The Latest Position on Vitamin D and Omega-3 Supplements!

Dietary vitamin and mineral supplements are widely used worldwide, especially in Western countries. More than half of United States adults, for example, use supplement products. In recent years the most popular supplements believed beneficial have been fish oil and vitamin D. Yet serious doubts remained about long-term benefits. The best and most comprehensive trial designed for this purpose, published in January 2019 in NEJM , was VITAL .

In the randomized, double-blind, placebo -controlled VITAL trial, participants received daily 2000 IU vitamin D3 and daily 1 gram omega-3 fatty acids to test prevention of cancer and cardiovascular diseases.

Lead investigator Manson and colleagues concluded: fish oil and vitamin D supplements do not reduce cancer or cardiovascular disease risk!

Some observational studies suggest fish consumption protects against cardiovascular disease. However, until an Italian study (GISSI) in the late 1990s, evidence that omega-3 reduced risk was absent. Based on that single trial and preclinical results, the American Heart Association (AHA) recommended omega-3 for secondary heart disease prevention. Later large randomized trials failed to confirm this, so the recommendation was revised. Nevertheless, based on one meta-analysis suggesting reduced mortality after heart attack, AHA maintained that omega-3 could, rather than should, be used. VITAL ended this confusion: in an unselected population, omega-3 did not protect against cardiovascular disease (heart attack, stroke, or cardiovascular death). This agrees with ASCEND, which found no cardiovascular prevention benefit from omega-3 in diabetes.

Unlike omega-3 findings, many observational data associate low vitamin D with higher cancer risk, emphasizing the need for randomized controlled studies.

VITAL was not the first randomized trial testing vitamin D for cardiovascular or cancer prevention;

VIDA was a 3-year randomized placebo-controlled New Zealand trial of 5110 people given monthly high-dose vitamin D (100 thousand IU). It found no effect on cardiovascular or cancer risk.

Despite negative trials, hopes of cancer protection persisted. First, active vitamin D suppresses cancer-cell growth in the laboratory. Second, a recent meta-analysis suggested people already diagnosed with cancer benefited in cancer mortality. One randomized placebo-controlled trial showed possible anticancer signals: daily 2000 IU vitamin D and 1500 mg calcium or placebo were given to 2303 postmenopausal women. Although cancer risk fell by %30, the confidence interval included 1, so it was not statistically significant.

VITAL followed participants for a median 5.3 years, enrolling approximately 26 thousand women and men. Supplement/placebo adherence was high, around %80. At baseline, every 13 participants included 1 with serum vitamin D (25-hydroxyvitamin D3) below 20 ng/ml, yet even this group showed no cancer-protective effect.

VITAL’s primary endpoints tested omega-3 and vitamin D effects on heart attack, stroke, cardiovascular death, and cancer occurrence. These supplement primary endpoints were all negative.

However, secondary endpoints had noteworthy findings;

Death from myocardial infarction was less frequent with omega-3 than placebo. Lower cancer mortality with vitamin D also attracts attention on detailed review. These “positive” results require caution. First, no correction for multiple comparisons was made despite many secondary endpoints. Second, these presumed omega-3 effects conflict with other large randomized trials. However, further analysis of one vitamin D trial found lower cancer incidence in supplemented women after excluding those withdrawn because of cancer during the first year.

Finally, medical literature contains many examples of secondary endpoints failing when assessed as primary endpoints. Without further compelling evidence, it is prudent to conclude that omega-3 or vitamin D supplementation cannot be recommended for cardiovascular or cancer protection.

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