Journal Article

Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial

Olivia I. Okereke, Francine Grodstein, Michelle A. Albert, Soshiro Ogata, JoAnn E. Manson, Nancy R. Cook, Jae H. Kang, Julie E. Buring, Denise M. D'Agostino, I. Min Lee, Chirag M. Vyas

2021

Overview

Low vitamin D levels have been associated with cognitive decline; however, few randomized trials have been conducted. In a trial, we evaluated vitamin D3 supplementation on cognitive decline. We included participants aged 60+ years (mean[SD] = 70.9[5.8] years) free of cardiovascular disease and cancer in two substudies in the VITAL 2 × 2 randomized trial of vitamin D3 (2000 IU/day of cholecalciferol) and fish oil supplements: 3424 had cognitive assessments by phone (eight neuropsychologic tests; 2.8 years follow-up) and 794 had in-person assessments (nine tests; 2.0 years follow-up). The primary, pre-specified outcome was decline over two assessments in global composite score (average z-scores of all tests); substudy-specific results were meta-analyzed. The pooled mean difference in annual rate of decline (MD) for vitamin D3 versus placebo was 0.01 (95% CI − 0.01, 0.02; p = 0.39). We observed no interaction with baseline 25-hydroxyvitamin-D levels (p-interaction = 0.84) and a significant interaction with self-reported race (p-interaction = 0.01). Among Black participants (19%), those assigned vitamin D3 versus placebo had better cognitive maintenance (MD = 0.04, 95% CI 0.01, 0.08, similar to that observed for Black participants 1.2 years apart in age). Thus, vitamin D3 (2000 IU/day cholecalciferol) supplementation was not associated with cognitive decline over 2–3 years among community-dwelling older participants but may provide modest cognitive benefits in older Black adults, although these results need confirmation. Trial registration ClinicalTrials.gov; VITAL (NCT01169259), VITAL-DEP (NCT01696435) and VITAL-Cog (NCT01669915); the date the registration for the parent trial (NCT01169259) was submitted to the registry: 7/26/2010 and the date of first patient enrollment in either of the ancillary studies for cognitive function in a subset of eligible VITAL participants: 9/14/2011.

• Publisher: Springer Science and Business Media LLC,Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 25-Hydroxyvitamin D / 692/308/2779/777 / 692/617 / Aged / Aged, 80 and over / Alzheimer's disease / Black or African American / Cardiovascular diseases / Cholecalciferol / Cholecalciferol - therapeutic use / Clinical trials / Cognition & reasoning / Cognitive ability / Cognitive Dysfunction / Cognitive Dysfunction - prevention & control / Dietary Supplements / Executive function / Female / Fish Oils / Fish Oils - therapeutic use / Health care / Hospitals / Humanities and Social Sciences / Humans / Male / Medicine / Memory / Middle Aged / multidisciplinary / NCT / NCT01169259 / NCT01669915 / NCT01696435 / Placebos / Preventive medicine / Q / R / Science / Science (multidisciplinary) / Supplements / Vitamin D / Vitamin D - analogs & derivatives / Vitamin D - blood / Vitamin D3 / Vitamin deficiency / Womens health