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Vitamin D

Evidence Level
Very Strong
6 Clinical Trials
8 Documented Benefits
5/5 Evidence Score

Vitamin D is a fat-soluble vitamin the body turns into a hormone that controls calcium absorption and bone mineralization. Most of it is made in the skin from sunlight, and few foods contain much. Vitamin D3 (cholecalciferol) raises blood levels more, and for longer, than vitamin D2 (ergocalciferol). Getting enough prevents rickets in children and osteomalacia in adults. Taking more when your level is already adequate is a different question: in large placebo-controlled trials of adults not selected for deficiency (VITAL, D-Health and the Finnish Vitamin D Trial), vitamin D did not prevent fractures, falls, heart attacks, cancer or depression, and pooled trials show no clear protection against respiratory infections. Very large single or monthly doses have been linked to more falls and fractures. For most adults, the recommended daily amount is enough.

Studied Dose RDA 600 IU/day (15 mcg) ages 1 to 70 and 800 IU/day (20 mcg) over 70; adult upper limit 4,000 IU/day. Trials used 2,000, 1,600 or 3,200 IU/day and 60,000 IU monthly.
Active Compound Vitamin D3 (cholecalciferol), usually made from lanolin, with a vegan form from lichen; or vitamin D2 (ergocalciferol), made from UV-treated yeast.
Deficiency information View details

Using National Academies thresholds, NHANES 2011 to 2014 found about 18% of people in the US aged 1 and older at risk of inadequacy (25(OH)D 12 to 19.6 ng/mL) and 5% at risk of deficiency (below 12 ng/mL). Severe deficiency causes rickets in children and osteomalacia (soft bones) in adults. Most low levels cause no symptoms and are found only by a blood test.

Common symptoms

  • Often no symptoms until deficiency is severe
  • Bone pain or aching (osteomalacia)
  • Muscle weakness
  • In children: rickets, with bowed legs, delayed growth and soft bones
  • In infants with severe deficiency: poor growth, muscle spasms or seizures from low blood calcium

At-risk groups

  • Breastfed infants not given a vitamin D supplement
  • Older adults (the skin makes less vitamin D with age)
  • People who get little sun on their skin, including those who stay indoors or cover their skin
  • People with darker skin (melanin reduces vitamin D production)
  • People with conditions that limit fat absorption, such as celiac disease, Crohn's disease or cystic fibrosis
  • People with obesity or who have had gastric bypass surgery
  • People taking orlistat or long-term corticosteroids
When to see a doctor: Persistent bone pain or muscle weakness, or a condition that affects vitamin D absorption, is a reason to ask a doctor about a 25-hydroxyvitamin D blood test; the Endocrine Society (2024) advises against routine testing of healthy people. The National Academies consider 20 ng/mL (50 nmol/L) or more sufficient for most people, with deficiency risk rising below 12 ng/mL (30 nmol/L). Do not take more than 4,000 IU a day without medical advice, because too much raises blood calcium.
Explore related deficiencies →
Sources: NIH ODS: Vitamin D Health Professional Fact Sheet · PMID 21646368: Endocrine Society clinical practice guideline on vitamin D deficiency (J Clin Endocrinol Metab, 2011)

Benefits

Bone health: essential when deficient, no fracture benefit when replete

Vitamin D lets the gut absorb calcium, and enough of it prevents rickets in children and osteomalacia in adults. Extra vitamin D does not add to bones that already have enough: in VITAL (25,871 adults, 2,000 IU a day for 5.3 years) fractures were unchanged at any starting level, a meta-analysis of 81 trials found no effect on fractures or bone density, and 4,000 to 10,000 IU a day lowered forearm bone density versus 400 IU.

Supported by Trial 5, Trial 6

Heart health: supplements did not lower cardiovascular events

People with low vitamin D have more heart disease in observational studies, but trials did not confirm a benefit. In VITAL (25,871 adults, 2,000 IU a day for 5.3 years), vitamin D did not reduce major cardiovascular events (HR 0.97), and the Finnish Vitamin D Trial (2,495 older adults, 1,600 or 3,200 IU a day for 5 years) also found no difference. The link likely reflects other differences in health.

Supported by Trial 1, Trial 3

Cancer: no fewer cancers and no clear effect on cancer death

VITAL found no reduction in invasive cancer (HR 0.96); cancer deaths were 17% lower but not significantly (HR 0.83). A meta-analysis found fewer cancer deaths only in trials of daily dosing. In D-Health (21,315 older Australians, 60,000 IU monthly), exploratory analyses pointed to more cancer deaths. Vitamin D should not be used to prevent or treat cancer.

Supported by Trial 1, Trial 4

Autoimmune diagnoses in VITAL: an early signal that faded

In a VITAL ancillary study, 2,000 IU a day for 5.3 years was followed by 22% fewer confirmed autoimmune diagnoses (123 vs 155; HR 0.78, P=0.05). When later-confirmed cases were added the estimate was no longer significant (HR 0.85), and 2 years after the capsules stopped there was no difference (HR 0.98). It is a single, unreplicated result and not a reason for healthy adults to supplement.

Supported by Trial 2

Falls in older adults: not reduced in large trials

A 2009 meta-analysis found 19% fewer falls in trials using 700 to 1,000 IU a day, but larger later trials did not confirm it. VITAL and D-Health found no reduction, a 2018 meta-analysis of 37 trials found no effect on falls, and a single yearly 500,000 IU dose increased falls by 15%. The US Preventive Services Task Force recommends against vitamin D to prevent falls in older adults without deficiency or osteoporosis.

Supported by Trial 2, Trial 5

Respiratory infections: no clear protection in updated evidence

A 2017 pooled analysis of 25 trials found 12% lower odds of acute respiratory infection, mostly in people with very low starting levels. The 2025 update (40 trials, 61,589 people) found no significant protection (OR 0.94, 95% CI 0.88 to 1.00), with no difference by starting level or dose. The CORONAVIT trial in 6,200 UK adults also found no fewer infections.

Supported by Trial 4

COVID-19: vitamin D3 trials found no benefit

Low vitamin D was linked to worse COVID-19 outcomes in observational data, but in trials a single 200,000 IU dose did not shorten hospital stay in 240 patients with moderate to severe COVID-19, and the CORONAVIT test-and-treat trial in 6,200 UK adults did not reduce infections. Vitamin D does not treat or prevent COVID-19 and does not replace vaccination or medical care.

Supported by Trial 4, Trial 5

Depression and mood: no benefit in a large prevention trial

Low vitamin D tracks with depression in observational studies. In VITAL-DEP (18,353 adults aged 50 and older, 2,000 IU a day for 5.3 years), vitamin D did not reduce new or recurrent depression or change mood scores. Whether correcting a true deficiency improves mood has not been settled by large trials. Persistent low mood needs medical care.

Supported by Trial 5, Trial 1

Mechanism of action

1

Metabolic Activation

Vitamin D (D2 or D3) is first converted in the liver to 25-hydroxyvitamin D [25(OH)D], the main circulating form measured in blood tests. The kidney then converts it to the active hormone 1,25-dihydroxyvitamin D (calcitriol). Enzymes called CYP2R1 (liver) and CYP27B1 (kidney) carry out these steps.

2

Genomic Actions

Calcitriol binds the vitamin D receptor inside cells. Together with the retinoid X receptor, it attaches to vitamin D response elements in DNA and switches on genes for calcium and phosphate absorption, bone turnover and immune function.

3

Non-Genomic Actions

Some vitamin D effects happen too quickly to involve gene changes, such as rapid calcium uptake into cells. These are thought to work through receptors at the cell membrane, including one called PDIA3.

Clinical trials

1
VITAL: vitamin D3 for prevention of cancer and cardiovascular disease
PubMed

Randomized double-blind placebo-controlled 2x2 factorial trial of vitamin D3 and omega-3 fatty acids; participants were not selected for low vitamin D, and mean starting 25(OH)D was about 77 nmol/L (31 ng/mL) (Manson et al. 2019, N Engl J Med)

25,871 US adults (men 50 and older, women 55 and older) given vitamin D3 2,000 IU a day or placebo for a median 5.3 years.

Both primary endpoints were null: vitamin D did not reduce invasive cancer (HR 0.96) or major cardiovascular events (HR 0.97) compared with placebo. Death from cancer, a secondary endpoint, was not significantly lower (HR 0.83, 95% CI 0.67 to 1.02).

2
VITAL autoimmune ancillary study (single trial, effect faded on follow-up)
PubMed

Ancillary study of the VITAL trial with confirmed new autoimmune disease as its endpoint, verified by medical record review (Hahn et al. 2022, BMJ)

25,871 VITAL participants followed for new-onset autoimmune disease over 5 years.

Vitamin D 2,000 IU/day (with or without omega-3) was followed by fewer confirmed autoimmune diagnoses: 123 vs 155 (HR 0.78, 95% CI 0.61 to 0.99, P=0.05). Vitamin D alone and vitamin D plus omega-3 gave similar estimates versus double placebo (HR 0.68 and 0.69). Diseases included rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease and psoriasis. In a 2024 follow-up that added later-confirmed cases, the in-trial effect was no longer significant (HR 0.85, 95% CI 0.70 to 1.04), and over 7 years of follow-up, including 2 years after supplements stopped, there was no difference (HR 0.98).

3
Finnish Vitamin D Trial (FIND)
PubMed

5-year randomized placebo-controlled trial comparing two vitamin D3 doses with placebo in older adults in Finland, a northern country with little winter sun (Virtanen et al. 2022, Am J Clin Nutr)

2,495 older Finnish adults (men 60 and older, women 65 and older): placebo, 1,600 IU a day or 3,200 IU a day for 5 years.

No significant differences among the three groups in major cardiovascular events, invasive cancer or deaths from any cause. Mean starting 25(OH)D in the measured subgroup was 75 nmol/L, so most people were already replete, which the authors suggested may explain the null result.

4
Vitamin D and respiratory infections (2017 meta-analysis, since updated)
PubMed

Individual participant data meta-analysis of randomized trials of vitamin D to prevent acute respiratory infections (Martineau et al. 2017, BMJ)

10,933 participants across 25 clinical trials. Various supplementation regimens (daily, weekly, bolus).

Across all participants, vitamin D lowered the odds of acute respiratory infection by 12% (adjusted OR 0.88, 95% CI 0.81 to 0.96). Daily or weekly dosing gave OR 0.81, bolus dosing gave no protection (OR 0.97), and people starting below 25 nmol/L on daily or weekly dosing had the largest effect (OR 0.30). A 2025 update with 40 trials no longer found significant protection.

5
Calcium or vitamin D and fractures in older adults living in the community (meta-analysis)
PubMed

Systematic review and meta-analysis of randomized trials in community-dwelling adults over 50; people in residential care were excluded (Zhao et al. 2017, JAMA)

51,145 community-dwelling older adults across 33 clinical trials.

Calcium, vitamin D, or both were not associated with fewer hip, nonvertebral, vertebral or total fractures. Vitamin D alone did not reduce hip fracture (RR 1.21, 95% CI 0.99 to 1.47), and results were generally consistent regardless of dose, sex, fracture history, dietary calcium and starting 25(OH)D. The review does not address nursing-home residents.

6
VITAL fracture study
PubMed

Ancillary study of the VITAL randomized placebo-controlled trial with confirmed incident fractures as the outcome (LeBoff et al. 2022, N Engl J Med)

25,871 generally healthy adults not selected for vitamin D deficiency, low bone mass or osteoporosis; 2,000 IU a day of vitamin D3 or placebo for a median 5.3 years.

Vitamin D3 did not lower total fractures (HR 0.98), nonvertebral fractures (HR 0.97) or hip fractures (HR 1.01), and results did not differ by age, sex, body weight or starting 25(OH)D level.

Side effects and drug interactions

Common Potential side effects

Toxicity is rare at usual doses; signs and symptoms are unlikely below 10,000 IU a day, though the adult upper limit is 4,000 IU a day (the RDA is 600 to 800 IU a day). At very high long-term doses, high blood calcium is the main concern.
High blood calcium can cause nausea, vomiting, weakness, frequent urination, thirst and kidney stones.
Severe toxicity (rare): confusion, kidney injury and heart rhythm problems.
Very large doses can backfire: a single yearly 500,000 IU dose increased falls by 15% and fractures by 26% in 2,256 women aged 70 and older. In a 3-year trial, 4,000 and 10,000 IU a day lowered forearm bone density compared with 400 IU a day. In D-Health, 60,000 IU monthly did not lower deaths, and the investigators cautioned against that regimen in people already replete.
People with sarcoidosis, primary hyperparathyroidism, lymphoma or some kidney diseases can develop high blood calcium at standard doses and should use vitamin D only under medical supervision.

Important Drug interactions

Thiazide diuretics: they reduce calcium loss in urine, and combined with vitamin D they might raise blood calcium, especially in older adults.
Orlistat: with a low-fat diet it can reduce vitamin D absorption and lower blood levels.
Corticosteroids (such as prednisone): they reduce calcium absorption and impair vitamin D metabolism, so long-term users may need their vitamin D status checked.
Statins: in a small study of 16 patients, 800 IU a day of vitamin D for 6 weeks lowered blood levels of atorvastatin and its active metabolites (LDL cholesterol also fell). NIH ODS notes high vitamin D intakes might reduce the potency of atorvastatin, lovastatin and simvastatin.

Standardized & branded forms of Vitamin D

Trademarked forms of Vitamin D with their own profiles on NutraSmarts. Results from one branded form do not automatically carry over to another, so check each profile for the studies run on that specific product:

Bone Health
Calcifediol (25-Hydroxyvitamin D3)
Calcifediol is 25-hydroxyvitamin D3, the form the liver makes from vitamin D and the one a…

Featured in these supplement guides

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Frequently asked questions about Vitamin D

How much vitamin D should I take?

The RDA is 600 IU (15 mcg) a day for adults up to 70 and 800 IU (20 mcg) over 70, which covers most people. Higher doses have not prevented fractures, falls, heart disease or cancer in large trials of adults not selected for deficiency, and the Endocrine Society (2024) suggests against routinely taking more than the RDA to prevent disease in healthy adults under 75 (it does suggest supplementation for children, adults over 75, pregnancy and high-risk prediabetes). People with a confirmed deficiency or malabsorption may need more, set with a doctor. The National Academies consider a blood level of 20 ng/mL (50 nmol/L) sufficient for most people.

Should I take vitamin D with food?

Yes. Vitamin D is fat-soluble, so it absorbs best taken with a meal that contains some fat. Time of day does not matter much. Consistency matters more than timing, so take it whenever you will remember it daily.

Do I need to take vitamin K2 with vitamin D?

It is not a requirement. Vitamin K is needed for proteins involved in handling calcium in bone and blood vessels, but large randomized trials showing that adding K2 to ordinary vitamin D doses prevents fractures or arterial calcification are lacking. The simpler safeguard is not taking high doses of vitamin D without medical supervision. If you take warfarin, do not start vitamin K without talking to your doctor.

Can you take too much vitamin D?

Yes, though it is uncommon at typical doses. Toxicity is rare; reported cases usually involve intakes far above the 4,000 IU daily upper limit, often more than 10,000 IU a day for long periods, and it shows up as high blood calcium and nausea. Staying at or below 4,000 IU daily without testing is generally considered safe for adults; go higher only under medical guidance with blood monitoring.

What is Vitamin D?

Vitamin D is a fat-soluble vitamin the body turns into a hormone that controls calcium absorption and bone mineralization. Most of it is made in the skin from sunlight, and few foods contain much. Vitamin D3 (cholecalciferol) raises blood levels more, and for longer, than vitamin D2 (ergocalciferol).

What is Vitamin D used for?

Vitamin D is researched primarily for Bone Health. Vitamin D lets the gut absorb calcium, and enough of it prevents rickets in children and osteomalacia in adults. Extra vitamin D does not add to bones that already have enough: in VITAL (25,871 adults, 2,000 IU a day for 5.

What are the signs of Vitamin D deficiency?

Using National Academies thresholds, Nhanes 2011 to 2014 found about 18% of people in the US aged 1 and older at risk of inadequacy (25(OH)D 12 to 19.6 ng/mL) and 5% at risk of deficiency (below 12 ng/mL). Severe deficiency causes rickets in children and osteomalacia (soft bones) in adults.

Is Vitamin D safe, and does it have side effects?

Side effects and cautions reported for Vitamin D include: Toxicity is rare at usual doses; signs and symptoms are unlikely below 10,000 IU a day, though the adult upper limit is 4,000 IU a day (the RDA is 600 to 800 IU a day). At very high long-term doses, high blood calcium is the main concern. It may also interact with some medications. Vitamin D is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Vitamin D interact with any medications?

Possible interactions include: Thiazide diuretics: they reduce calcium loss in urine, and combined with vitamin D they might raise blood calcium, especially in older adults. Orlistat: with a low-fat diet it can reduce vitamin D absorption and lower blood levels. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Vitamin D?

NutraSmarts rates the evidence for Vitamin D as Very Strong (5 out of 5). It is backed by 6 study summaries and 24 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(24 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Gordon D, Copeland T, D'Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, Buring JE; VITAL Research Group. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med. 2019;380(1):33-44. doi: 10.1056/NEJMoa1809944.PubMedUsed to support: VITAL primary trial: in 25,871 adults, vitamin D3 2,000 IU a day for a median 5.3 years did not reduce invasive cancer (HR 0.96) or major cardiovascular events (HR 0.97) compared with placebo; cancer death, a secondary endpoint, HR 0.83 (95% CI 0.67 to 1.02).
  2. Hahn J, Cook NR, Alexander EK, Friedman S, Walter J, Bubes V, Kotler G, Lee IM, Manson JE, Costenbader KH. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ. 2022;376:e066452. doi: 10.1136/bmj-2021-066452.PubMedUsed to support: VITAL ancillary study: 2,000 IU/day vitamin D3 for a median 5.3 years was followed by 22% fewer confirmed autoimmune diagnoses (123 vs 155; HR 0.78, 95% CI 0.61 to 0.99, P=0.05); vitamin D alone and with omega-3 gave similar estimates
  3. Virtanen JK, Nurmi T, Aro A, Bertone-Johnson ER, Hyppönen E, Kröger H, Lamberg-Allardt C, Manson JE, Mursu J, Mäntyselkä P, Suominen S, Uusitupa M, Voutilainen A, Tuomainen TP, Hantunen S. Vitamin D supplementation and prevention of cardiovascular disease and cancer in the Finnish Vitamin D Trial: a randomized controlled trial. Am J Clin Nutr. 2022;115(5):1300-1310. doi: 10.1093/ajcn/nqab419.PubMedUsed to support: Finnish Vitamin D Trial: 2,495 older Finnish adults given 1,600 or 3,200 IU/day vitamin D3 or placebo for 5 years; no reduction in major cardiovascular events or invasive cancer and no difference in total mortality; mean baseline 25(OH)D in a 551-person subcohort was 75 nmol/L, and the authors suggested sufficient vitamin D status may explain the null result
  4. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Griffiths CJ, Janssens W, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S Jr, Stelmach I, Kumar GT, Urashima M, Camargo CA Jr. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi: 10.1136/bmj.i6583.PubMedUsed to support: IPD meta-analysis of 25 RCTs (10,933 participants): vitamin D lowered the odds of acute respiratory infection overall (adjusted OR 0.88, 95% CI 0.81 to 0.96); daily or weekly dosing OR 0.81, bolus dosing no effect (OR 0.97), largest effect with baseline 25(OH)D below 25 nmol/L (OR 0.30)
  5. Zhao JG, Zeng XT, Wang J, Liu L. Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults: A Systematic Review and Meta-analysis. JAMA. 2017;318(24):2466-2482. doi: 10.1001/jama.2017.19344.PubMedUsed to support: Meta-analysis of 33 trials in 51,145 community-dwelling adults over 50: calcium, vitamin D or both were not associated with fewer hip, nonvertebral, vertebral or total fractures.
  6. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-30. doi: 10.1210/jc.2011-0385.PubMedUsed to support: 2011 Endocrine Society guideline on evaluating, treating and preventing vitamin D deficiency in people at risk: suggests measuring 25(OH)D in at-risk patients, treating deficiency with D2 or D3, and found insufficient evidence to screen people not at risk or to prescribe vitamin D for cardiovascular protection. Superseded in part by the 2024 guideline.
  7. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, Wong JB, Egli A, Kiel DP, Henschkowski J. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ. 2009;339:b3692. doi: 10.1136/bmj.b3692.PubMedUsed to support: Meta-analysis of 8 double-blind RCTs (2,426 older adults): in the 7 trials using 700 to 1,000 IU/day (1,921 participants), vitamin D reduced fall risk by 19% (RR 0.81, 95% CI 0.71 to 0.92); 200 to 600 IU/day did not reduce falls (RR 1.10)
  8. LeBoff MS, Chou SH, Ratliff KA, Cook NR, Khurana B, Kim E, Cawthon PM, Bauer DC, Black D, Gallagher JC, Lee IM, Buring JE, Manson JE. Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. N Engl J Med. 2022;387(4):299-309. doi: 10.1056/NEJMoa2202106.PubMedUsed to support: VITAL fracture ancillary study: in 25,871 adults not selected for deficiency or low bone mass, 2,000 IU/day vitamin D3 for 5.3 years did not reduce total (HR 0.98), nonvertebral (HR 0.97) or hip fractures (HR 1.01), with no modification by baseline 25(OH)D
  9. Jolliffe DA, Camargo CA Jr, Sluyter JD, Aglipay M, Aloia JF, Bergman P, Bischoff-Ferrari HA, Borzutzky A, Bubes VY, Damsgaard CT, Ducharme FM, Dubnov-Raz G, Esposito S, Ganmaa D, Gilham C, Ginde AA, Golan-Tripto I, Goodall EC, Grant CC, Griffiths CJ, Hibbs AM, Janssens W, Khadilkar AV, Laaksi I, Lee MT, Loeb M, Maguire JL, Majak P, Manaseki-Holland S, Manson JE, Mauger DT, Murdoch DR, Nakashima A, Neale RE, Pham H, Rake C, Rees JR, Rosendahl J, Scragg R, Shah D, Shimizu Y, Simpson-Yap S, Kumar GT, Urashima M, Martineau AR. Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of stratified aggregate data. Lancet Diabetes Endocrinol. 2025;13(4):307-320. doi: 10.1016/S2213-8587(24)00348-6.PubMedUsed to support: Updated meta-analysis of 40 RCTs (61,589 participants): vitamin D did not statistically significantly reduce acute respiratory infection risk (OR 0.94, 95% CI 0.88 to 1.00), with no effect modification by age, baseline vitamin D status, dosing frequency or dose
  10. Jolliffe DA, Holt H, Greenig M, Talaei M, Perdek N, Pfeffer P, Vivaldi G, Maltby S, Symons J, Barlow NL, Normandale A, Garcha R, Richter AG, Faustini SE, Orton C, Ford D, Lyons RA, Davies GA, Kee F, Griffiths CJ, Norrie J, Sheikh A, Shaheen SO, Relton C, Martineau AR. Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT). BMJ. 2022;378:e071230. doi: 10.1136/bmj-2022-071230.PubMedUsed to support: Open-label RCT in 6,200 UK adults: offering a vitamin D test and 800 or 3,200 IU/day to those below 75 nmol/L did not reduce all-cause acute respiratory infection or COVID-19 over 6 months
  11. Neale RE, Baxter C, Romero BD, McLeod DSA, English DR, Armstrong BK, Ebeling PR, Hartel G, Kimlin MG, O'Connell R, van der Pols JC, Venn AJ, Webb PM, Whiteman DC, Waterhouse M. The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality. Lancet Diabetes Endocrinol. 2022;10(2):120-128. doi: 10.1016/S2213-8587(21)00345-4.PubMedUsed to support: 21,315 unscreened Australians aged 60 and older given 60,000 IU vitamin D3 monthly for 5 years: no reduction in all-cause mortality (HR 1.04); cancer mortality HR 1.15 (95% CI 0.96 to 1.39), and exploratory analyses excluding the first 2 years were consistent with increased cancer death (HR 1.24)
  12. Costenbader KH, Cook NR, Lee IM, Hahn J, Walter J, Bubes V, Kotler G, Yang N, Friedman S, Alexander EK, Manson JE. Vitamin D and Marine n-3 Fatty Acids for Autoimmune Disease Prevention: Outcomes Two Years After Completion of a Double-Blind, Placebo-Controlled Trial. Arthritis Rheumatol. 2024;76(6):973-983. doi: 10.1002/art.42811.PubMedUsed to support: VITAL 2-year post-trial follow-up (21,592 participants): the protective effect of 2,000 IU/day vitamin D on autoimmune disease dissipated (HR 0.98 at 7 years), and adding newly confirmed in-trial cases made the randomized-period estimate non-significant (HR 0.85, 95% CI 0.70 to 1.04)
  13. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303(18):1815-22. doi: 10.1001/jama.2010.594.PubMedUsed to support: 2,256 community-dwelling women aged 70 and older: a single annual oral dose of 500,000 IU cholecalciferol increased falls (RR 1.15) and fractures (RR 1.26) compared with placebo
  14. Burt LA, Billington EO, Rose MS, Raymond DA, Hanley DA, Boyd SK. Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. JAMA. 2019;322(8):736-745. doi: 10.1001/jama.2019.11889.PubMedUsed to support: 311 healthy adults aged 55 to 70: 3 years of 4,000 or 10,000 IU/day vitamin D3 produced lower radial bone density than 400 IU/day, with no difference in bone strength; the authors found no support for a bone benefit of high doses
  15. LeBoff MS, Murata EM, Cook NR, Cawthon P, Chou SH, Kotler G, Bubes V, Buring JE, Manson JE. VITamin D and OmegA-3 TriaL (VITAL): Effects of Vitamin D Supplements on Risk of Falls in the US Population. J Clin Endocrinol Metab. 2020;105(9):2929-38. doi: 10.1210/clinem/dgaa311.PubMedUsed to support: 25,871 adults (mean baseline 25(OH)D 77 nmol/L): 2,000 IU/day vitamin D3 for 5.3 years did not reduce two or more falls (OR 0.97) or injurious falls, with no difference in those starting below 50 nmol/L
  16. Waterhouse M, Sanguineti E, Baxter C, Duarte Romero B, McLeod DSA, English DR, Armstrong BK, Ebeling PR, Hartel G, Kimlin MG, O'Connell RL, Pham H, van der Pols JC, Venn AJ, Webb PM, Whiteman DC, Neale RE. Vitamin D supplementation and risk of falling: outcomes from the randomized, placebo-controlled D-Health Trial. J Cachexia Sarcopenia Muscle. 2021;12(6):1428-1439. doi: 10.1002/jcsm.12759.PubMedUsed to support: D-Health: 60,000 IU vitamin D3 monthly did not reduce falls (OR 1.02); falls increased in participants with BMI below 25 (OR 1.25)
  17. Bolland MJ, Grey A, Avenell A. Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis. Lancet Diabetes Endocrinol. 2018;6(11):847-858. doi: 10.1016/S2213-8587(18)30265-1.PubMedUsed to support: Meta-analysis of 81 RCTs (53,537 adults): vitamin D had no effect on total fracture (RR 1.00), hip fracture (RR 1.11) or falls (RR 0.97), with similar results at doses above 800 IU/day, and no clinically relevant effect on bone density
  18. US Preventive Services Task Force, Grossman DC, Curry SJ, Owens DK, Barry MJ, Caughey AB, Davidson KW, Doubeni CA, Epling JW Jr, Kemper AR, Krist AH, Kubik M, Landefeld S, Mangione CM, Pignone M, Silverstein M, Simon MA, Tseng CW; US Preventive Services Task Force. Interventions to Prevent Falls in Community-Dwelling Older Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;319(16):1696-1704. doi: 10.1001/jama.2018.3097.PubMedUsed to support: USPSTF found adequate evidence that vitamin D has no benefit in preventing falls and recommended against vitamin D supplementation to prevent falls in community-dwelling adults 65 and older not known to have osteoporosis or vitamin D deficiency (D recommendation)
  19. Okereke OI, Reynolds CF 3rd, Mischoulon D, Chang G, Vyas CM, Cook NR, Weinberg A, Bubes V, Copeland T, Friedenberg G, Lee IM, Buring JE, Manson JE. Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial. JAMA. 2020;324(5):471-480. doi: 10.1001/jama.2020.10224.PubMedUsed to support: VITAL-DEP, 18,353 adults aged 50 and older: 2,000 IU/day vitamin D3 for 5.3 years did not reduce incident or recurrent depression (HR 0.97) or change mood scores
  20. Murai IH, Fernandes AL, Sales LP, Pinto AJ, Goessler KF, Duran CSC, Silva CBR, Franco AS, Macedo MB, Dalmolin HHH, Baggio J, Balbi GGM, Reis BZ, Antonangelo L, Caparbo VF, Gualano B, Pereira RMR. Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial. JAMA. 2021;325(11):1053-1060. doi: 10.1001/jama.2020.26848.PubMedUsed to support: 240 hospitalized patients with moderate to severe COVID-19: a single 200,000 IU dose of vitamin D3 did not shorten hospital stay or reduce mortality, ICU admission or mechanical ventilation
  21. Keum N, Chen QY, Lee DH, Manson JE, Giovannucci E. Vitamin D supplementation and total cancer incidence and mortality by daily vs. infrequent large-bolus dosing strategies: a meta-analysis of randomised controlled trials. Br J Cancer. 2022;127(5):872-878. doi: 10.1038/s41416-022-01850-2.PubMedUsed to support: Meta-analysis of RCTs: no effect on total cancer incidence (SRR 0.99); total cancer mortality not significantly reduced overall (SRR 0.92), but lower in trials of daily dosing (SRR 0.87) and not in trials of infrequent large-bolus dosing
  22. Demay MB, Pittas AG, Bikle DD, Diab DL, Kiely ME, Lazaretti-Castro M, Lips P, Mitchell DM, Murad MH, Powers S, Rao SD, Scragg R, Tayek JA, Valent AM, Walsh JME, McCartney CR. Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2024;109(8):1907-1947. doi: 10.1210/clinem/dgae290.PubMedUsed to support: 2024 Endocrine Society guideline: suggests empiric vitamin D for ages 1 to 18, adults over 75, pregnancy and high-risk prediabetes; suggests against empiric supplementation above the DRI in healthy adults under 75 and against routine 25(OH)D testing, noting no clear optimal target level
  23. Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: a new drug interaction with an unexpected consequence. Clin Pharmacol Ther. 2009;85(2):198-203. doi: 10.1038/clpt.2008.165.PubMedUsed to support: 16 patients on atorvastatin: 800 IU/day vitamin D for 6 weeks lowered atorvastatin and active metabolite concentrations while LDL and total cholesterol also fell
  24. Office of Dietary Supplements, National Institutes of Health. Vitamin D: Fact Sheet for Health Professionals. NIH Office of Dietary Supplements. 2025;Updated June 27, 2025..SourceUsed to support: Not PubMed-indexed (official NIH fact sheet). Vitamin D sufficiency prevents rickets in children and osteomalacia in adults; D3 raises blood 25(OH)D more and longer than D2; D3 is usually made from lanolin, with a lichen-sourced vegan form, and D2 from UV-treated yeast; RDAs are 600 to 800 IU for adults; 50 nmol/L (20 ng/mL) is sufficient for most people; NHANES 2011 to 2014 found 18% at risk of inadequacy and 5% at risk of deficiency; toxicity is unlikely below 10,000 IU a day; interactions with orlistat, statins, corticosteroids and thiazide diuretics.