Role of Supplemental Arginine and Potential Effects

Arginine is classified as a nonessential amino acid and therefore can be synthesized in the body in amounts adequate for the average, healthy adult. Interest in arginine as a supplement for athletes who are involved in sprint or power sports may be related to its involvement in the synthesis of creatine. The results from several studies also suggest that arginine may have some effects on immune function. These effects may be independent of or related to nitric oxide (NO) synthesis. Arginine functions as a precursor in the formation of NO. NO has several different functions in the body and one of these functions is to act as an important immune effector molecule. NO is formed from arginine and oxygen by nitric oxide synthase (NOS). There are several types of NOS, but the one that is important with respect to immune function is inducible NOS (iNOS). Microorganisms or cytokines produced by the immune system induce the formation of iNOS, which eventually results in the synthesis of NO. NO acts as a cytotoxic molecule and in that capacity can destroy tumor cells, invading microorganisms, and viral-infected cells.

Immune Effects

Although arginine is a precursor in the synthesis of NO, we are not aware of any studies to date that have demonstrated an increased production of NO, in either individuals or animals consuming additional arginine in the diet. Recall that the NO produced by immune cells is dependent on iNOS. The gene product iNOS is triggered by an encounter with microorganisms, or induced by cytokines. Typically, cytokines are released in response to immune activation, such as exposure to an infectious agent. Therefore, because NO production is dependent on immune activation, in the healthy state, it may be less likely to find an effect of arginine supplementation on NO production. In states of illness, injury, or patients undergoing surgery, some studies have demonstrated that arginine supplementation does enhance certain aspects of immune response. Surgical patients or breast cancer patients as well as injured animals demonstrate enhanced lymphocyte response to stimulation with mitogens. Other studies have found no effect on lymphocyte proliferation. Arginine supplementation may also have an antitumor effect in animal models, perhaps related to enhanced macrophage or NK cell cytotoxicity. However, arginine has also been shown to promote tumor growth and therefore the effect of arginine supplementation on tumor growth may be dependent on the type of tumor.

Fewer studies have been performed to evaluate the effect of arginine supplementation in healthy individuals. However, the findings from several studies show that approximately 30 g of arginine HCl or arginine aspartate supplementation for 1 to 2 weeks increases lymphocyte proliferation and wound healing in both young and elderly humans. We are unaware of any studies of healthy individuals that have demonstrated an enhanced resistance to infection in association with dietary arginine supplementation. One study did examine arginine plus zinc supplementation in the elderly as a potential method of increasing antibody response to influenza vaccination in the elderly. This study found no benefit of supplementation on antibody response. Arginine supplementation could have harmful effects. Excessive doses of arginine supplementation in vitro may inhibit or suppress immune response and an appropriate in vivo dose has not been determined. It is important to be aware that arginine supplementation may potentially be harmful for some types of patients, in particular those suffering from sepsis. This possibility is an important area of study and it has been suggested that the effects of arginine supplementation on NO production in septic burn patients be carefully evaluated.

The findings demonstrating an enhancement of immune function with arginine supplementation must be interpreted with caution. The mechanism by which arginine may alter immunity are unknown. The level of other nutrients has not always been well controlled in these studies and therefore the immune effects that were observed may be related to a lack of certain nutrients or adequate nitrogen in the control diets. It has also been suggested that arginine, by itself, does not alter immunity, but in combination with other nutrients may have an effect on immune response. Another possibility to consider is that the immunomodulatory effects of arginine are indirect and may result from the altered hormonal pattern following arginine intake. Catecholamines, corticosteroids, growth hormone, insulin, and prolactin release may be altered by arginine and each of these neuroendocrine factors has been shown independently to alter immunity. Therefore, the effects of arginine could be related to changes in the concentrations of these hormones and to our knowledge this possibility has not yet been investigated.

In conclusion, arginine supplementation may show some promise as to its potential enhancement of immune response particularly in those patients suffering from certain types of illness or injury. In healthy individuals, dietary supplementation with arginine requires further research before any clear conclusions can be made with respect to enhanced immunity. The role of supplemental arginine and the potential effects it may have in athletes remain to be established.

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