Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

You are viewing this page in draft mode.

Vitamin D supplementation: cholecalciferol, calcifediol, and calcitriol

Abstract

The specific compound that is meant for use in the context of vitamin D supplementation is often ambiguous. The term “supplementation” has been used in the context of cholecalciferol, ergocalciferol, calcidiol, and calcitriol. In nature, by far the major form of vitamin D that nurtures the body is cholecalciferol. In contrast, ergocalciferol is primarily a synthetic and less stable product which is less potent per microgram dose than is cholecalciferol. Calcidol is the major circulating metabolite of cholecalciferol, while calcitriol is the hormone that upregulates the active transport of calcium from the gut, and which suppresses parathyroid hormone secretion. Nutrition policy papers and guidelines leave unstated the obvious fact that calcidiol and calcitriol are not nutrients, and that those metabolites are not pertinent to food fortification or dietary supplementation. Recent evidence shows that ergocalciferol is not stable with storage, and it is far more susceptible to breakdown with cooking and baking than is cholecalciferol. Therefore, it must be concluded that cholecalciferol is the only form of vitamin D that should be considered in the context of the nutritional functions of fortification and supplementation.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: The compartments of cholecalciferol metabolism and points of its regulation through the system.

References

  1. 1.

    Vieth R. Why ‘Vitamin D’ is not a hormone, and not a synonym for 1,25-dihydroxy-vitamin D, its analogs or deltanoids. J Steroid Biochem Mol Biol. 2004;89–90:571–3.

    Article  Google Scholar 

  2. 2.

    Rosenfeld L. Vitamine-vitamin. The early years of discovery. Clin Chem. 1997;43:680–5.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Stedman TL. Stedman’s Medical Dictionary for the Health Professions and Nursing. Baltimore, MD, USA: Lippincott Williams & Wilkins; 2005.

  4. 4.

    Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. 2012;95:1357–64.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2014;1–177. https://doi.org/10.1002/14651858.CD007470.pub3.

  6. 6.

    Itkonen ST, Skaffari E, Saaristo P, Saarnio EM, Erkkola M, Jakobsen J, et al. Effects of vitamin D2-fortified bread v. supplementation with vitamin D2 or D3 on serum 25-hydroxyvitamin D metabolites: an 8-week randomised-controlled trial in young adult Finnish women. Br J Nutr. 2016;115:1232–9.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006;84:694–7.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    DeLuca HF. Vitamin D: historical overview. Vitam Horm. 2016;100:1–20.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Vieth R. How to optimize vitamin D supplementation to prevent cancer, based on cellular adaptation and hydroxylase enzymology. Anticancer Res. 2009;29:3675–84.

    CAS  PubMed  Google Scholar 

  10. 10.

    Vieth R, Fraser D. Kinetic behavior of 25-hydroxyvitamin D-1-hydroxylase and -24-hydroxylase in rat kidney mitochondria. J Biol Chem. 1979;254:12455–60.

    CAS  PubMed  Google Scholar 

  11. 11.

    Darling AL, Hart KH, Gibbs MA, Gossiel F, Kantermann T, Horton K, et al. Greater seasonal cycling of 25-hydroxyvitamin D is associated with increased parathyroid hormone and bone resorption. Osteoporos Int. 2014;25:933–41.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303:1815–22.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ, Staehelin HB, Meyer OW, Theiler R, et al. Monthly high-dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial. JAMA Intern Med. 2016;176:175–83.

    Article  PubMed  Google Scholar 

  14. 14.

    Kleinman LM, Letteri JM, Asad SN, Ellis KJ, Cohn SH. Effects of calcifediol on calcified tissue in uremia. Arch Intern Med. 1978;138:864–5.

    Article  PubMed  Google Scholar 

  15. 15.

    Orwoll ES, McClung MR, Oviatt SK, Recker RR, Weigel RM. Histomorphometric effects of calcium or calcium plus 25-hydroxyvitamin D3 therapy in senile osteoporosis. J Bone Min Res. 1989;4:81–88.

    CAS  Article  Google Scholar 

  16. 16.

    Vieth R. The pharmacology of vitamin D, including fortification strategies. In: Vitamin D, 2nd Ed. New York: Elsevier: 2005, p 995–1015.

  17. 17.

    Minisola S, Cianferotti L, Biondi P, Cipriani C, Fossi C, Franceschelli F, et al. Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and biochemical effects on bone and mineral metabolism of daily and weekly dosage regimens. Osteoporos Int. 2017;28:3239–49.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Schmid A, Walther B. Natural vitamin D content in animal products1. Adv Nutr. 2013;4:453–62.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Hollis BW, Wagner CL. Clinical review: the role of the parent compound vitamin D with respect to metabolism and function: Why clinical dose intervals can affect clinical outcomes. J Clin Endocrinol Metab. 2013;98:4619–28.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Fraser D, Kooh SW, Kind HP, Holick MF, Tanaka Y, DeLuca HF. Pathogenesis of hereditary vitamin-D-dependent rickets. An inborn error of vitamin D metabolism involving defective conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D. N. Engl J Med. 1973;289:817–22.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Isakova T, Nickolas TL, Denburg M, Yarlagadda S, Weiner DE, Gutiérrez OM, et al. KDOQI US commentary on the 2017 KDIGO clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease–mineral and bone disorder (CKD-MBD). Am J Kidney Dis. 2017;70:737–51.

    Article  PubMed  Google Scholar 

  22. 22.

    Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999;69:842–56.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Vieth R. Vitamin D toxicity, policy, and science. J Bone Miner Res: Off J Am Soc Bone Miner Res. 2007;22:V64–8.

    CAS  Article  Google Scholar 

  24. 24.

    Institute of Medicine Committee to Review Dietary Reference Intakes for Vitamin D, Calcium. The National Academies Collection: Reports funded by National Institutes of Health. In: Ross AC, Taylor CL, Yaktine AL, Del Valle HB (eds.). Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US) National Academy of Sciences; 2011 https://doi.org/10.17226/13050.

  25. 25.

    SACN. Scientific Advisory Committee on NutritionVitamin D and Health. https://www.gov.uk/government/groups/scientific-advisory-committee-on-nutrition. Accessed 20 Dec 2016.

  26. 26.

    Lips P, Cashman KD, Lamberg-Allardt C, Bischoff-Ferrari HA, Obermayer-Pietsch BR, Bianchi M et al. MANAGEMENT OF ENDOCRINE DISEASE: Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency; a position statement of the European Calcified Tissue Society. Eur J Endocrinol. 2019. https://doi.org/10.1530/EJE-18-0736.

  27. 27.

    Pilz S, März W, Cashman KD, Kiely ME, Whiting SJ, Holick MF et al. Rationale and plan for vitamin D food fortification: a review and guidance paper. Front Endocrinol. 2018;9. https://doi.org/10.3389/fendo.2018.00373.

  28. 28.

    Bouillon R. Comparative analysis of nutritional guidelines for vitamin D. Nat Rev Endocrinol. 2017;13:466–79.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Mocanu V, Stitt PA, Costan AR, Voroniuc O, Zbranca E, Luca V, et al. Long-term effects of giving nursing home residents bread fortified with 125 microg (5000 IU) vitamin D(3) per daily serving. Am J Clin Nutr. 2009;89:1132–7.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Al-Khalidi B, Chiu W, Rousseau D, Vieth R. Bioavailability and safety of vitamin D3 from pizza baked with fortified mozzarella cheese: a randomized controlled trial. Can J dietetic Pract Res. 2015;76:109–16.

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Reinhold Vieth.

Ethics declarations

Conflict of interest

The author declares that he has no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Vieth, R. Vitamin D supplementation: cholecalciferol, calcifediol, and calcitriol. Eur J Clin Nutr 74, 1493–1497 (2020). https://doi.org/10.1038/s41430-020-0697-1

Download citation

Further reading

Search

Quick links