Low vitamin B12 but not folate is associated with incident depressive symptoms in community-dwelling older adults: a 4 year longitudinal study

Br J Nutr. 2021 Dec 13;1-22. doi: 10.1017/S0007114521004748. Online ahead of print.


The objective was to examine the prospective relationship between folate and vitamin B12 (B12) status and incident depressive symptoms in a representative cohort of community-dwelling older people. This was a longitudinal study utilising the Irish Longitudinal Study on Aging (n =3,849 aged ≥50 years) and investigated the relationship between blood plasma folate and B12 levels at baseline (wave 1) and incident depressive symptoms at 2 and 4 years (waves 2 and 3). Participants with depression at wave 1 were excluded. A score ≥9 on the Center for Epidemiologic Studies Depression Scale-8 at wave 2 or 3 was indicative of incident depressive symptoms. Plasma B12 and folate concentrations were determined by microbiological assay. B12 status profiles (pmol/l) were defined as: <185, deficient-low; 185 - <258, low normal; >258 - 601, normal and >601 high. Folate status profiles (nmol/l) were defined as: ≤10.0, deficient-low; >10 - 23.0, low normal; >23.0 - 45.0, normal; >45.0, high. Logistic regression models reporting odds ratios were used to analyse the longitudinal association of B-vitamin categories with incident depression. Both B12 and folate plasma concentrations were lower in the group with incident depressive symptoms vs. non depressed (folate: 21.4 vs. 25.1 nmol/L; P=0.0003); (B12: 315.7 vs. 335.9 pmol/L; P=0.0148). Regression models demonstrated that participants with deficient-low B12 status at baseline had a significantly higher likelihood of incident depression four years later (odds ratio 1.51, 95% CI 1.01-2.27, P=0.043). This finding remained robust after controlling for relevant covariates including physical activity, chronic disease burden, vitamin D status. cardiovascular disease and antidepressant use. No associations of folate status with incident depression were observed. Older adults with deficient-low B12 status had a 51% increased likelihood of developing depressive symptoms over 4 years. Given the high rates of B12 deficiency, these findings are important and highlight the need to further explore the low cost benefits of optimising vitamin B12 status for depression in older adults.