A reference work, not a recommendation to use: this profile describes mechanism and evidence and does not replace medical advice. The claims come from marketing and forums and are tested here, not endorsed.

Claims checked

  • Strengthens bones and protects against fractures and falls

    No benefit

    Bones & joints · healthy (adults aged 50 and 55 years and older, respectively, not selected for deficiency) · Human, randomised

    VITAL: no effect on fractures overall (HR 0.98) or hip fractures [8]. Meta-analysis of 81 RCTs: no effect on fractures, falls or bone density [9]. With very high single doses, rather more falls and fractures [10]; according to a review, older care-home residents or people with deficiency benefit together with calcium [1].

  • Strengthens the immune system and protects against colds

    Small benefit

    Immune system & infections · mixed: healthy people and patients (0 to 95 years) · Human, randomised

    Meta-analysis of 43 RCTs with 48,488 participants: 61.3% versus 62.3% with at least one respiratory infection (OR 0.92); in subgroups clearer with daily dosing and in children, without a significant interaction; not significant in any subgroup by baseline level; conflicts of interest with supplement manufacturers [12].

  • Prolongs life and protects against cancer and myocardial infarction

    Mixed results

    Longevity · healthy (older adults) · Human, randomised

    VITAL and D-Health: no effect on cancer, cardiovascular events or all-cause mortality [5][6]. An older Cochrane review found slightly lower mortality for vitamin D3, mainly in older women [7]; genetic data suggest harm only in true deficiency [4].[5][6]

  • Lifts mood and prevents depression

    No benefit

    Mood & stress · healthy (aged 50 and older, without relevant depressive symptoms) · Human, randomised

    VITAL-DEP with 18,353 participants over 5.3 years: no difference in new or recurrent depression (HR 0.97) and in mood scores [13].

  • Improves memory and mental performance

    Mixed results

    Cognition & focus · healthy (middle and older age) · Human, randomised

    Cochrane: vitamin D3 with calcium without effect on cognition in cognitively healthy people for up to ten years [14]. A more recent meta-analysis with mixed populations found a small overall effect (g = 0.13), larger in deficiency and at-risk groups [15].

Mechanism of action

Evidence map: Vitamin D

Each line stands for a published finding; line style and color show where it comes from. The filter hides weaker evidence levels. Sources: see references.

Vitamin D is formed in the skin or taken up with food and supplements and converted to 25-hydroxyvitamin D, the storage form that is measured in the blood. From it, 1,25-dihydroxyvitamin D is formed, the ligand of the vitamin D receptor (VDR), a nuclear receptor that switches genes on and off. The effect on bone is mainly indirect: the hormone increases calcium absorption in the gut and keeps calcium and phosphate constant in the blood [1]. VDR and the activating enzymes occur in almost all tissues; immune cells even produce 1,25-dihydroxyvitamin D themselves, controlled by inflammatory signals rather than by calcium homeostasis. Many cell, animal and observational studies therefore suggest effects far beyond bone; according to the same review, the randomized studies on this are contradictory overall [1].

As supplements, vitamin D comes mainly as cholecalciferol (D3), ergocalciferol (D2) and calcifediol; the comparison of forms is in their profiles. In brief: D3 raised the 25-hydroxyvitamin D level more than D2 in a 2012 meta-analysis, mainly with rare large single doses [2]; a more recent meta-analysis found the advantage also with daily dosing; at a BMI above 25 it was no longer significant [3]. That a true deficiency harms is supported by a genetic analysis (Mendelian randomization) of 307,601 participants of the UK Biobank: the mortality risk fell steeply up to a level of about 50 nmol/l and stayed flat above it; at 25 nmol/l it was an estimated 25% higher than at 50 nmol/l [4]. This speaks for a benefit in deficiency, not for an advantage of higher levels.

This is exactly what the large randomized studies in people not selected for deficiency show. In VITAL (25,871 participants, 5.3 years), vitamin D3 reduced neither cancer (HR 0.96) nor major cardiovascular events (HR 0.97) [5]. In the Australian D-Health study of 21,315 people aged 60 and older, all-cause mortality remained unchanged (HR 1.04); in an exploratory analysis, cancer mortality after the first two years was rather higher [6]. An older Cochrane review had found slightly lower mortality for vitamin D3 (RR 0.94), mainly in older women in care homes or living alone, and more kidney stones with calcium [7]. Vitamin D3 did not prevent fractures in VITAL (HR 0.98) [8], nor in a meta-analysis of 81 randomized studies, which also found no influence on falls and no clinically relevant change in bone density [9]. Very high amounts can do harm: a single very high dose once a year led to more falls (RR 1.15) and fractures (RR 1.26) in older women [10], and daily amounts above the tolerable upper limit lowered bone density at the forearm over three years [11].

A meta-analysis of 43 studies shows a small benefit for acute respiratory infections (OR 0.92); in subgroups, the effect was clearer with daily dosing and in children, but the differences between subgroups were not significant; several authors report research funding from supplement manufacturers [12]. Vitamin D3 did not prevent depression in the VITAL substudy with 18,353 participants (HR 0.97) [13]. For cognition in cognitively healthy people, a Cochrane review found no effect [14]; a more recent meta-analysis with mixed populations saw a small overall effect (Hedges' g = 0.13), which was larger in deficiency and in at-risk groups [15]. The testosterone rise in a small study of overweight men with deficiency [16] was not confirmed in a randomized study of healthy men with normal testosterone [17].

Targets

TargetTypeActionKey dataEvidence
Vitamin D receptor (VDR, nuclear receptor)ReceptorAgonistLigand is 1,25-dihydroxyvitamin D, not vitamin D itself (review) Laboratory[1]
Calcium transport in the gutSignaling pathwayActivatorMain route of the bone effect, mostly indirect (review) Animal study[1]
CYP27B1 in immune cells (local formation of 1,25-dihydroxyvitamin D)EnzymeExpression ↑regulated by inflammatory and pathogen signals, not by calcium homeostasis (laboratory) Laboratory[1]

Effect profile

Which signaling systems the compound affects according to current data. ↑ enhanced, ↓ dampened, ≈ modulated, ○ no effect; dots = evidence level.

  • Dopamineno data
  • Noradrenalineno data
  • Serotoninno data
  • Acetylcholineno data
  • Glutamate · AMPAno data
  • Glutamate · NMDAno data
  • GABAno data
  • Histamineno data
  • Orexinno data
  • Adenosineno data
  • Opioidsno data
  • Melatoninno data
  • Neurotrophinsno data
  • Blood flowno data
  • Nitric oxideno data
  • Energy metabolismno data
  • Insulin · glucoseno data
  • Inflammation · oxidativeunclear · Immune cells produce the active hormone themselves (laboratory); clinically only a small protection against respiratory infections[1][12]
  • Stress axisno data
  • Testosterone axisno effect · No effect on testosterone in healthy men (RCT); rise only in one small study with deficiency and overweight[16][17]
  • Endocannabinoidsno data
  • Autophagy · senescenceno data
  • Immune systemno data
  • Lipid metabolismno data
  • Coagulation · fibrinolysisno data
  • Methylationno data

Routes of administration and bioavailability

How much of a compound reaches the blood or target tissue depends on the route into the body and on the dosage form. All routes of administration explained

  • Oral (swallowed) · Vitamin D3 (cholecalciferol) versus vitamin D2 (ergocalciferol)

    Vitamin D3 raised 25-hydroxyvitamin D more than D2, according to a 2012 meta-analysis mainly with large single doses [2]; according to a more recent meta-analysis also with daily dosing (overall rise under D2 40% lower), no longer significant at a BMI above 25 [3]. Details in the profiles cholecalciferol and ergocalciferol.

    Human, randomised

  • Oral (swallowed) · rare very high single doses (monthly or yearly)

    Levels rise markedly, e.g., on average 115 versus 77 nmol/l under placebo with monthly dosing [6]; a yearly very high dose, however, increased falls and fractures, especially in the first three months [10]. For respiratory infections, protection was significant only in the subgroup with daily dosing; there was no significant difference between the subgroups [12].

    Human, randomised

Human studies

  • VITAL (cancer and cardiovascular)

    RCT, double-blind, placebo-controlled, 2×2 factorial · healthy (men aged 50 and older, women aged 55 and older, US) · n = 25871 · median 5.3 years

    Measured: invasive cancer, major cardiovascular events

    Result: No effect (HR 0.96 and 0.97, respectively); all-cause mortality HR 0.99; no clustering of hypercalcemia.[5]

    Human, randomised

  • VITAL fracture study

    Substudy of the RCT · healthy (not selected for deficiency, osteopenia or osteoporosis) · n = 25871 · median 5.3 years

    Measured: Fractures overall, nonvertebral, hip

    Result: No effect (HR 0.98; 0.97; 1.01), also not in subgroups by baseline level.[8]

    Human, randomised

  • D-Health

    RCT, double-blind, placebo-controlled · healthy (Australia, aged 60 and older, without level measurement) · n = 21315 · 5 years

    Measured: All-cause mortality

    Result: HR 1.04; cancer mortality exploratory after two years rather elevated (HR 1.24).[6]

    Human, randomised

  • Meta-analysis musculoskeletal

    systematic review, meta-analysis of 81 RCTs with trial sequential analysis · Adults (mixed) · n = 53537

    Measured: Fractures, falls, bone density

    Result: Fractures RR 1.00, hip fractures 1.11, falls 0.97; no clinically relevant change in bone density.[9]

    Human, randomised

  • Yearly high dose

    RCT, double-blind, placebo-controlled · healthy (women aged 70 and older at increased fracture risk) · n = 2256 · 3–5 years

    Measured: Falls, fractures

    Result: More falls (RR 1.15) and fractures (RR 1.26) under vitamin D.[10]

    Human, randomised

  • Meta-analysis respiratory infections

    systematic review and meta-analysis of double-blind RCTs · mixed (0–95 years) · n = 48488

    Measured: at least one acute respiratory infection

    Result: OR 0.92 (95% CI 0.86–0.99); subgroup daily dosing OR 0.78, interaction not significant.[12]

    Human, randomised

  • VITAL-DEP

    Substudy of the RCT · healthy (aged 50 and older) · n = 18353 · median 5.3 years

    Measured: Depression, PHQ-8

    Result: HR 0.97; mood scores unchanged.[13]

    Human, randomised

  • Testosterone in healthy men

    RCT, double-blind, placebo-controlled · healthy (men with normal testosterone, 25(OH)D below 75 nmol/l) · n = 98 · 12 weeks

    Measured: Total testosterone (mass spectrometry)

    Result: No effect; insulin sensitivity index QUICKI slightly decreased.[17]

    Human, randomised

Risks and warnings

  • Falls and fractures after very high single doses

    Yearly very high single dose in 2256 older women: falls RR 1.15, fractures RR 1.26; in the first three months after the dose, RR 1.31 for falls [10].

    Human, randomised

  • Lower bone density with high daily amounts

    Three years with daily amounts above the tolerable upper limit lowered bone density at the forearm more than a low amount in 311 healthy people; bone strength did not differ significantly [11].

    Human, randomised

  • Kidney stones (together with calcium)

    Cochrane review: vitamin D3 with calcium increased the risk of kidney stones (RR 1.17; four studies, 42,876 participants) [7].

    Human, randomised

  • Hypercalcemia with active forms of vitamin D

    Alfacalcidol and calcitriol increased the risk of hypercalcemia (RR 3.18) [7]; under vitamin D3 in VITAL no clustering [5].

    Human, randomised

  • Cancer mortality (exploratory finding)

    In D-Health, cancer mortality after excluding the first two years was borderline higher under monthly vitamin D3 (HR 1.24; p = 0.05); exploratory, not confirmed [6].

    Human, randomised

Interactions

  • Calcium supplements: In combination with calcium, more kidney stones (RR 1.17) [7].

Fact check: common claims

  • refuted

    “Almost everyone is undersupplied, and more vitamin D brings everyone more health”

    The genetic data show a benefit only up to about 50 nmol/l [4]; in large RCTs in adults not selected for deficiency, no effect on cancer, heart, fractures, depression or mortality [5][6][8][13].

  • partly supported

    “Vitamin D protects against infections”

    Small protection against acute respiratory infections (OR 0.92); in subgroups clearer with daily dosing and in children, without a significant interaction [12].

  • not supported

    “Vitamin D raises testosterone”

    Rise only in the before-and-after comparison of a small study of overweight men with deficiency [16]; in an RCT of healthy men, no effect [17].

  • refuted

    “High-dose vitamin D is harmless because you cannot overdose”

    Very high single doses increased falls and fractures [10], high daily amounts lowered bone density [11], and with calcium the risk of kidney stones rose [7].

  • partly supported

    “Vitamin D3 is more effective than vitamin D2”

    D3 raises the level more, according to the 2012 meta-analysis mainly with large single doses [2], according to a more recent meta-analysis also with daily dosing, but no longer significant at a BMI above 25 [3]. Whether this matters clinically has hardly been tested; details in the profiles cholecalciferol and ergocalciferol.

Pharmacokinetics

Absorption
Formation in the skin or uptake with food and supplements; vitamin D3 raises the level more than D2 [1][2][3].
Half-life
Not verified. After a yearly high dose, 25-hydroxyvitamin D was about 120 nmol/l after one month, about 90 nmol/l after three months and still above placebo after twelve months [10].
Metabolism
Conversion to 25-hydroxyvitamin D (storage form) and on to 1,25-dihydroxyvitamin D (hormone); local formation of the hormone also in immune cells [1].
Entry into the brain
Not verified.

Legal status

Germany
Not verified.
EU
Annex II Part A, No. 2 of Directive 2002/46/EC (vitamin D) with the authorized compounds cholecalciferol (2 a), ergocalciferol (2 b) and calcidiol monohydrate (2 c, specification according to the Union list of novel foods) [18].
USA
Not verified.

Authorised EU health claims

EU claim authorised An authorised health claim is a legal statement about the nutrient, not about this form, and not a level of evidence. The evidence for this form is reported separately under the main claim and in the human studies.

  • “contributes to the maintenance of normal bones”

    Nutrient
    Vitamin D
    Legal basis
    Regulation (EU) No 432/2012[19]
    Reading
    legally permitted; in healthy people not selected for deficiency, no protection against fractures, see the promise “Strengthens bones and protects against fractures and falls”

  • “contributes to the normal function of the immune system”

    Nutrient
    Vitamin D
    Legal basis
    Regulation (EU) No 432/2012[19]
    Reading
    legally permitted; for respiratory infections, see the promise “Strengthens the immune system and protects against colds”

Related compounds

Cholecalciferol (Vitamin D3)same class (German only)Ergocalciferol (Vitamin D2)same class (German only)Calcifediol (Calcidiol-Monohydrat, 25(OH)D3)same class (German only)

Open questions

  • Does vitamin D specifically benefit people with severe deficiency (below 25 nmol/l), for whom there are hardly any randomized studies?
  • Is the exploratory finding of higher cancer mortality in D-Health a coincidence?
  • Why do rare very high single doses do harm, while daily doses act neutrally or slightly protectively?

References

  1. Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, et al. Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions. Endocr Rev. 2019;40(4):1109–51. doi:10.1210/er.2018-00126 · PubMed
  2. Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. 2012;95(6):1357–64. doi:10.3945/ajcn.111.031070 · PubMed
  3. van den Heuvel EG, Lips P, Schoonmade LJ, Lanham-New SA, van Schoor NM. Comparison of the effect of daily vitamin D2 and vitamin D3 supplementation on serum 25-hydroxyvitamin D concentration (total 25(OH)D, 25(OH)D2, and 25(OH)D3) and importance of body mass index: a systematic review and meta-analysis. Adv Nutr. 2024;15(1):100133. doi:10.1016/j.advnut.2023.09.016 · PubMed
  4. 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;175(11):1552–9. doi:10.7326/M21-3324 · PubMed
  5. Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380(1):33–44. doi:10.1056/NEJMoa1809944 · PubMed
  6. Neale RE, Baxter C, Romero BD, McLeod DSA, English DR, Armstrong BK, et al. The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality. Lancet Diabetes Endocrinol. 2022;10(2):120–8. doi:10.1016/S2213-8587(21)00345-4 · PubMed
  7. Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2014;(1):CD007470. doi:10.1002/14651858.CD007470.pub3 · PubMed
  8. LeBoff MS, Chou SH, Ratliff KA, Cook NR, Khurana B, Kim E, et al. Supplemental vitamin D and incident fractures in midlife and older adults. N Engl J Med. 2022;387(4):299–309. doi:10.1056/NEJMoa2202106 · PubMed
  9. 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):847–58. doi:10.1016/S2213-8587(18)30265-1 · PubMed
  10. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, et al. 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 · PubMed
  11. 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):736–45. doi:10.1001/jama.2019.11889 · PubMed
  12. Jolliffe DA, Camargo CA Jr, Sluyter JD, Aglipay M, Aloia JF, Ganmaa D, et al. 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;9(5):276–92. doi:10.1016/S2213-8587(21)00051-6 · PubMed
  13. Okereke OI, Reynolds CF 3rd, Mischoulon D, Chang G, Vyas CM, Cook NR, et al. 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):471–80. doi:10.1001/jama.2020.10224 · PubMed
  14. Rutjes AW, Denton DA, Di Nisio M, Chong LY, Abraham RP, Al-Assaf AS, et al. Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life. Cochrane Database Syst Rev. 2018;12(12):CD011906. doi:10.1002/14651858.CD011906.pub2 · PubMed
  15. Chen WY, Cheng YC, Chiu CC, Liu HC, Huang MC, Tu YK, et al. Effects of vitamin D supplementation on cognitive outcomes: a systematic review and meta-analysis. Neuropsychol Rev. 2024;34(2):568–80. doi:10.1007/s11065-023-09598-z · PubMed
  16. Pilz S, Frisch S, Koertke H, Kuhn J, Dreier J, Obermayer-Pietsch B, et al. Effect of vitamin D supplementation on testosterone levels in men. Horm Metab Res. 2011;43(3):223–5. doi:10.1055/s-0030-1269854 · PubMed
  17. Lerchbaum E, Pilz S, Trummer C, Schwetz V, Pachernegg O, Heijboer AC, et al. Vitamin D and testosterone in healthy men: a randomized controlled trial. J Clin Endocrinol Metab. 2017;102(11):4292–302. doi:10.1210/jc.2017-01428 · PubMed
  18. Richtlinie 2002/46/EG des Europäischen Parlaments und des Rates vom 10. Juni 2002 zur Angleichung der Rechtsvorschriften der Mitgliedstaaten über Nahrungsergänzungsmittel. ABl. L 183 vom 12.7.2002, S. 51. Konsolidierte Fassung vom 26.11.2025 (CELEX 02002L0046-20251126).
  19. Verordnung (EU) Nr. 432/2012 der Kommission vom 16. Mai 2012 zur Festlegung einer Liste zulässiger anderer gesundheitsbezogener Angaben über Lebensmittel als Angaben über die Reduzierung eines Krankheitsrisikos sowie die Entwicklung und die Gesundheit von Kindern. ABl. L 136 vom 25.5.2012, S. 1 (CELEX 32012R0432).
How this profile was checked

Last reviewed: 2026-10-24. All sources with a DOI or PMID were resolved automatically via Crossref or doi.org and PubMed.

Translated from the German profile (version of 2026-10-24); translation checked on 2026-10-26.

Checked

  • Local re-check October 24, 2026: abstracts [6], [8], [10] and [12] read again, key figures confirmed. For [12], according to the abstract, no significant interaction with dose, dosing frequency, duration or age and no significant effect in the subgroups by baseline level; statements on daily dosing therefore labeled as a subgroup finding
  • All abstracts read via PubMed (efetch); DOIs and PMIDs reconciled with tools/pruefe_profile.py.
  • Key figures checked against the abstracts: VDR ligand, indirect bone effect via gut calcium, mixed RCT picture [1]; D3 > D2, advantage with bolus, not with daily dosing [2]; n = 307,601, L-shaped up to 50 nmol/l, OR 1.25 [4]; n = 25,871, HR 0.96/0.97/0.99 [5]; n = 21,315, HR 1.04, cancer mortality exploratory 1.24, levels 115 vs. 77 nmol/l [6]; D3 RR 0.94, kidney stones RR 1.17, hypercalcemia RR 3.18 [7]; HR 0.98/0.97/1.01 [8]; 81 RCTs, RR 1.00/1.11/0.97 [9]; n = 2256, RR 1.15/1.26, 1.31 in the first three months [10]; n = 311, lower bone density at the radius [11]; OR 0.92, 61.3 vs. 62.3%, daily dosing 0.78, conflicts of interest [12]; n = 18,353, HR 0.97 [13]; D3 plus calcium without effect on cognition [14]; 24 studies, g = 0.128 [15]; n = 54 analyzed, before-and-after rise [16]; n = 98, no effect, QUICKI −0.02 [17].
  • In the full text (PMC6626501) [1]: formation in the skin under UV-B light or uptake with food; immune cells produce 1,25-dihydroxyvitamin D locally, CYP27B1 regulated by immune signals rather than by calcium homeostasis.
  • PubChem: cholecalciferol, CID 5280795.
  • ClinicalTrials.gov: 5436 entries for “vitamin D” (October 23, 2026).
  • Approval K8 (October 24, 2026) implemented: legal status checked against the consolidated text CELEX 02002L0046-20251126 (Cellar, XHTML, October 24, 2026): Annex II Part A, No. 2 a “cholecalciferol,” 2 b “ergocalciferol,” 2 c “calcidiol monohydrate” with footnote 4 (reference to the Union list) [18]. Abstract [3] read: 20 comparison studies, daily dosing (12 comparisons, LC-MS/MS) −10.39 nmol/l (40%) under D2, loss of significance mainly at BMI above 25.
  • Health claims on vitamin D read in the wording of Regulation (EU) No 432/2012: base text CELEX 32012R0432 and consolidated version CELEX 02012R0432-20250820 (Cellar, XHTML, October 24, 2026), same wording [19]. Abstracts [5] and [8] read again: VITAL gave vitamin D3 (cholecalciferol).

Not verified

  • Conflicts of interest of the authors of [12] not re-checked locally (abstract: “Funding: None”; full text not freely available in either PMC or Europe PMC)
  • Legal status in Germany and the US (food supplement, medicinal product) not checked in registers; EFSA pages not reachable.
  • Half-life of 25-hydroxyvitamin D not checked against a primary source.
  • The review's [1] statement that older care-home residents or people with deficiency are protected against fractures together with calcium was not checked against the primary studies.
  • Calcium transport in the gut is documented only via the review [1]; evidence level 2 in the field ziele was therefore chosen cautiously.
  • Whether the group comparison against placebo in [16] was also significant (the abstract reports only before-and-after comparisons).

No dosages, no sources of supply. This information does not replace medical advice.

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