The VITamin D and OmegA-3 TriaL (VITAL): Rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease

Abstract

Data from laboratory studies, observational research, and/or secondary prevention trials suggest that vitamin D and marine omega-3 fatty acids may reduce risk for cancer or cardiovascular disease (CVD), but primary prevention trials with adequate dosing in general populations (i.e., unselected for disease risk) are lacking. The ongoing VITamin D and OmegA-3 TriaL (VITAL) is a large randomized, double-blind, placebo-controlled, 2×2 factorial trial of vitamin D (in the form of vitamin D3 [cholecalciferol], 2000 IU/day) and marine omega-3 fatty acid (Omacor® fish oil, eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA], 1 g/day) supplements in the primary prevention of cancer and CVD among a multi-ethnic population of 20,000 U.S. men aged ≥50 and women aged ≥55. The mean treatment period will be 5 years. Baseline blood samples will be collected in at least 16,000 participants, with follow-up blood collection in about 6000 participants. Yearly follow-up questionnaires will assess treatment compliance (plasma biomarker measures will also assess compliance in a random sample of participants), use of non-study drugs or supplements, occurence of endpoints, and cancer and vascular risk factors. Self-reported endpoints will be confirmed by medical record review by physicians blinded to treatment assignment, and deaths will be ascertained through national registries and other sources. Ancillary studies will investigate whether these agents affect risk for diabetes and glucose intolerance; hypertension; cognitive decline; depression; osteoporosis and fracture; physical disability and falls; asthma and other respiratory diseases; infections; rheumatoid arthritis, systemic lupus erythematosus, thyroid diseases, and other autoimmune disorders.

Scientific Opinion on the extension of use for DHA and EPA-rich algal oil fromSchizochytriumsp. as a Novel Food ingredient

“…No information is available as yet from on-going intervention studies which investigate the effect of DHA and EPA supplementation on cancer risk, such as the VITAL trial (Manson et al, 2012).…”

“…On 29 April 2013, the competent authorities of the United Kingdom forwarded to the Commission their initial assessment report, which came to the conclusion that this algal oil, at levels up to 3 000 mg EPA and DHA per day in food supplements and not exceeding the maximum use levels previously described for other foods, meets the criteria for acceptance of a novel food defined in Article (3) Although, overall, evidence from studies is inconsistent, a positive association between a) high intake levels and b) high plasma concentrations of DHA/EPA and the risk of high-grade prostatic intraepithelial neoplasia, a precursor of prostate cancer, has been found in some meta-analyses (Chua et al, 2012;Dahm et al, 2012;Chua et al, 2013;Sorongon-Legaspi et al, 2013). It was noted that a placebo-controlled, double-blind intervention study is in progress in the US which investigates the possibility of a link between intake of vitamin D (50 µg/day) and DHA/EPA (1 g/day) and the incidence of cancer and cardiovascular disease (Manson et al, 2012). (ACNFP, 2012;FSA, 2012).…”

Vitamin D and Cancer Risk and Mortality: State of the Science, Gaps, and Challenges

“…Large cancer chemoprevention trials of vitamin D are ongoing, most notably the Vitamin D and Omega-3 (VITAL) trial that has randomized women and men to 2,000 IU/day of vitamin D (plus 1 g of fish oil) or placebo, and should be completed before 2020 (146). Given that the trial is powered to test the preventive efficacy for overall cancer and major cardiovascular disease events combined, it is likely to have insufficient statistical power to definitively examine individual cancer sites and provide conclusive evidence for benefit (or harm).…”

VDR Potentiation and NMDA R Inhibition Facilitates Axo-Dendritic Process Formation in Melanocyte Model for Pigmented Cells in Parkinsonism

“…The fish oil have also been found to be rich in Vitamin D 3 , as this oil has been found to be abundant in the skin of the fishes, also Vitamin D 3 receptors have been found in the brain, thus suggesting the relationship between MTs, melanocytes, neurons and Vitamin D 3 activities [16]. Vitamin D 3 is capable of stimulating MT activity and regulating the aggregation and dispersion of pigments in the scale of fishes, in the skin of humans.…”