More Doubt About Benefits of Vitamin D and Omega-3 Supplements

The landmark VITAL study tested the ability of vitamin D and omega-3 (fish oil) supplements—two of the top-selling dietary supplements—to protect against a wide array of diseases. The Harvard-run trial included more than 25,000 generally healthy adults ages 50 and older who were randomly assigned to take vitamin D (2,000 international units, or IU, a day) plus a placebo; omega-3s (1 gram a day) plus a placebo; both vitamin D and omega-3s; or two placebos, for an average of about five years. 

The first VITAL findings, published in November 2018, concerned the supplements’ effects on cardiovascular disease and cancer, and the results were largely disappointing: Neither vitamin D nor omega-3s reduced the overall incidence of major cardiovascular events or cancer, though subgroup analyses showed some possible benefits for specific groups (especially from omega-3s). 

Now comes round two: the publication of additional VITAL analyses looking at a long list of other primary endpoints, including diabetes, cognition, bone health, depression, asthma, infections, and autoimmune disorders. The first five of these “ancillary” studies, as they’re called, were published in late 2019 and early 2020, in various journals, with more expected to come out throughout this year. Overall, they’ve brought more disappointing news about the potential of either vitamin D or omega-3s to improve various health outcomes. Here’s a summary: 

• Bone health and falls. Taking vitamin D for two years had no effect on bone density in a subset of 687 VITAL participants living in New England, according to results published in the Journal of Bone and Mineral Research. Nor did vitamin D reduce the risk of falls over five years in the overall VITAL cohort (more than 25,800 adults), a not-yet-published analysis by the same researchers found. But both studies looked at a generally healthy population, and the results may not apply to people with osteoporosis, extremely low vitamin D levels, or a high risk of falls. What’s more, the studies tested vitamin D alone and not with calcium, with which it is often paired and may be more effective. 
• Colorectal polyps. Supplemental omega-3s did not reduce the overall incidence of adenomas or serrated polyps (both precursors to colorectal cancer) in a study in JAMA Oncology, which included more than 25,000 VITAL participants. Over five years of follow-up, the number of adenomas and polyps were virtually the same between the omega-3 and placebo groups. 

In subgroup analyses, the researchers found a “suggestive beneficial association” between omega-3s and precancerous lesions in African American people and those with low baseline blood levels of omega-3s. (These same subgroups appeared to get a heart benefit from omega-3s in the initial VITAL studies.) But note that subgroup analyses as well as secondary endpoints (see “Heart failure,” below) are less reliable and harder to interpret than primary endpoints; they’re useful mostly for generating hypotheses that can then be tested in further studies and over longer follow-up periods. A VITAL paper looking at vitamin D and colorectal cancer precursors is forthcoming, according to the lead researcher. (Some previous observational research has linked higher blood levels of vitamin D to a lower risk of colorectal cancer.) 

• Inflammation. In an analysis of about 1,500 VITAL participants, a daily vitamin D or omega-3 pill did not reduce overall levels of three markers of systemic inflammation—interleukin-6 (IL-6), tumor necrosis factor, and C-reactive protein (CRP)—over one year. In fact, IL-6 levels rose slightly (8 percent) in the group taking vitamin D. CRP levels did decline in a subgroup of people taking omega-3s who had a lower intake of fish (a source of omega-3s) at the start of the trial. Higher levels of systemic inflammation are associated with numerous chronic diseases, including coronary artery disease, type 2 diabetes, Alzheimer’s disease, asthma, and rheumatoid arthritis. The results appeared in the journal Clinical Chemistry. Since the study was in generally healthy people, it’s unclear whether the findings would translate to those with inflammatory disorders.
• Heart failure. In a study published in Circulation, neither vitamin D nor omega-3s reduced the chance of having a first hospitalization for heart failure, the study’s primary endpoint, among 25,835 VITAL participants over five years. There was a decrease in the omega-3 group (but not the vitamin D group) in recurrent hospitalizations for heart failure, a secondary outcome; but this would require confirmation in future trials.
• Diabetic kidney disease. In a paper in the Journal of the American Medical Association, which included 1,312 VITAL participants with type 2 diabetes from all 50 states, researchers found that neither vitamin D nor omega-3 capsules slowed the decline of kidney function over five years, compared to a placebo. (Chronic kidney disease is a common complication of diabetes.) 

No major adverse effects were reported from either supplement in any of the studies. 

To D or not to D? 
There’s no question that vitamin D plays a role in bone health, in large part by helping your body absorb calcium. People at high risk of bone fractures, such as those with osteoporosis or very low blood levels of vitamin D, may well benefit from supplements. Though the research has been inconsistent, some studies have shown that vitamin D pills, when paired with calcium, can help maintain bone health and reduce fractures in people at risk for them. On its own, in contrast, vitamin D has often flopped.

It’s looking less and less likely that the multitude of other benefits for which vitamin D (and omega-3s) have been promoted will pan out, based on the accumulating findings from VITAL and other trials. This isn’t necessarily surprising: Keep in mind that there’s a long history of observational studies suggesting a benefit of a particular nutrient or other substance that subsequent clinical trials (in which nutrients are tested in people against placebos) fail to bear out. Remember antioxidants? That’s why “gold standard” supplement studies like VITAL are so important. A number of additional VITAL analyses are still underway, including one on vitamin D and depression expected to come out this year. 

What to do 
Unlike with other essential vitamins, it’s difficult for many people to get enough vitamin D from food (and sun exposure) alone, since few foods naturally contain the vitamin. For that reason, we’ve recommended that unless you’ve had your vitamin D blood level tested and know that it’s adequate—defined by the Institute of Medicine (IOM) as at least 20 ng/mL, though many other experts think at least 30 ng/mL is better—you should take a modest supplement to ensure that you’re meeting the recommended daily intake. The IOM advises 600 IU a day for adults up to age 70 and 800 IU after age 70; we’ve recommended aiming for a slightly higher range—800 to 1,000 IU. We are sticking with that advice for now, but it will be interesting to see what the additional VITAL studies still underway find. The results may help inform what we recommend on vitamin D in the future.

In the meantime, your health care provider may advise a higher dose (usually 1,000 to 3,000 IU a day) if your blood level is very low or if you have osteoporosis, inflammatory bowel disease, or certain other disorders.

As for omega-3s, most people should get these healthful fats through eating two or three servings a week of fatty fish (such as salmon, mackerel, herring, or lake trout), rather than from pills. An exception is people with high triglycerides, for whom several prescription preparations of omega- 3s are approved. Certain other people at high cardiovascular risk may also benefit from omega-3 supplements, but the evidence here is conflicting. If you go by the VITAL findings (both the original ones and the newer ones reported here), African American people and those who eat very little fish have the most to potentially gain from daily omega-3s (and there doesn’t seem to be any harm in taking them). It’s hoped that further research will provide more definitive answers.