COMMENTARY

VITAL Results for Vitamin D and Omega-3s

JoAnn E. Manson, MD, DrPH

Disclosures

November 15, 2018

Hello. This is Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women's Hospital in Boston, Massachusetts. I would like to talk to you about the results of the VITamin D and OmegA-3 TriaL (VITAL) which were presented at the American Heart Association 2018 meeting in November. It was also published as two reports in the New England Journal of Medicine.[1,2]

VITAL is a large-scale, randomized clinical trial of vitamin D3 (at a dose of 2000 IU per day) and the marine omega-3 fatty acid eicosapentaenoic acid (EPA) (at a dose of 1 g per day) in the primary prevention of cancer and cardiovascular disease. The EPA used was Omacor (GlaxoSmithKline), available by prescription in the United States.

Omega-3 supplements have been studied previously, primarily for secondary prevention and in high-risk populations, including those with prior history of cardiovascular disease (CVD) or risk factors for CVD. VITAL instead was conducted in a usual-risk, ethnically diverse population of nearly 26,000 men and women aged 50, including over 5000 African Americans.

Omega-3 Supplementation

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Overall, omega-3 supplements were associated with only a small, nonsignificant 8% reduction in the primary composite endpoint of stroke, myocardial infarction (MI), and CV-related death. For secondary, prespecified endpoints, we found a 28% reduction in MI and no reduction in stroke or CV mortality.

We looked at participants with low versus high fish consumption to see if there might be a modifying effect. We did collect a detailed [dietary] assessment at baseline from participants. We saw an interesting interaction: Those with fish consumption below the average of 1.5 servings per week did have a significant reduction of 19% in total, major CV events and a 40% reduction in MI.

However, participants who already had fish intake equal to or greater than 1.5 servings per week did not appear to benefit. So there was effect modification by fish consumption. We also saw a signal for a greater benefit among African Americans than other groups. However, this needs to be studied further.

We saw no effect of the marine omega-3s on cancer or cancer death

Vitamin D Supplementation

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For vitamin D, we saw no reduction in any of the CV endpoints. This was true even when we looked at those who started out with serum levels of 25-hydroxyvitamin D below 20 ng/ml (50 nmol/L).

We did see a signal in the vitamin D findings for a potential benefit for reducing cancer death.

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In aggregate, some previous clinical trials have suggested that vitamin D supplementation may have a greater benefit for cancer death than for cancer incidence. This may be because vitamin D can affect tumor biology and may decrease the invasiveness of or the propensity to metastasize the tumor cells. We saw no significant reduction in the incidence of cancer but did see a signal toward a reduction in cancer death. After accounting for latency of cancer by excluding the first 2 years [of the trial], we did see a 25% reduction in cancer death. However, we think that these findings should be interpreted with caution.

We saw no significant side effects or adverse events with either supplement. We did not see hypercalcemia with this dose of vitamin D and we didn't see excess bleeding with 1 g a day of the omega-3.

As far as what clinical, public health messages should be given [as a result of this trial], we think that for those people in the population already taking these supplements over the counter—and there are large numbers of them—we don't find clear reasons to stop taking them. We do encourage avoiding megadosing because there can be risks with these much higher doses.

For those who are not currently taking these supplements, we think it's maybe best to stay tuned for additional research. VITAL will have results on diabetes, cognitive function, mood, depression, autoimmune disease, and many other outcomes which could help inform the risk-benefit profile.

In those who have low consumption of fish, who will just not eat fish, we should still encourage increasing fish in the diet because it can replace red meat and saturated fat and generally lead to a healthier diet. But for those not consuming fish, it may be reasonable to discuss potentially beginning an omega-3 supplement on a case-by-case basis.

Hopefully, guidelines about the use of supplements will be revisited, based not only on VITAL but on other randomized trials to determine whether there should be any changes.

Thank you so much for your attention.

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