Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care

Osteoporos Int. 2017 Mar;28(3):841-851. doi: 10.1007/s00198-016-3833-y. Epub 2016 Dec 16.


This trial compared the effects of daily treatment with vitamin D or placebo for 1 year on blood tests of vitamin D status. The results demonstrated that daily 4000 IU vitamin D3 is required to achieve blood levels associated with lowest disease risks, and this dose should be tested in future trials for fracture prevention.

Introduction: The aim of this trial was to assess the effects of daily supplementation with vitamin D3 4000 IU (100 μg), 2000 IU (50 μg) or placebo for 1 year on biochemical markers of vitamin D status in preparation for a large trial for prevention of fractures and other outcomes.

Methods: This is a randomized placebo-controlled trial in 305 community-dwelling people aged 65 years or older in Oxfordshire, UK. Outcomes included biochemical markers of vitamin D status (plasma 25-hydroxy-vitamin D [25[OH]D], parathyroid hormone [PTH], calcium and alkaline phosphatase), cardiovascular risk factors and tests of physical function.

Results: Mean (SD) plasma 25(OH)D levels were 50 (18) nmol/L at baseline and increased to 137 (39), 102 (25) and 53 (16) nmol/L after 12 months in those allocated 4000 IU, 2000 IU or placebo, respectively (with 88%, 70% and 1% of these groups achieving the pre-specified level of >90 nmol/L). Neither dose of vitamin D3 was associated with significant deviation outside the normal range of PTH or albumin-corrected calcium. The additional effect on 25(OH)D levels of 4000 versus 2000 IU was similar in all subgroups except for body mass index, for which the further increase was smaller in overweight and obese participants compared with normal-weight participants. Supplementation with vitamin D had no significant effects on cardiovascular risk factors or on measures of physical function.

Conclusions: After accounting for average 70% compliance in long-term trials, doses of 4000 IU vitamin D3 daily may be required to achieve plasma 25(OH)D levels associated with lowest disease risk in observational studies.

Keywords: Clinical trial; Markers of vitamin D status; Optimum dose; Vitamin D.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Alkaline Phosphatase / blood
  • Bone Density Conservation Agents / administration & dosage*
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use
  • Calcium / blood
  • Cardiovascular Diseases / prevention & control
  • Cholecalciferol / administration & dosage*
  • Cholecalciferol / adverse effects
  • Cholecalciferol / therapeutic use
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Medication Adherence / statistics & numerical data
  • Osteoporotic Fractures / blood
  • Osteoporotic Fractures / prevention & control*
  • Parathyroid Hormone / blood
  • Physical Fitness
  • Primary Health Care / methods
  • Risk Factors
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / drug therapy


  • Bone Density Conservation Agents
  • PTH protein, human
  • Parathyroid Hormone
  • Vitamin D
  • Cholecalciferol
  • 25-hydroxyvitamin D
  • Alkaline Phosphatase
  • Calcium