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Vitamin D

Vitamin D supports calcium absorption and bone mineralization. Preventive supplementation in otherwise healthy people and treatment of established deficiency are different decisions. The 2024 Endocrine Society prevention guideline replaces its 2011 guideline; it does not cover all management of osteoporosis, malabsorption, or other conditions that substantially alter vitamin D physiology.[1][2]

Metabolism and Testing​

Vitamin D3 (cholecalciferol) comes from skin synthesis, food, or supplements; D2 (ergocalciferol) is another dietary or supplemental form. Hepatic hydroxylation produces 25-hydroxyvitamin D [25(OH)D], the usual status marker. Renal conversion produces 1,25-dihydroxyvitamin D (calcitriol), regulated by calcium, phosphate, PTH, and FGF23. A 1,25-dihydroxyvitamin D level is not a substitute for 25(OH)D when assessing nutritional status.[3][4]

Interpretation frameworkMeaning
NAM nutritional assessmentBelow 12 ng/mL indicates risk of deficiency; 12 to below 20 ng/mL may be inadequate; at least 20 ng/mL is adequate for most people. Multiply ng/mL by 2.5 for nmol/L.
Endocrine Society 2024 prevention guidanceCould not determine a blood target for disease prevention.
Condition-specific treatmentOsteoporosis, bariatric malabsorption, and CKD require their own assessment and treatment context.

Thresholds are not interchangeable across these settings. Interpret an actual result alongside symptoms, calcium, kidney function, nutrition, and the reason for testing.[1][3][4]

Prevention: What to Recommend​

For generally healthy adults aged 19–74, the Endocrine Society suggests against routine supplementation beyond dietary reference intake, and against routine 25(OH)D screening. Obesity or dark complexion alone does not establish a screening indication. These recommendations do not preclude testing for a clinical indication such as hypocalcemia.[1][2]

The usual adult RDA is 600 IU/day through age 70 and 800 IU/day after 70, counting food and supplements.[3]

The guideline conditionally supports empiric supplementation in these groups:[1]

PopulationRationale and limits
Ages 1–18Rickets prevention and possible respiratory-infection benefit.
Age ≥75Possible small mortality benefit; overall recommendation has moderate-certainty evidence.
PregnancyPossible obstetric/neonatal benefit; low-certainty evidence.
High-risk prediabetesPossible reduction in diabetes progression alongside lifestyle intervention.

Trial doses varied substantially. Reported trial averages were roughly 2,500 IU/day in pregnancy and 3,500 IU/day in prediabetes; these are not prescribed doses for all patients. For adults ≥50 with an indication for supplementation or treatment, the guideline favors lower daily dosing over intermittent large doses.[1]

Large Trials and Clinically Important Outcomes​

Fractures​

  • VITAL: 25,871 participants; D3 2,000 IU/day; median 5.3 years. Total fracture risk was not significantly reduced: HR 0.98 (95% CI 0.89–1.08). Participants were not selected for deficiency, low bone mass, or osteoporosis.[5]
  • D-Health: 21,315 randomized, 20,326 included in the linked-data fracture analysis; D3 60,000 IU/month. Over median 5.1 years, at least one fracture occurred in 5.6% versus 5.9%; HR 0.94 (0.84–1.06).[6]

Diabetes Prevention​

A 2023 individual-participant meta-analysis of three randomized trials (4,190 people with prediabetes) found an adjusted diabetes HR of 0.85 (0.75–0.96), with 3.3 percentage points absolute risk reduction over three years; NNT approximately 30. This is a pooled result and not a statistically significant primary D2d result alone. Two trials used cholecalciferol and one used the active analogue eldecalcitol.[7]

Analyses associating achieved 25(OH)D ≥50 ng/mL with larger benefit did not randomize patients to blood-level targets. They do not justify escalating everyone to that concentration; the Food and Nutrition Board notes that serum 25(OH)D above 50 ng/mL can be associated with adverse effects.[3] Safety events were uncommon, with imprecise estimates; supplementation does not replace weight, activity, or other indicated diabetes-prevention care.[7]

Cardiovascular Disease and Cancer​

VITAL did not significantly reduce major cardiovascular events (MI, stroke, or cardiovascular death), HR 0.97 (0.85–1.12), or invasive cancer, HR 0.96 (0.88–1.06). Overall cancer mortality was not significantly lower; HR 0.75 arose from an analysis excluding the first two years, not the overall analysis.[8]

The 2025 D-Health cancer analysis included 21,308 participants and found no reduction in cancer incidence excluding keratinocyte cancers, HR 1.02 (0.95–1.10).[9]

Autoimmune Disease​

VITAL's prespecified ancillary study initially reported fewer confirmed autoimmune diagnoses with vitamin D, HR 0.78 (0.61–0.99).[10] The 2024 follow-up both extended observation and identified additional cases: the revised randomized-period estimate was 0.85 (0.70–1.04); over approximately seven years it was 0.98 (0.83–1.17). The follow-up did not support the original 22% reduction as a durable preventive effect.[10][11]

Deficiency Treatment and Safety​

Treatment depends on the cause, severity, absorption, calcium balance, and kidney function. Correct deficiency when indicated.

SettingPractical approach
Postmenopausal osteoporosisAACE 2020 describes D3 5,000 IU/day for 8–12 weeks for low levels, then usually 1,000–2,000 IU/day, adjusted to the measured response and its condition-specific target above 30 ng/mL. AACE's regimen applies to postmenopausal osteoporosis.[4]
Bariatric malabsorptionUse the bariatric team's procedure-specific surveillance and replacement plan; standard nutritional intake may be insufficient.
CKDKDIGO permits assessing 25(OH)D and correcting deficiency with nutritional vitamin D. In adults with CKD G3a–G5 not on dialysis, calcitriol/analogues are not routine; reserve them for selected severe, progressive hyperparathyroidism, generally in G4–G5. Dialysis regimens require renal-team assessment.
Active granulomatous disease or hypercalcemiaRepletion needs caution and calcium monitoring; avoid an automatic loading regimen.

D3 is generally preferred for replacement; D2 is an alternative in appropriate circumstances. When using D2, ensure the assay adequately measures both 25(OH)D2 and 25(OH)D3. Do not prescribe calcitriol simply because someone has kidney or liver disease.[4][12][13]

The adult tolerable upper intake level is 4,000 IU/day for routine intake. Clinician-directed deficiency treatment can exceed this temporarily with monitoring; 10,000 IU/day is not a general maintenance recommendation. Excess can cause hypercalcemia, hypercalciuria, and kidney injury.[3] In the Calgary trial (311 adults), 4,000 or 10,000 IU/day for three years produced lower radial volumetric bone density than 400 IU/day.[14]

Reconstructive Relevance​

  • Augmentation or diversion: chronic metabolic acidosis from urine contact with bowel mucosa can contribute to bone demineralization.[15] Evaluate acidosis, kidney function, dietary intake, immobility, and fracture risk. For postmenopausal women with osteoporosis, AACE advises assessing 25(OH)D when deficiency risk is present and correcting documented deficiency during bone care.[4] Vitamin D and mineral-bone tests are added when clinically indicated; a 25(OH)D–PTH–phosphate panel is not required for every diversion patient. Follow Renal Function & Metabolic Surveillance.
  • Urogynecology: use age- and risk-based osteoporosis screening. Prolapse surgery alone does not mandate DXA plus vitamin D testing.
  • Gender-affirming care: assess actual bone-risk factors, including prolonged hypogonadism or gonadectomy without adequate hormone replacement.
  • Bariatric or congenital care: malabsorption, restricted intake, reduced weight bearing, acidosis, and CKD may warrant targeted evaluation. Deficiency is not inevitable after every bariatric operation. Routine FGF23 or 1,25-dihydroxyvitamin D testing is not a standard nutritional screen.[12][13]

See Also​

References​

1. Demay MB, Pittas AG, Bikle DD, et al. Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2024;109:1907–1947. doi:10.1210/clinem/dgae290.

2. Correction to the Endocrine Society vitamin D guideline. J Clin Endocrinol Metab. 2025;110:e916. Published December 2024. doi:10.1210/clinem/dgae854.

3. NIH Office of Dietary Supplements. Vitamin D: Health Professional Fact Sheet. Dietary reference intakes, status assessment, and toxicity.

4. Camacho PM, Petak SM, Binkley N, et al. AACE/ACE Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis—2020 Update. Endocr Pract. 2020;26(Suppl 1):1–46. doi:10.4158/GL-2020-0524SUPPL.

5. LeBoff MS, Chou SH, Ratliff KA, et al. Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. N Engl J Med. 2022;387:299–309. doi:10.1056/NEJMoa2202106.

6. Waterhouse M, Ebeling PR, McLeod DSA, et al. The effect of monthly vitamin D supplementation on fractures: a tertiary outcome from the D-Health trial. Lancet Diabetes Endocrinol. 2023;11:324–332. doi:10.1016/S2213-8587(23)00063-3.

7. Pittas AG, Kawahara T, Jorde R, et al. Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes: A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials. Ann Intern Med. 2023;176:355–363. doi:10.7326/M22-3018.

8. Manson JE, Cook NR, Lee IM, et al. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med. 2019;380:33–44. doi:10.1056/NEJMoa1809944.

9. Neale RE, English DR, McLeod DSA, et al. The effect of vitamin D supplementation on cancer incidence in the randomised controlled D-Health Trial: Implications for policy and practice. J Steroid Biochem Mol Biol. 2025;250:106738. doi:10.1016/j.jsbmb.2025.106738.

10. Hahn J, Cook NR, Alexander EK, et al. 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.

11. Costenbader KH, Cook NR, Lee IM, et al. 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;76:973–983. doi:10.1002/art.42811.

12. KDIGO. 2017 Clinical Practice Guideline Update for CKD–Mineral and Bone Disorder. Recommendations 3.1.3 and 4.2.1–4.2.5. Guideline.

13. Parrott J, Frank L, Rabena R, et al. ASMBS Integrated Health Nutritional Guidelines for the Surgical Weight Loss Patient—2016 Update: Micronutrients. Surg Obes Relat Dis. 2017;13:727–741. doi:10.1016/j.soard.2016.12.018.

14. Burt LA, Billington EO, Rose MS, et al. Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. JAMA. 2019;322:736–745. doi:10.1001/jama.2019.11889.

15. Pozo C, Pradere B, Rebhan K, et al. "Impact of intestinal urinary diversion on the risk of fracture and loss of bone mass: A systematic review." Bladder Cancer. 2021;7(3):365–376. doi:10.3233/BLC-201526