Folate deficiency in the periconceptional period significantly increases the risk of neural tube defects (NTDs) such as spina bifida and anencephaly, because adequate folate is required for proper closure of the embryonic neural tube in the first month of pregnancy. Large observational datasets and randomized trials have shown that appropriate folic acid supplementation before conception and in early pregnancy can reduce NTD risk by roughly 50–70% in the general population, with even greater risk reduction in women with a prior NTD‑affected pregnancy. The practical implication is that all women of childbearing potential, not just those actively planning pregnancy, are typically advised to maintain adequate daily folic acid intake so that red‑cell folate stores are sufficient well before conception occurs. This medication is commonly used for Diabetes.
Viswanathan M, Urrutia RP, Hudson KN, Middleton JC, Kahwati LC. Folic Acid Supplementation to Prevent Neural Tube Defects: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2023;330(5):460–466. Wald NJ. Folic acid and neural tube defects: Discovery, debate and the need for policy change. J Med Screen. 2022 Sep;29(3):138-146. Mathieu d'Argent E, Ravel C, Rousseau A, Morcel K, Massin N, Sussfeld J, Simon T, Antoine JM, Mandelbaume J, Daraï E, Kolanska K. High-Dose Supplementation of Folic Acid in Infertile Men Improves IVF-ICSI Outcomes: A Randomized Controlled Trial (FOLFIV Trial). J Clin Med. 2021 Apr 26;10(9):1876. Jadhav, S. N., & Pitale, D. L. (2020). Effectiveness of folic acid in unexplained infertility. International Journal of Reproduction, Contraception, Obstetrics and Gynecology, 9(9), 3780–3783.
Some side effects may be linked to nutrient depletion caused by this medication.
Long term treatment with Biguanides, such as Metformin or Metformin combinations with other drugs, are found in research to reduce vitamin B12 absorption due to it hindering the activity of a calcium-dependent mechanism. Insufficient levels of vitamin B12 can lead to higher circulating homocysteine levels and the elevated risk of neurological problems and cardiovascular diseases.
Biguanide (anti-diabetic) drugs have been found in scientific evidence to decrease serum levels of coenzyme Q10. Type 2 diabetes can increase oxidative stress in the body, weakening its defenses and potentially harming cells. CoQ10, a powerful antioxidant, plays a crucial role in protecting cells from this damage. CoQ10 supplementation may help restore these levels, potentially improving mitochondrial function and protecting the kidneys from damage.
Research has shown that anti-diabetic Biguanide drugs may reduce folic acid absorption. Folic acid is a powerful antioxidant and low levels make the body more susceptible to oxidative stress, which can damage enzymes involved in homocysteine metabolism, and subsequently increase its accumulation. Elevated levels of homocysteine (hyperhomocysteinemia) are a risk factor for various health problems including cardiovascular diseases, neurological problems, osteoporosis, and vision problems.
Biguanides, such as Metformin or Metformin combinations with other drugs, may contribute to reduced levels of thiamine (vitamin B1) in end-stage renal failure patients. Research has found metformin encephalopathy present in patients on hemodialysis for end-stage diabetic renal failure (ESRD). Patients with ESRD should consider having thiamine (vitamin B1) status monitored and supplementing with thiamine when levels are insufficient or deficient.