Life Extension Magazine October 2005
Why Our Arteries Become Clogged As We Age
By John Colman
Maintaining Vascular Health During Aging
Endothelial cells line the arteries, veins, arterioles, and capillaries of the vascular system. Twenty years ago, the endothelium was seen as a relatively inert structure that played no active role in vascular function. Since then, however, research has shown that the endothelium is dynamic and participates in vital aspects of arterial structure and function.39
Arterial blood vessel dilation depends on endothelial cells triggering the production of a signaling molecule called cyclic guanosine monophosphate (cyclic GMP) in the muscle cells. Cyclic GMP prompts a change in calcium flux at the smooth muscle cell surface, producing relaxation of the muscle. Relaxation of the artery muscle cells allows the artery to expand and then subsequently contract, helping to pump blood back to the heart.40 Nitric oxide production by endothelial cells also regulates vascular tone, changes cardiac contraction, prevents vessel injury, and helps prevent the development of atherosclerosis. Once atherosclerosis is present, however, endothelial cells cannot function properly, and this blocks nitric oxide-induced dilation, thus stiffening the arteries.
The endothelium’s ability to manufacture enough nitric oxide to maintain artery dilation is one of its most crucial functions. When arteries lose their ability to respond to sudden increased demand for blood flow, endothelial dysfunction develops. This condition is a hallmark of cardiovascular disease.
Endothelial dysfunction is also the earliest measurable functional abnormality of the vessel wall. Tests of endothelial dysfunction may detect abnormalities in the initial stages of atherosclerotic disease before clinical symptoms are present.40,41 In subjects with coronary artery disease, hypertension, and hypercholesteremia, endothelial dysfunction is always present.41 Furthermore, endothelial dysfunction is present in type I and type II diabetes, and is related to the development of diabetic vascular complications.41
Preventing endothelial dysfunction may be possible through innovative nutritional strategies. Emerging research suggests that propionyl-L-carnitine and PEAK ATP™ may protect cardiovascular health by preventing endothelial dysfunction, restoring healthy endothelial function, and optimizing the energy available to cardiac and vascular cells. PEAK ATP™ also works synergistically with propionyl-L-carnitine to protect cardiovascular function while promoting enhanced cellular energy for people with conditions ranging from chronic fatigue syndrome to erectile dysfunction.42,43
Research suggests that propionyl-L-carnitine (PLC) plays an important role in protecting the function and health of endothelial cells.44-46 Studies also indicate that PLC may act as a nutritional corrective agent, relieving clinical symptoms of cardiovascular conditions such as peripheral arterial disease, angina, coronary artery disease, cardiomyopathy, intermittent claudication, ischemic heart disease, atherosclerosis, and congestive heart failure.47-54 PLC appears to be more potent than L-carnitine in improving vascular function.55
PLC passes across the mitochondrial membrane to supply L-carnitine directly to the mitochondria, the energy-producing organelles of all cells. Carnitines are essential for mitochondrial fatty acid transport and energy production. This is important because heart muscle cells and endothelial cells burn fatty acids rather than glucose for 70% of their energy. By contrast, most cells generate 70% of their energy from glucose and only 30% from fatty acids.56
Carnitine deficiency has been associated with congestive heart failure.50 PLC supplementation has been reported to increase exercise capacity, optimize energy production, and reduce ventricular size in patients with congestive heart failure.50
The myocardium, the muscular substance of the heart, comprises cells called cardiomyocytes. A study of cardiomyocytes found that PLC helped to correct an imbalance between the production and utilization of adenosine triphosphate (ATP), the energy currency used throughout the body. This suggests that PLC may improve cardiac performance by improving energy metabolism and optimizing ATP levels.57
An animal study suggests PLC may help to prevent or decrease the severity of atherosclerosis. In rabbits fed a high-cholesterol diet, which normally induces endothelial dysfunction and subsequent atherosclerosis, supplementation with PLC resulted in reduced plaque thickness, markedly lower triglyceride levels, and reduced proliferation of foam cells, thereby preventing the progression of atherosclerosis.53
PLC has been shown to have a protective role against vascular cell inflammation that other carnitines do not. When rodents were exposed to irritating chemicals, PLC protected their vascular cells from this source of damage, but L-carnitine and acetyl-L-carnitine did not, leading the study authors to support “a specific protective role of PLC in the vascular component of the inflammatory process.”45
PLC improves endothelial function by increasing nitric oxide production in animals with normal blood pressure and in animal models of hypertension. The increased nitric oxide production induced by PLC is related to its antioxidant properties; PLC reduces reactive oxygen species and increases nitric oxide production in the endothelium in the presence of superoxide dismutase (SOD) and catalase.58
Oxygen-deprived endothelial cells produce large amounts of free radicals. Laboratory findings suggest that PLC protects these cells during periods of oxygen deprivation. When blood flow is restored, PLC also allows the cells to regain their lost energy charge much faster.46
An animal study indicates that PLC prevents abnormal heart muscle function associated with diabetes. The researchers found that PLC significantly increased both fatty acid and glucose utilization while restoring cardiac muscle function. These findings suggest PLC prevents diminished cardiac function associated with diabetes, possibly by promoting a favorable shift in glucose and fatty acid metabolism.59
PLC Improves Physical Performance
Intermittent claudication is a condition caused by narrowing of the leg arteries. Patients typically experience pain in their calf muscles that makes walking long distances difficult or impossible.
In a 24-week study, patients supplemented with PLC gradually increased the distance they were able to walk on a treadmill by up to 73%. The study authors concluded, “The response rate during the entire titration course was significantly in favor of [PLC] compared with placebo. Although the precise mode of therapeutic action requires clarification, [PLC], at a dose of 1000 mg to 2000 mg a day appears to be effective and well tolerated, with minimal adverse effects.”60
Several studies have shown that PLC increases the walking capacity of patients with peripheral arterial disease. A study comparing PLC to L-carnitine showed that PLC increased patient walking distance from 245 to 349 meters, while carnitine was only slightly better than placebo.55 Ultrasound testing found that PLC acts through a metabolic mechanism rather than by altering blood velocity or flow.55 Another study suggested that PLC increases muscle strength in patients with peripheral arterial disease.54
PLC and Male Sexual Dysfunction
In a study of male sexual dysfunction, testosterone supplementation was compared to supplementation with a combination of oral PLC and acetyl-L-carnitine. Both the carnitine combination and testosterone improved the following penile functions: peak systolic velocity, end-diastolic velocity, resistive index, nocturnal penile tumescence, and the International Index of Erectile Function score.
The combination of 2 grams each of PLC and acetyl-L-carnitine daily was more effective than testosterone at improving nocturnal penile tumescence and the International Index of Erectile Function score, an important measure of erectile and sexual function. PLC and acetyl-L-carnitine thus appear to be safe, effective agents for managing male sexual dysfunction.42
PLC and Chronic Fatigue
In a landmark study, researchers examined carnitine’s effects on patients with chronic fatigue syndrome. In this 24-week study, investigators followed three groups of 30 patients who supplemented daily with 2 grams of acetyl-L-carnitine, 2 grams of PLC, or a combination of the two.
The results were remarkable: the clinical global impression of change after treatment improved significantly in 59% of the patients taking acetyl-L-carnitine and in 63% of patients taking PLC. While the main effect of acetyl-L-carnitine was improving mental fatigue, PLC helped to improve symptoms of general fatigue.43
Replenishing Cellular Energy Stores
Adenosine triphosphate (ATP) is the primary molecule used by all human cells as energy currency. ATP is stored in the organs and red blood cells, but is especially concentrated in the liver. A study measuring ATP levels in human red blood cells found that people in their seventies had about 50% less ATP than young adults in their twenties.61
For 40 years, scientists have worked to create an effective, orally ingested form of ATP that is able to boost endogenous ATP levels. Five years ago, they developed an orally administered ATP that can effectively raise pools of ATP throughout the body.62-64 Orally administered ATP expands ATP in the liver, red blood cells, blood plasma, and organs. Supplemental ATP improves blood vessel tone and relaxes blood vessel walls, increasing blood flow to the lungs, heart, and peripheral areas without affecting heart rate or blood pressure.62-64
ATP supplementation can also elevate the body’s intracellular and extracellular stores of ATP, providing increased energy and improved athletic performance. Additionally, ATP supplementation enhances the delivery of glucose, nutrients, and oxygen to recovering and working muscles, while speeding the muscles’ removal of waste products. ATP benefits muscle growth, recovery, and strength, and lessens the perception of fatigue and exercise-associated pain.62 Supplementing with ATP helps to restore youthful levels of ATP in the body.62,63,65,66
Studies Confirm Benefits of PEAK ATP™
The patented brand of ATP tested in numerous human and animal studies—PEAK ATP™—elevates red blood cell and plasma ATP levels, producing effects similar to those achieved by intravenous ATP administration.62-64 Studies show that PEAK ATP™ is readily absorbed, broken down into adenosine and organic phosphate, and incorporated in the liver and red blood cells to raise ATP pools. PEAK ATP™ boosts circulating ATP levels for at least six hours and should reach a steady-state plasma level within 24 hours.62-64
When administered orally to rabbits, ATP regulates and normalizes their cardiopulmonary functions, increasing blood flow, reducing overall vascular resistance, and increasing arterial oxygen pressure.65 In baboons, ATP infusions increased cerebral blood flow by nearly 50% and boosted oxygen consumption in the brain.65
During exercise, vascular blood flow increases due to the release of ATP into the blood. Infusing ATP into the legs of resting subjects increases blood flow in the thighs similar to that produced by exercise, suggesting that exogenously administered ATP may likewise promote increased circulation.66
Recent studies show that arterial and vein diameter is regulated by red blood cells sensing low blood oxygen levels. The red blood cells then release ATP, which produces endothelial vasodilation, or widening of the arteries. This mechanism of artery widening has been demonstrated in studies involving various species and tissues.67,68 Thus, red blood cells use ATP to help meet local tissue oxygen needs. Ensuring adequate red blood cell pools of ATP to help regulate vascular tone is now seen as critical to maintaining circulatory health.68
ATP release decreases with advancing age, which may be a cause of age-related increases in blood pressure. In fact, patients with primary pulmonary hypertension have been shown to suffer from impaired ATP release from red blood cells.69 This is also true of patients with cystic fibrosis who also develop pulmonary hypertension.70
Adenosine, a breakdown product of ATP, may act as an endogenous protector of the heart. Research suggests that through various chemical processes, adenosine may inhibit the damaging effects of ischemic heart disease and heart failure.71 Adenosine may increase coronary blood flow and alleviate the harmful effects of chronic heart failure.71
Adenosine is released from the heart primarily when the heart’s oxygen supply is limited as a result of increased oxygen consumption during exercise, restricted blood flow due to atherosclerosis, or ischemic events such as heart attack.71 Thus it is vitally important to maintain optimal levels of adenosine produced by the heart and arteries internally, as well as of adenosine supplied from external sources such as dietary plant and animal foods