Oxidative Stress, Nutritional Antioxidants, and Testosterone Secretion in Men

The biochemistry of testosterone synthesis within the Leydig cells of the human testes is well characterized. Reliance on the mitochondrial electron transfer system for the energy to drive testosterone synthesis exposes Leydig cell mitochondria to oxidative stress. Leydig cells experiencing oxidative stress exhibit reduced activities of antioxidant enzymes, increased lipid peroxidation, reductions in mitochondrial membrane potential required for testosterone synthesis, and reduced expression of the StAR steroidogenic acute regulatory (StAR) protein, culminating in inhibition of the synthesis and secretion of testosterone. Evidence obtained from in vitro, laboratory, and animal experiments, and from human trials, provides strong support for the hypothesis that reducing oxidative stress releases Leydig cells from oxidative inhibition of testosterone synthesis and can improve testosterone status. Selected dietary antioxidants (e.g., the phytonutrients in pomegranates, phosphatidylserine, vitamin C, vitamin E, α-lipoic acid, zinc, and selenium) can contribute safely to oxidative stress reduction and enhanced androgenic status in otherwise healthy adult males. In this era of science-based medical decision-making, addressing oxidative stress and its potential role in undermining testosterone status deserves closer scrutiny.