Trial identifies 4 grams a day as the tested safe level for L-tyrosine in healthy men

By Tarun Sai LomteReviewed by Susha Cheriyedath, M.Sc.Jun 23 2026

A new crossover trial suggests that daily L-tyrosine was well tolerated in healthy men, but researchers caution that safety beyond 4 weeks, at higher doses, and across more diverse groups remains untested.

Study: Evaluation of the Safety and Tolerability of L-Tyrosine Supplementation in Healthy Adult Men: A Randomized Crossover Trial. Image Credit: StudioMolekuul / Shutterstock

A recent study published in the journal Nutrients assessed the tolerability and safety of L-tyrosine (L-Tyr) supplementation in healthy adult men in Japan.

L-Tyr is primarily derived from the diet and endogenous protein recycling. It is found in common foods, including meat, dairy, and soy products. Previous studies have reported context-specific effects of L-Tyr supplementation on cognitive control in healthy young women, work performance in sleep-deprived young men, and stress-related response markers during acute stress. Despite these reports, studies assessing multiple doses, medium- or long-term administration, and comprehensive safety are scarce.

About the Study

In the present study, researchers investigated the tolerability and safety of a four-week L-Tyr supplementation in healthy adult men. This randomized, double-blind, placebo-controlled trial recruited community-dwelling adults aged 20-60 years from Osaka, Japan. Individuals using medicinal products or supplements containing amino acids, those with thyroid disorders, and those treated with monoamine oxidase inhibitors were excluded.

Moreover, individuals with allergies or a chronic disease and those with a history of gastrointestinal (GI), metabolic, respiratory, hepatic, cardiovascular, or renal disorders were excluded. Participants were randomized to five sequence groups in a crossover design, including placebo (0 g/day) and four L-Tyr doses (1-4 g/day). Each individual received four of the five possible doses for four weeks each in a crossover manner, with a washout period of at least two weeks between interventions.

Fasting blood samples were collected at baseline and after each intervention period. The primary endpoints were biochemical and hematological parameters. Biochemical parameters were liver enzymes, renal function markers, lipid profile, electrolytes, proteins, total bilirubin, uric acid, glucose, phospholipids, and creatine kinase. Hematological parameters were platelet count, red blood cell (RBC) count, hemoglobin, white blood cell (WBC) count, and hematocrit.

Secondary endpoints were the severity and incidence of adverse events (AEs). The brief self-administered diet history questionnaire was used to evaluate dietary intake. Blood pressure, heart rate, and anthropometric measurements were obtained. In addition, plasma levels of 19 amino acids were estimated as an exploratory measure using liquid chromatography-tandem mass spectrometry. The researchers estimated the no-observed-adverse-effect level (NOAEL) for L-Tyr supplementation.

NOAEL was the highest experimental intake dose with no measurable adverse effects in primary endpoints, secondary endpoints, and dietary and anthropometric parameters during the supplementation period. Both the intention-to-treat and per-protocol populations were included in the statistical analysis. Student’s t-test was performed to evaluate differences in plasma L-Tyr levels between baseline and post-intervention time points. Linear mixed-effects models were used to compare different dose levels.

Findings

Of the 200 individuals screened, 30 were included in the study. On average, participants were aged 43.4 years and had a body mass index (BMI) of 23.2 kg/m². Six participants were assigned to each sequence group, and the crossover design generated up to 24 observations per dose. Two subjects discontinued the study for reasons unrelated to the supplementation. There were no significant differences between any L-Tyr dose condition and the placebo condition for any of the primary endpoint parameters.

In addition, there were no clinically meaningful changes in any hematological or biochemical parameters throughout the intervention. In total, 18 AEs occurred, including nine moderate and nine mild AEs, with no serious AEs reported. Moderate AEs were viral infection, apathy, dermatitis, GI disorders, and upper respiratory infection. Mild AEs included upper respiratory infection, fatigue, headache, pyrexia, and bronchitis. Although AE incidence was significantly different among treatment groups, including placebo, there was no dose-dependent trend, and the difference was likely attributable to the lower AE incidence in the 3 g/day group.

Furthermore, there were no significant differences in dietary intake or anthropometric measures between any L-Tyr dose condition and placebo. Plasma L-Tyr levels were modestly but significantly elevated in the 4 g/day group compared to placebo. Plasma concentrations of other amino acids in the L-Tyr groups did not differ from those in the placebo group. Notably, across the randomized, washout-separated crossover sequence, post-supplementation L-Tyr concentrations were comparable to pre-supplementation baseline values, supporting negligible carryover and no accumulation.

Conclusions

In sum, L-Tyr supplementation at doses up to 4 g/day for four weeks was well tolerated in healthy adult men, with no observed adverse effects on clinical safety markers or metabolic health indices. The findings support the highest tested L-Tyr dose, 4 g/day, as the NOAEL under the present four-week study conditions. Notably, the exclusive inclusion of healthy males limits generalizability to people with medical conditions and females. The study also did not assess doses above 4 g/day, longer-term intake, or thyroid- and catecholamine-related biomarkers, including TSH, T3, T4, dopamine, noradrenaline, and adrenaline.

The small sample size and moderate power for detecting small effects should also be considered. Further research is needed with longer follow-up, higher doses, and diverse populations. The study was funded by Ajinomoto Co., Inc., and two authors were company employees, although the paper states that the funder had no role in data collection, analysis, or interpretation, and that company-employed authors did not access unblinded data until the database was locked.