Why Arginine Failed as a Cardiovascular Drug

L-arginine increases nitric oxide, which enables arteries to expand with youthful elasticity.¹

Back in the 1980s, there was excitement about using the amino acid L-arginine to prevent and treat atherosclerosis.

Boosting nitric oxide improves circulation throughout the body.²

A drug company obtained a patent to sell an L-arginine powder to cardiologists for coronary heart disease patients.

Others promoted the sex-enhancing effects of improved blood flow to male and female genitalia.

L-arginine, however, has some major limitations.

Much of it gets degraded by enzymes before being converted to nitric oxide in the arterial wall.³

With age, the activity of arginine-degrading enzymes increases in many tissues, most notably the cardiovascular system.^4,5

I was pleased to learn of a novel method to protect L-arginine from degrading in the stomach and enhance nitric oxide availability.

This new formula utilizes a low-dose arginine compound to sustain higher arginine plasma levels, plus a berry extract that helps stabilize endothelial nitric oxide.

The berry extract alone was shown to increase a validated measure of circulation.⁶

Low-dose, sustainable L-arginine combined with aronia berry extract offers intriguing potential to support circulatory health.

Cardiologists may eventually prescribe this novel approach now that longer-acting, low-dose arginine plus aronia polyphenols can be conveniently taken together.

Nitric Oxide: “Molecule of The Year”

In 1992, the journal Science nominated nitric oxide as the “Molecule of the Year.”⁷

Not only does nitric oxide support theinner arterial wall to enable healthy circulation, but it is also a neurotransmitter.^8,9

Over the past three decades, nitric oxide has demonstrated value through its diverse applications in medicine. Dr. Solomon Snyder, founder of the Solomon H. Snyder Department of Neuroscience at Johns Hopkins Medical School wrote:

“In my 25 years of research, I have never seen a molecule [nitric oxide] that so pervasively influences normal and abnormal body functions.”¹⁰

Discovering Nitric Oxide’s Health Effects

In 1987, scientists were seeking to “relax” the inner wall of arteries, called the endothelium.¹¹

A major advance occurred when nitric oxide was found to be released from the endothelium.

The release of nitric oxide induces relaxation of the lining of the artery.^8,12

Nitric oxide is now understood to be a principal regulator of blood pressure.

Arginine Needed to Make Nitric Oxide

Nitric oxide is synthesized in the body from the amino acid L-arginine.¹³

Since the mid-1980s, arginine has been a popular supplement for body builders,^14,15 along with aging people wanting to protect against nitric oxide deficit.

L-arginine has demonstrated other benefits, such as accelerating wound healing, and helping to maintain kidney function.^16-18

After more than four decades of study, it appears that the most important role of L-arginine is its ability to produce nitric oxide, and thus protect against endothelial dysfunction (and subsequent atherosclerosis).^19-21

The elderly often suffer from accelerated atherosclerosis.²²

One reason is that nitric oxide-blocking compounds in the body increase with age, thus causing disruption to the artery’s endothelial lining.

It is encouraging to know that arginine is able to helpreverse this particular atherogenic event.²⁰

Reversing Arterial Stiffness

The age-related decline in L-arginine bioavailability reduces nitric oxide production.^4,5

The result is a disruption of healthy endothelial function and structure.²²

Endothelial dysfunction inhibits the ability of arteries to expand and contract (vasodilation). This contributes to hypertension.²³

Arginase is an enzyme present in multiple tissues in the body.²⁴

In the intestinal tract, the arginase enzyme degrades about 40% of ingested arginine before it can be absorbed into the bloodstream.

Once in the bloodstream, L-arginine is further degraded by three other enzymes with only a small amount remaining that can be converted to nitric oxide.^3,25

In one study, when the arginase enzyme was blocked in rat arteries, L-arginine levels went up. While arterial dilation increased only modestly in young animals, it increased an astounding 680% in old animals!²⁶

Even more impressive was that the arteries of old rats (23 months) regained the same vasodilation as young rats (three months) in response to blocking the L-arginine-degrading enzyme called arginase.

This rat study provides evidence of the adverse effects that aging inflicts on the endothelium, including elevated blood pressure.

This study demonstrated that aged arteries can be rejuvenated by providing the vascular system with more L-arginine.

Human Data

More recent studies show that 70-to-80-year-old humans lose up to 75% of their endothelial nitric oxide compared to healthy 20 year olds.^27,28 This helps explain why so many elderly people suffer vascular disorders, and how fast they sometimes accelerate after initial diagnosis.

One problem up to now has been that people could not obtain arginine’s benefits because of its rapid enzymatic degradation in the intestines and blood.³

Protect Against Endothelial Dysfunction

Aging people can slow the breakdown of their delicate endothelium (inner artery wall linings).

Folate, vitamin C, fish oil, lipoic acid, and pomegranate are a few of the nutrients that help maintain healthy endothelial function.^29-36

It is no coincidence that these same nutrients have been shown in some studies to reduce the incidence of cardiovascular pathology in animals and humans.^37-42 Statin drugs and agents that suppress chronic inflammation also help protect the endothelium.^43-46

Nitric oxide is one important factor required for the endothelium to function properly.

The amino acid L-arginine serves as a precursor to nitric oxide in the body.

Challenge of Obtaining Arginine Benefits

A major drawback to L-arginine supplementation has always been that, in order to achieve a sustained blood level, people had to take high doses throughout the day. It was difficult to comply with this rigorous dosing requirement and there may be side effects with ingesting this much arginine on a consistent basis.

A more troublesome shortcoming of L-arginine is the age-related increase in the activity of the arginase enzyme that rapidly degrades arginine. This means that little ingested arginine is available to promote nitric oxide synthesis.^3,24

For people with increased arginase activity, supplemental L-arginine may not provide adequate nitric oxide synthesis to protect against endothelial dysfunction.

Dual Combination to Boost Nitric Oxide

In a significant advance, a form of arginine has been shown to decrease the arginase enzyme, allowing L-arginine to remain present in the plasma for a greater length of time.⁴⁷

In a preclinical study, polyphenols from aronia berries demonstrate the ability to increase activation of an enzyme called endothelial nitric oxide synthase that is responsible for producing nitric oxide from arginine.⁴⁸

In addition, these polyphenols have been shown, in another preclinical study, to stimulate nitric oxide formation in coronary arteries.⁴⁹

This means that lower doses of L-arginine can be used to enable more sustained nitric oxide synthesis needed for healthy endothelial function.

Support for Aging Arteries

People who follow a healthy lifestyle often develop a false sense of security that they will not suffer the circulatory disorders that are the leading killers in the Western world.

One reason for this optimism is that heart disease death rates have declined dramatically since 1980.⁵⁰ Much of this can be attributed to reduced tobacco use, improved diets and medical treatments, better control of hypertension, along with increased use of supplements, and drugs that lower heart attack risk.⁵¹

A lot of people who would have suffered from blocked coronary arteries or a heart attack around age 50 are delaying this problem until later in life.

Atherosclerosis is usually associated with heart attack risk, but many of the disorders of aging, including kidney impairment and memory loss, are related to circulatory disorders.^52-54

Sales of sex-enhancing drugs are strong mainly because so many men suffer from endothelial dysfunction that causes erectile dysfunction.⁵⁵

In this issue of Life Extension®, we describe a novel approach to help prevent and/or partially reverse endothelial dysfunction.

Life Extension® readers take aggressive steps to maintain healthy circulation, but haven’t had access to a slowly released, continuous flow of L-arginine to boost nitric oxide.

For longer life,

William Faloon, Co-Founder

Life Extension Buyers Club

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