Compound or practice · Supplement
Vitamin D
A steroid hormone precursor that most temperate-latitude adults run low on — worth correcting, oversold as a cure-all.
- Overall grade
- Grade A
- Last revised
- 5
- graded outcomes
- 2
- references listed
A structured monograph in Prometheus's bundled library. Its grades are the monograph's own reading of the evidence, not a peer-reviewed review.
1 at grade A · 2 at grade B · 3 at grade C · 2 at grade D — 8 graded rows
What is known
Each outcome with its grade (how strong the evidence is, A to D), the size of the effect where the entry records one, and how often studies agree.
- Correcting deficiency (25(OH)D)Evidence grade A
Dose-dependent, predictable rise
Largehigh
- Fracture / fall risk (deficient elderly + calcium)Evidence grade B
Benefit concentrates in the deficient and institutionalized
Moderatemixed
- Respiratory infection riskEvidence grade C
Small effect, largest in the most deficient
Smallmixed
- Cancer / CVD prevention (replete adults)Evidence grade D
VITAL and others null
Trivialhigh
- Type 2 diabetes preventionEvidence grade D
D2d trial null in prediabetes
Trivialhigh
Conditions
How the entry reads its effect on diagnosed conditions: the direction first, then the grade. Never a substitute for the person who treats you.
- Osteoporosis / bone loss May improveEvidence grade BWith calcium, in deficiencyGrade B
- Seasonal low mood May improveEvidence grade CSignal mostly in deficient individualsGrade C
- Autoimmune disease No clear effectEvidence grade CVITAL hinted at a small reduction; not establishedGrade C
What is uncertain
Read off the same rows as above. Nothing here is added that the entry does not itself record.
- Thin evidence: Respiratory infection risk (grade C); Cancer / CVD prevention (replete adults) (grade D); Type 2 diabetes prevention (grade D).
- Studies disagree: Fracture / fall risk (deficient elderly + calcium) (mixed agreement).
Interactions
Documented pairings with supplements and medicines. A medicine on this list is a conversation for whoever prescribes it.
Vitamin K2Works together
K2 directs the calcium D mobilizes into bone rather than soft tissue.
MagnesiumWorks together
Magnesium is a required cofactor for activating vitamin D; low magnesium blunts the response.
CalciumWorks together
D improves calcium absorption; the bone benefit needs both.
BoronWorks together
Boron modestly slows vitamin D catabolism.
Up: Serum 25(OH)D (ng/mL). Across: IU/day. Roughly linear in the ordinary range; individual response varies with body fat and baseline.
The evidence in words
What it is
Vitamin D is a fat-soluble secosteroid the skin makes from UVB sunlight and the gut absorbs from food or supplements. It is measured in blood as 25-hydroxyvitamin D (25(OH)D). Despite the name it behaves like a hormone: the active form, calcitriol, binds a nuclear receptor expressed in most tissues. Deficiency is common at higher latitudes, in darker skin, in the elderly, and in anyone who avoids the sun.
How it works
Calcitriol regulates the transcription of hundreds of genes, most importantly those controlling intestinal calcium and phosphate absorption and bone remodeling. It also modulates immune-cell behavior, which is the mechanistic hook behind the (largely unproven) claims about infections and autoimmunity. Blood 25(OH)D is a storage marker; the body tightly controls how much active calcitriol it makes from it.
What the evidence shows
The strongest evidence is unglamorous: correcting a genuine deficiency improves bone-mineral markers and reduces fracture and fall risk when paired with calcium in deficient older adults. Large trials in already-replete populations (VITAL, D2d) found no benefit for preventing cancer, cardiovascular events, or type 2 diabetes — a clean signal that vitamin D fixes a deficiency rather than adding a bonus. The respiratory-infection literature is genuinely mixed: meta-analyses suggest a small protective effect concentrated in the most deficient. Test, treat to sufficiency, and stop expecting miracles.
How to use it
Dose against a blood level, not a calendar. 1,000–2,000 IU/day maintains most adults; frank deficiency often needs 4,000 IU/day for 8–12 weeks then a re-test. Take it with the largest fatty meal of the day for absorption. Pair with vitamin K2 and adequate magnesium, both cofactors for putting the mobilized calcium where it belongs.
Safety & interactions
Very safe in the ordinary range; toxicity (hypercalcemia) is real but requires sustained megadosing, typically well above 10,000 IU/day for months. The classic mistake is high-dose D without magnesium (a required cofactor) or K2 (which directs calcium to bone rather than arteries). Vitamin K2 — K2 directs the calcium D mobilizes into bone rather than soft tissue. Magnesium — Magnesium is a required cofactor for activating vitamin D; low magnesium blunts the response. Calcium — D improves calcium absorption; the bone benefit needs both. Boron — Boron modestly slows vitamin D catabolism.
Bottom line
If you live away from the equator, get a 25(OH)D test. If you're low, 1,000–2,000 IU/day with a fatty meal, K2 and magnesium alongside, re-test at 12 weeks. If you're already replete, more does nothing — the megadose-prevents-everything story did not survive the big trials.
How it is used
As the entry records it, from the studies it summarises. Not a recommendation for you — doses that suit a trial population may not suit you.
- Maintenance
- 1,000–2,000 IU (25–50 µg) D3 daily with a fatty meal.
- Repletion
- 4,000 IU/day for 8–12 weeks against a low 25(OH)D, then re-test.
- Cofactors
- Take with vitamin K2 (MK-7 90–180 µg) and ensure magnesium sufficiency.
Goes with
- Vitamin K2K2 directs the calcium D mobilizes into bone rather than soft tissue.Evidence grade B
- MagnesiumMagnesium is a required cofactor for activating vitamin D; low magnesium blunts the response.Evidence grade B
- CalciumD improves calcium absorption; the bone benefit needs both.Evidence grade B
- BoronBoron modestly slows vitamin D catabolism.Evidence grade C
Questions people ask
IU or a blood level?
Dose to the blood level. IU is the input; 25(OH)D is the output that actually matters, and people respond very differently to the same dose.
D2 or D3?
D3 (cholecalciferol) raises and holds 25(OH)D more reliably than D2 (ergocalciferol).
Related reading
Entries that share this one's tags or conditions.
- Vitamin D for Autoimmune diseaseEvidence grade C — VITAL hinted at a small reduction; not establishedEvidence grade C
- Vitamin D for Cancer / CVD prevention (replete adults)Evidence grade D — VITAL and others nullEvidence grade D
- Vitamin D for Correcting deficiency (25(OH)D)Evidence grade A — Dose-dependent, predictable riseEvidence grade A
- Vitamin D for Fracture / fall risk (deficient elderly + calcium)Evidence grade B — Benefit concentrates in the deficient and institutionalizedEvidence grade B
Sources
As this entry records them: title, journal and year. None carries a DOI or PubMed id, so none is linked as a verified paper. Each link searches PubMed for the title; check that what you find is what the entry describes.
- 1.Vitamin D supplements and prevention of cancer and cardiovascular disease (VITAL) — N Engl J Med, 2019. Search PubMed (opens in a new tab)
- 2.Vitamin D and type 2 diabetes prevention (D2d) — N Engl J Med, 2019. Search PubMed (opens in a new tab)
Last revised . A grade is this entry's reading of the evidence, not medical advice.