Are Vitamin D3 and Vitamin D2 equivalent?

Are vitamin D3 and vitamin D2 equivalent?

  • A presumption of equivalence between vitamin D3 and vitamin D2 was based on studies of rickets prevention in infants conducted 70 years ago1
  • The weaker binding affinity of vitamin D2 metabolites to vitamin D binding protein than vitamin D3 results in a shorter circulating half-life and increased rate of clearance for vitamin D2 from the circulation1
  • As a result, vitamin D3 has proven to be the more potent form of vitamin D in all primate species, including humans1
Vitamin D3 and vitamin D2 are not equivalent
  • Tjellesen et al gave 4,000 IU of vitamin D3 or vitamin D2 to 19 healthy premenopausal women daily for 8 weeks2
  • Vitamin D2 treatment increased serum concentration of 25(OH)D2 but caused a decrease in serum concentration of 25(OH)D3, resulting in an unchanged value for total 25(OH)D2
  • Vitamin D3 treatment increased the serum concentrations of 25(OH)D3 and D3 hydroxy metabolites2

Study conclusion: vitamin D2 and vitamin D3 have a different effect on serum concentration of vitamin D metabolites and biochemical indices of calcium metabolism.2

  • In Trang et al, a 1.7 times greater efficacy was seen with a 4,000 IU daily dose of vitamin D3 (n=55) compared to a 4,000 daily dose of vitamin D2 (n=17) over 14 days3
  • Bischoff-Ferrari’s 2009 Meta-Analysis demonstrated, in sub-group analysis, a 23% reduction in nonvertebral fractures among subjects given vitamin D3 compared to a 10% reduction, in those given vitamin D2, over 1-7 years4


National Osteoporosis Society (NOS) position on vitamin D3 vs. vitamin D2:5

  • Based on current medical consensus, as well as problems related to the measurement of 25(OH)D2, vitamin D3 is recommended by NOS as the vitamin D preparation of choice for the treatment of vitamin D deficiency5
  • Vitamin D2 does appear to have quicker clearance than vitamin D3 and lower tissue bioavailability, especially after intermittent bolus dosing5

1. Houghton L, Vieth, R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr October 2006, vol 84, no. 4, 694-697.
2. Tjellesen L, Hummer L, Christiansen C, Rødbro P. Serum concentration of vitamin D metabolites during treatment with vitamin D2 and D3 in normal premenopausal women. Bone Miner. 1986:1:407-413.
3. Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. 1998; 68: 854-858.
4. Bischoff-Ferrari H et al. Prevention of Nonvertebral Fractures With Oral Vitamin D and Dose Dependency. Arch Intern Med. Vol 169 (No. 6) March 23, 2009.
5. National Osteoporosis Society. Vitamin D and Bone Health: A Practical Clinical Guideline for Patient Management. April 2013. V1.1.