Does Vitamin A increase androgens?

INTRODUCTION: Despite observations suggesting androgens might protect against cardiovascular disease, evidence is slowly emerging from more robust study designs, such as meta-analysis of randomized controlled trials and Mendelian randomization, indicating that androgens increase cardiovascular events and generate an unhealthier cardiovascular risk factor profile. Exposures that drive androgens could be a new target for cardiovascular disease prevention. Vitamin A at high doses increases mortality in well-fed populations, and is thought to have reproductive effects. No randomized controlled trial has assessed the effects of vitamin A on androgens. We assessed the association of two different androgen biomarkers with vitamin A in a nationally representative study of US men from NHANES III phase 1.

METHODS: We used linear regression in 1470 men to assess the adjusted association of serum testosterone and androstanediol glucuronide (3α-diol-G), expressed as z-scores for comparability, with serum vitamin A. Testosterone measures circulating gonadal production, whilst 3α-diol-G is a correlate of the final breakdown production of all androgens including those generated from the adrenals or produced and used locally.

RESULTS: Serum testosterone and 3α-diol-G were poorly correlated. Vitamin A was not associated with serum testosterone (-0.06 z-score per umol/L vitamin A, 95% confidence interval (CI) -0.19 to 0.06) but was positively associated with 3α-diol-G (0.17, 95% CI 0.03 to 0.30), adjusted for age, education, race/ethnicity, alcohol use and smoking and taking into account the clustering and complex survey design.

CONCLUSIONS: Although we cannot rule out reverse causality or confounding, it is physiologically more plausible that vitamin A drives androgen activity, as indicated by the association for 3α-diol-G, than the reverse given serum testosterone is known to be a marker of health status. As such, raising androgens could provide one reason for vitamin A’s harmful effects with corresponding implications for supplementation and fortification with vitamin A in well-fed populations.