Abstract

Evidence is discussed that puts in question the widely held belief that adult mammals, including human beings, can meet all of their arginine needs by endogenous synthesis. Arginine, used in synthesis of body proteins, is essential for ammonia detoxification via urea synthesis, which prevents metabolic derangements caused by elevations in tissue ammonia. It is a precursor for polyamine synthesis and is the only source of amidino groups for the formation of creatine, a major source of high energy phosphate for regeneration of ATP in muscle. Arginine at supraphysiologic doses is thymotropic and a secretagogue for hormones that control growth and metabolism. Studies in mature rats show that glucose tolerance, the rate of repletion from severe protein undernutrition and recovery from trauma are significantly accelerated by dietary arginine. Oral or intravenous administration of excessive arginine reverses nitrogen loss and immune suppression after trauma in rats, and healthy human volunteers consuming 30 g of oral supplements or arginine have shown significantly enhanced immunoreactivity of the lymphocytes of their peripheral blood. Calculations based on creatinine excretion show that 0.8 g of protein/kg body weight of the quality supplied by the usual American diet barely provides sufficient arginine for synthesizing the quantity of creatinine excreted daily in the urine of 70-kg adults. Human patients who often consume less than this amount of protein show a decline in creatinine excretion during illness; the decrease suggests that their intake of arginine is less than optimal. Recent studies of intraspecies and interspecies differences in responses to arginine reemphasize that dispensability or indispensability of arginine is a matter of definition and that growth and nitrogen balance data impose significant limitations on the drawing of far-reaching conclusions about the needs for arginine by mammalian adults including humans. Orotic acid excretion, immune responsiveness and circulating hormone levels are measures that should be evaluated for identifying when enhancement of arginine intakes might prove beneficial.