Research Progress on the Effects of Methylmalonic Acid on Male Reproductive Function

Zhao Lu; Zhongsheng Yang; Long Gan

doi:10.62051/ijphmr.v6n5.03

Authors

Zhao Lu
Zhongsheng Yang
Long Gan

DOI:

https://doi.org/10.62051/ijphmr.v6n5.03

Keywords:

Methylmalonic acid, Male infertility, Mitochondrial dysfunction, Oxidative stress, Vitamin B12

Abstract

Methylmalonic acid (MMA), a sensitive marker of vitamin B₁₂ deficiency, exerts multifaceted adverse effects on male reproductive function when accumulated. This systematic review examines how MMA leads to reduced sperm count, decreased motility, and DNA damage by inhibiting mitochondrial complex II, inducing oxidative stress, and disrupting one-carbon metabolism; causing Leydig cell atrophy, impaired testosterone synthesis, and compromised Sertoli cell function; and disrupting endocrine regulation within the hypothalamic-pituitary-testicular axis. Mechanistically, MMA induces reactive oxygen species (ROS) production, ATP synthesis inhibition, inflammatory responses, and epigenetic modifications, forming a pathological cascade of “energy crisis–oxidative damage–apoptosis.” Clinical observations indicate that MMA levels are negatively correlated with sperm quality and testosterone levels, and supplementation with vitamin B₁₂ can effectively reverse the associated damage. It is recommended that MMA monitoring be incorporated into the screening system for male infertility etiology, and that early nutritional intervention be implemented for high-risk populations to improve male reproductive health.

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