Numerous studies have shown the amino acid L-arginine is an essential nutrient for optimal cardiovascular functioning. L-arginine is biochemically converted in vascular endothelial cells (the one-layer-thick lining inside blood vessels) into nitric oxide (NO), which causes vascular relaxation. This increases blood flow, makes the vessel less likely to be blocked with cholesterol plaques, and can lower blood pressure.
A study in the July 2007 journal Circulation (the official journal of the American Heart Association) reports that a group of 133 individuals with peripheral artery disease did not benefit from dosing with L-arginine. The study participants, who were an average 73 years of age, suffered from leg pain and restricted walking capacity. Researchers gave the participants one gram L-arginine three times daily for six months. Blood arginine levels rose significantly during the study; however, NO levels did not. Both the arginine group and the placebo group experienced significantly increased walking distance at six months, but the placebo group had a greater improvement. Blood flow in the L-arginine group actually decreased at six months, while the placebo group improved.
COMMENT: These researchers, who are very familiar with the pharmacokinetics of L-arginine (they have done other L-arginine research) for some reason chose to use a relatively small dose in this study. Previous peripheral artery disease studies used a higher oral dose (3 grams BID) or a very high intravenous dose (8 grams BID). L-arginine is absorbed and utilized very quickly (within 3 hours), which is why studies using non-sustained-release L-arginine have used high doses.
The fact that the vascular NO levels did not increase is probably the reason these individuals did not improve. They had high plasma asymmetrical dimethylarginine (ADMA) levels, which inhibits the conversion of L-arginine to NO, necessitating higher L-arginine dosing (or possibly sustained-release dosing) as well as the addition of antioxidants and NO cofactors like 5-methyltetrahydrofolate. This is another example of researchers who are stuck in the drug model trying to fix a long-term health problem in a short period of time using a single substance (and in too low a dose) instead of a combination of nutrients that work together biochemically.
Wilson AM, Harada R, Nair N, et al. L-arginine supplementation in peripheral artery disease - no benefit and possible harm. Circulation 2007;116:188-195.
