Arginine has gained recent attention in critical care nutrition and is considered a conditionally essential amino acid. Arginine is the specific precursor for nitric oxide production and a potent secretagogue for anabolic hormones such as insulin, prolactin, and growth hormone. Under normal circumstances, arginine is considered a nonessential amino acid because it is adequately synthesized endogenously via the urea cycle. However, research suggests that during times of metabolic stress, optimal amounts of arginine are not synthesized to promote tissue regeneration or positive nitrogen balance (7). Research studies in animals and humans have shown positive outcomes from supplementation to include improved nitrogen balance, wound healing, and immune function, and increased anabolic hormones, insulin, and growth hormone (7).
Arginine is reported to damage pancreatic acinar cells. Arginine induced a dose- related necrotizing pancreatitis in rats, as shown by histological evaluation, and an increase in serum amylase. Severe pancreatitis induced by 4.5 g/kg arginine was accompanied by dramatic changes in the actin cytoskeleton. Arginine-induced acute pancreatitis alters the actin cytoskeleton and increases heat shock protein expression in pancreatic acinar cells (6).
Acute pancreatitis was induced in male Wistar rats by injecting 250 mg/100 g body weight of arginine intraperitoneally twice at an interval of 1 hour, as a 20% solution in 0.15 NaCl. In this study, Takacs et al. reported that endogenous nitric oxide is involved in the formation of pancreatic edema in arginine-induced acute pancreatitis by increasing the vascular permeability and protein extravasation (1).
Mizunuma et al. reported that a single intraperitoneal administration of arginine (500 mg/100 g body weight) results in selective pancreatic acinar cell damage in rats without any morphological change in the Langerhans islets (8).
Czako et al. reported that oxygen-derived free radicals and cytokines play a role in the pathogenesis of L-arginine-induced acute pancreatitis in rats (2). In studies about pathogenesis, it has been demonstrated that endogenous cholecystokinin does not seem to play an essential role (2, 5). Furthermore, prophylactic allopurinol treatment prevents the generation of reactive oxygen metabolites, reduces the serum amylase level, and partially attenuates the development of histopathological changes (2, 3).
L-arginine sometimes reactivates latent herpes virus infections. Those with certain psychoses may experience worsened symptoms if they take L-arginine supplements. Persons who have not completed their bone growth (children and teenagers) and pregnant or lactating women should not use L-arginine. Diabetics and borderline diabetics should use growth hormone releasers with care. L-arginine might worsen a diabetic condition (9, 10).
Like our patient, world-class athletes and professional bodybuilders use L-arginine. The benefits of L-arginine supplementation are clearly dose-dependent. Beneficial dosages of L-arginine range from between 3 to 30 gr taken orally per day.
In our patient, no biochemical change was found except increased serum and urine amylase. It may be because of the low dose of L-arginine, i.e. 500 mg/day. The effect of arginine is enhanced when combined with zinc (Zn). Zinc contributes to the proper functioning of a number of hormones, including growth and sex hormones. Acute pancreatitis has been reported in humans and animals, following the ingestion of zinc as well (11, 12). The mechanism of toxicity is unknown, although the pathophysiology may relate to the role of the pancreas in zinc excretion. Analysis of zinc in rats with acute pancreatitis showed the serum levels of Zn were significantly elevated. These observations indicate that Zn could play an important role in acute pancreatitis (13). But, we consider that L-arginine seems to be the likely cause of pancreatitis in this patient possibly via the mechanism mentioned above. Zn might have additionally contributed to this damage.
In conclusion, arginine may be a causative agent of acute pancreatitis; physicians must keep this in mind. We reported this case to note a possible consequence of arginine use for bodybuilding.