Vitamin B12 and Reproductive Health: Clinical Insights, Emerging Mechanistic Understanding, and Nutritional Aspects

Epidemiological data from assisted reproductive technologies (ART) link vitamin B12 (VitB12) deficiency to shorter gestation, low birth weight, and reduced live birth rates. VitB12 also plays a critical role in fertility for both sexes by supporting gamete quality. Despite some contradictions, emerging evidence suggests early-life VitB12 deficiency may affect learning and cognitive development. Collectively, these findings suggest that VitB12 is a key determinant of both reproductive and developmental health. Mechanistically, VitB12 acts as a coenzyme in one-carbon metabolism, and its deficiency leads to elevated homocysteine (Hcy) and methylmalonic acid (MMA) levels, promoting oxidative stress and thereby impairing fertility. Although this remains the most established mechanism, other yet unidentified pathways may also mediate the effects of VitB12 on reproductive function. While the effects of severe VitB12 deficiency are well established, mild deficiencies may develop silently in individuals following plant-based diets or those with gastrointestinal disorders. Plant-based sources of VitB12 remain controversial, as many provide only trace amounts or biologically inactive analogs such as pseudovitamin B12, which may interfere with absorption. Further research is needed to evaluate their bioavailability and clinical effectiveness. This review synthesizes clinical evidence, mechanistic insights, and dietary considerations to highlight how VitB12 status shapes reproductive health.