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Cerebral Vascular Disease
Alpha-Lipoic Acid
Alpha-lipoic acid is a commercially available supplement with a variety of actions that may be beneficial during acute stroke. These actions include inhibiting platelet and leukocyte activation and adhesion, reducing free-radical generation, and increasing cerebral blood flow.
The effects of alpha-lipoic acid were studied on strokes induced in mice. Alpha-lipoic acid (100 mg/kg subcutaneous injection) or placebo was administered 1.5 hours before transient middle cerebral artery occlusion was induced. Infarct volume was significantly reduced, and neurologic function was significantly improved in the alpha-lipoic acid group as compared to placebo (Clark et al. 2001).
Most of the tissue damage that occurs from a stroke is observed during reperfusion, which is primarily attributed to oxidative injury from the production of oxygen free radicals. During the process, antioxidants such as glutathione and alpha-lipoic acid are depleted. Pretreatment with alpha-lipoic acid in rats subjected to reperfusion following cerebral ischemia dramatically reduced the mortality rate from 78% to 26% during 24 hours of reperfusion (Panigrahi et al. 1996).
Another study examined the neuroprotective effects of alpha-lipoic acid using models of focal cerebral ischemia in mice and rats. Alpha-lipoic acid was able to reduce the infarct area only when it was administered subcutaneously 1-2 hours before the occlusion of the middle cerebral artery (Wolz et al. 1996).
Minerals
Calcium, magnesium, and potassium are the most abundant minerals in the body. They play an important role in many of the functions of the body.
Calcium
Calcium is needed for the transmission of signals between neurons. Ionized calcium initiates the formation of blood clots. It stimulates the release of thromboplastin from platelets and is a cofactor in the conversion of prothrombin to thrombin.
An article in the journal Stroke described a study of calculated dietary intakes of calcium, potassium, and magnesium in the Nurses' Health Study cohort. Women in the highest quintile of calcium intake had an adjusted relative risk of ischemic stroke that was 31% lower compared with those in the lowest quintile; for potassium intake the corresponding relative risk was 28% lower. The authors concluded that low calcium intake (and perhaps low potassium intake) may contribute to increased risk of ischemic stroke in middle-aged American women (Iso et al. 1999).
Magnesium
Magnesium regulates the absorption of calcium and complements its actions. Magnesium is a natural medicine calcium channel blocker which inhibits calcium ions into cells and can reduce stroke risk. Calcium functions to contract muscles, while magnesium relaxes them. Taking too much magnesium will loosen the stools, causing diarrhea. Magnesium also functions to decrease coagulation, while calcium is involved in increasing coagulation. It is important to maintain a proper ratio between calcium and magnesium.
The use of magnesium in acute stroke cases is at present controversial. Several studies report positive effects, while others do not. There are several reasons for this. The time-to-treatment variable is important because the damage from a stroke happens quickly. Studies in rats show that magnesium is extremely effective if used within 2 hours, but the effectiveness rapidly decreases. A 6-hour window of opportunity is recommended (Yang et al. 2000).
An interesting article in the journal Alcohol proposed that intravenous magnesium may be particularly useful in alcohol-induced hemorrhagic strokes , which are preceded by a rapid fall in intracellular free magnesium ions. They also propose that women are more prone to this fall in magnesium due to the hormonal effects on free magnesium. In support of this hypothesis, they state that premenstrual tension headaches and alcohol-induced headaches (e.g., hangovers) can be ameliorated with intravenous injections of magnesium sulfate (Altura et al. 1999; Babu et al. 1999).
A randomized, placebo-controlled, double-blind study examined the effects of magnesium sulfate given intravenously during the first 24 hours following a stroke. Intravenous magnesium was shown to have a significant positive effect (Lampl et al. 2001).
Potassium
Potassium is also used by the body for conducting impulses between neurons. Potassium works with sodium to maintain muscle tone, blood pressure, and water balance. Studies have shown that a low potassium diet is related to a higher incidence of stroke (Bazzano et al. 2001). In a study reported in Circulation, diets rich in potassium, magnesium, and cereal fiber reduced the risk of stroke, particularly among hypertensive men. The authors concluded that potassium supplements may also be beneficial, but because of potential risks, use of potassium should be carefully monitored (Ascherio et al. 1998).
Selenium
Selenium is a trace mineral that is involved in the synthesis of glutathione peroxidase, a key detoxification enzyme. A study examined the association between serum selenium concentration and 5-year risk of cardiovascular disease in 1110 men aged 55-74 years in two rural areas of Finland . In the total cohort, all-cause and cardiovascular deaths were associated significantly with serum selenium of less than 45 mcg/L, with an adjusted relative risk of 1.4 and 1.6, respectively. 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).
Homocysteine-Lowering Supplements
Elevated levels of serum homocysteine strongly predict stroke risk. Homocysteine detoxification requires several nutrients, including vitamin B6, vitamin B12 (cobalamin), and folic acid. Although these three vitamins are currently well publicized, other nutritional factors are also involved in detoxifying homocysteine. Methyl donors, such as trimethylglycine (TMG) and SAMe, are also needed.
B Vitamins and Trimethylglycine (TMG)
Currently, several studies are underway to evaluate the effectiveness of lowering homocysteine with vitamins. The Vitamins in Stroke Prevention (VISP) study is evaluating vitamin B6, B12, and folic acid in patients at least 35 years old that had a nondisabling ischemic stroke within 120 days and high plasma homocysteine (Spence et al. 2001).
The Life Extension Foundation recommends that people measure their homocysteine levels. Homocysteine is of particular concern for those at risk of stroke and victims of stroke. Supplementation with vitamin B6, vitamin B12, folic acid, and trimethylglycine are essential for stroke risk reduction in those whose homocysteine levels are above 7.2 (micromol/L) of blood. The methylating effects of TMG produce SAMe which has been shown to ease depression and remyelinate nerve cells. TMG should be taken with the B vitamin cofactors mentioned above for the full effects to be reached. See the Cardiovascular Disease protocol for more information.
SAMe
S-adenosyl-L-methionine (SAMe) is an amino acid made naturally in the body. It has been shown to be a potent antidepressant in several double-blind studies (Bell et al. 1988; Kagan et al. 1990). SAMe is so effective that it has rapidly become one of the best-selling dietary supplements in the United States . Studies found that SAMe increases glutathione levels and decreases free radical activity. SAMe also inhibits lipid peroxidation. SAMe is a methyl donor that improves brain methylation which may account for its antidepressant properties.
In experiments with rats, SAMe was found to increase cellular energy levels (ATP and cAMP) and suppress the elevation of lactic acid that commonly follows ischemia. The authors concluded that SAMe protected energy failure and accelerated recovery from ischemia and that it is beneficial for treatment of cerebral ischemia in the acute stage (Katayama et al. 1985).
Cholesterol-Lowering Supplements
Policosanol
Policosanol is a natural supplement made from sugarcane. The main ingredient is octacosanol, an alcohol found in the waxy film that plants have over their leaves and fruit.
Octacosanol is a "long chain fatty alcohol" (similar to cholesterol which is also an alcohol). Policosanol is a combination of octacosanol and several other long chain fatty alcohols--hence the name "poli"-cosanol. Keeping octosanol together with other naturally occurring fatty alcohols makes it more stable. There is evidence that octosanol also works better when it is combined with other fatty alcohols. Research has shown that policosanol has the following benefits:
- Lowers cholesterol. Several studies have compared policosanol with pr a o vastatin, lovastatin, and sim-vastatin. Policosanol was found to be more effective than all three at lowering LDL and total cholesterol, increasing HDL cholesterol, and improving the ratios of LDL to HDL and total cholesterol to HDL (Castano et al. 1999; Crespo et al. 1999; Prat et al. 1999).
- Inhibits the oxidation of LDL (Menendez et al. 1999). Oxidized LDL is dangerous. It promotes the destruction of blood vessels by creating a chronic inflammatory response. Oxidized LDL can also provoke metalloproteinase enzymes (Xu et al. 1999). These enzymes promote blood vessel destruction, partly by interfering with HDL's protective effect. Studies show that rats treated with policosanol have fewer foam cells, reflecting less inflammatory response causing less blood vessel destruction (Noa et al. 1996; Lindstedt et al. 1999).
- Reduces the proliferation of cells. Healthy arteries are lined with a smooth layer of cells so that blood can race through with no resistance. One of the features of diseased arteries is that this layer becomes thick and overgrown with cells. As the artery narrows, blood flow slows down or is blocked completely. Policosanol was tested for its ability to stop the proliferation of these cells (Noa et al. 1996). According to the results, policosanol's ability to stop cell overgrowth "is in agreement with the anti - proliferative effects reported for other lipid-lowering drugs, such as most of the statins" (Negre-Aminou et al. 1996).
- Inhibits the formation of clots. Policosanol may work synergistically with aspirin in this respect. In a comparison of aspirin and policosanol, aspirin was better at reducing one type of platelet aggregation (clumping together of blood cells). But policosanol was better at inhibiting another type. Together, policosanol and aspirin worked better than either alone (Arruzazabala et al. 1997; Stusser et al. 1998). A related effect is that significant reductions in the level of thromboxane occur in humans after 2 weeks of policosanol (Carbajal et al. 1998). Thromboxane is a blood vessel-constricting eicosanoid produced by platelets.
Note: Eicosanoids are powerful chemicals created in cells that can do things such as create fever to kill infections; cause blood vessels in lungs to expand so you can breathe; and reduce inflammation. The body could not function without eicosanoids. Problems arise when eicosanoid reactions are disrupted by drugs, disease, poor diet, and other factors that interfere with their natural balance.
- Decreases thrombus weight. Policosanol was shown to significantly decrease the thrombus weight in venous thrombosis experimentally induced in rats, with the protective effect persisting up to 4 hours after its oral administration (Carbajal et al. 1994).
Garlic
Garlic is a well-known herb that is of great benefit in decreasing the risk of arteriosclerosis. It has been shown to decrease total and LDL-cholesterol; increase HDL-cholesterol; reduce serum triglyceride and fibrinogen concentration; lower arterial blood pressure and promote organ perfusion; enhance fibrinolysis; inhibit platelet aggregation; and lower plasma viscosity.
In a prospective, 4-year clinical trial, standardized garlic caused a 9-18% reduction and 3% regression in plaque volume; a decrease in LDL level by 4%; an increase in HDL concentration by 8%; and lowering in blood pressure by 7%. These effects resulted in a reduction of relative cardiovascular risk for infarction and stroke by more than 50% (Siegel et al. 1999).
Fibrinogen-Lowering Supplements
Low-dose aspirin and certain nutrients can provide partial protection against abnormal blood clots, but if you have high fibrinogen levels, additional measures should be taken to prevent heart attack and stroke. Platelet-aggregation inhibitors reduce the risk of fibrinogen causing an abnormal blood clot. Some effective nonprescription platelet-aggregation inhibitors include low-dose aspirin, green tea, ginkgo biloba, garlic, and vitamin E.
High vitamin A and beta-carotene serum levels have been reported to reduce fibrinogen levels in humans. For example, animals fed a vitamin A-deficient diet have an impaired ability to break down fibrinogen, but when they are injected with vitamin A, they produce tissue plasminogen activators that break down fibrinogen (Kooistra et al. 1991). A study in the October 1997 Diabetes Care Journal indicates that no one antioxidant may be effective and that total antioxidant capacity is important in reducing the risk associated with fibrinogen and cardiovascular disease (Ceriello et al. 1997).
Additionally, both fish and olive oil have been shown to lower fibrinogen in women with elevated fibrinogen levels (Oosthuizen et al. 1994). The minimum daily amount of fish oil required to produce a fibrinogen-lowering effect is 6 grams. In study results reported in the July 1997 issue of the American Journal of Clinical Nutrition, researchers at Louisiana State University (Baton Rouge) indicated, based on two randomized, double-blind, placebo-controlled, parallel studies conducted in human subjects, that increasing the amount of fish oil consumed to 15 grams a day "decreased fibrinogen concentrations" (Hwang et al. 1997).
Elevated homocysteine levels have been shown to block the natural breakdown of fibrinogen by inhibiting the production of tissue plasminogen activators (Midorikawa et al. 2000). Folic acid, trimethylglycine (TMG), and vitamins B12 and B6 significantly reduce elevated homocysteine levels.
The therapeutic benefits of vitamins B6 and B12 were discussed in a 1998 Cardiovascular Reviews and Reports (United States), reinforcing the use of these vitamins as part of an integrated therapy or disease prevention approach. Another study in 1998, based on data from 80 clinical and epidemiological studies that included more than 10,000 patients, suggested that supplementation with B vitamins, in particular with folic acid, is an efficient, safe, and inexpensive means to reduce the elevated homocysteine levels implicated in cardiovascular risk and disease (Refsum et al. 1998).
Since the 1980s, vitamin C has been studied and found beneficial in the reduction of fibrinogen levels. In a report 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 detectable change in fibrinolytic activity (fibrinogen breakdown) or cholesterol. At 2000 mg a day of vitamin C, however, there was a 27% decrease in the platelet-aggregation index, a 12% reduction in total cholesterol, and a 45% decrease in fibrinolytic activity (Bordia 1980).
For additional fibrinogen-lowering effect, the proteolytic enzyme bromelain derived from the pineapple plant may also be effective for coagulation inhibition (Lotz-Winter 1990).
For those seeking to lower elevated fibrinogen levels and inhibit coagulation, 2-6 capsules a day of a supplement called Herbal Cardiovascular Formula containing a standardized bromelain concentrate should be considered.
Low-dose niacin was reported effective in reducing plasma fibrinogen in a 1998 American Journal of Cardiology study that "demonstrated that niacin supplementation decreases plasma fibrinogen and low-density lipoprotein cholesterol in subjects with peripheral vascular disease." The researchers reported further that those changes in fibrinogen levels are highly correlated with changes in low-density lipoprotein cholesterol in subjects taking niacin (Philipp et al. 1998).
While niacin is considered relatively safe, like cholesterol-lowering prescription drugs, it can cause liver toxicity when taken in high doses. Monitoring liver enzymes every 6 months is important when taking more than 1000 mg of niacin a day. Those with hepatitis should avoid niacin to avoid complications. |