Vitamin D and Omega-3 Trial - VITAL

Contribution To Literature:

The VITAL trial showed that supplementation with either n–3 fatty acid at a dose of 1 g/day or vitamin D3 at a dose of 2000 IU/day was not effective for primary prevention of CV or cancer events among healthy middle-aged men and women over 5 years of follow-up.

Description:

The goal of the trial was to assess the cardiovascular (CV) and cancer benefits of n–3 (also called omega-3) fatty acid and vitamin D3 supplementation compared with placebo among healthy participants.


Study Design

In a 2 x 2 factorial design, healthy participants were randomized in a 1:1 fashion to either vitamin D3 (at a dose of 2000 IU per day) (n = 12,927) or placebo (n = 12,944), or n–3 fatty acids (1 g per day as a fish-oil capsule containing 840 mg of n–3 fatty acids, including 460 mg of eicosapentaenoic acid [EPA] and 380 mg of docosahexaenoic acid [DHA]) (n = 12,933) or matching placebo (n = 12,938).

  • Total number of enrollees: 25,871
  • Duration of follow-up: 5.3 years
  • Mean patient age: 67.1 years
  • Percentage female: 51%

Inclusion criteria:

  • Men >50 years or women >55 years
  • No known cardiovascular disease or cancer

Exclusion criteria:

  • Renal failure or dialysis
  • Cirrhosis
  • History of hypercalcemia

Other salient features/characteristics:

  • African American: 20%
  • Mean body mass index: 28 kg/m2
  • Diabetes: 13.7%

Principal Findings:

The primary CV outcome of CV death, nonfatal myocardial infarction (MI), or stroke, for vitamin D3 vs. placebo, was 3.1% vs. 3.2%, hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.85-1.1, p = 0.69.

  • CV death: 1.2% vs. 1.1%, for vitamin D3 vs. placebo, respectively
  • Stroke: 1.1% vs. 1.2%
  • MI: 1.3% vs. 1.4%
  • Primary cancer outcome, invasive cancer: 6.1% vs. 6.4%, HR 0.96, 95% CI 0.88-1.06, p = 0.47

The primary CV outcome of CV death, nonfatal MI, or stroke, for n–3 fatty acid vs. placebo, was 3.0% vs. 3.2%, HR 0.92, 95% CI 0.80-1.06, p = 0.24.

  • CV death: 1.1% vs. 1.1%, for n–3 fatty acid vs. placebo, respectively
  • Stroke: 1.1% vs. 1.1%
  • MI: 1.1% vs. 1.5%, HR 0.72, 95% CI 0.59-0.90
  • Primary cancer outcome, invasive cancer: 6.3% vs. 6.2%, HR 1.03, 95% CI 0.93-1.13, p = 0.56

Secondary outcomes for vitamin D3 vs. placebo:

  • All-cause mortality: 3.8% vs. 3.8%

Secondary outcomes for n–3 fatty acid vs. placebo:

  • Total coronary heart disease: 0.3% vs. 0.4%
  • All-cause mortality: 3.8% vs. 3.7%

Interpretation:

The results of this trial indicate that supplementation with either n–3 fatty acid at a dose of 1 g/day or vitamin D3 at a dose of 2000 IU/day was not effective for primary prevention of CV or cancer events among healthy middle-aged men and women over 5 years of follow-up. This is one of the largest trials on this topic. The finding of a lower MI risk with n–3 fatty acid is hypothesis generating and deserves further study. The authors also noted some interaction with baseline fish consumption, with greater CV benefit observed among participants who had low fish intake at baseline.

References:

Manson JE, Cook NR, Lee IM, et al., on behalf of the VITAL Research Group. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med 2019;380:33-44.

Manson JE, Cook NR, Lee IM, et al., on behalf of the VITAL Research Group. Marine n−3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med 2019;380:23-32.

Editorial: Keaney JF Jr, Rosen CJ. VITAL Signs for Dietary Supplementation to Prevent Cancer and Heart Disease. N Engl J Med 2019;380:91-3.

Presented by Dr. JoAnn E. Manson at the American Heart Association Annual Scientific Sessions (AHA 2018), Chicago, IL, November 10, 2018.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins

Keywords: AHA Annual Scientific Sessions, AHA18, Cholecalciferol, Coronary Disease, Docosahexaenoic Acids, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Fish Oils, Middle Aged, Myocardial Infarction, Neoplasms, Primary Prevention, Stroke, Vitamin D


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