In older adults, low folate status has been associated with a higher risk of mild cognitive impairment (MCI) and faster cognitive decline over time, likely through effects on one‑carbon metabolism and homocysteine. Several longitudinal cohort studies have found that individuals with lower serum or red‑cell folate and higher homocysteine show steeper declines on memory and global cognition tests, and in some cohorts have a significantly higher incidence of MCI or dementia over follow‑up. The clinically important takeaway is that, when folate deficiency is detected and corrected (usually along with ensuring adequate vitamin B12), some patients demonstrate stabilization or modest improvement in cognitive performance, particularly when interventions are combined with aggressive management of vascular risk factors such as hypertension and diabetes. This medication is commonly used for Diabetes.
Ma, F., Wu, T., Zhao, J. et al. Folic acid supplementation improves cognitive function by reducing the levels of peripheral inflammatory cytokines in elderly Chinese subjects with MCI. Sci Rep 6, 37486 (2016). Wang M, Fang M, Zang W. Effects of folic acid supplementation on cognitive function and inflammation in elderly patients with mild cognitive impairment: A systematic review and meta-analysis of randomized controlled trials. Arch Gerontol Geriatr. 2024 Nov;126:105540. O’Connor, D.M.A., Scarlett, S., De Looze, C. et al. Low folate predicts accelerated cognitive decline: 8-year follow-up of 3140 older adults in Ireland. Eur J Clin Nutr 76, 950–957 (2022).Putu Eka Widyadharma. Folic acid supplementation improves cognitive function: A systematic review. December 2020 Romanian Journal of Neurology 19(4):219-223.
Some side effects may be linked to nutrient depletion caused by this medication.
Sulfonylureas, a class of anti-diabetic drugs, have been found in research to significantly deplete Coenzyme Q10 (COQ10). This nutrient may be beneficial to individuals with diabetes as it is found to assist: high blood pressure, decrease triglycerides, improve HDL cholesterol, and provide glycemic control.
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.
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.
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.