Ingredient review

Vitamin D


What is it?

Vitamin D is a prohormone and a non-essential, fat-soluble vitamin that can be synthesized in the skin following UV exposure. (149)(435) Vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol) are the naturally occurring forms found in supplements, though synthetic vitamin D analogs are also available. (415) Supplementation is often used to establish sufficient vitamin D levels, which typically correlates with the prevention and treatment of a wide variety of health conditions.

The Institute of Medicine (IOM) uses the following 25-hydroxyvitamin D (25(OH)D) levels as indicators of vitamin D health status:

  • Deficiency: <12 ng/ml (<30 nmol/L)
  • Insufficiency: 12-20 ng/ml (30-50 nmol/L)
  • Sufficiency: >20 ng/ml (>50 nmol/L)
  • High: >50 ng/ml (>125 nmol/L)
  • Increased risk of adverse effects: > 60ng/ml (>150 nmol/L) (189

Other authorities, including the American Geriatrics Society, the Endocrine Society, and the International Osteoporosis Foundation, recommend 25(OH)D levels >30 ng/ml (>75 nmol/L) for optimal vitamin D status to reduce risk of falls and fractures in the older population. Further, adverse effects from excess vitamin D may only become prevalent if blood levels reach >100 ng/ml (>250 nmol/L). (18)(105)(177

Not be confused with: 

  • Calcidiol (25(OH)D3)
  • Calcitriol (1,25-dihydroxyvitamin D3)
  • Doxercalciferol (1-α-hydroxyergocalciferol)
  • Ercalcidiol (25(OH)D2)
  • Ercalcitriol (1,25-dihydroxyvitamin D2)
  • Falecalcitriol (F6-1α,25-dihydroxyvitamin D3)
  • Maxacalcitol (22-oxacalcitriol)
  • Paricalcitol (19-Nor-1,25-dihydroxyvitamin D2)

Main uses

Bone and musculoskeletal disorders
Cardiovascular disorders
Chronic pain
Fractures and falls
Kidney disorders
Immune and inflammatory disorders
Metabolic disorders
Neurological disorders
Prenatal health
Psychological disorders
Respiratory disorders
Thyroid disorders


Vitamin D3 and D2 are the two naturally occurring forms of vitamin D found in supplements. However, synthetic, pharmaceutical vitamin D analogs are also clinically approved for a variety of indications. Examples include (but will not be further described) D2 analogs, such as ercalcidiol, ercalcitriol, doxercalciferol, or paricalcitol, and D3 analogs, such as calcidiol, calcitriol, maxacalcitol, and falecalcitriol. (150)

Bioavailability and supplement sources
Vitamin D2 (ergocalciferol)
Follows similar absorption pattern to D3, with food and supplements being equally well absorbed, but is not as effective in raising vitamin D status as D3 (284)(415)
Supplement sources: mushrooms (84)(282)
Vitamin D3 (cholecalciferol)
More effective than D2 for raising vitamin D status due to its greater half-life; possibly more potent than D2 due to higher affinity of its metabolites for the vitamin D receptor (284)(415)
Supplement sources: lanolin (secreted from the sweat glands of sheep) & lichen (155)(176)

Dosing & administration

Adverse effects

Adverse effects reported with vitamin D supplementation include nausea, vomiting, upset stomach, diarrhea, constipation, rashes, itchiness, allergic reactions, cardiovascular events, pain, cancer, and mortality. However, meta-analyses demonstrate that there are no significant effects associated with long term administration of doses of 4000 IU or less in adults. (270)

Vitamin D supplementation can increase the risk of hypercalcemia, hypercalciuria, and gastrointestinal (GI) events when used in conjunction with calcium supplementation. (38)(270) Single doses up to 200,000 IU can be administered in healthy, elderly populations without side effects, though GI complaints have been reported in some subjects. Doses greater than 500,000 IU have been reported to increase fracture risk, increase GI discomfort, and alter biochemical markers. (218)  Vitamin D toxicity has been reported in mega-doses ranging from 2,220,000 to 6,360,000 IU, administered in an attempt to correct deficiencies. (217)



  • Vitamin D is primarily synthesized (80%) in the skin upon the exposure of 7-dehydrocholecalciferol to UV light from the sun. 
  • When ingested orally, vitamin D is released from food and fatty matrices in the stomach and absorbed in the jejunum and ileum of the stomach. 
  • Vitamin D3 and D2 are thought to be absorbed by enterocytes through incorporation into micelles and chylomicrons.
  • At low concentrations, enzymatic transport is likely the primary uptake mechanism. At high concentrations, passive diffusion may dominate. (284)


  • CYP27B1, the enzyme responsible for the conversion of vitamin D to its active form, can be found in many tissues and cells throughout the body, thereby promoting vitamin D’s widespread physiological actions. (96)(172)
  • CYP27B1 is primarily found in the kidneys, but extrarenal sites include the GI tract, macrophages, monocytes, osteoblasts, osteoclasts, placenta, skin, and vasculature. (96)(172)(422)
  • Vitamin D3 is stored in adipose tissue with a half-life of two days, while the active form’s half-life is three weeks. (220)


  • Vitamin D is metabolized by vitamin D hydroxylases, particularly by CYP2R1  to form calcidiol,  but CYP2D11 and CYP2D25 may also be used in this function. 
  • 25(OH)D3 is the primary form of vitamin D that circulates in the blood and is used as a measure of vitamin D status. 
  • 25(OH)D3 can be further hydroxylated by CYP27B1 in the kidneys to calcitriol, the active form of vitamin D. 
  • However, 25-hydroxyvitamin D3 24 hydroxylase (CYP24), also found in the kidneys, can metabolize calcitriol to 1,24,25(OH)3D3. Subsequent oxidation of this metabolite results in the production of calcitroic acid, which is readily excreted.
  • Importantly, CYP27B1 can also be found in the placenta, monocytes, and macrophages, which may promote vitamin D’s active effects in placental development and in the regulation of the immune system. (96)


  • Calcitroic acid is excreted in the urine or used in bile.
  • Similarly, other vitamin D metabolites such as 1,25(OH)2D may proceed through the C23 lactone pathway for excretion or use in bile. (56)(205)

View our vitamin D metabolism infographic.