Evaluation of the Safety and Tolerability of L-Tyrosine Supplementation in Healthy Adult Men: A Randomized Crossover Trial

Background: L-tyrosine, classified as a dispensable amino acid, is widely consumed as a component of commonly consumed foods and as a dietary supplement. However, 4-week safety data on supplementation with this amino acid remain limited. Methods: The aim of this study was to evaluate the safety and tolerability of L-tyrosine supplementation over a 4-week period and to estimate the no-observed-adverse-effect level (NOAEL). In a randomized, double-blind, placebo-controlled crossover trial, 30 healthy adult men received L-tyrosine at graded daily doses (0, 1, 2, 3, or 4 g/day). Each participant received four of the five doses in a randomized sequence, with each intervention period separated by a 2-week washout period. The primary endpoints were clinical laboratory parameters, and the secondary endpoint was the incidence of adverse events. Anthropometric and dietary parameters were also assessed. In addition, plasma amino acid concentrations following L-tyrosine supplementation were evaluated as exploratory outcomes. Results: No clinically meaningful or statistically significant dose-related abnormalities were observed in hematological, biochemical, or electrolyte parameters at any dose. Anthropometric and dietary parameters remained unchanged. No serious adverse events occurred, and the incidence of mild-to-moderate adverse events was comparable to that observed with placebo. At the end of each supplementation period and under fasting conditions, plasma L-tyrosine concentrations modestly increased at the highest dose (4 g/day), whereas concentrations of other amino acids remained unchanged. Conclusions: Four-week supplementation with L-tyrosine at doses up to 4 g/day was well tolerated in healthy adult men and was not associated with biochemical and clinically relevant adverse effects under the conditions of this study. These findings suggest that 4 g/day represents the highest tested intake level without observable adverse effects and may serve as the NOAEL under the present 4-week study conditions.