Vitamin D

Pronunciation

Vitamin D3 (cholecalciferol, koh-luh-kal-sif-uh-rawl)
Vitamin D2 (ergocalciferol, er-go-kal-sif-uh-rol)

Summary

Vitamin D is a prohormone and a non-essential vitamin. (8) Small quantities are found in fish liver oils, the skin of fatty fish, beef liver, cheese, and egg yolks, primarily in the form of vitamin D3 and its metabolite 25(OH)D3. (18) Another form, vitamin D2 is found in variable amounts in mushrooms. (19) Vitamin D3 is synthesized through UV irradiation of 7-dehydrocholesterol found in the skin, whereas D2 derives from the exposure of ergosterol to UV radiation. (22)

Main Medical Uses

The most important role of vitamin D may be to promote general well being. (1) Vitamin D has been studied for many outcomes, covering a diverse range of diseases. Class A evidence suggests that vitamin D may be beneficial for the following:

  • Balance sway
  • Birthweight and smallness for gestational age
  • Body Mass Index (BMI)
  • Cognition
  • CVD and CVD prevalence
  • Dental caries
  • Depression and Seasonal Affective Disorder (SAD)
  • Hypertension
  • Ischaemic stroke and stroke
  • Maternal vitamin D levels at term
  • Metabolic syndrome prevalence
  • Osteoporosis/fractures (with calcium)
  • Parathyroid hormone and alkaline phosphatase in CKD requiring dialysis
  • Parathyroid hormone in CKD not requiring dialysis
  • Type II and gestational diabetes (2, 3, 5, 6, 20, 21, 23)

Dosing and Administration

The following table has been adapted from the Endocrine Society Expert Committee. (11)
NOTE: Ongoing doses should commence when 25(OH)D concentrations reach 30 ng/ml. (7)

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 (14). However, Class A evidence demonstrates that there are no significant effects associated in adults with long term administration of doses of 4000 IU or less (14). Further, vitamin D supplementation does not increase the risk of non-calcemic adverse effects. (14) Vitamin D supplementation can increase the risk of hypercalcemia, hypercalciuria, and GI events when used in conjunction with calcium supplementation. (3, 15) 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, GI discomfort, and alter biochemical markers. (13) Vitamin D toxicity has been reported in mega-doses ranging from 2,220,000-6,360,000 IU administered in attempt to correct deficiencies. (12)

Forms

Vitamin D3 (Cholecalciferol):

  • Lanolin (from sweat glands of sheep or cod liver): Converts to vitamin D3 after UV-B exposure. (11)
  • Lichen (from moss): Plant alternative providing previtamin form of vitamin D3. (9)

Vitamin D2 (Ergocalciferol): Previtamin form that converts to D2 after UV-B exposure. (17)

The two forms differ by the structure of their side chains, though class A evidence suggests that Vitamin D3 is more effective at increasing serum 25(OH)D levels compared with D2. (22)

Associated Depletions and Interactions

For an explanation of the classes of evidence, please see the Rating Scales for Evidence-Based Decision Support.

Mechanism of Action and Metabolism

The following diagram depicts the metabolism of vitamin D in the body.

Download the reference sheet
  1. Allan, G. M., Cranston, L., Lindblad, A., Mccormack, J., Kolber, M. R., Garrison, S., & Korownyk, C. (2016). Vitamin D: A narrative review examining the evidence for ten beliefs. Journal of General Internal Medicine, 31(7), 780-791.
  2. Anglin, R. E., Samaan, Z., Walter, S. D., & Mcdonald, S. D. (2013). Vitamin D deficiency and depression in adults: Systematic review and meta-analysis. British Journal of Psychiatry, 202(02), 100-107.
  3. Avenell, A., Mak, J. C., & O’connell, D. (2014). Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database of Systematic Reviews, 14(4).
  4. Davidson, M. H., Hauptman, J., Digirolamo, M., Foreyt, J. P., Halsted, C. H., Heber, D., … Heymsfield, S. B. (1999). Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. Jama, 281(3), 235-242.
  5. Dumville, J. C., Miles, J. N., Porthouse, J., Cockayne, S., Saxon, L., & King, C. (2006). Can vitamin D supplementation prevent winter-time blues? A randomised trial among older women. The Journal of Nutrition, Health and Aging, 10(2), 151-153.
  6. Frandsen, T. B., Pareek, M., Hansen, J. P., & Nielsen, C. T. (2014). Vitamin D supplementation for treatment of seasonal affective symptoms in healthcare professionals: A double-blind randomised placebo-controlled trial. BMC Research Notes, 7(1), 528.
  7. Garland, C. F., Kim, J. J., Mohr, S. B., Gorham, E. D., Grant, W. B., Giovannucci, E. L., … Heaney, R. P. (2014). Meta-analysis of all-cause mortality according to serum 25-Hydroxyvitamin D. American Journal of Public Health, 104(8), E43-E50.
  8. Gois, P., Ferreira, D., Olenski, S., & Seguro, A. (2017). Vitamin D and infectious diseases: Simple bystander or contributing factor? Nutrients, 9(7), 651.
  9. Göring, H. (2018). Vitamin D in Nature: A product of synthesis and/or degradation of cell membrane components. Biochemistry (Moscow), 83(11), 1350-1357.
  10. Holick, M. F., Biancuzzo, R. M., Chen, T. C., Klein, E. K., Young, A., Bibuld, D., … Tannenbaum, A. D. (2008). Vitamin D2 is as effective as Vitamin D3 in maintaining circulating concentrations of 25-Hydroxyvitamin D. The Journal of Clinical Endocrinology & Metabolism,9 3(3), 677-681.
  11. Holick, M. F., Binkley, N. C., Bischoff-Ferrari, H. A., Gordon, C. M., Hanley, D. A., Heaney, R. P., . . . Weaver, C. M. (2011). Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, 96(7), 1911-1930.
  12. Kaur, P., Mishra, S. K., & Mithal, A. (2015). Vitamin D toxicity resulting from overzealous correction of vitamin D deficiency. Clinical Endocrinology, 83(3), 327-331.
  13. Kearns, M., Alvarez, J., & Tangpricha, V. (2014). Large, single-dose, oral vitamin D supplementation in adult populations: A systematic review. Endocrine Practice, 20(4), 341-351.
  14. Malihi, Z., Wu, Z., Lawes, C. M., & Scragg, R. (2017). Noncalcemic adverse effects and withdrawals in randomized controlled trials of long-term vitamin D2 or D3 supplementation: A systematic review and meta-analysis. Nutrition Reviews, 75(12), 1007-1034.
  15. Malihi, Z., Wu, Z., Stewart, A. W., Lawes, C. M., & Scragg, R. (2016). Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: A systematic review and meta-analysis. The American Journal of Clinical Nutrition, 104(4), 1039-1051.
  16. Mattila, P. H., Pilronen, V. I., Uusi-Rauva, E. J., & Kolvistolnen, P. E. (1994). Vitamin D contents in edible mushrooms. Journal of Agricultural and Food Chemistry, 42(11), 2449-2453.
  17. Ovesen, L., Brot, C., & Jakobsen, J. (2003). Food contents and biological activity of 25-Hydroxyvitamin D: A vitamin D metabolite to be reckoned with? Annals of Nutrition and Metabolism, 47(3-4), 107-113.
  18. Schwartz, J. (2009). Effects of vitamin D supplementation in atorvastatin-treated patients: A new drug interaction with an unexpected consequence. Clinical Pharmacology & Therapeutics, 85(2), 198-203.
  19. Tang, B. M., Eslick, G. D., Nowson, C., Smith, C., & Bensoussan, A. (2008). Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: A meta-analysis. Obstetrical & Gynecological Survey, 63(1), 30-31.
  20. Theodoratou, E., Tzoulaki, I., Zgaga, L., & Ioannidis, J. P. (2014). Vitamin D and multiple health outcomes: Umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ, 348, G2035.
  21. Tripkovic, L., Lambert, H., Hart, K., Smith, C., Bucca, G., Penson, S., … Lanham-New, S. (2012). Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: A systematic review and meta-analysis. The American Journal of Clinical Nutrition, 95(6), 1357-1364.
  22. Weaver, C. M., Alexander, D. D., Boushey, C. J., Dawson-Hughes, B., Lappe, J. M., Leboff, M. S., … Wang, D. D. (2015). Calcium plus vitamin D supplementation and risk of fractures: An updated meta-analysis from the National Osteoporosis Foundation. Osteoporosis International, 27(1), 367-376.