Adverse gastrointestinal effects of arginine and related amino acids.
Level 5 - mechanism / opinion, no new human data
Narrative review of intestinal physiology and clinical trials
PubMed 17513449 · doi:10.1093/jn/137.6.1693S
What was done
The authors reviewed the intestinal physiology, transport mechanisms, and adverse effect profiles of oral arginine, citrulline, ornithine, cystine, and N-acetylcysteine (NAC). They analyzed reported gastrointestinal symptoms across clinical trials evaluating arginine supplementation over an intake range from 3 g/day to greater than 100 g/day.
What was found
Single oral doses of 3 to 6 g of arginine rarely caused side effects. Most adverse gastrointestinal events (nausea, vomiting, and diarrhea) occurred with single doses greater than 9 g in adults (>140 mg/kg), frequently within daily regimens exceeding approximately 30 g/day (>174 mmol/day). L-arginine induced water and electrolyte secretion via high-level nitric oxide secretagogue activity. Athletes appeared more susceptible to symptoms at individual doses >9 g than individuals with diabetes. Adverse effects disappeared when arginine was ingested in divided doses.
Why it matters
This review identifies clinical dosing thresholds for oral arginine, showing that concentration-dependent gastrointestinal toxicity can be prevented by dividing large daily doses into smaller individual portions.
Limits
The abstract describes a narrative review without systematic search parameters, meta-analytic pooling, or total participant numbers. Adverse effect reporting across the original trials was noted to be highly variable, and physiological differences between patient populations limit generalizability.
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