Skip to main content Accessibility help

Vitamin D deficiency as a public health issue: using vitamin D2 or vitamin D3 in future fortification strategies

  • Louise R. Wilson (a1), Laura Tripkovic (a1), Kathryn H. Hart (a1) and Susan A Lanham-New (a1)


The role of vitamin D in supporting the growth and maintenance of the skeleton is robust; with recent research also suggesting a beneficial link between vitamin D and other non-skeletal health outcomes, including immune function, cardiovascular health and cancer. Despite this, vitamin D deficiency remains a global public health issue, with a renewed focus in the UK following the publication of Public Health England's new Dietary Vitamin D Requirements. Natural sources of vitamin D (dietary and UVB exposure) are limited, and thus mechanisms are needed to allow individuals to achieve the new dietary recommendations. Mandatory or voluntary vitamin D food fortification may be one of the mechanisms to increase dietary vitamin D intakes and subsequently improve vitamin D status. However, for the food industry and public to make informed decisions, clarity is needed as to whether vitamins D2 and D3 are equally effective at raising total 25-hydroxyvitamin D (25(OH)D) concentrations as the evidence thus far is inconsistent. This review summarises the evidence to date behind the comparative efficacy of vitamins D2 and D3 at raising 25(OH)D concentrations, and the potential role of vitamin D food fortification as a public health policy to support attainment of dietary recommendations in the UK. The comparative efficacy of vitamins D2 and D3 has been investigated in several intervention trials, with most indicating that vitamin D3 is more effective at raising 25(OH)D concentrations. However, flaws in study designs (predominantly under powering) mean there remains a need for a large, robust randomised-controlled trial to provide conclusive evidence, which the future publication of the D2–D3 Study should provide (BBSRC DRINC funded: BB/I006192/1). This review also highlights outstanding questions and gaps in the research that need to be addressed to ensure the most efficacious and safe vitamin D food fortification practices are put in place. This further research, alongside cost, availability and ethical considerations (vitamin D3 is not suitable for vegans), will be instrumental in supporting government, decision-makers, industry and consumers in making informed choices about potential future vitamin D policy and practice.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Vitamin D deficiency as a public health issue: using vitamin D2 or vitamin D3 in future fortification strategies
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Vitamin D deficiency as a public health issue: using vitamin D2 or vitamin D3 in future fortification strategies
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Vitamin D deficiency as a public health issue: using vitamin D2 or vitamin D3 in future fortification strategies
      Available formats


Corresponding author

* Corresponding author: Dr L. R. Wilson, email


Hide All
1. DeLuca, HF (2004) Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 80, 1689S1696S.
2. Holick, MF, Binkley, NC, Bischoff-Ferrari, HA et al. (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96, 19111930.
3. Norman, AW (2008) From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr 88, 491S499S.
4. Autier, P, Boniol, M, Pizot, C et al. (2014) Vitamin D status and ill health: a systematic review. Lancet Diab Endocrinol 2, 7689.
5. Bates, B, Cox, L, Nicholson, S et al. (2016) National Diet and Nutrition Survey Results from Years 5 and 6 (combined) of the Rolling Programme (2012/2013–2013/2014) A survey carried out on behalf of Public Health England and the Food Standards Agency.
6. Macdonald, HM, Mavroeidi, A, Fraser, WD et al. (2011) Sunlight and dietary contributions to the seasonal vitamin D status of cohorts of healthy postmenopausal women living at northerly latitudes: a major cause for concern? Osteo Int 22, 24612472.
7. Spiro, A & Buttriss, JL (2014) Vitamin D: an overview of vitamin D status and intake in Europe. Nutr Bull 39, 322350.
8. Bassir, M, Laborie, S, Lapillonne, A et al. (2001) Vitamin D de ciency in Iranian mothers and their neonates: a pilot study. Acta Paediatr 90, 577579.
9. Molla, AM, Al Badawi, M, Hammoud, MS et al. (2005) Vitamin D status of mothers and their neonates in Kuwait. Pediatr Int 47, 649652.
10. Jain, RB (2016) Recent vitamin D data from NHANES: variability, trends, deficiency and sufficiency rates, and assay compatibility issues. J Adv Nutr Hum Metab 2, e1208.
11. Hyppönen, E & Power, C (2007) Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr 85, 860868.
12. Bates, B, Lennox, A, Prentice, A et al. (2014) National Diet and Nutrition Survey Rolling Programme (NDNS RP). Results from years 1–4 (combined) for Scotland (2008/9–2011/12). Public Health England and Food Standards Agency in Scotland.
13. Darling, AL, Hart, KH, Macdonald, HM et al. (2013) Vitamin D deficiency in UK South Asian Women of childbearing age: a comparative longitudinal investigation with UK Caucasian women. Osteo Int 24, 477488.
14. Scientific Advisory Committee on Nutrition (2016) Vitamin D and Health Report. London: The Stationary Office.
15. Scientific Advisory Committee on Nutrition (2007) Update on Vitamin D. Position Statement. London: The Stationary Office.
16. Holmberg, I, Berlin, T, Ewerth, S et al. (1986) 25-Hydroxylase activity in subcellular fractions from human liver. Evidence for different rates of mitochondrial hydroxylation of vitamin D2 and D3 . Scand J Clin Lab Invest 46, 785790.
17. Cheng, JB, Levine, MA, Bell, NH et al. (2004) Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci USA 101, 77117715.
18. Houghton, LA & Vieth, R (2006) The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr 84, 694697.
19. Horst, RL, Reinhardt, TA, Ramberg, CF et al. (1986) 24-Hydroxylation of 1, 25-dihydroxyergocalciferol. An unambiguous deactivation process. J Biol Chem 261, 92509256.
20. Park, EA (1940) The therapy of rickets. J Am Med Assoc 115, 370379.
21. Armas, LA, Hollis, BW & Heaney, RP (2004) Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 89, 53875391.
22. Binkley, N, Gemar, D, Engelke, J et al. (2011) Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults. J Clin Endocrinol Metab 96, 981988.
23. Cipriani, C, Romagnoli, E, Pepe, J et al. (2013) Long-term bioavailability after a single oral or intramuscular administration of 600,000 IU of ergocalciferol or cholecalciferol: implications for treatment and prophylaxis. J Clin Endocrinol Metab 98, 27092715.
24. Glendenning, P, Chew, GT, Seymour, HM et al. (2009) Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Bone 45, 870875.
25. Heaney, RP, Recker, RR, Grote, J et al. (2011) Vitamin D3 is more potent than vitamin D2 in humans. J Clin Endocrinol Metab 96, E447E452.
26. Itkonen, ST, Skaffari, E, Saaristo, P et al. (2016) Effects of vitamin D 2-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 115, 12321239.
27. Lehmann, U, Hirche, F, Stangl, GI et al. (2013) Bioavailability of vitamin D2 and D3 in healthy volunteers, a randomized placebo-controlled trial. J Clin Endocrinol Metab 98, 43394345.
28. Leventis, P & Kiely, PDW (2009) The tolerability and biochemical effects of high-dose bolus vitamin D2 and D3 supplementation in patients with vitamin D insufficiency. Scand J Rheumatol 38, 149153.
29. Logan, VF, Gray, AR, Peddie, MC et al. (2013) Long-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months. British Journal of Nutrition 109(06), 10821088.
30. Mehrotra, A, Calvo, MS, Beelman, RB et al. (2014) Bioavailability of vitamin D2 from enriched mushrooms in prediabetic adults: a randomized controlled trial. Eur J Clin Nutr 68, 11541160.
31. Oliveri, B, Mastaglia, SR, Brito, GM et al. (2015) Vitamin D3 seems more appropriate than D2 to sustain adequate levels of 25(OH)D: a pharmacokinetic approach. Eur J Clin Nutr 69, 697702.
32. Romagnoli, E, Mascia, ML, Cipriani, C et al. (2008) Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab 93, 30153020.
33. Shieh, A, Chun, RF, Ma, C et al. (2016) Effects of high-dose vitamin D2 versus D3 on total and free 25-hydroxyvitamin D and markers of calcium balance. J Clin Endocrinol Metab 101, 30703078.
34. Stepien, M, O'Mahony, L, O'Sullivan, A et al. (2013) Effect of supplementation with vitamin D2-enhanced mushrooms on vitamin D status in healthy adults. J Nutr Sci 2, 29.
35. Tjellesen, L, Hummer, L, Christiansen, C et al. (1986) Serum concentration of vitamin D metabolites during treatment with vitamin D2 and D3 in normal premenopausal women. Bone Miner 1, 407413.
36. Trang, HM, Cole, DE, Rubin, LA et al. (1998) Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2 . Am J Clin Nutr 68, 854858.
37. Biancuzzo, RM, Young, A, Bibuld, D et al. (2010) Fortification of orange juice with vitamin D2 or vitamin D3 is as effective as an oral supplement in maintaining vitamin D status in adults. Am J Clin Nutr 91, 16211626.
38. Fisk, CM, Theobald, HE & Sanders, TA (2012) Fortified malted milk drinks containing low-dose ergocalciferol and cholecalciferol do not differ in their capacity to raise serum 25-hydroxyvitamin D concentrations in healthy men and women not exposed to UV-B. J Nutr 142, 12861290.
39. Holick, MF, Biancuzzo, RM, Chen, TC et al. (2008) Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab 93, 677681.
40. Nimitphong, H, Saetung, S, Chanprasertyotin, S et al. (2013) Changes in circulating 25-hydroxyvitamin D according to vitamin D binding protein genotypes after vitamin D3 or D2 supplementation. Nutr J 12, 39.
41. Tripkovic, L, Lambert, H, Hart, K et al. (2012) 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 95, 13571364.
42. Tripkovic, L, Wilson, LR, Hart, K et al. (2015) The D2-D3 Study: a randomised, double-blind, placebo-controlled food-fortification trial in women, comparing the efficacy of 15ug/d vitamin D2 vs vitamin D3 in raising serum 25OHD levels. Proc Nutr Soc 74, OCE1, E16.
43. Department for Environment, Food and Rural Affairs (2014) Consultation on revoking Regulation 4 of the Spreadable Fats (Marketing Standards) and Milk and Milk Products (Protection of Designations) (England) Regulations 2008 – margarine fortification. Summary of response.
44. Cashman, KD & Kiely, M (2013) EURRECA-estimating vitamin D requirements for deriving dietary reference values. Crit Rev Food Sci Nutr 53, 10971109.
45. Hayes, A & Cashman, KD (2017) Food-based solutions for vitamin D deficiency: putting policy into practice and the key role for research. Proc Nutr Soc 76, 5463.
46. Cashman, KD, Kiely, M, Seamans, KM et al. (2016) Effect of ultraviolet light-exposed mushrooms on vitamin D sta- tus: liquid chromatography-tandem mass spectrometry re- analysis of biobanked sera from a randomized controlled trial and a systematic review plus meta-analysis. J Nutr 146, 565575.
47. Lipkie, TE, Ferruzzi, MG & Weaver, CM (2016) Low bioaccessibility of vitamin D2 from yeast-fortified bread compared to crystalline D2 bread and D3 from fluid milks. Food Funct 7, 45894596.
48. Natri, AM, Salo, P, Vikstedt, T et al. (2006) Bread fortified with cholecalciferol increase the serum 25-hydroxyvitamin D concentration in women as effectively as a cholecalciferol supplements. J Nutr 136, 123127.
49. Hayes, A, Duffy, S, O'Grady, M et al. (2016) Vitamin D-enhanced eggs are protective of wintertime serum 25-hydroxyvitamin D in a randomized controlled trial of adults. Am J Clin Nutr 104, 629637.
50. Buttriss, JL (2015) Vitamin D: sunshine vs. diet vs. pills. Nutr Bull 40, 279285.
51. Lanham-New, SA & Wilson, LR (2016) Vitamin D – has the new dawn for dietary recommendations arrived? J Hum Nutr Diet 29, 36.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed