Evidence explainerVitamin D3 vs D2
Does Vitamin D Protect Your Bones? The 25,871-Person Trial That Surprised Everyone
Millions of adults over 50 take vitamin D for their bones. The biggest trial to test it in healthy older adults found no drop in fractures, and a 3-year trial found more is not better.
Key takeaways
- In VITAL, 2,000 IU/day of D3 for a median 5.3 years did not reduce total, nonvertebral or hip fractures in 25,871 US adults aged 50+ (men) and 55+ (women) [1].
- Participants were not selected for deficiency, low bone mass or osteoporosis, so the result does not apply to people with those conditions [1].
- A meta-analysis of 23 trials found no bone-density benefit except a small one at the femoral neck (+0.8%) [2].
- Higher is not better: in a 3-year trial, 4,000 and 10,000 IU/day led to more bone-density loss at the wrist than 400 IU/day [3].
- The adult upper limit is 4,000 IU/day; the RDA is 600 IU, or 800 IU after 70 [4].
Safety at a glance
From our Vitamin D3 vs D2 monograph. Published interactions and cautions only, each with its source.
Interactions
- Orlistat. With a reduced-fat diet, can reduce vitamin D absorption and lower 25(OH)D.[1]
- Statins. High vitamin D intakes might reduce the potency of these statins because both appear to share a metabolizing enzyme; statins may also reduce vitamin D synthesis.[1]
- Thiazide diuretics. Thiazides reduce urinary calcium loss; combined with vitamin D supplements this might lead to hypercalcemia, especially in older adults and people with reduced kidney function or hyperparathyroidism.[1]
- Corticosteroids. Can reduce calcium absorption and impair vitamin D metabolism; in NHANES 2001–2006, vitamin D deficiency was about twice as common in oral steroid users (11% vs 5%).[1]
Who should be careful
- Pregnancy and breastfeeding. The RDA is the same as for other adults (600 IU), and the 4,000 IU UL applies. Higher amounts should be discussed with a clinician.[1]
- Kidney disease, kidney stones or high calcium. Vitamin D raises calcium absorption. People with reduced kidney function, a history of kidney stones, hyperparathyroidism or high blood calcium face higher hypercalcemia risk, especially with thiazide diuretics.[1]
- High-dose use. Toxicity is almost always from supplements: hypercalcemia, nausea, vomiting, muscle weakness, kidney stones and, in extreme cases, kidney failure and heart rhythm problems. A 3-year trial found lower bone density at 4,000–10,000 IU/day than at 400 IU/day.[1][7]
- Children. ULs are lower for children: 1,000 IU (0–6 months) up to 3,000 IU (4–8 years); 4,000 IU from age 9.[1]
The evidence, graded
Pulled from our monograph evidence tables. Grades follow our evidence-grading policy.
- No effectNo effectFracturesNo significant effect on total fractures (HR 0.98), nonvertebral fractures (HR 0.97) or hip fractures (HR 1.01). No effect modification by baseline 25(OH)D.
- No effectNo effectBone mineral density (general adults)Small benefit at the femoral neck only (+0.8%), with heterogeneity and possible bias toward positive results; no effect at the total hip, spine or other sites.
- Grade CWorsenedBone density at high daily dosesRadial volumetric bone density fell more with 4,000 IU (-2.4%) and 10,000 IU (-3.5%) than with 400 IU (-1.2%); tibial density was lower only at 10,000 IU. No significant difference in estimated bone strength.
- No effectNo effectMajor health events in healthy older adults (VITAL primary end points)No lower incidence of invasive cancer (HR 0.96) or major cardiovascular events (HR 0.97) vs placebo. Cancer death HR 0.83 (95% CI 0.67–1.02, not significant). No excess hypercalcemia.
The trial: VITAL
VITAL randomized 25,871 US men aged 50 and older and women aged 55 and older to 2,000 IU/day of vitamin D3 or placebo, and followed them for a median of 5.3 years [1]. Importantly, people were not chosen because they were deficient, had low bone mass or had osteoporosis [1].
The result was flat: total fractures (hazard ratio 0.98), nonvertebral fractures (0.97) and hip fractures (1.01) were essentially the same with vitamin D as with placebo [1]. Baseline vitamin D level did not change that picture [1].
The same trial also found no lower incidence of invasive cancer or major cardiovascular events with vitamin D [5].
What about bone density?
A 2014 meta-analysis pooled 23 trials with 4,082 adults, mostly women with an average age of 59 [2]. The only benefit was a small 0.8% gain at the femoral neck, with signs of heterogeneity and possible bias; there was no effect at the total hip, spine or other sites [2]. The authors concluded that routine vitamin D for bone density in community-dwelling adults without risk factors for deficiency was not supported [2].
Why megadoses are not the answer
A 3-year trial in Calgary randomized 311 healthy adults aged 55 to 70 to 400, 4,000 or 10,000 IU/day [3]. Bone density at the radius fell more with 4,000 IU (-2.4%) and 10,000 IU (-3.5%) than with 400 IU (-1.2%) [3]. Estimated bone strength did not differ, and the authors said more research is needed to judge harm [3].
NIH sets the adult upper limit at 4,000 IU (100 mcg) per day and notes that toxicity, almost always from supplements, can cause high blood calcium, nausea, vomiting, muscle weakness and kidney stones [4].
Who these results do not cover
VITAL tells us about generally healthy older adults. It does not tell us about people with diagnosed deficiency, osteoporosis, malabsorption, or those on medicines that affect vitamin D, such as corticosteroids, which NIH says roughly doubled the rate of deficiency in one national survey (11% vs 5%) [4]. Those situations are a conversation for your clinician, often with a blood test.
Vitamin D still matters as a nutrient; the RDA is 600 IU for adults through age 70 and 800 IU after [4]. For form choice, see vitamin D3 vs D2, and for the popular pairing, D3 and K2 together.
Quick answers
Should I stop my vitamin D?
That is a question for your clinician, especially if you were told you are deficient or have osteoporosis; VITAL did not enroll people selected for those conditions [1].
Does vitamin D help with colds?
Slightly, on average: a 2021 meta-analysis of 43 trials found 61.3% vs 62.3% of people had at least one respiratory infection [6].
Keep reading
Full monographs
Related articles
- Vitamin D3 and K2 Together: Smart Pairing or Marketing? What the Research Actually Shows
- Vitamin D3 vs D2: Why the Letter on the Label Changes How Much You Absorb
- 400 IU of Vitamin E Is Either 268 mg or 180 mg. The "d" or "dl" on the Label Decides
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Browse the full Supplement & Nutrient Encyclopedia or all supplement articles.
References
- [1]Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. N Engl J Med, 2022.
- [2]Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet, 2014.
- [3]Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. JAMA, 2019.
- [4]Vitamin D: Fact Sheet for Health Professionals. NIH Office of Dietary Supplements, 2025.
- [5]Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med, 2019.
- [6]Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol, 2021.