A new crossover study suggests that daily L-tyrosine is well tolerated in healthy men, but researchers caution that safety at higher doses over four weeks and in a more diverse group has not yet been tested.
Study: Evaluation of the safety and tolerability of L-tyrosine supplementation in healthy adult men: a randomized crossover trial. Image credit: StudioMolekuul / Shutterstock
Recent research published in journals nutrients evaluated the tolerability and safety of L-tyrosine (L-Tyr) supplementation in healthy adult Japanese men.
L-Tyr is primarily derived from dietary and endogenous protein recycling. Found in common foods such as meat, dairy products, and soy products. Previous studies have reported context-specific effects of L-Tyr supplementation on cognitive control in healthy young women, job performance in sleep-deprived young men, and stress-related response markers during acute stress. Despite these reports, there are few studies evaluating multiple doses, mid- to long-term administration, and comprehensive safety.
About research
In this study, researchers investigated the tolerability and safety of 4 weeks of L-Tyr supplementation in healthy adult men. This randomized, double-blind, placebo-controlled trial recruited community-dwelling adults between the ages of 20 and 60 living in Osaka Prefecture. Participants were excluded if they were using medicines or supplements containing amino acids, had thyroid disease, or were being treated with monoamine oxidase inhibitors.
Additionally, individuals with allergies or chronic diseases and those with a history of gastrointestinal (GI), metabolic, respiratory, hepatic, cardiovascular, or renal disorders were excluded. Participants were randomly assigned to five sequence groups in a crossover design, including placebo (0 g/day) and four L-Tyr doses (1 to 4 g/day). Each individual received four of the five possible doses in a crossover fashion for 4 weeks each, with a washout period of at least 2 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, protein, 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 severity and incidence of adverse events (AEs). A brief self-administered dietary history questionnaire was used to assess dietary intake. Blood pressure, heart rate, and anthropometric measurements were obtained. Additionally, liquid chromatography-tandem mass spectrometry was used to estimate plasma levels of 19 amino acids as an exploratory measurement. The researchers estimated the no observed adverse effect level (NOAEL) of L-Tyr supplementation.
The NOAEL was the highest experimental intake with no measurable adverse effects on the primary endpoint, secondary endpoints, dietary parameters, and anthropometric parameters during the supplement period. Both intention-to-treat and per-protocol populations were included in the statistical analysis. Student’s t-test was performed to assess differences in plasma L-Tyr levels between baseline and post-intervention time points. Linear mixed-effects models were used to compare different dose levels.
Survey results
Of the 200 people screened, 30 were included in the study. The average age of the participants was 43.4 years and body mass index (BMI) was 23.2 kg/m2. Six participants were assigned to each sequence group, and the crossover design generated a maximum of 24 observations per dose. Two subjects withdrew from the study for reasons unrelated to the supplement. There were no significant differences between the L-Tyr and placebo conditions for any of the primary endpoint parameters.
Additionally, there were no clinically meaningful changes in hematological or biochemical parameters throughout the intervention. A total of 18 AEs occurred, including 9 moderate and 9 mild AEs, but no serious AEs were reported. Moderate adverse events were viral infection, lethargy, dermatitis, gastrointestinal disturbances, and upper respiratory tract infection. Mild adverse events include upper respiratory tract infection, fatigue, headache, fever, and bronchitis. AE rates were significantly different between treatment groups, including placebo, but there was no dose-related trend, and this difference was likely due to a lower AE rate in the 3 g/day group.
Additionally, there were no significant differences in dietary intake or anthropometric measurements between L-Tyr treatment conditions and placebo. Plasma L-Tyr levels were modestly but significantly increased in the 4 g/day group compared with placebo. Plasma concentrations of other amino acids in the L-Tyr group did not differ from those in the placebo group. Notably, throughout the randomized washout-separation crossover sequence, post-supplementation L-Tyr concentrations were comparable to pre-supplementation baseline values, supporting the absence of negligible carryover and accumulation.
conclusion
In summary, in healthy adult men, L-Tyr supplementation up to 4 g per day for 4 weeks was well tolerated, and no adverse effects on clinical safety markers or metabolic health indicators were observed. This result supports the highest L-Tyr dose tested, 4 g/day, as the NOAEL under the current 4-week study conditions. In particular, only healthy men are included, which limits generalizability to people with medical conditions and women. This study also did not evaluate doses higher than 4 g/day, long-term intake, or thyroid and catecholamine-related biomarkers such as TSH, T3, T4, dopamine, noradrenaline, and adrenaline.
Small sample sizes and moderate power to detect small effects should also be considered. Further studies with longer follow-up, higher doses, and diverse populations are needed. Although the study was funded by Ajinomoto Co., and both authors were employees, the paper states that the funders had no role in data collection, analysis, or interpretation, and that the employee authors did not have access to unblinded data until the database was locked.
Reference magazines:
- Matsumoto, H., Miura, N., Naito, T., and Elango, R. (2026). Evaluation of the safety and tolerability of L-tyrosine supplementation in healthy adult men: a randomized crossover trial. Nutrients, 18(12), 2020. Doi: 10.3390/nu18122020, https://www.mdpi.com/2072-6643/18/12/2020
