Life Extension Magazine

Life Extension Magazine September 2006

Report

Why Aging Humans Need More Carnitine

By Julius G. Goepp, MD

By Julius G. Goepp, MD

Propionyl-L-Carnitine Enhances Muscle Energy

Another advanced carnitine formulation, known as propionyl-L-carnitine, is gaining increasing recognition for its role in increasing muscle energy.

Evidence of Targeted Cardiovascular Effects

Because of carnitine’s impact on both muscle and energy utilization, it is an ideal supplement to improve one of the body’s most important muscles—the heart.

Scientists have looked at numerous applications of propionyl-L-carnitine for cardiac health. Scientists believe that propionyl-L-carnitine appears to work by protecting heart muscle cells from damage caused by lack of blood flow (ischemia) and the subsequent free radical damage that can occur following restoration of blood flow (reperfusion).39-43 Propionyl-L-carnitine quickly penetrates into heart muscle cells,43 an effect thought to account for its superiority in supporting heart muscle recovery following a heart attack (myocardial infarction).3,44 In animal models of heart attack, propionyl-L-carnitine not only prevented tissue damage related to lack of blood flow (ischemia), but also prevented further progression of existing damage.45 Propionyl-L-carnitine’s antioxidant effects46 have been shown to protect animal tissues from damage related to hypertension, another source of danger to the cardiovascular system.47

This impressive animal data prompted researchers to explore propionyl-L-carnitine’s potential benefits in managing heart disease in humans.48 An early study demonstrated that intravenous administration of propionyl-L-carnitine in a small group of patients with chronic ischemic heart disease improved the heart’s left ventricular function by enhancing cardiac muscle efficiency.49 In a separate study, propionyl-L-carnitine greatly improved exercise tolerance in those with stable chest pain, without contributing to changes in heart rate or blood pressure.50

Because of the increased vulnerability of diabetics’ hearts to injury, researchers in 2005 examined the effects of propionyl-L-carnitine on chemical markers of heart muscle blood flow during coronary surgery.51 The study authors concluded that propionyl-L-carnitine improved multiple aspects of heart function during surgery, through mechanisms affecting metabolism and blood vessel function. These findings have important implications for protecting heart health in at-risk groups, such as people who have diabetes or require cardiac surgery.

Beneficial Actions in Skeletal Muscle

Propionyl-L-carnitine has important effects on skeletal as well as cardiac muscle. As early as 1990, a human study demonstrated that propionyl-L-carnitine could combat the destructive effects of low oxygen status and muscle fatigue.52 By 1997, propionyl-L-carnitine was found to contribute to the body’s ability to increase muscle glycogen stores.53 Since glycogen is the body’s most immediately available form of glucose energy storage, this observation likely explains propionyl-L-carnitine’s fatigue-reducing effects.

In peripheral arterial disease, plaque-filled arteries reduce blood flow to the muscles, resulting in pain and cramping in the legs with activity. However, very recent studies of propionyl-L-carnitine in this context have shed new light on the phenomenon of peripheral arterial disease. An article published in 2004 points out that the pain of peripheral arterial disease can also be caused by alterations in skeletal muscle metabolism.54 The authors note that propionyl-L-carnitine helped increase treadmill walking distance and may improve the metabolic performance of the skeletal muscles in these patients.

Success in Fighting Sexual Dysfunction

Both propionyl-L-carnitine and acetyl-L-carnitine can help men with sexual dysfunction. In one study, scientists looked at a group of diabetic men suffering from erectile dysfunction. They found that men who took propionyl-L-carnitine plus Viagra® showed significant measurable improvements compared to men who took only Viagra®.55

In a related study of sexual dysfunction in aging males, researchers gave patients testosterone, a combination of acetyl-L-carnitine and propionyl-L-carnitine, or placebo.While both testosterone and the carnitine combination notably improved penile blood flow and night-time erections, as well as the International Index of Erectile Dysfunction, depression, and fatigue scores, the carnitine combination outperformed testosterone on measures of erectile function.56 The authors concluded that the carnitine combination was especially useful in managing sexual dysfunction as well as other symptoms associated with male aging.

One of the most dreaded aspects of prostate surgery is the potential side effect of erectile dysfunction. The same investigators mentioned above also examined the effects of propionyl-L-carnitine and acetyl-L-carnitine in restoring sexual function after radical prostate surgery. They concluded that the combination of propionyl-L-carnitine and acetyl-L-carnitine safely and reliably augmented Viagra®’s effectiveness in restoring sexual function following prostate surgery.57

Acetyl-L-Carnitine Arginate May Halt Brain Aging

Acetyl-L-carnitine arginate—which is simply acetyl-L-carnitine with an additional molecule of arginine attached—may be the most important of all forms of carnitine in preventing age-related disease. This addition of arginine appears to give the molecule privileged access to nerve cells, priming them for the effects of nerve growth factor and other factors important in the development and function of nerve cells.58,59

Acetyl-L-carnitine alone is known to be neuroprotective, reducing the rate of nerve cell death in cultured cells exposed to some of the neurotoxic agents that are important in the development of Alzheimer’s disease.16 The observation that acetyl-L-carnitine makes cultured nerve cells much more sensitive to the effects of nerve growth factor,60,61 thereby rescuing them from the effects of aging, led scientists to seek out other compounds with this remarkable capability. What they found was that acetyl-L-carnitine arginate produced rapid differentiation of early brain cells into mature neurons, while increasing the cells’ content of GABA, an important neurotransmitter.62

A subsequent study demonstrated that acetyl-L-carnitine arginate increased the availability of crucial calcium channels in nerve cells by a factor of more than four—even more than the increase produced by nerve growth factor itself.59 This means that acetyl-L-carnitine arginate not only enhances the growth of nerve cells, but also increases their ability to respond to calcium ions in performing their primary function of transmitting electrical signals. A later study showed that acetyl-L-carnitine arginate’s effect on calcium channels was responsible for the supplement’s ability to rescue nerve cells in culture from the toxic effects of amyloid beta peptide, which is thought to play a role in Alzheimer’s disease.63

In 1995, researchers published the remarkable finding that acetyl-L-carnitine arginate stimulated the outgrowth of neurites, the minute projections from nerve cell bodies that lead to new connections (synapses) between cells and allow increased signaling throughout the central nervous system (comprising the brain and spinal cord).64 Aging in the central nervous system involves a loss of neurons and a reduction in the number of synapses between the surviving cells, possibly as a result of declining levels of nerve growth factor.64

The research group’s insight was connecting acetyl-L-carnitine’s effects in stimulating nerve growth factor activity with acetyl-L-carnitine arginate’s ability to increase cell survival. Their experiment demonstrated that acetyl-L-carnitine arginate increased neurite outgrowth and did it independently of common growth factors—meaning that it might actually be capable of replacing, and not just augmenting, nerve growth factor in the aging brain.64 Acetyl-L-carnitine arginate may thus be a key component of a therapeutic strategy to avert the neurodegenerative diseases of aging.

Summary

The discovery of carnitine’s ability to maximize cellular fuel efficiency while minimizing the wear and tear on delicate cellular machinery has led to a revolution in the way scientists think about some of the most troubling age-related conditions.

The recognition that several advanced formulations of carnitine—including acetyl-L-carnitine, propionyl-L-carnitine, and acetyl-L-carnitine arginate—have very different and complementary effects opens the door to “customized” supplementation regimens, in which individuals can choose the types of carnitine that are most beneficial in addressing their unique health concerns.

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