Vitamin D supplementation and adverse skeletal and non-skeletal outcomes in individuals at increased cardiovascular risk: Results from the International Polycap Study (TIPS)-3 randomized controlled trial

Nutr Metab Cardiovasc Dis. 2023 Feb;33(2):434-440. doi: 10.1016/j.numecd.2022.11.001. Epub 2022 Nov 15.

Abstract

Background and aims: Vitamin D has mostly been tested in Western populations. We examined the effect of high dose vitamin D in a population drawn predominantly from outside of Western countries.

Methods and results: This randomized trial tested vitamin D 60,000 IU monthly in 5670 participants without vascular disease but at increased CV risk. The primary outcome was fracture. The secondary outcome was the composite of CV death, myocardial infarction stroke, cancer, fracture or fall. Death was a pre-specified outcome. Mean age was 63.9 years, and 3005 (53.0%) were female. 3034 (53.5%) participants resided in South Asia, 1904 (33.6%) in South East Asia, 480 (8.5%) in South America, and 252 (4.4%) in other regions. Mean follow-up was 4.6 years. A fracture occurred in 20 participants (0.2 per 100 person years) assigned to vitamin D, and 19 (0.1 per 100 person years) assigned to placebo (HR 1.06, 95% CI 0.57-1.99, p-value = 0.86). The secondary outcome occurred in 222 participants (1.8 per 100 person years) assigned to vitamin D, and 198 (1.6 per 100 person years) assigned to placebo (HR 1.13, 95% CI 0.93-1.37, p = 0.22). 172 (1.3 per 100 person years) participants assigned to vitamin D died, compared with 135 (1.0 per 100 person years) assigned to placebo (HR 1.29, 95% CI 1.03-1.61, p = 0.03).

Conclusion: In a population predominantly from South Asia, South East Asia and South America, high-dose vitamin D did not reduce adverse skeletal or non-skeletal outcomes. Higher mortality was observed in the vitamin D group.

Registration number: NCT01646437.

Keywords: Cancer; Cardiovascular disease; Death; Falls; Fractures; Vitamin D.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Dietary Supplements / adverse effects
  • Double-Blind Method
  • Female
  • Fractures, Bone*
  • Heart Disease Risk Factors
  • Humans
  • Male
  • Middle Aged
  • Risk Factors
  • Vitamin D
  • Vitamins / therapeutic use

Substances

  • Vitamins
  • Vitamin D

Associated data

  • ClinicalTrials.gov/NCT01646437