Higher tyrosine levels correlate with shorter male lifespan

Higher blood concentrations of tyrosine, an amino acid commonly sold in supplements marketed for focus and mental performance, have been associated with a shorter lifespan in men in a large UK Biobank analysis, although the study does not show that taking tyrosine supplements shortens life.

Researchers examining 272,475 participants found that elevated circulating tyrosine was associated with increased all-cause mortality among men and, in genetic analyses designed to probe causality, with an estimated reduction of about 0.91 years of life after accounting for the related amino acid phenylalanine. The corresponding estimate for women was smaller and statistically inconclusive.

The study, published in the journal Aging, combined conventional observational analysis with Mendelian randomisation, a method that uses naturally occurring genetic differences associated with an exposure to test whether an observed relationship may be causal. The researchers were from the University of Hong Kong and the University of Georgia.

Among the participants, 125,359 were men. Death records identified 23,964 deaths, including 14,230 among men and 9,734 among women. After adjustment for age, body mass index, deprivation, smoking, alcohol use, physical activity, ethnicity and education, each standard-deviation increase in plasma tyrosine was associated with a 3 per cent higher risk of death in men. No significant association was detected in women.

The sex difference in the observational results itself did not reach statistical significance, a qualification that limits claims that tyrosine necessarily acts differently in men and women. The genetic findings nevertheless pointed more strongly towards a male-specific effect after researchers controlled for phenylalanine.

Using multivariable Mendelian randomisation, the team estimated that genetically predicted higher tyrosine was associated with 0.91 fewer years of life in men, with a 95 per cent confidence interval ranging from 0.21 to 1.60 years fewer. For women, the estimated reduction was 0.36 years, but the confidence interval crossed zero, meaning the result could not rule out no effect.

Phenylalanine, a precursor from which the body can produce tyrosine, initially appeared in the observational data to be associated with higher mortality in both sexes. Once the genetic analysis accounted for tyrosine, however, phenylalanine showed no independent association with lifespan in either men or women.

Tyrosine is a non-essential amino acid, meaning the body can make it, and it is also obtained from protein-rich foods including meat, dairy products, eggs, fish, beans and nuts. It contributes to production of neurotransmitters including dopamine, noradrenaline and adrenaline, which are involved in attention, stress responses and other nervous-system functions.

The compound is also sold as L-tyrosine in dietary supplements promoted for alertness, cognitive performance and coping with demanding conditions. The new findings do not establish that supplement use raises mortality risk because the study measured circulating tyrosine rather than supplement consumption, dosage or duration. Blood levels are shaped by diet, metabolism, health status and genetic factors as well as any supplemental intake.

That distinction is important because observational associations can reflect underlying metabolic conditions rather than direct harm from a nutrient. Mendelian randomisation can reduce some forms of confounding, but it depends on assumptions about how genetic variants influence an outcome and cannot substitute for a randomised clinical trial of long-term supplementation.

The researchers said lowering tyrosine among people with elevated concentrations might contribute to longer life, particularly in men, but described the finding as a basis for further investigation rather than a clinical recommendation. They called for work to clarify the biological pathways behind the apparent sex difference.

The analysis also found that tyrosine was not significantly associated with deaths specifically from cardiovascular disease or cancer, while phenylalanine showed modest positive associations with both categories in observational analyses. Those disease-specific findings did not establish that either amino acid caused the deaths.