Folic acid deficiency may contribute to erectile dysfunction (ED), a new systematic review concludes.

In a meta‐analysis of 6 studies comparing 982 men with ED and 860 healthy men without ED, mean serum folic acid level in men with ED was a significant 0.94 ng/mL lower, Xiansheng Zhang, MD, PhD, of The First Affiliated Hospital of Anhui Medical University in Anhui Province, China, and colleagues reported in Sexual Medicine. A meta-analysis of 3 studies further showed that serum folic acid levels decreased with ED severity. Serum folic acid levels were 9.5, 6.6, and 5.6 ng/mL in men with mild, moderate, and severe ED, respectively, compared with 11.8 ng/mL in healthy men.

International Index of Erectile Function (IIEF-5) score increased by a standardized mean difference (SMD) of 1.89 with folic acid administration in patients with ED, based on 2 studies, the investigators reported. In 1 study, a combination of folic acid and tadalafil improved IIEF score by 0.90 compared with tadalafil and placebo.

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Dr Zhang’s team concluded that folic acid deficiency may be an independent risk factor for ED. With respect to possible mechanisms, folic acid deficiency may impair nitric oxide metabolism and contribute to endothelial dysfunction and, in turn, vascular ED. Whether folic acid supplementation could improve ED requires further research, according to the investigators.


Zhang Y, Zhang W, Dai Y, Jiang H, Zhang X. Serum folic acid and erectile dysfunction: a systematic review and meta-analysis. Sex Med. 9(3):100356. Published online May 26, 2021. doi:10.1016/j.esxm.2021.100356