Folic Acid Supplementation and Risk of Gestational Diabetes Mellitus: A Systematic Review of the Literature

Gestational diabetes mellitus (GDM) affects approximately 14% of pregnancies globally and has been hypothesized to be influenced by periconceptional and early pregnancy folic acid (FA) supplementation, a practice recommended to prevent neural tube defects. To evaluate this association, we conducted a systematic review of studies published between 2015 and 2024 examining FA use and GDM risk. Twelve studies met the inclusion criteria, including ten cohort studies and two case-control studies. While findings were mixed, several prospective studies suggested that high daily FA intake (≥800 μg) or prolonged use (>3-6 months) may be associated with increased odds of GDM, especially when initiated preconceptionally. Conversely, standard-dose supplementation (≈400 μg) appeared neutral or potentially protective in some populations. Notably, high folate status combined with low vitamin B12 was linked to increased GDM risk, suggesting metabolic interaction. Overall, most studies were of moderate to high methodological quality. Although current evidence is inconclusive, these results support cautious use of high-dose FA supplementation and the importance of individualized prenatal nutrition, particularly considering B12 status. Further research is needed to clarify biological mechanisms.