The short version
- VITAL randomised 25,871 adults to 2,000 IU of vitamin D3 daily for a median 5.3 years and found hazard ratios of 0.96 for invasive cancer, 0.97 for major cardiovascular events and 0.99 for all-cause death.
- D-Health randomised 21,315 Australians aged 60 and over to 60,000 IU monthly for five years and found an all-cause mortality hazard ratio of 1.04, with an exploratory cancer mortality hazard ratio of 1.24 after excluding the first two years.
- A Mendelian randomisation study in 307,601 UK Biobank participants found an L-shaped relationship, with 25% higher odds of death at 25 nmol/L compared with 50 nmol/L and no further benefit above that.
- Annual doses of 500,000 IU given to 2,256 women aged 70 and over increased falls (rate ratio 1.15) and fractures (rate ratio 1.26) compared with placebo, with risk concentrated in the three months after dosing.
- The evidence supports correcting deficiency rather than supplementing people who are already replete, which makes a 25-hydroxyvitamin D blood test the decision point rather than the supplement.
For about fifteen years, low vitamin D looked like the answer to almost everything. Observational studies linked it to cancer, heart disease, infection, depression and early death. Then the randomised trials arrived, one after another, and the answer was no. Understanding why is more useful than either headline.
The two big trials
VITAL randomised 25,871 US adults — men over 50, women over 55 — to 2,000 IU of vitamin D3 daily or placebo, and followed them a median 5.3 years. Invasive cancer: hazard ratio 0.96. Major cardiovascular events: 0.97. Death from any cause across 978 deaths: 0.99. Nothing.
D-Health randomised 21,315 Australians aged 60 and over to 60,000 IU monthly or placebo for five years. Blood levels responded exactly as designed — a mean 25-hydroxyvitamin D of 115 nmol/L in the treated group against 77 in placebo. Over 1,100 deaths, the hazard ratio for all-cause mortality was 1.04. Cardiovascular mortality 0.96. Cancer mortality 1.15, and in an exploratory analysis excluding the first two years of follow-up, 1.24 with a confidence interval from 1.01 to 1.54.
The trialists' own framing of that last number is the responsible one, and worth quoting in spirit: pending further evidence, the precautionary principle suggests this dosing regimen might not be appropriate in people who are already vitamin D-replete.
That is a supplement trial telling you its intervention may have done harm in people who did not need it. It is not the sentence anyone was hoping for and it is the sentence that should shape your behaviour.
The finding that rescues the nutrient
Here is where "vitamin D does nothing" becomes too simple. Randomised trials answer the question they asked, and both of these asked: does supplementing a general older population help? Neither asked: does correcting deficiency help?
Sutherland and colleagues used nonlinear Mendelian randomisation in 307,601 UK Biobank participants, using 35 confirmed genetic variants to estimate lifelong 25-hydroxyvitamin D exposure. This design is largely immune to the reverse causation that plagues observational vitamin D work, because your genotype was fixed before you got ill.
Over 14 years and 18,700 deaths, the relationship with all-cause mortality was L-shaped. Risk fell steeply with rising concentration up to 50 nmol/L and then flattened. A person at 25 nmol/L had an estimated 25% higher odds of death than a person at 50. The same pattern appeared for cancer, cardiovascular and respiratory mortality. The larger Emerging Risk Factors Collaboration analysis, retracted and republished with corrections in 2024, reported the same structure: no association across the population as a whole, a strong inverse association among the deficient.
Put the three studies side by side and they stop contradicting each other. Deficiency is genuinely bad. Fixing it in people who have it is likely to matter. Adding more to people who already have enough does nothing measurable, and at high intermittent doses may do worse than nothing.
More is not better, and there is a trial for that
Sanders and colleagues gave 2,256 community-dwelling women aged 70 and over a single annual dose of 500,000 IU of cholecalciferol or placebo for three to five years. The vitamin D group had 171 fractures against 135 on placebo, and fell more: an incidence rate ratio for falls of 1.15, and for fracture 1.26. Risk was concentrated in the first three months after each dose. Median baseline vitamin D was 49 nmol/L, and fewer than 3% of the substudy participants were below 25.
Large intermittent boluses given to people who were not deficient increased falls and fractures. That is the clearest available demonstration that the dose-response here is not a straight line going up.
So what should you actually do?
Measure, then decide. This is the same argument we make about the omega-3 index and for the same reason: the intervention has a plausible benefit at one end of the distribution and none in the middle, so knowing where you sit is the whole decision.
A 25-hydroxyvitamin D test is inexpensive and available through your doctor, who is also the person who should interpret it, because kidney disease, malabsorption, certain medications and some cancers all change how the number should be read.
If you are below 50 nmol/L, the genetic evidence says that gap is worth closing, and modest daily dosing is the form with the least evidence of harm. If you are comfortably above it, the two largest trials ever run say another capsule will not extend your life.
What we would actually tell you
Vitamin D is a correction, not an enhancement. Treat it like iron: valuable if you are short, pointless if you are not, and capable of causing problems if you assume more must be better.
People at genuine risk of being short — limited sun exposure, darker skin at high latitude, housebound, covered clothing, older age — are the ones this is for. Everyone else is buying insurance against a deficiency they can cheaply confirm they do not have.
And when you are ranking a longevity budget, notice that a blood test that changes a decision is worth more than a bottle that does not.
Good questions
Does vitamin D help you live longer?
Not if you already have enough. Two randomised trials totalling more than 47,000 adults found no reduction in all-cause mortality. Genetic evidence in 307,601 people does support a real cost to being deficient, with 25% higher odds of death at 25 nmol/L versus 50. The benefit is in correcting a shortfall, not in topping up.
How much vitamin D should I take, and does more help?
Ask what your level is first, because the answer depends entirely on it. If you are below 50 nmol/L, a modest daily dose is the form with the least evidence of harm, and your doctor should set it. If you are above it, the largest trials say more will not extend your life. Very large intermittent doses have increased falls and fractures.
Can vitamin D be harmful?
Yes, at high intermittent doses in people who are not deficient. An annual 500,000 IU dose in 2,256 older women raised fractures by 26% and falls by 15% against placebo, concentrated in the three months after each dose. A five-year monthly-dosing trial also reported a numerically higher cancer mortality in exploratory analysis. More is not automatically safer.
Should I get my vitamin D tested?
If a supplement decision hangs on it, yes. A 25-hydroxyvitamin D test is inexpensive through your doctor, who should interpret it, because kidney disease, malabsorption, some medications and some cancers change how the number reads. A test that changes what you do is worth more than a bottle that changes nothing.
Who actually needs vitamin D supplements?
People genuinely likely to be short: limited sun exposure, housebound or in residential care, darker skin at high latitude, covered clothing, older age, malabsorption conditions. That is a real and sizeable group. It is a much smaller group than the number of people currently buying it, which is roughly everyone.
Why did the observational studies get this so wrong?
Mostly reverse causation. People who are ill go outside less, eat worse and carry more inflammation, all of which lower measured vitamin D, so low readings can be a marker of poor health rather than a cause of it. Mendelian randomisation avoids that trap because genotype is fixed before illness, and it found the effect confined to deficiency.
Sources
- Manson JE, Cook NR, Lee IM, et al. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med, 2019. View study
- Neale RE, Baxter C, Romero BD, et al. The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality. Lancet Diabetes Endocrinol, 2022. View study
- Sutherland JP, Zhou A, Hyppönen E. Vitamin D Deficiency Increases Mortality Risk in the UK Biobank: A Nonlinear Mendelian Randomization Study. Ann Intern Med, 2022. View study
- Emerging Risk Factors Collaboration/EPIC-CVD/Vitamin D Studies Collaboration. Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses. Lancet Diabetes Endocrinol, 2024. View study
- Sanders KM, Stuart AL, Williamson EJ, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA, 2010. View study
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