AbstractBackgroundVitamin B12 and homocysteine have been shown to be associated with depression or depressive symptoms, but the relationship has not been universal. Both vitamin B12 and homocysteine may exert an effect via vascular mechanisms; it is possible that other mechanisms apply. Holotranscobalamin is a novel, more accurate measure of tissue vitamin B12.ObjectivesTo examine associations between vitamin B12, serum folate, holotranscobalamin, homocysteine and depressive symptoms in a sample of healthy elderly.MethodsCross‐sectional, observational community based study.ResultsLower levels of holotranscobalamin and vitamin B12 were associated with higher levels of depressive symptoms when controlled for Mini‐mental state examination scores and psychosocial and cardiovascular risk factors. Homocysteine was not associated with depressive symptoms when biological and psychosocial covariates were included.ConclusionsIt is possible that low levels of vitamin B12 or holotranscobalamin are associated with depressive symptoms via mechanisms other than vascular pathology.Copyright © 2010 John Wiley & Sons, Ltd.