Vitamin supplements are a triumph of marketing over evidence, where sales continue to grow despite the evidence that they are neither necessary nor beneficial for the majority of people that take them. There are absolutely cases where vitamins are beneficial, however. While medically significant deficiencies of vitamins are generally rare in developed countries (you don’t see scurvy much anymore), dietary restrictions, pregnancy, and even socio-economic status may increase the possibility of a deficiency, and supplementation may be evidence based. It’s more of an open question if supplementation in the absence of any clear medical need is advisable or necessary. As a pharmacist I have spent a lot of time “in front of the counter” discussing the merits of vitamin supplements and trying to convince people that more is not necessarily better. Many patients take the view of vitamins as a reasonable “insurance policy” for their diet, and a net positive thing they can do to support healthy living. And for most of my career, I viewed vitamin supplementation without any clear medical need as producing “expensive urine” for the user, but unlikely to cause much harm. But over the past 25 years, my view has changed, and I’m far more skeptical of the net benefits of vitamin supplementation. That position is based on the results of multiple studies that have shown that vitamin supplementation is not always harmless – in some cases vitamins even appear to be harmful.
Many of the problems with vitamin supplementation have emerged when we have assumed that isolated vitamins are an appropriate or equivalent substitute for foods that contain those same vitamins. Compound this with the equally bad idea that more=better, and you have supplement doses much higher than would be consumed in diet alone. Antioxidants are the most representative example. The idea for antioxidants emerged from observations about oxidative stress and their contribution to illness and aging, and the hypothesis that antioxidant supplements could minimize these effects. Yet trials have failed to show that antioxidant supplements have the same effects as antioxidant-rich foods. Over time it became clear that beta-carotene supplements could raise your risk of cancer. Vitamin E supplements also appears to raise, rather than lower, prostate cancer risk.
Vitamin D deficiency results in the bone disease rickets and supplementation (in combination with calcium supplements) has established effectiveness in the prevention of fractures in those with osteoporosis. But there has been widespread interest for some time about the purported ability of vitamin D to prevent or treat almost any condition, driven by observational studies have linked low vitamin D levels to a range of illnesses. This has in turn driven widespread interest in supplementation, as well as the interest in testing vitamin D levels in the blood, in the hopes that apparent “deficiencies” can be identified and treated. Back in 2016 I summarized a narrative review that looked at vitamin D use for multiple health outcomes. It concluded that the evidence for supplementation was unconvincing for most uses. In that post, I noted that there was little evidence to show supplementation had any meaningful effect in cancer, but better quality evidence was needed. In mid-2018, I summarized a paper that examined the relationship between vitamin D levels and colorectal cancer risk, and found, again, the evidence for supplementation was unconvincing. Now a new, large randomized trial provides good evidence that vitamin D supplementation to prevent cancer (and cardiovascular disease) is ineffective.
VITAL answers
This was the VITamin D and OmegA-3 TriaL (VITAL) (NIH funded, thank you residents of America) that looked at vitamin D (as D3, cholecalciferol) 2,000 IU per day and marine n-3 (omega-3) fatty acids at a dose of 1,000 mg per day. For this blog post I will focus only on the vitamin D results and leave the omega fatty acids for a future post. 25,871 participants (including 5,106 black participants) were recruited from across the United States, and balanced with respect to sex. Participants had to have no history of cancer or cardiovascular disease. They were randomized to one of: vitamin D + omega-3, vitamin D + placebo, placebo + omega-3, or dual placebos. Men had to be at least 50 years of age, and women, 55 years of age. The primary endpoints of interest were (1) cancer of any type and (2) a major cardiovascular event (heart attack, stroke, or death from cardiovascular disease.) There were a number of secondary endpoints.
Participants received periodic surveys to assess adherence, use of additional vitamin D supplements, development of major illnesses, and potential side effects of trial agents.
Results
There was an increase in average vitamin D levels from 31 ng/mL to 42 ng/mL in vitamin D recipients and no change in the group that received placebo. There were no significant differences with respect to adverse (side) effects reported either group. Over a median of 5.3 years, there was no significant difference found between vitamin D recipients and placebo recipients in terms of the major endpoints: cancer or major cardiovascular events. Additional, there were zero difference in all-cause mortality. No impressive graphs to show with this study – all the lines can be superimposed, as there are no differences between the groups. In terms of secondary endpoints, there was a reduction in deaths from cancer. The authors note that vitamin D was associated with a 25% decrease in cancer deaths that started one to two years after participants began treatment (which they argue is relevant for slowly developing diseases, like cancer). However it’s important to note that overall, there were no mortality differences.
Discussion
This new trial answers important questions that had been raised in previous reviews. The US Preventive Services Task Force has previous concluded that there was insufficient evidence to evaluate vitamin D for the prevention of cancer or cardiovascular disease. The Institute of Medicine reached a similar conclusion. This new trial used a larger dose of vitamin D, and also included a substantial number of black participants, for whom the self-synthesis of vitamin D is lower than other ethnic groups. From this study we can conclude that for healthy adults, supplementing with 2,000 IU/day of vitamin D is not effective for the prevention of cardiovascular disease or cancer. If you’re taking vitamin D with the hope of preventing cardiovascular disease or cancer, this study doesn’t suggest that you need to stop supplementing. But neither does it suggest that your supplementing is doing anything beneficial. Given the totality of evidence for vitamin D, supplementation may be appropriate in some circumstances, such as the prevention or treatment of osteoporosis. But there is now convincing evidence that supplementing to prevent against cancer or cardiovascular disease is not warranted.