Serum 25-hydroxyvitamin D in the VITamin D and OmegA-3 TriaL (VITAL): Clinical and demographic characteristics associated with baseline and change with randomized vitamin D treatment

Contemp Clin Trials. 2019 Dec;87:105854. doi: 10.1016/j.cct.2019.105854. Epub 2019 Oct 24.


Background: The VITamin D and OmegA-3 TriaL (VITAL) is a completed randomized, placebo-controlled trial of vitamin D3 (2000 IU/day) and marine omega-3 (1 g/day) supplements in the primary prevention of cancer and cardiovascular disease. Here we examine baseline and change in 25-hydroxyvitamin D (25(OH)D) and related biomarkers with randomized treatment and by clinical factors.

Methods: Baseline 25(OH)D was measured in 15,804 participants (mean age 68 years.; 50.8% women; 15.7% African Americans) and in 1660 1-year follow-up samples using liquid chromatography-tandem mass spectrometry and chemiluminescence. Calcium and parathyroid hormone (iPTH) were measured by chemiluminescence and spectrophotometry respectively.

Results: Mean baseline total 25(OH)D (ng/mL ± SD) was 30.8 ± 10.0 ng/mL, and correlated inversely with iPTH (r = -0.28), p < .001. After adjusting for clinical factors, 25(OH)D (ng/mL ± SE) was lower in men vs women (29.7 ± 0.30 vs 31.4 ± 0.30, p < .0001) and in African Americans vs whites (27.9 ± 0.29 vs 32.5 ± 0.22, p < .0001). It was also lower with increasing BMI, smoking, and latitude, and varied by season. Mean 1-year 25(OH)D increased by 11.9 ng/mL in the active group and decreased by 0.7 ng/mL in placebo. The largest increases were noted among individuals with low baseline and African Americans. Results were similar for chemiluminescent immunoassay. Mean calcium was unchanged, and iPTH decreased with treatment.

Conclusion: In VITAL, baseline 25(OH)D varied by clinical subgroups, was lower in men and African Americans. Concentrations increased with vitamin D supplementation, with the greatest increases in those with lower baseline 25(OH)D. The seasonal trends in 25(OH)D, iPTH, and calcium may be relevant when interpreting 25(OH)D levels for clinical treatment decisions.

Clinical trial registration: VITAL number NCT01169259.

Keywords: 25-hydroxyvitamin D; Parathyroid hormone; Seasonal effects; VITAL trial; Vitamin D.

Publication types

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

MeSH terms

  • African Americans
  • Age Factors
  • Biomarkers
  • Body Mass Index
  • Calcium / blood
  • Cardiovascular Diseases / ethnology
  • Cardiovascular Diseases / prevention & control
  • Cholecalciferol / administration & dosage*
  • Comorbidity
  • Dietary Supplements*
  • Double-Blind Method
  • European Continental Ancestry Group
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / ethnology
  • Neoplasms / prevention & control
  • Residence Characteristics
  • Seasons
  • Sex Factors
  • Smoking / epidemiology
  • Socioeconomic Factors
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood


  • Biomarkers
  • Fatty Acids, Omega-3
  • Vitamin D
  • Cholecalciferol
  • 25-hydroxyvitamin D
  • Calcium

Associated data