Medicine traditionally has been intended to either be curative or palliative. That intent far predated the FDA and the European Commission. As modern pharmacology developed, however, prescription medications expanded to more than life-and-death issues and enveloped what are now termed quality-of-life issues. To that end, such products as the amino acid L-arginine have been widely studied as potential remedies for an entire continuum of health problems.

Background

L-arginine, an amino acid essential for protein synthesis, is found in such foods as red meat, fish, and dairy products.1 This compound is the main precursor for the body’s production of nitric oxide.1 Nitric oxide provides the vasodilatory effects that counterbalance the prostaglandin-induced vasoconstriction.2 Ideally, these compounds operate in harmony, producing a vascular tone with a pulse of 72 beats per minute and BP well under 140/90 mm Hg.

The CDC estimates that in 2010, heart disease will cost the United States approximately $316.4 billion.3 A readily available supplement to offset some of these staggering expenses would certainly be a hot commodity.

Science

In a small study of 29 healthy humans, a sustained-release form of L-arginine was dosed twice daily over a one-week period. Endpoints measured included systolic and diastolic BP as well as brachial artery resting tone. The results were statistically significant for systolic BP reduction (average reduction 4 mm Hg per participant).4

In a second study, researchers sought to improve the sustainability of the L-arginine supplementation by compounding it into a “medical food bar” that was consumed by 30 patients with known coronary artery disease. These bars were eaten twice daily for a period of one month and contained the equivalent of 9 g/day of L-arginine.5 The formulation improved flow-mediated vasodilatation, increased treadmill exercise time by 20% over placebo, and improved quality-of-life scores, all without manifestations of ischemia or angina onset time.6

More recent research has validated the long-suspected correlation between peripheral vascular issues with central cardiovascular and cerebrovascular disease. Peripheral artery disease (PAD) and erectile dysfunction (ED) are now known to herald significant increases in risks for morbidity and mortality from all-cause vascular problems.7 Studies of L-arginine also have examined any impact this supplementation might have on these more peripheral vascular issues.

One group of researchers enrolled 80 patients with known PAD and symptomatic intermittent claudication. Patients were randomized to placebo or one of three daily dose groups (3 g, 6 g, and 9 g of L-arginine). Although there was no statistically significant difference in absolute claudication distance between the groups after 12 weeks, greater increase in walking distance in the group treated with 3 g/day was noted, and there was improvement in walking speed in patients in all dose groups.8

The main support for the use of L-arginine in ED comes from a small, double-blind trial in which 50 men with ED received either 5 g of L-arginine or placebo daily for six weeks. More men in the treated group experienced improvement in sexual performance than in the placebo group.9 It was again noted, however, that the more sustained the use of the test supplement the better the erectile results achieved, possibly indicating some level of improvement in actual endothelial function.

Safety

Some studies indicate a negative side to L-arginine supplement. In one trial, 153 patients (77 of whom were aged 60 years or older) who had just sustained an initial ST-segment deviation MI were randomized to either standard therapy or supplementation with L-arginine and monitored for a period of six months. The study was closed early due to the deaths of six patients in the treatment arm compared with none in the placebo arm.10 While there are obviously many unanswered questions regarding these outcomes, it is clear that L-arginine is not a benign supplement. Additionally, due to its potential for vasodilatation, L-arginine should be used with extreme caution in patients already taking nitrates or other antihypertensives.1

Dose, how supplied, cost

Dose recommendations vary widely because of the lack of a standardized controlled release mechanism for this oral supplement. However, most studies used 6-20 g/day, usually in three divided doses.1 The cost is approximately $30-$40/month.

Summary

L-arginine is definitely an intriguing supplement but comes with some extremely serious safety issues. With the ready availability of safety-proven prescription therapies, this supplement is not recommended for general use. n

References

  1. Natural Standard Monograph (2010). L-arginine. Natural Standard, Inc. Medicines Comprehensive Database.
  2. Cheng JW, Baldwin SN. L-arginine in the management of cardiovascular diseases. Ann Pharmacother. 2001;35:755-764.
  3. Centers for Disease Control and Prevention (2010). Heart disease facts.
  4. Miller AL. The effects of sustained-release L-arginine formulation on blood pressure and vascular compliance in 29 healthy individuals. Altern Med Rev. 2006;11:23-29.
  5. Cannon RO 3rd. Oral L-arginine (and other active ingredients) for ischemic heart disease? J Am Coll Cardiol. 2002;39:46-48.
  6. Maxwell AJ, Zapien MP, Pearce GL, et al. Randomized trial of a medical food for the dietary management of chronic, stable angina. J Am Coll Cardiol. 2002;39:37-45.
  7. Cylwik D, Mogielnicki A, Buczko W. L-arginine and the cardiovascular system. Pharmacol Rep. 2005;57:14-22.
  8. Oka RK, Szuba A, Giacomini JC, Cooke JP. A pilot study of L-arginine supplementation on functional capacity in peripheral arterial disease. Vasc Med. 2005;10:265-274.
  9. Chen J, Wollman Y, Chernichovsky T, at al. Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study. BJU Int. 1999;83:269-273.
  10. Schulman SP, Becker LC, Kass DA, et al. L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA. 2006;295:58-64.

All electronic documents accessed May 15, 2010.

By Sherril Sego, FNP-C, DNP. Ms. Sego is a staff clinician at the Kansas City VA Medical Center in Kansas City, Mo., where she practices adult medicine and women’s health. She also teaches at the nursing schools of the University of Missouri and the University of Kansas.