ABSTRACT
BACKGROUND: The relevance of vitamin D for prevention of cardiovascular disease is uncertain. The BEST-D (Biochemical Efficacy and Safety Trial of vitamin D) trial previously reported effects of vitamin D on plasma markers of vitamin D status, and the present report describes the effects on blood pressure, heart rate, arterial stiffness, and cardiac function. METHODS AND RESULTS: This was a randomized, double-blind, placebo-controlled trial of 305 older people living in United Kingdom, who were allocated vitamin D 4000 IU (100 µg), vitamin D 2000 IU (50 µg), or placebo daily. Primary outcomes were plasma concentrations of 25-hydroxy-vitamin D and secondary outcomes were blood pressure, heart rate, and arterial stiffness in all participants at 6 and 12 months, plasma N-terminal prohormone of brain natriuretic peptide levels in all participants at 12 months, and echocardiographic measures of cardiac function in a randomly selected subset (n=177) at 12 months. Mean (SE) plasma 25-hydroxy-vitamin D concentrations were 50 (SE 2) nmol/L at baseline and increased to 137 (2.4), 102 (2.4), and 53 (2.4) nmol/L after 12 months in those allocated 4000 IU/d, 2000 IU/d of vitamin D, or placebo, respectively. Allocation to vitamin D had no significant effect on mean levels of blood pressure, heart rate, or arterial stiffness at either 6 or 12 months, nor on any echocardiographic measures of cardiac function, or plasma N-terminal prohormone of brain natriuretic peptide concentration at 12 months. CONCLUSIONS: The absence of any significant effect of vitamin D on blood pressure, arterial stiffness, or cardiac function suggests that any beneficial effects of vitamin D on cardiovascular disease are unlikely to be mediated through these mechanisms. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrialsregister.eu/ctr-search/search. Unique identifier: EudraCT number: 2011-005763-24a.
Subject(s)
Atrial Function, Left/drug effects , Blood Pressure/drug effects , Cardiovascular Diseases/prevention & control , Dietary Supplements , Vascular Stiffness/drug effects , Ventricular Function, Left/drug effects , Vitamin D/administration & dosage , Age Factors , Aged , Aging , Biomarkers/blood , Cardiovascular Diseases/blood , Cardiovascular Diseases/diagnostic imaging , Cardiovascular Diseases/physiopathology , Dietary Supplements/adverse effects , Double-Blind Method , Echocardiography , England , Female , Heart Rate/drug effects , Humans , Male , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Time Factors , Treatment Outcome , Vitamin D/adverse effects , Vitamin D/analogs & derivatives , Vitamin D/bloodABSTRACT
BACKGROUND: Previous large trials of vitamin D for prevention of fractures and other disease outcomes have reported conflicting results, possibly because the doses tested were insufficient to maintain optimum blood levels of vitamin D (25[OH]D) predicted by the observational studies. This report describes the design and baseline characteristics of the BEST-D (Biochemical Efficacy and Safety Trial of vitamin D) trial which aims to establish the best dose of vitamin D to assess in a future large outcome trial. METHODS: The BEST-D trial will compare the biochemical and other effects of daily dietary supplementation with 100 µg or 50 µg vitamin D3 or placebo, when administered for 12 months, in 305 ambulant community-dwelling older people living in Oxfordshire, England. The primary analyses will compare 12-month mean plasma concentrations of 25(OH)D as well as the proportion of participants with a 12-month concentration >90 nmol/L between participants allocated 100 µg and participants allocated 50 µg daily. Secondary analyses will compare the two active doses (both separately and when combined) with placebo. Additional end-points include biochemical assessments of safety, blood pressure, arterial stiffness, falls, fractures, heel and wrist bone density, grip strength and physical performance and echocardiographic assessments of cardiac function in a random sample of participants. RESULTS: About one-third of eligible participants agreed to participate in the trial. The mean age was 72 (SD 6) years with equal numbers of men and women. About one third reported a prior history of fracture or hypertension, one-fifth reported a prior cardiovascular event, and one tenth reported diabetes or a fall in the previous 6 months. CONCLUSIONS: The results of this trial will help determine the optimum dose of vitamin D to test in a larger trial investigating whether vitamin D supplementation can reduce the risk of fractures, cardiovascular disease or cancer.