The Potential and Promise of Arginine in Human Nutrition

Several years ago, the European Food Safety Authority (EFSA) reviewed more than six proposed health claims relative to the potential benefits associated with arginine supplementation (EFSA 2011). In each case, the expert panel typically responded that “the claimed effect is general and non-specific and does not refer to any specific health claim as required.” Within the United States, similar health claims for arginine are popular, yet the appropriate regulatory agencies appear to exercise enforcement discretion.

According to one marketing firm, the global L-arginine market was estimated at $501.6 million in 2018 and projected to reach $957.9 million by 2028 at a compound annual growth rate of 6.7% (Market.US 2019).

As background, the reader is urged to remember that amino acids are integral constituents of proteins. These constituents, essential for synthesizing, and various nitrogenous metabolites and their post-translational modifications, are involved in cell signaling and serve as key regulators for the secretion of hormones and metabolizing nutrients (Wu 2010).

The amino acid L-arginine is synthesized from the amino acids glutamine, glutamate, and proline in humans. Arginine degradation occurs via multiple pathways that are initiated by arginase and nitric oxide synthase, among other enzymes. These pathways produce nitric oxide, polyamines, proline, glutamate, and creatine, with each having enormous biological importance. As the nitrogenous precursor for the synthesis of nitric oxide (a key signaling molecule in virtually every cell type) by nitric oxide synthase, arginine regulates vital metabolic pathways, so there continues to be growing interest in arginine nutrition and physiology well beyond protein synthesis (Morris 2016).

For example, arginine is also required for the detoxification of ammonia, which is an extremely toxic substance for the central nervous system and other tissues (Wu, Bazer, Davis, et al. 2009). There is compelling evidence that arginine regulates inter-organ metabolism of energy substrates and the function of multiple organs. The results of both experimental and clinical studies indicate that arginine is a nutritionally essential amino acid for spermatogenesis, embryonic survival, fetal and neonatal growth, as well as maintenance of vascular tone and hemodynamics (Palmer, Ashton, and Moncada 1988). Some evidence supports the benefit of L-arginine supplementation for reducing systolic and diastolic blood pressure in hypertensive adults and reducing the incidence of hospital-acquired infections and the length of stay in the hospital for surgical patients (McRae 2016). A 2011 meta-analysis of 11 double-blind, placebo-controlled clinical studies among 387 participants that evaluated the impact of arginine on blood pressure suggested this intervention may reduce both systolic and diastolic blood pressure among those consuming 4–24 g/day (Dong, Qin, Zhang, et al. 2011).

Multiple toxicologic studies have shown that supplementation of L-arginine in rats and pigs is safe, and there is ample evidence that in appropriate doses it is safe for human beings as long as there are no specific contraindications as a result of prior medical history. The apparent no-observed-adverse-effect level for arginine is 30 g/day, which translates to a safe intake of 300 mg/day (Cynober, Bier, Kadowaki, et al. 2016). A similar study among 101 adult participants indicated a 30 g/day dose of arginine-HCl over a 90-day period was well tolerated. No adverse effects were noted based on an array of blood chemistries, metabolic parameters, and organ functions.

Despite the EFSA position on potential health claims attributed to arginine consumption, there is a growing body of evidence that clearly indicates that dietary supplementation of arginine may be beneficial in improving reproductive, cardiovascular, pulmonary, renal, gastrointestinal, liver, and immune functions, as well as facilitating wound healing, enhancing insulin sensitivity, and maintaining tissue integrity in humans as well as livestock.

In addition, emerging research is exploring mechanisms in which arginine may provide novel adjunctive therapies for obesity, diabetes, and the metabolic syndrome. The effect of arginine in treating many developmental and health problems is unique among amino acids. Arginine may offer opportunities for improved health and well-being of humans and other mammals (Wu, Bazer, Satterfield, et al. 2013).