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Vitamin D3

Corrects vitamin D deficiency reliably; in people who already had enough, large trials show no gain in survival, and evidence for sleep and mood is small and short-term.

Longevity Sleep Anxiety

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Research

SleepLimited · benefitAnxietyLimited · no benefitLongevityStrong · no benefit

REALITY CHECK // Vitamin D3 fixes a deficiency, and that is where the clear benefit lies.

Levels: how we grade evidence. Grey = evidence of no benefit; amber = evidence it makes this goal worse.

Ratings are self-reported by a self-selected group of users: how it felt, not proof that it works.

>_ Protocol data coming soon: label checker ("Check your bottle"), study snapshot and form comparison for Vitamin D3.

How it was studied

NERD'S NOTENerd Protocols · a clinical and sports dietitian based in the EU

Summary

Vitamin D3 fixes a deficiency, and that is where the clear benefit lies. In large RCTs of mostly vitamin-D-replete older adults, VITAL (2000 IU/day) found no drop in cancer or cardiovascular events, and D-Health (60,000 IU/month) found no drop in all-cause mortality. A 52-trial meta-analysis found no effect on all-cause mortality, but fewer cancer deaths (about 16% fewer). Test your 25(OH)D level before you take high doses.

Mechanism

D3 (cholecalciferol) is converted in the liver to 25(OH)D, the form a blood test measures, and then to active calcitriol. Calcitriol regulates calcium absorption and acts on vitamin D receptors in many tissues. Benefit depends mainly on your starting level.

Typical studied dose

VITAL tested 2000 IU (50 µg) per day for a median 5.3 years. D-Health tested 60,000 IU per month; in an exploratory analysis this monthly high-dose (bolus) pattern hinted at more cancer deaths, so daily dosing is the better-studied pattern. Depression trials ranged up to 8000 IU/day. These are study doses, not a universal instruction; dosing is best guided by a 25(OH)D test.

Upper limit

EFSA sets the adult tolerable upper intake at 100 µg (4000 IU) per day (EFSA, 2012). Lower limits apply to children by age. Toxicity comes from hypercalcaemia (raised blood calcium), usually after long-term megadoses. Symptoms include nausea, thirst, frequent urination, heart rhythm problems and kidney stones.

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Red flags: interactions and who should avoid it

Interactions

Thiazide diuretics reduce calcium excretion, so combining them with D3 and calcium raises the risk of hypercalcaemia. With digoxin, hypercalcaemia increases the risk of toxicity. Anti-epileptics, rifampicin and glucocorticoids may lower vitamin D status. Orlistat and cholestyramine reduce absorption. If you take warfarin, avoid D3 products that also contain vitamin K2.

Avoid or ask a doctor first if

Do not take it without medical advice if you have hypercalcaemia, sarcoidosis or another granulomatous disease, primary hyperparathyroidism, calcium kidney stones or severe kidney disease. If you take thiazides or digoxin, talk to your doctor first. In pregnancy, standard doses are considered safe, but take high doses only under medical supervision.

Sources (PubMed)

  1. Association between vitamin D supplementation and mortality: systematic review and meta-analysis.
    PMID 31405892 · 2019 · Meta-analysis of 52 RCTs (n=75,454)
    No effect on all-cause mortality (RR 0.98, 95% CI 0.95-1.02)
  2. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease.
    PMID 30415629 · 2019 · RCT (VITAL, n=25,871, US adults 50+/55+)
    2000 IU/day did not reduce cancer or major cardiovascular events
  3. The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality.
    PMID 35026158 · 2022 · RCT (unscreened older Australians, monthly 60,000 IU)
    No reduction in all-cause mortality; caution in replete people
  4. Vitamin D Supplementation and Sleep: A Systematic Review and Meta-Analysis of Intervention Studies.
    PMID 35268051 · 2022 · Systematic review; meta-analysis of 3 RCTs
    PSQI improved in 3 RCTs; other sleep outcomes inconsistent
  5. The effect of vitamin D supplementation on depression: a systematic review and dose-response meta-analysis of randomized controlled trials.
    PMID 39552387 · 2024 · Dose-response meta-analysis of RCTs (31 trials)
    No significant effect on anxiety; depression benefit short-term only

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