blood, causing a stroke. Thrombophlebitis, local infection, and cardiac arrhythmias are other valid concerns.
Data reported in the JAMA debated the relevancy of widespread angiogram usage (Graboys et al. 1987, 1992). A study chronicled 168 patients who were advised to have an angiogram to determine the need for either angioplasty or cardiac surgery: 80%, or 134, of the 168 patients who were evaluated noninvasively were determined not to need catheterization. From the 168 patients, an annual fatal heart attack of 1.1% was observed over a 5-year period compared to a 5-10% mortality rate from coronary bypass surgery and a 1-2% mortality rate from angioplasty. The conclusion of the published report was that noninvasive testing to access the heart's performance is a better and safer determinant of a suitable therapeutic program than searching for blocked arteries. If the patient fails some of the noninvasive tests, an angiogram is warranted to determine the need for surgery ( Murray 1999).
Magnetic Resonance Imaging
Up to 70% of heart attacks occur in blood vessels that appear normal on an angiogram. The journal Circulation reported that plaque without any calcium deposits is not detectable by angiograms or CT scans, but it is the most common cause of sudden death from a heart attack. While calcification may lead to a more extensive form of heart disease, it is less likely to lead to a heart attack (Fayad et al. 2000, LEF 2000).
Fatty buildup on arterial walls, although not detectable by an angiogram, can result in a small fraction of plaque breaking free. The circulating particle ultimately increases the risk of a heart attack or stroke.
A special type of MRI, with a sensitive screening technique, is promising in regard to detecting even a slight buildup in coronary arteries, including plaque without calcium deposits. This is especially praiseworthy since coronary arteries are very small and the constant movement of the heart makes a clear image difficult. The newer technique, black blood imaging, blacks out the blood and produces an image of just the artery. Besides being of much greater advantage in diagnosing early-stage heart disease, this process is noninvasive. It is hoped that this newer, more responsible means of assessing the health of coronary arteries will become part of a routine check-up (Fayad et al. 2000).
Coronary Bypass Surgery
Blocked arteries are not always prognosticators of an impending heart attack. The Coronary Artery Surgery Study (CASS) demonstrated that heart patients with healthy hearts, but with one, two, or three of the heart vessels blocked, did amazingly well without heart surgery. The number of blockages did not alter the 1% a year death rate observed in the study groups (Hueb 1989; Alderman et al. 1990).
A study conducted by researchers in Iowa and published in the New England Journal of Medicine evaluated the efficiency of arteries that were 96% blocked (diagnosis made by angiogram) (White et al. 1984; CASS Principle Investigators, 1983, 1984). The researchers found that arteries blocked 96% had a greater thrust of blood than similar arteries only 40% blocked. The conclusion of the report was that the degree of closure did not correlate to the briskness of blood flow. Michael Murray, N.D., states that the most critical assessment regarding the heart's performance is how well the left ventricular pump is working, not necessarily the degree of closure ( Murray 1999).
It seems that aggressive procedures to open the vessels do not influence the course of the disease, except in the most advanced stages of atherosclerosis. Bypass appears most helpful when the ejection fraction is less than 40%. Many bypass procedures are performed when the ejection fraction is greater than 50%, a percentage that appears adequate for meeting the demands of circulation. (White et al. 1984; Winslow et al.1988; Murray 1999).
A study by Harvard Medical School 's Department of Public Health revealed that 84% of patients who obtained a second opinion after being scheduled to undergo a heart bypass procedure were told that they did not need it. During the study's 2-year follow-up, there were no deaths in the group who canceled their surgeries based upon the second opinion (Perlmutter 2002). Often individuals undergoing the surgery live no longer and with no more quality than a matched group of patients treated without surgery. Conversely, if coronary bypass surgery or angioplasty is appropriately advised, the procedures definitely increase long-term survival and give symptomatic relief to about 85% of patients (Murray 1999).
Although coronary bypass surgery can bring relief to many patients, the procedure is weighted with danger and chance. Infections, problems with blood coagulation, nerve damage, and the possibility of a heart attack or stroke are risks that must be factored into the patient's final decision. According to Harvard researchers, up to 30% of patients have their heart arteries reclog badly in just a year. Few patients survive 10 years without needing retreatment, and high risk patients--such as those who already have undergone repeat surgery--reclog at even greater rates. It should be noted that morbidity and mortality rates vary considerably between hospitals. If considering any heart procedure, ask for an analysis of patient outcome.
Steven Whiting, Ph.D., states that although the odds of surviving bypass surgery have improved since the operation was first introduced, the risk of experiencing a decline in mental function following surgery has remained consistent since the 1980s. Signals of this type of decline may include difficulty following directions, mood swings, and short tempers. Many doctors have downplayed the importance of alterations in intellectual abilities that occur in about 50-80% of patients following bypass surgery, believing the decline to be temporary. It now appears a transient display of incompetency may predict an increased risk of intellectual instability several years later.
Researchers (reporting in the New England Journal of Medicine) followed 261 bypass patients for 5 years. Enrollees in the study underwent intellectual testing before and after surgery, as well as at the 6-week, 6-month, and 5-year interval. Intellectual function declined by 20-53% considering presurgical and postsurgical mental status. The decline was 36% at 6 weeks and 24% at 6 months. In 5 years after surgery, 41% of the patients had experienced neurocognitive impairment. The researchers concluded that an intellectual decline in patients following heart surgery was significantly associated with diminished mental abilities 5 years postsurgery (Newman 2001).
In 1977, Dr. Andreas Gruentzig introduced the procedure known as balloon angioplasty, and by 1980 balloon angioplasty had become a popular cardiac option. Angioplasty is used 3-10 times more often in the United States than in other developed nations.
Balloon angioplasty widens coronary arteries by inserting a specially designed catheter (a long, thin, bendable tube) with a balloon on its tip into a blocked coronary artery. After centering the tip of the catheter in the blocked area, the balloon is inflated, stretching the artery and compressing the plaque. The arteries do not fully constrict, which leaves a larger opening than before. Unfortunately, any procedure using an arterial catheter may cause plaque to be dislodged (resulting in a cardiovascular event) or the wall of an artery to be torn. Other concerns associated with angioplasty are arterial spasms and blood clots, fluid accumulation in the lungs, and impaired kidney function.
From the University of Giessen ( Germany ) comes a detailed analysis of 300 patients who underwent primary angioplasty for an acute myocardial infarction. At 1 year, 34% had experienced a cardiac event, 23% required repeat angioplasty, and 6% had died from cardiac disease (Peterson et al. 1994; Noninvasive Heart Center, http://www.heartprotect.com/mortality-stats.shtml; Waldecker et al. 1995).
Dr. Eric Peterson (and associates) at Duke University Medical Center reported the following survival statistics among various age groups undergoing angioplasty:
| Mortality After Angioplasty in 225,915 Patients |
| Ages || 30 Day || 1 Year |
| || % || % |
| 65-69 || 2.1 || 5.2 |
| 70-74 || 3.0 || 7.3 |
| 75-79 || 4.6 || 10.9 |
| > 80 || 7.8 || 17.3 |
Chart extracted from material provided by The Noninvasive Heart Center, 2550 Fifth Avenue, Suite 706 , San Diego , California 92103 email@example.com (619) 544-0200.
After collaborating with several universities, Ian Gilchrist, M.D., cardiologist at the Penn State Milton S. Hershey Medical Center ( Philadelphia , PA ), announced that 178 angioplasty patients (from a total of 2064 subjects) experienced a heart attack, required additional surgery, or died, and 82% of those numbers patients experienced the trauma within 18 hours of the procedure. Gilchrist said that despite efforts to minimize risk, angioplasty complications are nonetheless common (Gilchrist et al. 2000).
The original focus of the trial was to establish the worthiness and dosage of eptifibatide, an IV platelet inhibitor. Dr. James Tcheng ( A associate P professor of M medicine at Duke University Medical Center , Durham , NC ) reported that eptifibatide, a cost-effective drug, reduced the risk of major complications during angioplasty 40% in the first 48 hours following the procedure. While evaluating the worth of eptifibatide (a landmark study in itself) researchers were able to target the period requiring greatest watchfulness among angioplasty patients.
Angioplasty vs. Thrombolytic Therapy For Acute Heart Attack
An interesting study with far-reaching implications compared primary angioplasty to intravenous thrombolytic therapy for acute myocardial infarctions (heart attacks). An example of a thrombolytic is streptokinase (Streptase), which enhances the conversion of plasminogen to the fibrinolytic enzyme plasmin. Plasmin has a high specificity for fibrin and the particular ability to dissolve formed fibrin clots. Other drugs used to open clogged arteries during and after a heart attack are t-PA (Activase) and anistreplase (Eminase). Angioplasty is fully described in the preceding section.
Most cases of acute myocardial infarctions are caused by thrombotic occlusion of a ruptured plaque, diminishing blood circulation. Earlier research suggested there might be a time frame in human beings during which restoration of blood flow in the infarct-related artery might limit infarct size (Reimer et al. 1977). Research verified the concept, showing that timely reperfusion (a procedure in which blocked arteries are opened to reestablish forward flow of blood) resulted in less heart muscle damage and enhanced survival (Davies et al. 1985). The period from symptom onset to thrombolytic administration was related to reduced infarct size and mortality, with the greatest benefits within the first several hours following early symptoms. From these observations arose the premise that "time is muscle," establishing the need for swift treatment in progressive cardiac care (FTTCG 1994).
Based on its widespread availability, intravenous thrombolytic therapy has been the standard care for patients with acute myocardial infarction. Despite its popularity, thrombolytic therapy has limitations. Of those patients deemed candidates for anticoagulants, 10 to 15% had persistent occlusion or re-occlusion of the infarct-related artery. Consequently, primary percutaneous transluminal coronary angioplasty (primary PTCA) has been advocated as a better treatment for patients with acute myocardial infarction.
Proponents cited higher rates of opened vessels and improved blood flow to the heart among users of PTCA. In addition, avoiding thrombolytic administration virtually eliminates the approximate 1% risk of intracranial hemorrhage inherent with systemic clot-reducing procedures (Stone et al. 2001a). Naysayers (in turn) point ed out negatives associated with primary angioplasty, citing excessive delays to treatment compared with thrombolytic therapy, unproven results in large clinical trials, and a lack of widespread availability of treatment centers.
Yet, 22 trials (involving 6889 patients) demonstrated that for every 1000 patients treated with primary angioplasty (rather than thrombolytic therapy) an additional 20 lives were saved, 43 rei -nfarctions were prevented, 10 less strokes occurred, and 13 intracranial hemorrhages were avoided (meta-analysis by Ellen C. Keeley, University of Texas Southwestern, and Cindy L. Grines, William Beaumont Hospital in Detroit). The angioplasty advantage was still observed even if the patient had to be transported (by 3 hour ambulance trip) to a center equipped to perform the procedure. (It typically takes about 2 hours to mobilize the medical team to perform the angiography and angioplasty in the United States compared to 60 to 90 minutes in European hospitals) (Cannon et al. 2000; Weaver et al. 2000).
Despite the inherent delays apparent with angioplasty, the evidence that primary PTCA offers advantage compared to thrombolytic therapy appears convincing. Optimizing angioplasty with coronary stents and drug regimens has significantly improved the early safety profile and long-term results of percutaneous intervention in acute myocardial infarctions (Stone et al. 2002).
In conclusion, The Lancet recently described the CAPTIM trial (a current appraisal of the worth of angioplasty compared to thrombolytic therapy). In CAPTIM, 840 patients (within 6 hours of the onset of a heart attack) were randomized to fibrinolysis with accelerated doses of tissue plasminogen activators or to primary PTCA. Because of funding woes and slow enrollment, the trial ended before the planned recruitment of 1200 patients was reached (the number needed to demonstrate a 40% relative reduction in 30-day composite endpoints). Even so, the results demonstrated a trend toward a 24% reduction in the occurrence of adverse events (Bonnefoy et al. 2002).
Survival trends were similar between patients undergoing angioplasty and those receiving thrombolytic therapy, but the lower-risk population initially enrolled in the study appeared to explain the similarity in mortality statistics. (The survival benefit of primary angioplasty is mostly seen in high-risk patients, such as the elderly, and those with anterior myocardial infarction, or in shock [Stone et al. 2001b; Zahn et al. 2001]). The lack of a survival benefit in low-risk patients does not diminish the clinical relevance of fewer strokes, rei -nfarctions, a reduction in urgent revascularization procedures, and shorter hospital stays with primary PTCA, compared to fibrinolytic therapies.
Some advocate facilitated primary PTCA trials, i.e., combining thrombolysis with primary PTCA. However, the additional costs and bleeding complications that will certainly accrue by adding thrombolytic therapy before primary angioplasty cannot be dismissed without evidence of overriding benefit. To date, four modest-sized randomized trials have found facilitated PTCA either inferior to or no better than primary PTCA alone.
PTCA enthusiasts avow that (currently) the best therapy for most patients with developing acute heart attack should no longer be debated: administer antiplatelet therapy (aspirin, a thienopyridine, and possibly abciximab), and transfer the patient for primary PTCA to an experienced center, regardless of whether the nearest catheterization suite is three floors or three hours away. To do less, they caution, can no longer be considered standard care (Stone 2002). Comment: According to Dr. Philip O'Dowd, the thienopyridines (clopidogrel and ticlopidine) are slightly more effective than aspirin in preventing morbid vascular events in certain patients (O'Dowd http://www.brown.edu/Departments/Clinical_Neurosciences/articles/po401.html).
Angioplasty Among Diabetics
Although about 700,000 angioplasties are performed annually in the United States , the procedure is not a worthy consideration for everyone. Patients with diabetes mellitus, who are in need of revascularization, have better survival odds with coronary artery bypass grafting (CABG) compared to angioplasty, according to study findings published in the Journal of the American College of Cardiology (Bari Investigators 2000). According to Dr. Katherine M. Detre ( University of Pittsburgh ): "Diabetic patients did very much worse in both respects, heart attacks and mortality, when undergoing angioplasty." For diabetics, the 7-year survival rate was 76.4% in the CABG group and 55.7% in the angioplasty group. Among non-diabetics, the survival rates were 86.4% in the CABG group and 86.8% in the angioplasty group.
Does Multivessel Stenting Improve Odds?
More than 80% of patients worldwide are treated with endovascular prostheses during coronary procedures. So great are the numbers, Martin Leon, M.D., refers to the year 2000 as the era of the stent frenzy. A stent is a rod or threadlike device inserted within a closed or partially closed artery to allow adequate blood flow through the vessel ( Leon 1998).
According to Korean researchers, the excitement regarding stents appears to be justified. In fact, research suggests that some patients with coronary artery disease may be excellent candidates for multivessel coronary artery stenting, instead of bypass surgery. Dr. Seung-Jung Park ( University of Ulsan , Seoul ) reviewed observational data, evaluating 200 patients with multivessel coronary artery disease and normal left ventricular function. Half of the patients underwent bypass surgery and the other half had multivessel stenting. Complete revascularization, the restoration of blood flow, was achieved in 95% of the patients who had bypass surgery and in 69% of the stent group. Over a 21-month follow-up period, survival in the two groups was similar (99% for the stent group and 97% for the bypass group), but a higher incidence of angina recurrence and target lesion revascularization occurred in the stent group (Kim et al. 2000).
What Is Brachytherapy?
Because re -stenosis (closure) is a major concern after angioplasty, strategies that will benefit patients prone to vascular re -closure are being developed. Vascular brachytherapy, the placement of intracoronary radioactive sources, has dramatically lowered neo - (new) intimal growth patterns following angioplasty trauma.
A Scripps research team in LaJolla , California , headed by Dr. Paul S. Teirstein, inserted a ribbon of radioactive pellets into the artery for 20-45 minutes to help prevent the growth of scar tissue. In a preliminary clinical study conducted by Teirstein and colleagues, the incidence of in-stent re -stenosis (at the 6-month follow-up) declined from 54% without intra-coronary radiation to 17% with radiation, a difference of almost 70%. At 3-year follow-up, re -stenosis was reduced by 48% (a significant reduction considering the time frame). The need for repeat revascularization procedures was reduced 74% (from 45% to 12%) at 6 months. The clinical efficacy observed at 6 months was maintained at the 3-year follow-up (Teirstein et al. 2000; Carrington 2000).
Research carried out at the Division of Cardiology ( Washington Hospital Center ) showed overwhelmingly that gamma-radiation therapy delivers impressive results. For example, at 6 months, the in-stent re -stenosis rate was 21% among 60 patients assigned brachytherapy compared to 44% in a control group. At 12 months, the rate of revascularization of the target lesion was 70% less among the persons receiving gamma-radiation therapy; the incidence of a major cardiac event was 49% less (Waksman et al. 2002).
The one-time exposure to radiation does no apparent harm to heart tissue or the artery. The Journal of the American Heart Association reported that an assessment of the procedure at the 3-year interval indicated it was both safe and effective. However, Dr. Teirstein cautions that until much longer follow-ups demonstrate the benefits and safety of the radiation technique, it would be premature to recommend radiation therapy for the first line of treatment for patients with clogged coronary arteries (Teirstein et al. 2000). In the interim, major hospitals are gearing for brachytherapy as an option for patients with chronic coronary artery disease who are subject to adhesions following cardiac procedures.
Chelation Therapy: Is It a Bonafide Alternative to Heart Surgery?
Chelation therapy represents to some a safe, effective, and relatively inexpensive treatment to restore blood flow through atherosclerotic vessels. The word chelation is derived from a Greek translation meaning "claw-like," or capable of expunging accumulated atheromatous materials from the body.
During chelation, ethylenediaminetetraacetic acid (EDTA), a synthetic amino acid drug, is intravenously infused, along with other nutrients, to enact the extraction process. EDTA encircles and holds elements, passing them from the body in urine. With progressive treatments, accumulated pollutants are exhumed from body stores, along with materials that encourage free-radical damage and cellular breakdown. The heart-related conditions currently treatable with chelation therapy include arteriosclerosis and atherosclerosis, angina pectoris, hypertension, transient ischemic attacks, circulatory diseases, hemochromatosis, and Type II diabetes (Walker 1990; Powell et al. 1999).
Historically, chelation had an inception quite different from that of an anti -arteriosclerotic. EDTA's first medicinal usage appears to have been around 1941 when it was used to extract lead accumulations. A decade later, Dr. Norman Clarke (director of research at Providence Hospital in Detroit ) observed that patients treated for lead poisoning with chelation therapy had a simultaneous cessation of angina attacks. This chance beginning introduced EDTA to a few cardiovascular physicians who were searching for alternatives, apart from heart surgery, to remove plaque from diseased arteries.
Chelation therapy has had many deterrents along its controversial pathway. Even today, the American Heart Association, after reviewing the literature in regard to chelation and arteriosclerotic heart disease, has announced that the scientific evidence does not demonstrate any benefit from the therapy. The American Medical Association compared its effectiveness to that of a sugar pill. JAMA recently reported that based on exercise time to ischemia and exercise capacity, there is no evidence to support a chelation benefit in patients with ischemic heart disease, stable angina, or a positive treadmill test for ischemia (Knudtson et al. 2002).
Chelation supporters quickly rose to the accusation, among them Dr. Elmer Cranton, author of Bypassing Bypass. Dr. Cranton referred to the JAMA report as "sham science," citing statistical errors and patient disparities as compromising factors. One-third of the patients did not have angina, according to Cranton, and almost twice as many patients in the placebo group received antianginal drugs--and angina was supposedly one of the endpoints. Cranton avows that the study was inadequate to show any response, beneficial or otherwise. Researchers agreed (in part), citing the need for larger trials with a broad range of patients.
Dr. Terry Chappell (former president of ACAM) enrolled 32 physicians who were using the standard ACAM chelation protocol--20-30 treatments of EDTA, oral nutritional supplements, and lifestyle changes--in a study to assess the cardiovascular value of treatment. All of the patients participating in the study were appropriately diagnosed with vascular disease before the therapy began. Objective testing was done before and after each treatment. The results showed that chelation therapy (in union with supplements and lifestyle intervention) was yielding positive results. The patients, 1086 of 1241, or 88%, reported subjective betterment improvement; physicians reported "significant clinical improvement" ( Walker 1990).
Dr. Morton Walker, author of The Chelation Way, reminds us that an aspirin is less than one-third as safe as IV EDTA at supra p harmaceutical doses. The LD50 of aspirin is only 558 mg/kg in humans, while EDTA's LD50 is 2000 mg/kg. Note: LD50 indicates the pharmaceutical term lethal dose 50, or the dose of a substance that is fatal to 50% of test animals. Dr. Walker, a staunch advocate of chelation therapy, believes that the danger of death from bypass surgery is about 6000 times greater than from chelation therapy ( Walker 1990).
The success of chelation therapy appears directly related to the refusion of minerals withdrawn during the extraction process. A physician trained in autonomic balancing, a process described earlier in the material, appears essential to the success or failure of the process.
Dr. Edward Olszewer and associates published two reports (a retrospective analysis of 2870 patients with vascular and other chronic degenerative diseases and a single-blind, crossover study of a small group of patients with peripheral vascular disease) suggesting a beneficial effect from chelation. In the former study, objective testing indicated marked or good improvement in 87% of patients. In the latter study, all 10 subjects receiving chelation benefited (Olszewer et al. 1988, 1990). Note: The National Center for Complementary and Alternative Medicine and the National Heart, Lung, and Blood Institute have launched the first large-scale clinical trial to determine the safety and efficacy of EDTA chelation therapy in individuals with confirmed coronary artery disease. Plans for the 5-year study, involving over 2300 patients at more than 100 research sites across the country, are currently being finalized.
Coronary Gene Therapy
Coronary gene therapy is another alternative to either angioplasty or coronary artery bypass surgery for high risk patients. Gene therapy increases the options of individuals who have failed drug treatment and appear to be poor candidates for aggressive surgical procedures. A battery of tests confirms the acceptability of a patient wishing to be enrolled in the gene program.
During coronary gene therapy, x-ray imaging allows the gene for the human vascular endothelial growth factor (VEGF2) to be delivered to the heart via a catheter inserted through a puncture in the inguinal (groin) region. A needle is advanced out of the catheter and used to inject DNA into the inner wall of the heart, a sequence that produces the vascular endothelial growth factor and stimulates the growth of new blood vessels. Data reported in the New York Times (August 29, 1999) suggest that VEGF2 is capable of invoking the growth of new blood vessels, with some individuals experiencing regrowth in about 60% of the area previously occluded. Although the process is constantly being advanced and refined, many patients have successfully undergone the treatment since 1998.
Two concerns researchers had concerning gene therapy were that blood vessel growth factors might nourish the blood supply of undetected cancers and cause damaging overgrowth of vessels in tissues such as the retina of the eye. Dr. Timothy Henry ( Hennepin County Medical Center , Minneapolis ) reported that among 106 patients enrolled in a VEGF trial, four patients in the placebo group developed cancer compared with one patient in the low dose VEGF group and none in the high dose group. Overall mortality was 3% in the placebo group, 6% in the low dose VEGF group, and 0% in the high dose group. The incidence of myocardial infarction was 3% in the placebo patients, 0% in the low dose group, and 6% in the high dose VEGF group.
Currently, there appears to be no retinal damage in diabetic patients who have undergone the procedure. These results are preliminary and inconclusive, but early assessments deem VEGF therapy a burgeoning alternative to either bypass surgery or angioplasty for coronary and vascular disease. For more information concerning coronary gene therapy, contact St. Elizabeth's Medical Center of Boston at (888) 311-GENE.
EVIDENCE THAT CARDIAC CELLS DIVIDE AFTER A HEART ATTACK
Most tissues and organs are equipped to deal with injury more efficiently than the heart. For example, the mending of broken bones and renewal of injured skin is so mundane they are taken for granted. Until recently, it was thought that myocytes (muscle cells) of the adult heart were incapable of self-renewal; once damaged, always damaged, without hope of regeneration. Reports published in the New England Journal of Medicine indicate this may not be the case (Beltrami et al. 2001).
Researchers looked at heart muscle cells from the hearts of 13 deceased patients, 4-12 days after their heart attack. These findings were compared to the hearts of 10 patients who had not died of cardiovascular disease. Samples of heart tissue were taken from the area near the site of the heart attack and from a site more distant from the damage. Scientists found that the number of myocytes multiplying in diseased hearts was 70 times higher in the border zone and 24 times higher in the remote area. The presence of cell division in the nondiseased portion of the heart suggests a continuous turnover of cells during the lifespan of the organism. It is now thought that cardiac muscle cells can reproduce, advancing the premise that this process may be a component of the growth reserve of the human heart. The ramifications of this research allow for the prospect of replacing damaged myocardium by stimulating the heart's own repair capacity.
The focus of current study is to identify the premature stem cells that give rise to multiplying myocytes, encouraging growth and repair in damaged areas. The challenge will be to persuade these cells to move to regions of tissue damage to facilitate repair and reduce heart failure. While these reports raise hopes for employing the body's capacity for self-renewal, the excitement must be tempered by the scope of the obstacles. While the hurdles to overcome are sizable, current studies have advanced understanding by challenging dogma. Demonstrating that cardiac muscles are capable of regeneration opens up remarkable pathways for healing an ailing heart (Mercola 2001a).
This summary provides a brief review of the nutritional supplements discussed in this protocol. The list describes many options to choose from and is not intended to be used in its entirety. Selections should be made with a slant toward prevention and clinically confirmed weaknesses. Complexes of nutrients are available, lessening the quantity of individual supplements required in a far-reaching program.
The (+) in the margin (to the left of the supplement in the Recall section) indicates the supplement has preventive as well as therapeutic qualities. Individuals classed as heart healthy may profit most from supplements bearing the (+) code.
Readers with established heart disease should take solace in the quantity of the therapeutics presented and the documentation supporting their value. Although natural medicine conveys tremendous possibilities for heart patients, courses should not be charted without the help of a trained healthcare professional. If possible, select a cardiologist who respects natural medicine, substituting nutrients for drugs whenever possible. In this situation, larger doses of the nutraceutical may be required. Although the window of safety is generally judged wider when comparing natural medicine to drug therapy, megadosages can change the disposition of a supplement, pressing it in some instances to the rank of a drug; therefore, close professional supervision is essential to accomplish one's intent with safety. Pregnant women should always seek the counsel of a qualified practitioner who understands fetal and nutrient responses.
- + Alpha-lipoic acid is an antioxidant and antidiabetic; is beneficial in congestive heart failure and stroke prevention, hypercholesterolemia, and hypertension; and inhibits protein glycation. A suggested therapeutic dosage is 500-1000 mg daily. A preventive dose is 250-500 mg a day.
- Angelica (A. archangelica) is an antianginal, anti-inflammatory, vasodilator, calcium antagonist, ACE inhibitor, and diuretic; dosage, 15-30 drops 1-3 times a day. (See Angelica in the Therapeutic section for an explanation regarding milligrams per drop.)
- L-arginine dilates blood vessels; reduces the atherogenesity of atherogenic foods; and mimics the actions of nitroglycerine; suggested dose, 1800 mg of L-arginine 3 times a day or 4500 mg before bedtime.
- Artichoke (Cynara scolymus) lowers total serum cholesterol and triglycerides; recommended dose, 1 capsule 3 times a day, containing 300 mg of artichoke standardized to contain 13-18% caffeoylquinic acid.
- + Aspirin reduces fibrinogen levels, platelet aggregation, C-reactive protein (CRP), and inflammatory conditions. Low dose aspirin is usually begun at about 50 years of age, according to the American College of Chest Physicians, if no physical condition precludes its usage; suggested dosage, 1 low dose tablet (81 mg a day with a heavy meal). Higher doses may be required to impact newer risk factors such as CRP.
- Bromelain is anti-inflammatory, hypotensive, and anti -anginal. It reduces fibrinogen levels and atrial fibrillation, lessens risk of blood clots, and is particularly beneficial to smokers. Suggested dosage is 1/8 to 1/4 tsp taken between meals to relieve inflammation.
- Bugleweed has diuretic and digitalis-like properties; use 30-40 drops in a little water, 2-4 times a day. (See Angelica in the Therapeutic section for an explanation of milligrams per drop.)
- + Calcium reduces blood pressure, acts as an antiarrhythmic, reduces iron overload, and strengthens the bone around the gingival; preventive and therapeutic doses, 1 gram or more of elemental calcium a day. Factor amount of calcium obtained from foodstuffs into the amount required through supplementation.
- + L-carnitine is an energizer and hypolipidemic, aids weight loss, improves circulation, and is beneficial in angina and diabetic management. Most clinical trials use 1500-3000 mg daily; preventive dosage, 600-1500 mg a day.
- + Carnosine acts as an antioxidant and reduces glycation and possibly the likelihood of stroke damage; suggested dosage, 1000-1500 mg a day. (Not recommended during pregnancy or lactation.)
- Chondroitin sulfate is an anti-inflammatory and antioxidant and inhibits LDL oxidation; suggested daily dose, one to three 400-mg tablets.
- + Chromium, 300-400 mcg a day in divided doses, modulates blood glucose levels; decreases cholesterol; and is helpful in weight management; preventive dosage, 200 mcg a day.
- + Coenzyme Q10 reduces angina attacks, arrhythmias, congestive heart failure, periodontal disease, and heart valve irregularities; lowers blood pressure; is protective to smokers; and supplies energy to the heart; suggested dosage, 30-400 mg a day, depending upon the amount of cardiac support required. (Higher doses require physician supervision.)
- Conjugated linoleic acid (CLA) aids in weight loss and utilization of beneficial fats; reduces cholesterol and triglycerides; increases insulin sensitivity; and has antioxidant activity; suggested dosage, three 1000-mg capsules taken early in the day.
- Curcumin is an anti-inflammatory and hypocholesterolemic; offers protection to smokers; and inhibits platelet aggregation; recommended dosage, 900 mg 1-2 times daily.
- + DHEA suppresses the activity of pro -inflammatory cytokines; inhibits inflammation; and is helpful in lipid management; suggested dosage, 15-75 mg a day, taken early in the day (50 mg a day is a typical dose). Read about DHEA in the Therapeutic section for caveats.
- + Essential fatty acids modulate blood lipids and body weight; improve heart function; lessen risk of re -stenosis and strokes; inhibit platelet clumping; have hypotensive and anti-inflammatory activity; reduce fibrinogen, homocysteine, and C-reactive protein levels; and improve insulin sensitivity. Perilla oil, 1000-mg capsules, provides 550-620 mg of alpha-linolenic acid, a precursor to EPA and DHA. Use 6 capsules a day. Blends of fish oils are available, supplying varying amounts of EPA and DHA. Borage oil is a source of gamma-linolenic acid (GLA). A supplement called Super GLA/DHA provides high concentrations of GLA from borage oil, along with DHA and EPA from fish oil extract.
- Fiber assists in weight management and is a hypolipidemic and antidiabetic. Begin with 1 tsp until the system adjusts to the new material; increase to 1 tsp 3 times a day. It is essential to drink additional water when fiber is added to the diet.
- + Garlic acts as a hypotensive; decreases fibrinogen; protects against LDL oxidation and arterial wall damage; inhibits platelet aggregation; thins the blood; modestly lowers blood glucose levels; and reduces damage associated with iron overload and the incidence of cardiac arrhythmias. Dosage suggestions are 1-2 Kyolic caplets (1000 mg) twice daily with meals or 2-8 capsules of Pure-Gar Caps (900 mg) daily with food.
- Ginger reduces cholesterol and risk of a blood clot and has anti-inflammatory, vasodilating, ACE inhibiting, and calcium antagonistic properties; suggested dosage, one to two 300-mg capsules, 1-3 times a day.
- + Ginkgo biloba improves circulation and memory; reduces platelet aggregation, arrhythmias, and fibrinogen levels; has antioxidant activity; prevents capillary fragility; lessens angina attacks, dyspnea, and intermittent claudication; and decreases the area in the brain plundered by a stroke; suggested dosage, 120 mg a day (preventive dose) and 120-240 mg daily (therapeutic dose). Note: Some clinicians routinely prescribe ginkgo for patients ages 50 and older.
- Grapefruit pectin is an effective hypocholesterolemic. If using the powder, begin with less than 1 scoop a day, gradually increasing to 2-3 scoops. If using tablets, use one 1000-mg tablet a day with meals.
- + Green tea has antithrombotic, antioxidant, hypotensive, anti-inflammatory, ACE inhibiting, calcium and iron antagonistic, diuretic, and beta-adrenergic receptor blocking properties. Drink several cups a day or use two to four 300-mg capsules a day. Each capsule should provide 95% active polyphenols.
- Gugulipid lowers cholesterol and triglycerides; regresses plaque formation; opposes platelet aggregation; and has fibrinolytic activity; suggested dosage, 500 mg 3 times a day.
- Hawthorn berry is an antioxidant, antihypertensive, diuretic, and an aid to weight loss; reduces hypoxia and premature ventricular contractions; lowers cholesterol; is beneficial in congestive heart failure; acts as a vasodilator, ACE inhibitor, and calcium antagonist; and increases exercise tolerance; daily dosages, 250-900 mg a day.
- + The following daily supplements (used alone or in combination) are recommended for lowering homocysteine levels: 500-9000 mg of TMG; 800-5000 mcg of folic acid; 1000-3000 mcg of vitamin B12; 250-3000 mg of choline; 250-1000 mg of inositol; 30-90 mg of zinc; 200-800 mg of SAMe; and 100-500 mg of B6. (Use SAMe with other cofactors listed.)
- + Magnesium reduces blood pressure; acts as a calcium antagonist and anti -arrhythmic; blocks the sympathetic nervous system; and is beneficial in mitral valve prolapse. Use up to 1500 mg in divided doses throughout the day; preventive dose, about 400 mg elemental magnesium a day.
- Niacin lowers Lp(a) and fibrinogen and normalizes cholesterol levels; 1-3 grams of niacin a day may be needed to lower cholesterol, a dose that must be closely monitored. Lower doses of niacin may be effective if taken in union with chromium. If high dose niacin is to be used, liver function tests should be performed regularly.
- Olive leaf extract is hypotensive and antidiabetic; is helpful in some types of arrhythmias; and is protective against LDL oxidation. Use one to two 500-mg capsules 3 times a day, with meals.
- Administering 300 mg of pantethine 3 times a day typically results in a significant improvement in blood lipids.
- Policosanol is hypocholesterolemic; protects LDL cholesterol against oxidation; inhibits thromboxane and the proliferation of vascular cells; discourages blood clot formation; has antiplatelet aggregating activity; and increases exercise tolerance; suggested dose, some individuals will need only 5-10 mg to maintain healthy levels of cholesterol; others will require 20 mg a day.
- Polyenylphosphatidylcholine (PPC) increases levels of beneficial HDL2b, reduces angina attacks, improves exercise tolerance, lowers undesirable blood lipids, and improves apoB/apoA-1 ratio. Take two 900-mg capsules daily.
- + Potassium reduces blood pressure and maintains fluid balance. (The estimated safe and adequate daily dietary intake of potassium, as set by the Committee on Recommended Daily Allowances, is 1.9 grams to 5.6 grams per day.) Many foods richly supply potassium; these sources should be relied upon to meet nutritional needs (when possible). (See the Therapeutic Section for a list of dietary sources plus additional dosing instructions and caveats.)
- + Proanthocyanidins are antioxidants and ACE and beta-adrenergic receptor inhibitors; protect endothelium against white blood cell adherence; reduce blood cholesterol and existing cholesterol deposits; and are beneficial to smokers; the daily dose, 100 mg from grape seed, is considered a preventive dose; 150-300 mg is a therapeutic dose.
- + Selenium is protective against cardiomyopathy and is beneficial in ventricular tachycardia, hyperlipidemia, congestive heart failure, and diabetes; dosage, 200-300 mcg per a day; preventive dose, 200 mcg a per day.
- Taurine is hypotensive; arouses the parasympathetic nervous system; is beneficial in congestive heart failure and arrhythmias; and has blood thinning and diuretic properties; suggested dosage, 1500-4000 mg in divided dosages daily.
- Testosterone modulates cholesterol; dilates blood vessels; improves circulation; lessens angina attacks; and reduces blood pressure. The objective is to restore testosterone level to that of a healthy 21-year-old.
- + Thiamine (vitamin B1) reduces cardiac arrhythmias, palpitations, congestive heart failure, and elevated venous pressure. Some patients may realize benefit from 200-250 mg of thiamine a day; refractory cardiac arrhythmias may require 500-1000 mg a day.
- + Tocotrienols inhibit platelet-clumping; reduce cholesterol; and have antioxidant activity. A suggested daily dosage is 100 IU mixed tocopherols and 100 IU tocotrienols if the person is healthy, young, and without a family history of heart disease, and 200 IU of mixed tocopherols and 200 IU of tocotrienols for young adults with some cardiac risk factors or healthy people (50 years of age) without risk factors. 400 IU of mixed tocopherols and 400 IU of tocotrienols for people who have a personal or family history of cardiac disease. This dosage is appropriate for senior subjects and severely stressed or poorly nourished individuals.
- Beta-carotene (25,000 to 50,000 IU) may assist in modulating fibrinogen levels. Beta-carotene is widely available in 25,000 IU strengths.
- + Vitamin C strengthens and dilates blood vessels; promotes gingival healing; lowers blood pressure; reduces fibrinogen, Lp(a), C-reactive protein, and atheromatous plaque; lessens damage inflicted by smoking; and has diuretic activity; suggested preventive and therapeutic dose, 6 grams daily, in divided dosages.
- + Vitamin D appears to lower risk of heart attack in older women; suggested dosage, 400 IU per a day; if housebound, use 800 IU per a day.
- + Vitamin E assists in preventing plaque formation; protects LDL from oxidation; strengthens blood vessels; prevents blood viscosity; is beneficial in atrial and ventricular fibrillation; reduces C-reactive protein; and is considered an antidiabetic nutrient; suggested preventive and therapeutic dosage, 400-1200 IU of dry powder vitamin E daily.
- + Vitamin K prevents calcium from tying up binding in arteries and reduces the inflammatory process and risk of a blood clot; suggested daily dose, 10 mg.
- + Zinc, 30-60 mg per a day, may increase testosterone levels and is beneficial to diabetics and those who are overweight. Because high doses of zinc can increase blood glucose levels, prediabetics and diabetics should use no more than 35 mg per a day.
Simplifying Your Daily Program
You can take each of the nutrients recommended in this protocol separately if you choose to. This will involve spending a lot of time and money. Most people find it more convenient to take specially designed formulas that provide most of the recommended cardiovascular-protecting nutrients. Here is a brief description of six formulas that provide optimal potencies of most of the nutrients described in this protocol:
Life Extension Mix
This formula contains 89 different ingredients including the following nutrients that have been shown to benefit cardiovascular health:
- Vitamin A
- Beta Carotene
- Alpha carotene
- Vitamin C
- Vitamin E
- Vitamin B1
- Vitamin B6
- Vitamin B12
- Vitamin D
- Vitamin E (alpha - tocopherol)
- Folic Acid
Super Life Extension Booster
This softgel oil capsule provides many important nutrients, including the following that have been shown beneficial in protecting cardiovascular health:
- Vitamin K
- Ginkgo biloba extract
- Gamma tocopherol
- Folic acid
- Vitamin B12
These capsules contain potent anti-aging nutrients, including the following that have demonstrated benefit in preventing and treating cardiovascular disease:
- Alpha Lipoic acid
Provides optimal potencies of essential fatty acids from fish oil (DHA and EPA) plus a potent dose of GLA from borage oil.
Provides high potency coenzyme Q10 in an emulsified oil base along with added tocotrienols.
Participate in Your Healthcare
Laboratory testing to determine values of traditional and newer risk factors are valuable to all age groups. Tests are essential in preventive programs and as a means of monitoring progress for those with established cardiovascular disease. Be sure that you are being tested using the latest in screening tools, that is, technology capable of measuring the smaller, denser LDL particles (the form most susceptible to oxidation) and high sensitivity CRP screening.
There are many ways that you can improve your health odds. Become a participant in your healthcare program. Learn the medical terminology, request specific tests, and suggest and reject various medicines.
Recall that the heart beats best when the host is peaceful and less stressful. Communicate a spirit of contentment and fearlessness to your inner self. Unresolved stress cannot be justified when you realize the price of the aggravation may be life-threatening.
For Assistance Obtaining Blood Tests Reflecting Newer Risk Factors
If you are having difficulty obtaining blood tests reflecting newer risk factors, the Life Extension Foundation will be able to help, and at a substantially lower cost. When you purchase a blood test from the Life Extension Buyers Club, you will be privately paying for the evaluation as opposed to Medicare, Medicaid, or insurance carriers. For information contact
Life Extension Foundation
1100 W. Commercial Blvd.
Fort Lauderdale, FL 33309
Life Extension Mix; Life Extension Super Booster; ChronoForte; Super GLA/DHA; Super CoQ10; alpha-lipoic acid; L-arginine; artichoke leaf extract; aspirin; beta-carotene; bromelain tablets; bromelain powder; calcium; L-carnitine; carnosine; choline; chondroitin sulfate; chromium; CLA; curcumin; DHEA; essential fatty acids; fiber; folic acid; GastroPro (Polyenylphosphatidylcholine); Ginkgo biloba; grape seed-skin extract; green tea; Kyolic Garlic; magnesium; olive leaf extract; Pecta-Sol (citrus pectin); policosanol; Pure Gar Caps; Pure Gar Caps w/EDTA; SAMe; selenium; taurine; TMG; tocotrienols; vitamins A, B1, B3, B6, B12, C, E; and zinc are available by calling (800) 544-4440 or by ordering online.