Metformin associated with B-vitamin deficiency, cognitive dysfunction in older patients

This observational study suggests that metformin use in hyperglycemic older patients is associated with vitamin B12 and B6 (pyridoxine) deficiency and poorer cognitive performance.


Older patients with diabetes who are taking metformin may develop vitamin deficiencies that could affect cognition, a recent study found.

Researchers in Ireland performed an observational study using data from the Trinity, Ulster and Department of Agriculture cohort, which included community-dwelling adults who were at least 60 years of age and had no existing diagnosis of dementia. The goal of the study was to examine the effect of hyperglycemia and use of metformin on B-vitamin biomarkers and cognitive outcomes. The main outcome measures were biomarkers of folate, vitamin B12, vitamin B6, and riboflavin, along with cognitive function as assessed by the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) and the Frontal Assessment Battery (FAB). The researchers also considered whether consumption of fortified food could help improve B-vitamin levels. The study results were published March 28 by the Journal of Clinical Endocrinology and Metabolism.

Overall, 4,160 adults without dementia were classified as being normoglycemic (n=1,856) or hyperglycemic (n=2,304), with an HbA1c level of 5.7% or higher as the cutoff. Among patients who were hyperglycemic, 318 were taking metformin and 1,986 were not. Mean patient age was 74.1 years. After adjustment for relevant variables, the researchers found that metformin use was associated with higher risk for vitamin B12 deficiency, vitamin B6 deficiency, and cognitive dysfunction. Most patients (72%) ate food fortified with B vitamins, and consumption of at least five portions of fortified food weekly was associated with higher B-vitamin biomarker status among both hyperglycemic and normoglycemic patients. B-vitamin levels were lowest and deficiency rates were highest in hyperglycemic patients who did not regularly consume fortified food.

The authors noted that the study design was cross-sectional and that causal relationships between metformin use and B-vitamin deficiency or B-vitamin deficiency and cognitive impairment cannot be confirmed, among other limitations. They concluded that metformin use in older patients is associated with worse cognitive performance, possibly because of related deficiencies of vitamins B12 and B6. “Fortified foods can provide a bioavailable source of B-vitamins and may be beneficial for maintaining better cognitive health in older people with or at risk of diabetes, but this requires confirmation in an intervention trial,” the authors wrote. “Research is warranted to further investigate the interrelationships of diabetes, B-vitamin status and cognitive health in aging.”