Effects of Vitamin D3 Supplementation on Cardiovascular and Cancer Outcomes by eGFR in VITAL

Kidney360. 2022 Oct 28;3(12):2095-2105. doi: 10.34067/KID.0006472022. eCollection 2022 Dec 29.

Abstract

Background: Reduced 25-hydroxyvitamin D (25[OH]D) metabolism and secondary hyperparathyroidism are common with lower estimated glomerular filtration rate (eGFR) and may contribute to cardiovascular disease and cancer risk.

Methods: We assessed for heterogeneity by baseline eGFR of the effects of vitamin D3 on cardiovascular and cancer outcomes in the Vitamin D and Omega-3 Trial (VITAL). Participants were randomized to 2000 IU vitamin D3 and/or 1 g Ω-3 fatty acids daily using a placebo-controlled, two-by-two factorial design (5.3 years follow-up). Primary study end points were incident major cardiovascular events and invasive cancer. Changes in serum 25(OH)D and parathyroid hormone (PTH) were examined.

Results: Baseline eGFR was available for 15,917 participants. Participants' mean age was 68 years, and 51% were women. Vitamin D3 resulted in higher serum 25(OH)D compared with placebo (difference in change 12.5 ng/ml; 95% CI, 12 to 13.1 ng/ml), without heterogeneity by eGFR (P interaction, continuous eGFR=0.2). Difference in change in PTH between vitamin D3 and placebo was larger with lower eGFR (P interaction=0.05): -6.9 (95% CI, -10.5 to -3.4), -5.8 (95% CI, -8.3 to -3.4), -4 (95% CI, -5.9 to -2.2), and -3.8 (95% CI, -5.6 to -2) pg/ml for eGFR <60, 60-74, 75-89, and ≥90 ml/min per 1.73 m2, respectively. Effects of vitamin D3 supplementation on cardiovascular events (P interaction=0.61) and cancer (P interaction=0.89) did not differ by eGFR: HR=1.14 (95% CI, 0.73 to 1.79), HR=1.06 (95% CI, 0.75 to 1.5), HR=0.92 (95% CI, 0.67 to 1.25), and HR=0.92 (95% CI, 0.66 to 1.27) across eGFR categories for cardiovascular events and HR=1.63 (95% CI, 1.03 to 2.58), HR=0.85 (95% CI, 0.64 to 1.11), HR=0.84 (95% CI, 0.68 to 1.03), and 1.11 (95% CI, 0.92 to 1.35) for cancer, respectively.

Conclusions: We observed no significant heterogeneity by baseline eGFR in the effects of vitamin D3 supplementation versus placebo on cardiovascular or cancer outcomes, despite effects on 25(OH)D and PTH concentrations.

Keywords: cholecalciferol; dietary supplements; mineral metabolism; neoplasms.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Cholecalciferol / therapeutic use
  • Dietary Supplements
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Male
  • Neoplasms* / drug therapy
  • Neoplasms* / epidemiology
  • Parathyroid Hormone
  • Vitamin D / therapeutic use

Substances

  • Cholecalciferol
  • Vitamin D
  • Parathyroid Hormone