Hyperglycemia and metformin use are associated with B-vitamin deficiency and cognitive dysfunction in older adults

Kirsty Porter, M Ward, Catherine Hughes, Maurice O'Kane, L. Hoey, Adrian McCann, Anne M Molloy, Conal Cunningham, Miriam Casey, Fergal Tracey, Sean Strain, Kevin McCarroll, Eamon Laird, Alison M Gallagher, H McNulty

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CONTEXT: Emerging evidence suggests that deficiencies of folate-related B vitamins can arise with metformin treatment and are independently linked with cognitive dysfunction, a comorbidity of diabetes. OBJECTIVE: To determine the impact of hyperglycemia and metformin use on relevant B vitamin biomarkers and cognitive outcomes in older adults. SETTING AND PARTICIPANTS: Community-dwelling older adults (74.1 ± 8.3 years, n = 4160) without dementia, recruited to the Trinity, Ulster and Department of Agriculture cohort study in 2008 to 2012, were classified as normoglycemic (n = 1856) or hyperglycemic, based on HbA1c ≥5.7% (39 mmol/mol), either with (n = 318) or without (n = 1986) metformin treatment. MAIN OUTCOME MEASURES: Biomarkers of folate, vitamin B12, vitamin B6, and riboflavin were measured. Cognitive assessments included the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) and the Frontal Assessment Battery (FAB). RESULTS: Metformin use was associated with higher risk of deficiency of vitamin B12 (combined B12 index ≤-1; OR 1.45; 95% CI, 1.03 to 2.02) and vitamin B6 (plasma pyridoxal 5-phosphate <30.0 nmol/L; OR 1.48; 95% CI, 1.02 to 2.15). Fortified foods when eaten regularly had a positive impact on all relevant B vitamin biomarkers, even with hyperglycemia. After adjustment for relevant covariates, metformin use was associated with an increased risk of cognitive dysfunction as assessed with the RBANS (OR 1.36; 95% CI, 1.03 to 1.80) and FAB (OR 1.34; 95% CI, 1.03 to 1.74). CONCLUSIONS: Use of metformin by older adults is associated with poorer cognitive performance; B vitamin deficiency may be implicated. Fortified foods can optimize B vitamin status and may be beneficial for maintaining better cognitive health in older people with or at risk for diabetes.

Original languageEnglish
Pages (from-to)4837-4847
Number of pages11
JournalThe Journal of Clinical Endocrinology & Metabolism
Issue number10
Early online date28 Mar 2019
Publication statusPublished (in print/issue) - 1 Oct 2019

Bibliographical note

Publisher Copyright:
Copyright © 2019 Endocrine Society.

This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine


  • hyperglycaemia
  • metformin
  • B-vitamins
  • cognitive dysfunction
  • fortified food


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