Extraskeletal effects of vitamin D in older adults: Cardiovascular disease, mortality, mood, and cognition

Abstract

Background: Vitamin D insufficiency is prevalent among older adults and may be associated with higher risk for cardiovascular (CV) disease, mortality, depression, and cognitive deficits. Objective: The aim of this article was to review published observational and experimental studies that explored the association between vitamin D insufficiency and CV disease, mortality, mood, and cognition with an emphasis on older adults. Methods: PubMed and Web of Science databases were searched for English-language articles from January 1966 through June 2009 relating to vitamin D, using the following MeSH terms: aged, vitamin D deficiency, physiopathology, drug therapy, cardiovascular diseases, blood pressure, mortality, delirium, dementia, cognitive disorders, depression, depressive disorder, seasonal affective disorder, mental disorders, and vitamin D/therapeutic use. Publications had to include patients ≥65 years of age who had ≥1 recorded measurement of 25-hydroxyvitamin D (25[OH]D) or were receiving vitamin D supplementation. All case-control, cohort, and randomized studies were reviewed. Results: Forty-two case-control, cohort, and randomized trials were identified and included in the review. Based on these publications, the prevalence of vitamin D insufficiency (25[OH]D concentration <30 ng/mL) in communitydwelling older adults (≥65 years of age) ranged from 40% to 100%. Epidemiologic data and several small randomized trials found a potential association between vitamin D deficiency (25[OH]D concentration <10 ng/mL) and CV disease, including hypertension and ischemic heart disease. Although subgroup analyses of data from the Women's Health Initiative Randomized Trial (the largest randomized, placebo-controlled trial of vitamin D plus calcium therapy) did not find reductions in blood pressure, myocardial infarction, or CV disease-related deaths, intervention contamination limited the findings. Observational studies and a meta-analysis of randomized controlled trials found a mortality benefit associated with higher serum 25(OH)D concentrations or vitamin D 2 or D 3 supplementation (mean dose, 528 IU/d). Observational and small randomized trials found a potential benefit of sunlight or vitamin D on symptoms of depression and cognition, but the findings were limited by methodologic problems. Conclusions: Vitamin D insufficiency appears to be highly prevalent among older adults. Evidence from epidemiologic studies and small clinical trials suggests an association between 25(OH)D concentrations and systolic blood pressure, risk for CV disease-related deaths, symptoms of depression, cognitive deficits, and mortality. The Women's Health Initiative Randomized Trial did not find a benefit of vitamin D supplementation on blood pressure, myocardial infarction, or mortality in postmenopausal women.