Vitamin D3 is the form the body makes in skin with sunlight, and the form used in most supplements. For years it was expected to prevent many chronic diseases. The large trials, most of them in people not chosen for low vitamin D, have tested that expectation, and the results are more limited than the marketing suggests.
VITAL: heart disease and cancer
VITAL randomized 25,871 adults, most over 50, to 2,000 IU of vitamin D3 a day or placebo, for a median of 5.3 years. Major cardiovascular events were 396 on vitamin D and 409 on placebo (hazard ratio 0.97, 95% CI 0.85 to 1.12). Invasive cancer was 793 and 824 (hazard ratio 0.96, 95% CI 0.88 to 1.06). Neither difference was statistically meaningful.
VITAL: an autoimmune signal
In a secondary analysis of VITAL, vitamin D lowered the rate of confirmed autoimmune disease: hazard ratio 0.78 (95% CI 0.61 to 0.99) for vitamin D against placebo. Omega-3 alone was not significant. A secondary analysis generates a hypothesis; it is not a prespecified primary result, and it needs confirmation.
D-Health: monthly high dose in older Australians
D-Health gave 60,000 IU of vitamin D3 once a month, or placebo, to Australians aged 60 and over for a median of about 5 years. All-cause mortality did not differ (hazard ratio 1.04, 95% CI 0.93 to 1.18), and cardiovascular mortality did not differ either. An exploratory analysis excluding the first two years found a higher cancer death rate in the vitamin D group, which the investigators treated with caution.
Vitamin K2 and bone
A 3-year trial in 244 postmenopausal women aged 55 to 65 gave MK-7 (vitamin K2, 180 micrograms a day) or placebo. Bone density and bone strength declined less with K2. The trial measured bone density, not fractures, and it tested K2, not vitamin D3.
What this does not say
- These trials did not select people for low vitamin D, so they do not tell us about people who are deficient.
- Benefit for autoimmune disease is a secondary analysis and needs a trial designed to test it.
- The K2 result applies to the MK-7 product, and the combination with D3 has no outcome trial of its own.
How we use this
Our physicians measure vitamin D when there is a reason to, and treat deficiency when it is found. We do not recommend high-dose vitamin D to prevent disease in people who are not deficient, because the large trials did not show that benefit.
If you take a combined vitamin D3 and K2 product, we tell you that the K2 evidence is for MK-7 and bone density.
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- 1.Manson JE et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 2019;380:33-44. NEJM
- 2.Hahn J et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ 2022;376:e066452. BMJ
- 3.Neale RE et al. The D-Health trial: a randomised controlled trial of the effect of vitamin D on mortality. Lancet Diabetes Endocrinol 2022;10:120-128. The Lancet Diabetes & Endocrinology
- 4.Knapen MH et al. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int 2013;24:2499-2507. Osteoporosis International
- 5.Vitamin D: health professional fact sheet. NIH Office of Dietary Supplements