Their time is (past) up: Vitamin D & omega-3 supplements

Recent evidence continues to challenge the routine use of two common supplements: vitamin D and omega-3 fatty acids.

A quick web search on vitamin D finds Mayo Clinic, UpToDate, and WebMD all extoling its benefits despite a lack of evidence to support its widespread use. Dr. Lin asked on the blog in 2016, "Is Vitamin D supplementation is good for anything?" Although there are a few clinical situations where vitamin D supplementation may be indicated (chronic kidney disease with secondary hyperparathyroidism, for example), vitamin D does not otherwise support mood or reduce the risk of osteoporotic fracture. An ancillary study of VITAL (Vitamin D and Omega-3 Trial) published last month in the New England Journal of Medicine randomized nearly 26,000 middle and older aged community-dwelling adults and found no benefit to vitamin D supplementation regarding fracture risk:

VITAL was a two-by-two factorial, randomized, controlled trial that investigated whether supplemental vitamin D3 (2000 IU per day), n−3 fatty acids (1 g per day), or both would prevent cancer and cardiovascular disease in men 50 years of age or older and women 55 years of age or older in the United States. Participants were not recruited on the basis of vitamin D deficiency, low bone mass, or osteoporosis. 

An accompanying NEJM editorial declares VITAL's ancillary analysis a "decisive verdict on vitamin D supplementation." Of note, the original VITAL found no benefit for vitamin D to reduce the risk of cancer or cardiovascular disease (CVD), and it found no reduction in CVD from use of omega-3 fatty acid supplementation, either.

Another trial, REDUCE-IT, published in 2019 did find CVD benefit to omega-3 supplementation (specifically, 2 grams of icosapent ethyl daily) in persons with "elevated triglyceride levels despite the use of statins," but REDUCE-IT's findings are now being called into question. A recently published biomarker substudy found that REDUCE-IT's placebo, a pharmaceutical grade mineral oil capsule, may have increased CVD event risk among participants in the placebo group, creating a false appearance of benefit in the intervention group. These unintended harms from the study's placebo may explain why REDUCE-IT purportedly found benefit when multiple, large, previous studies have not. Like vitamin D, however, omega-3 fatty acid supplements continue to be used by millions of persons in the United States.

Changing clinical habits can be challenging. In this 2018 AFP editorial, Drs. Ebell, Shaughnessy, and Slawson describe several factors that contribute to this difficulty including practice inertia, emphasis on inductive (instead of patient-oriented, evidence-based) reasoning in medical training, and limited advertising for changes that don't benefit medical and/or pharmaceutical industries. They urge "physicians [to] accept that change is uncomfortable" and remind us that "[w]e need to remain flexible in our thinking if we are to meet our goal of doing our best when caring for every patient."

If you'd like to read more, this 2021 AFP Putting Prevention into Practice article reviews the current United States Preventive Services Task Force (USPSTF) "I" statement for vitamin D screening, and this 2019 AFP Medicine By the Numbers article reviews The NNT Group "red" rating for omega-3 fatty acid supplementation to prevent CVD.