Vitamin D and Omega-3 Trial (VITAL) (VITAL)

The VITamin D and OmegA-3 TriaL (VITAL) is an ongoing randomized clinical trial of vitamin D (in the form of vitamin D3 [cholecalciferol]) and marine omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements in the primary prevention of cancer and cardiovascular disease. Existing data from laboratory studies, epidemiologic research, small primary prevention trials, and/or large secondary prevention trials strongly suggest that these nutritional agents may reduce risk for cancer or cardiovascular disease, but large primary prevention trials with adequate dosing in general populations are lacking.

Eligible participants were assigned by chance (like a coin toss) to one of four groups: (1) daily vitamin D3 and omega-3; (2) daily vitamin D3 and omega-3 placebo; (3) daily vitamin D placebo and omega-3; or (4) daily vitamin D placebo and omega-3 placebo. Participants had an equal chance of being assigned to any of these four groups and a 3 out of 4 chance of getting at least one active agent.

Participants in all groups take two pills each day -- one softgel that contains either vitamin D3 or vitamin D placebo and one capsule that contains either omega-3 or omega-3 placebo. Participants receive their study pills in convenient calendar packages via U.S. mail.

Participants also fill out a short (15-20 minute) questionnaire each year. The questionnaire asks about health; lifestyle habits such as physical exercise, diet, and smoking; use of medications and dietary supplements; family history of illness, and new medical diagnoses. Occasionally, participants may receive a phone call from study staff to collect information or to clarify responses on the questionnaire.

At baseline, 16,954 VITAL participants provided an optional blood sample. Approximately 6,000 of these participants will provide a follow-up blood sample during years 1-4 of the trial.

At baseline and year 2 of the trial, a subcohort of 1,054 VITAL participants living within driving distance of Boston, Massachusetts received detailed in-clinic health assessments at the Clinical and Translational Science Center (CTSC) of Brigham and Women's Hospital. During CTSC visits, participants have a clinical exam, including measurement of height, weight, other anthropometrics, blood pressure, and physical performance. They also provide fasting blood and urine samples, and undergo 2-hour oral glucose tolerance testing, lung function testing (spirometry), electrocardiograms, bone mineral density testing, 2D-echocardiography, and assessments of thinking and mood.

• Cancer
• Cardiovascular Disease

• Dietary Supplement: vitamin D3
  Vitamin D3 (cholecalciferol), 2000 IU per day.
  Other Name: cholecalciferol
• Drug: omega-3 fatty acids (fish oil)
  Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
• Dietary Supplement: Vitamin D3 placebo
  Vitamin D placebo
• Dietary Supplement: Fish oil placebo
  Fish oil placebo

• Active Comparator: Vitamin D + fish oil
  Interventions:

  • Dietary Supplement: vitamin D3
  • Drug: omega-3 fatty acids (fish oil)
• Active Comparator: Vitamin D + fish oil placebo
  Interventions:

  • Dietary Supplement: vitamin D3
  • Dietary Supplement: Fish oil placebo
• Active Comparator: Vitamin D placebo + fish oil
  Interventions:

  • Drug: omega-3 fatty acids (fish oil)
  • Dietary Supplement: Vitamin D3 placebo
• Placebo Comparator: Vitamin D placebo + fish oil placebo
  Interventions:

  • Dietary Supplement: Vitamin D3 placebo
  • Dietary Supplement: Fish oil placebo

• Bassuk SS, Manson JE, Lee IM, Cook NR, Christen WG, Bubes VY, Gordon DS, Copeland T, Friedenberg G, D'Agostino DM, Ridge CY, MacFadyen JG, Kalan K, Buring JE. Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL). Contemp Clin Trials. 2016 Mar;47:235-43. doi: 10.1016/j.cct.2015.12.022. Epub 2016 Jan 6.
• Pradhan AD, Manson JE. Update on the Vitamin D and OmegA-3 trial (VITAL). J Steroid Biochem Mol Biol. 2016 Jan;155(Pt B):252-6. doi: 10.1016/j.jsbmb.2015.04.006. Epub 2015 Apr 9.

To be eligible for the study, respondents had to, at study entry,:

1. be men aged 50 or older or women aged 55 or older;
2. have no history of cancer (except non-melanoma skin cancer), heart attack, stroke, transient ischemic attack, angina pectoris, CABG, or PCI;
3. have none of the following safety exclusions: history of renal failure or dialysis, hypercalcemia, hypo- or hyperparathyroidism, severe liver disease (cirrhosis), or sarcoidosis or other granulomatous diseases such as active chronic tuberculosis or Wegener's granulomatosis;
4. have no allergy to fish or soy;
5. have no other serious illness that would preclude participation;
6. be consuming no more than 800 IU of vitamin D from all supplemental sources combined (individual vitamin D supplements, calcium+vitamin D supplements, medications with vitamin D [e.g., Fosamax Plus D], and multivitamins), or, if taking, willing to decrease or forego such use during the trial;
7. be consuming no more than 1200 mg/d of calcium from all supplemental sources combined, or, if taking, willing to decrease or forego such use during the trial;
8. not be taking fish oil supplements, or, if taking, willing to forego their use during the trial

• National Cancer Institute (NCI)
• National Heart, Lung, and Blood Institute (NHLBI)
• Office of Dietary Supplements (ODS)
• National Institute of Neurological Disorders and Stroke (NINDS)
• National Center for Complementary and Integrative Health (NCCIH)