Interactive explainerVitamin D

How vitamin D becomes a hormone

The liver turns vitamin D into 25(OH)D (half-life about 15 days). The kidneys then make calcitriol, the active hormone (half-life about 15 hours).

Published 3 Nov 20266 min read

Vitamin D from sunlight, food or a supplement is not active. The body changes it twice. First the liver turns it into 25-hydroxyvitamin D, written 25(OH)D. Then the kidneys turn 25(OH)D into calcitriol, the active hormone.[1] Half of the 25(OH)D in the blood is gone after about 15 days, and half of the calcitriol after about 15 hours.[2] Parathyroid hormone (PTH) is one of the hormones that control how much calcitriol the kidneys make.[3] The calcitriol level does not usually fall until a vitamin D deficiency is severe.[1]

A real left kidney, Human Reference Atlas

    An adult kidney

    An adult kidney is 10 to 12 cm long and 5 to 7 cm wide. That is about the size of a closed fist.[4] The renal artery enters it at the hilum, the notch on its inner edge. The renal vein leaves from the same place.[4]

    Vitamin D arrives as 25(OH)D

    Vitamin D reaches the kidney already changed. The liver has turned it into 25(OH)D.[1] This is the form a vitamin D blood test measures. Its level reflects the vitamin D that comes from the skin, food and supplements.[1]

    The cortex makes calcitriol

    The outer layer of the kidney, the cortex, holds the proximal tubules.[4] Their cells take up 25(OH)D together with its carrier, vitamin D-binding protein, through a receptor called megalin.[5] An enzyme in these cells, 1-alpha-hydroxylase (CYP27B1), turns 25(OH)D into calcitriol.[3][6]

    The darker pyramids are the medulla. They hold the loops of Henle and the collecting ducts.[4]

    25(OH)D rises over months

    In a trial of 61 healthy adults, the average level at the start was about 41 nmol/L. 4000 IU of vitamin D3 a day raised 25(OH)D to about 96 nmol/L, and 1000 IU a day raised it to about 69 nmol/L. In both groups the level rose for about 3 months and then stayed flat.[7]

    25(OH)D stays in the blood for weeks. Its half-life is about 15 days.[1]

    Calcitriol stays steady

    PTH comes from the parathyroid glands. It makes the kidney produce more calcitriol, and calcitriol in turn lowers the release of PTH.[3]

    In lab records of about 65,000 apparently healthy people in northern China, PTH changed little when 25(OH)D was above 55 nmol/L and rose steeply below 22 nmol/L.[8] PTH, calcium and phosphate hold calcitriol in a narrow range. It does not usually fall until vitamin D deficiency is severe.[1]

    What does calcitriol do in the body?

    Calcitriol helps the gut absorb calcium. It also keeps the calcium and phosphate in the blood high enough for bones to mineralize.[1] The gut needs vitamin D to move calcium across its wall by active transport.[9] From dairy and fortified foods, the gut absorbs about 30% of the calcium.[9]

    The path runs through several organs. The skin makes vitamin D3 when UVB light, at about 290 to 320 nm, reaches it. Food and supplements add vitamin D2 or D3, which the small intestine absorbs.[1] The liver makes 25(OH)D, the kidneys make calcitriol, and calcitriol acts on the gut and on bone.[1]

    Schematic, not anatomy. The numbers follow the scenario in the figure above.

    Without enough vitamin D, bones can become thin, brittle or misshapen. Enough vitamin D prevents rickets in children and osteomalacia in adults.[1]

    Why does a vitamin D blood test measure 25(OH)D?

    A blood test measures 25(OH)D because it stays in the blood for weeks and reflects vitamin D from the skin, food and supplements.[1] Calcitriol is a poor measure of vitamin D status. It lasts only hours, and PTH, calcium and phosphate hold its level in a narrow range.[1]

    The Food and Nutrition Board of the US National Academies uses these levels of 25(OH)D:

    • below 30 nmol/L: risk of deficiency[1]
    • 30 to 50 nmol/L: some people may not have enough[1]
    • 50 nmol/L or more: enough for most people[1]
    • above 125 nmol/L: may be linked to adverse effects[1]

    The Institute of Medicine set the recommended daily intake (RDA) at 600 IU for ages 1 to 70 and 800 IU from age 71. These amounts match a 25(OH)D level of at least 50 nmol/L and cover the needs of at least 97.5% of people. They assume little sun on the skin.[10]

    The rise from a dose is not a straight line.[1] In the trial of 61 adults, who started at about 41 nmol/L on average, 1000 IU a day brought 25(OH)D to about 69 nmol/L and 4000 IU a day to about 96 nmol/L.[7] A 2014 analysis pooled 33 trials of vitamin D3 in adults. From an average start of 50 nmol/L, vitamin D3 raised 25(OH)D by about 37 nmol/L. The rise was larger with a higher dose, a longer trial, a lower starting level and older age.[11]

    Start
    Vitamin D a day

    Does more vitamin D mean more active hormone?

    Usually not. Extra vitamin D raises 25(OH)D, but PTH, calcium and phosphate hold calcitriol in a narrow range.[1] In animal experiments with vitamin D poisoning, 25(OH)D and several other vitamin D forms rose, but calcitriol did not.[2]

    The effect on calcium absorption is small. In a 1-year trial, 230 women after menopause with 25(OH)D of 35 to 68 nmol/L took a placebo, 800 IU a day, or 50,000 IU twice a month. In the high-dose group, calcium absorption rose by 1%, about 10 mg a day. In the other two groups it fell by 1.3 to 2%. Bone density, muscle mass and falls did not differ between the groups.[12]

    Calcitriol PTH, both as a share of their usual level, for the scenario above. Drag on the first chart to move through the months.

    What happens when the kidneys cannot make calcitriol?

    People whose kidneys cannot turn 25(OH)D into calcitriol can become vitamin D deficient, like people with little sun or poor absorption from the gut.[1] Some other tissues also turn 25(OH)D into calcitriol, but the kidney is the main site.[1]

    In short

    • The liver turns vitamin D into 25(OH)D, and the kidneys turn 25(OH)D into calcitriol, the active hormone.[1]
    • Half of the 25(OH)D in the blood is gone in about 15 days, half of the calcitriol in about 15 hours.[2]
    • A vitamin D blood test measures 25(OH)D. A level of 50 nmol/L or more is enough for most people.[1]
    • In one trial, a daily dose of 1000 or 4000 IU took about 3 months to bring 25(OH)D to a new steady level.[7]
    • PTH, calcium and phosphate keep calcitriol in a narrow range. It does not usually fall until deficiency is severe.[1]

    What this figure leaves out

    The kidney and its vessels come from the Human Reference Atlas, version 1.3: a female left kidney and the female blood vessels, shared under the CC BY 4.0 licence.[13][14] The amber dots and the glow are signs, not single molecules. The motion and the numbers come from a small model. It uses the 15-day half-life of 25(OH)D.[2] Its rise with a dose is fitted to trials, so its numbers can differ from a single trial by about 10 nmol/L.[7]

    The model leaves out what changes how much vitamin D the skin makes: season, time of day, cloud cover, skin pigment and sunscreen.[1] It also leaves out FGF23, a hormone from bone that lowers calcitriol production,[3] and CYP24A1, the enzyme that breaks down both 25(OH)D and calcitriol.[6] For education; not for diagnosis.

    Sources (14)
    1. Vitamin D: Fact Sheet for Health Professionals. NIH Office of Dietary Supplements. ods.od.nih.gov
    2. Pharmacokinetics of vitamin D toxicity. Jones G Am J Clin Nutr, 2008. PMID 18689406
    3. Interaction of Vitamin D with Peptide Hormones with Emphasis on Parathyroid Hormone, FGF23, and the Renin-Angiotensin-Aldosterone System. Latic N, Erben RG Nutrients, 2022. PMID 36501215
    4. Anatomy, Abdomen and Pelvis: Kidneys. Garza FA, Leslie SW StatPearls, 2025. PMID 29494007
    5. Proximal tubule endocytic apparatus as the specific renal uptake mechanism for vitamin D-binding protein/25-(OH)D3 complex. Negri AL Nephrology (Carlton), 2006. PMID 17199789
    6. Vitamin D metabolism, mechanism of action, and clinical applications. Bikle DD Chem Biol, 2014. PMID 24529992
    7. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Vieth R, Chan PC, MacFarlane GD Am J Clin Nutr, 2001. PMID 11157326
    8. Threshold of 25(OH)D and consequently adjusted parathyroid hormone reference intervals: data mining for relationship between vitamin D and parathyroid hormone. Gong M, Wang K, Sun H, Wang K, Zhou Y, Cong Y, et al. J Endocrinol Invest, 2023. PMID 36920734
    9. Calcium: Fact Sheet for Health Professionals. NIH Office of Dietary Supplements. ods.od.nih.gov
    10. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. J Clin Endocrinol Metab, 2011. PMID 21118827
    11. Serum 25(OH)D response to vitamin D3 supplementation: a meta-regression analysis. Shab-Bidar S, Bours S, Geusens PP, Kessels AG, van den Bergh JP Nutrition, 2014. PMID 24993750
    12. Treatment of Vitamin D Insufficiency in Postmenopausal Women: A Randomized Clinical Trial. Hansen KE, Johnson RE, Chambers KR, Johnson MG, Lemon CC, Vo TN, et al. JAMA Intern Med, 2015. PMID 26237520
    13. 3D Reference Organ for Kidney, Female, Left, v1.3. Human Reference Atlas, NIH HuBMAP (CC BY 4.0), 2026. lod.humanatlas.io
    14. 3D Reference Organ for Blood Vasculature, Female, v1.3. Human Reference Atlas, NIH HuBMAP (CC BY 4.0), 2026. lod.humanatlas.io

    For education; not medical advice. Talk to a doctor before you start, stop or change a supplement.