Metformin Use Linked to Worse Cognition, B-Vitamin Deficiency

By Reuters Staff

April 15, 2019

NEW YORK (Reuters Health) - Metformin is associated with worse cognitive function in older adults, which could be explained by B-vitamin deficiency, new research suggests.

"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 for diabetes, but this requires confirmation in an intervention trial," Dr. Kirsty M. Porter of Ulster University in Coleraine, Northern Ireland, and colleagues conclude in the Journal of Clinical Endocrinology and Metabolism, online March 28.

An association between long-term metformin treatment and vitamin B12 malabsorption was first reported more than 40 years ago, Dr. Porter and colleagues note. Deficiencies in B12, along with folate, vitamin B6 and riboflavin, have also been linked to cognitive dysfunction, they add.

To investigate the relationships among hyperglycemia, metformin use and B-vitamin status, the researchers looked at 4,160 community-dwelling, dementia-free older people participating in the Trinity, Ulster and Department of Agriculture (TUDA) study.

The cohort included 1,856 normoglycemic individuals, 318 who were on metformin but hyperglycemic and 1,986 who were hyperglycemic and not taking metformin.

Metformin users had 45% higher odds of having B12 deficiency and 48% higher odds of being vitamin B6 deficient, both significant results.

The adjusted odds of cognitive dysfunction in study participants on metformin were 36% (P=0.03) higher based on the Repeatable Battery for the Assessment of Neuropsychological Status, and 34% (P=0.03) higher with the Frontal Assessment Battery.

"This is the first study to assess the impact of hyperglycemia and metformin on the biomarker status of all relevant B-vitamins within one-carbon metabolism and to investigate associations with cognitive health," Dr. Porter and colleagues write.

"The findings showed that hyperglycemia with metformin is associated with an increased risk of cognitive dysfunction in older adults and we provide some evidence to suggest that specific B-vitamin deficiencies may contribute at least in part to this risk," they add.


J Clin Endocrinol Metab 2019.