The Nation's Health

l-arginine: How important is l-arginine?

Perhaps more than any other supplement, l-arginine causes frustration and confusion. It’s difficult to find, sometimes quite expensive, and some preparations cause loose stools.

Just how necessary is it?

L-arginine, you’ll recall, is a source of nitric oxide, or NO. Though it’s the same stuff as in car exhaust, NO provides a critical signaling role in your body’s cells that regulate a multitude of functions. Among the important roles of NO is to powerfully dilate, or relax, arteries. A constant flow of NO is required for health, particularly since each molecule persists only a few seconds.

L-arginine is the body’s source of nitric oxide. In addition, a peculiar but very effective blocker of l-arginine called asymmetric dimethylarginine, or ASDM, has recently been discovered to prevent the production of NO. Varied conditions like hypertension, diabetes, high cholesterol, excessive saturated fat or processed carbohydrate intake all lead to heightened levels of ASDM, often several-fold greater levels, and thereby effectively blocking NO production.

The “Arginine Paradox” is the name that some researchers in this field have given to the unusual property of l-arginine supplementation to “overpower” the blocking effects of ASDM. This is somewhat unusual in biologic systems in that an agent that blocks a receptor cannot usually be outmuscled by providing excess material for a reaction. Kind of like hoping that your car runs faster simply by topping up the gas tank.

Concrete observable benefits have been made for l-arginine in clinical trials, such as arterial relaxation that results in arterial enlargement (which can actually be seen in the cath lab); anti-inflammatory effects; reduction of blood pressure; enhancement of insulin responses, etc. All of these effects can be connected to beneficial properties that may facilitate atherosclerotic plaque regression and, indeed, there are limited data to document that this is true.

Drug companies may be greedy, but they’re not stupid. They’ve been vigorously pursuing this line of research for some years, a research path that led inadvertently to the erectile dysfunction agent, sildenafil (Viagra), and all its subsequent competitors. (Erectile dysfunction is another expression of endothelial dysfunction, since male erections are driven by the ability to dilate penile arteries.) The wonderful properties of NO enhancement continue to occupy research labs around the world.

Wow. So what’s the reluctance? In the early years of the Track Your Plaque program (meaning just a short 7-8 years ago), I was thoroughly convinced that l-arginine was a crucial, necessary part of a plaque regression program. Without it, you would rarely succeed. With it, the odds were tipped in your favor.

However, something curious has emerged recently. I’ve seen more and more people dropping their heart scan scores. Not just a little bit, but a huge amount. Witness our most recent record holder, Neal, who dropped his score 51% in 15 months. Just five years ago, this magnitude of reversal was unimaginable. Granted, Neal is our record holder, but others are obtaining 10, 18, 24, 30% drops in scores all the time. Many have done it without l-arginine.

Now, how about the people who have failed to stop a rising score? Would they do better with l-arginine as part of the mix? I believe so, but sometimes we never quite know except in retrospect. It has been a great dilemma for us trying to predict from the starting gate who will or who won’t drop their heart scan score.

My view from the trenches is that l-arginine packs its greatest atherosclerosis-fighting punch in the first year or two of use, when “endothelial dysfunction” is likely to be present (abnormal artery constriction). But as all other strategies take hold—fish oil, correction of lipid and lipoprotein abnormalities, weight loss (big effect), vitamin D (another very big effect), etc.—endothelial behavior improves over time. Perhaps l-arginine becomes a less necessary component over time.

There’s no doubt that uncertainty still surrounds the use and science surrounding l-arginine. However, if you’re interested in stacking the odds in your favor, particularly during the first year or two of your plaque-reducing efforts, I think that l-arginine is worth considering. It is cumbersome, it can be expensive, some preparations may even be foul. But in the big picture of life, with hospitals trying every possible ploy to get your body on a table for a procedure, doctors perverting their mission by signing employment contracts with hospitals and agreeing to usher you into the hospital as a paying patient whenever possible, and drug companies viewing you and me as a market for medications which may or may not be helpful, l-arginine is surely not that big a burden.