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Interrelationship of Vitamin D Supplementation, Adiposity and CVD Risk Factors in a Randomized Clinical Trial

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Trial Information

Interrelationship of Vitamin D Supplementation, Adiposity and CVD Risk Factors in a Randomized Clinical Trial

Observational studies suggest that low 25-hydroxyvitamin D (25(OH)D) levels are associated
with high BMI and fat mass (FM), but it is unknown whether vitamin D supplementation can
alter body composition or adiposity. Despite enthusiasm for the use of vitamin D supplements
to reduce FM, the hypothesis that vitamin D can modify adiposity remains unproven. Finding
strategies to prevent obesity is of critical public health importance due to the high
prevalence of overweight/obesity and its role in causing diabetes, hypertension,
dyslipidemia, cardiovascular disease (CVD), among others. Observational studies also link
low 25(OH)D levels to CVD risk factors related to obesity, but sequestration of vitamin D in
fat tissue may be a confounding factor. The effects of vitamin D supplementation on body
composition, adiposity and CVD risk factors are best tested in a randomized clinical trial
(RCT), and according to the Institute of Medicine (IOM) 2011 report, more data from
randomized clinical trials on these outcomes are needed. Previous trials of vitamin D have
been limited by the inability to separate effects of supplemental calcium from vitamin D,
small sample size, insufficient vitamin D dose, failure to monitor 25(OH)D levels or
inadequate ascertainment of body composition. The NIH-funded VITamin D and OmegA-3 TriaL
(VITAL) (1 U01 CA138962) affords a unique and cost-effective opportunity to investigate the
effect of vitamin D on changes in body composition and to assess whether changes in CVD risk
factors are mediated, at least in part, by these parameters. VITAL is a large-scale,
randomized, primary prevention trial testing 2000 IU/d vitamin D3 (cholecalciferol) and 1
g/day omega-3 fatty acids (840 mg EPA+DHA in 1.3:1 ratio) in a 2x2 factorial design among
20,000 men and women (≥50 and ≥55 years, respectively), with mean participant follow-up of 5
years for CVD and cancer. This ancillary study will address understudied areas and two
overarching hypotheses that vitamin D supplementation (1) lowers total and regional (trunkal
and abdominal/androidal) body fat as measured by dual x-ray absorptiometry (DXA) scans,
improving biomarkers of adiposity (leptin, adiponectin) and (2) impacts CVD risk factors, at
least in part through adiposity. The investigators also seek to define how circulating
achieved 25(OH)D levels, due to supplementation, may be affected by body composition and
BMI, thus elucidating how adiposity, BMI, and body composition (total and regional) may
influence vitamin D intake needs in the population. To critically evaluate these hypotheses,
the investigators will examine a representative, randomized subcohort of 1000 racially
diverse VITAL participants (25% African American) over two years.

Inclusion Criteria

Inclusion criteria:

- Participants in VITAL (NCT 01169259) who are willing to participate in this ancillary
study and undergo DXA evaluation (baseline and 2 years)

Exclusion criteria:

- Inability to travel to the Clinical and Translational Science Center in Boston where
imaging, anthropometric measurements, and blood work will be performed.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Outcome Measure:

Body Composition

Outcome Description:

We will measure by DXA, changes in body composition (i) total body fat and lean mass, (ii) regional and standardized body fat and lean mass (trunkal, androidal (abdominal), appendicular (limb) and derived ratios (trunk/limb; android/gynoid)) among those randomized to vitamin D supplementation vs. those randomized to placebo.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Jacqueline S. Danik, MD, DrPH

Investigator Role:

Principal Investigator

Investigator Affiliation:

Brigham and Women's Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

July 2012

Completion Date:

Related Keywords:

  • Adiposity
  • Adiposity
  • Body composition
  • Vitamin D
  • Adipokines
  • Omega-3 fatty acid
  • Obesity



Brigham and Women's Hospital Boston, Massachusetts  02115