There has been a flurry of discussion, speculation and even hard to believe health claims surrounding the supplementing of the amino acid L-arginine.
L-arginine is considered a conditionally-essential amino acid, meaning that it is not found in sufficient levels in the “normal” human diet. Amounts that produce the clinical effects suggested by research highlighted below must be received in supplement form. In 1998 the Nobel Prize for physiology or medicine was awarded to three scientists for their discovery of the signaling properties of nitric oxide on the cardiovascular system.
L-arginine stimulates the natural production of nitric oxide (NO) in the cardiovascular system. The formation of nitric oxide is dependent on the action of endothelial nitric oxide synthase (eNOS) on its substrate L-arginine.1 Nitric oxide’s enhancement of blood vessel compliance manifests its salutary effect in hypertension, decreased peripheral vascular resistance and enhanced cardiac function.2,3 Downstream metabolites of nitric oxide improve vasocompliance and enhance capillary circulation, enhance inflammation control and cognitive function, and equilibrate neurotransmitter function. Some research is indicating that nitric oxide might be one of the most important signaling molecules of the body.
This nitric oxide science went on to be used in the synthesis of the family of male enhancement drugs while the major natural heart health benefits were largely ignored.
NO concentrations are also known to decrease with advancing age.4 Food sources of L-arginine include wheat germ, oat flakes, cheese, cottage cheese, eggs, whole milk, chocolate, yogurt, pork, chicken and turkey and avocado.5
To date, L-arginine has been used primarily as a supplement to enhance muscle mass in athletes as well as increasing circulation. More recently, in concert with other amino acids (including L-citrulline)6 and other nutrients, the more significant effects of nitric oxide health are becoming more evident.
The rationale behind recommending an L-arginine nutrient blend to patients is based on its ability to support optimal cardiovascular function and control inflammation, two very significant players in virtually every metabolic process in the body.
L-Arginine and heart health: The Science
The benefits of good nitric oxide levels supported by sufficient intake of an L-arginine product include greatly decreased risk of a cardiovascular event. Endothelial damage is crucial for the progress of atherosclerosis; risk factors for atherosclerosis represent crucial factors associated with endothelial dysfunction. Patients with cardiovascular disease are characterized by impaired endothelial function and several agents have been proposed as potential modulators include antioxidants and L-arginine.7
L-arginine stimulates the natural production of nitric oxide (NO) in the cardiovascular system.
Asymmetric dimethylarginine (ADMA) inhibits production of nitric oxide by competing with arginine for nitric oxide synthase binding. Since ADMA has been implicated as a cardiovascular risk factor in congestive heart failure,8 increased carotid artery intima-medial thickening,9 chronic kidney disease,10 L-arginine supplementation has therefore been indicated as a treatment in cardiac diseases.8
Nitric oxide synthase, the enzyme responsible for nitric oxide formation, has been found in the hypothalamus and pituitary gland itself. Nitric oxide down-regulates the release of corticotrophin releasing hormone from the rat hypothalamus in vitro, suggesting its role in regulating the secretion of pituitary ACTH and of corticosteroids from the adrenal cortex. These results are direct evidence that endogenous NO significantly inhibits the HPA response to central stimulation under in vivo conditions.11 In socially organized mammals, the predominating stressors are not physical events but arise from the immediate social environment. In laboratory rats, social stress inhibits the modulating nitric oxide effect on the corticotrophin releasing hormone-induced ACTH response.12
Because the combination of high stress and suboptimal nutrition contributes to increased cardiovascular risk, the importance of reducing that risk with supplementation with L-arginine is even more advisable for our patients. The science supporting the benefits of supplemental L-arginine is underscored by almost two decades of research and thousands of scientific papers and articles. This humble amino acid, properly combined with a supporting blend of nutrients, can provide a very powerful tool to strengthen the body’s resistance to one of the highest health risks of modern day life.
Dr. Chinn is a 1986 Life graduate (Marietta) and has been practicing in Seattle for 24 years and is a board member of the Gonstead Clinical Studies Society. He is the co-creator of the nutritional cardiovascular formula Acctrix, co-founder of Unisal Wellness Technologies and is the author of Symphony of Wellness and Soaring Beyond Fear. His book Symphony of Wellness focuses on the science and benefits of L-arginine and nitric oxide for cardiovascular health. He can be reached at
Bob Anderson, M.D., University of Washington Medical School, is the founding president of the American Board of Integrative Holistic Medicine and an Adjunct Faculty Instructor at Bastyr University. He is the chief medical consultant for Unisal Wellness and contributing advisor for Unisal Wellness. He is the author of several books, including Clinician’s Guide to Holistic Medicine, published in 2001.
1. Joshi, MS, et al. Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells. Proc Natl Acad Sci U S A 2007; 104:9982
2. Davies, SA, et al. Neuropeptide stimulation of the nitric oxide signaling pathway in Drosophila melanogaster Malpighian tubules. Am J Physiol 1997; 273:R823
3. Yin H, et al. Nitric oxide mediates cardiac protection of tissue kallikrein by reducing inflammation and ventricular remodeling after myocardial ischemia/reperfusion. Life Sci 2008; 82:156
4. Dumitriu IL, et al. [New insight into nitric oxide involvement in regulation of airways smooth muscle tone] in Romanian. Rev Med Chir Soc Med Nat Iasi 2007; 111:454.
5. Braverman, ER, Pfeiffer, CC. The Healing Nutrients Within. New Canaan, CT, Keats Publishing, 1987 p. 169.
6. Romero, M, et al. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev 2006; 24:275
7. Tousoulis, D, et al. Endothelial dysfunction: potential clinical implications. Minerva Med 2010; 101:271.
8. Visser, M, et al. The role of asymmetric dimethylarginine and arginine in the failing heart and its vasculature. Eur J Heart Fail 2010; 12:1274.
9. Riccioni, G et al. Relationship between asymmetric dimethylarginine and asymptomatic carotid atherosclerosis. J Biol Regul Homeost Agents 2010; 24:351
10. Mihout F, et al. Asymmetric dimethylarginine (ADMA) induces chronic kidney disease through a mechanism involving collagen and TGF-β1 synthesis. J Pathol 2011; 223:37
11. Bugajski J, et al. Mediation by nitric oxide of the carbachol-induced corticosterone secretion in rats. J Physiol Pharmacol 1997; 48:277.
12. Bugajski J. Social stress adapts signaling pathways involved in stimulation of the hypothalamic-pituitary-adrenal axis. J Physiol Pharmacol 1999; 50:367.