Skip to main content
Top
Published in: BMC Endocrine Disorders 1/2019

Open Access 01-12-2019 | Research article

Vitamin-D2 treatment-associated decrease in 25(OH)D3 level is a reciprocal phenomenon: a randomized controlled trial

Authors: Muhammad M. Hammami, Kafa Abuhdeeb, Safa Hammami, Ahmed Yusuf

Published in: BMC Endocrine Disorders | Issue 1/2019

Login to get access

Abstract

Background

Vitamin-D2 (D2) treatment has been associated with a decrease in 25-hydroxy (25(OH)) vitamin-D3 (D3) level, suggesting that D3 treatment would be preferred to raise total 25(OH) vitamin-D (D) level. We postulated that D2 treatment-associated decrease in 25(OH)D3 level is related to the increase in 25(OH)D level rather than being D2-specific, and thus there would be a similar D3 treatment-associated decrease in 25(OH)D2 level.

Methods

Fifty volunteers were block-randomized to 50,000 IU D2 or placebo orally once (study-1) and fifty volunteers received 50,000 IU D2 orally once and 4 days later block-randomized to 50,000 IU D3 or placebo orally once (study-2). Interventions were concealed from volunteers and research coordinators and blindly-administered. Serum 25(OH)D2 and 25(OH)D3 levels were blindly-determined at baseline and days 14, 28, 42, and 56, post-randomization by high performance liquid chromatography assay. Results of 97 participants were analyzed. Primary outcome measure was day-28 D2-associated change in 25(OH)D3 level in study-1 and D3-associated change in 25(OH)D2 level in study-2, adjusted for baseline levels.

Results

Mean (95% confidence interval) difference between the active and placebo arms in the decrease in day-28 25(OH)D3 (study-1) and 25(OH)D2 (study-2) levels was 13.2 (9.7 to 16.6) and 9.8 (5.2 to 14.4) nmol/L, respectively. Corresponding differences at day-56 were 10.8 (6.8 to 14.8) and 1.7 (− 7.6 to 11.1) nmol/L, respectively. The difference between the placebo and active arms in area-under-the-curve at day-28 (AUC28) and day-56 (AUC56) were 262.3 (197.8 to 326.7) and 605.1 (446.3 to 784.0) for 25(OH)D3 (study-1) and 282.2 (111.2 to 453.3) and 431.2 (179.3 to 683.2) nmol.d/L for 25(OH)D2 (study-2), respectively. There were significant correlations between day-28 changes in 25(OH)D2 and 25(OH)D3 levels in study-1 (rho = − 0.79, p < 0.001) and study-2 (rho = − 0.36, p = 0.01), and between day-28 changes in 25(OH)D2 level and baseline 25(OH)D level in study-2 (rho = − 0.42, p = 0.003).

Conclusions

Compared to placebo, D3 treatment is associated with a decrease in 25(OH)D2 level similar in magnitude to D2-treatment associated decrease in 25(OH)D3 level; however, the D3-placebo difference in 25(OH)D2 level is shorter-lasting. Changes in 25(OH)D2 and 25(OH)D3 levels are correlated with each other and with baseline 25 (OH) D levels, suggesting a common regulatory mechanism.

Trial registration

ClinicalTrial.​gov identifier: NCT03035084 (registered January 27, 2017).
Literature
3.
go back to reference Hartwell D, Hassager C, Christiansen C. Effect of vitamin D2 and vitamin D3 on the serum concentrations of 1,25(OH)2D2 in normal subjects. Acta Endocrinol. 1987;115:378–84.CrossRef Hartwell D, Hassager C, Christiansen C. Effect of vitamin D2 and vitamin D3 on the serum concentrations of 1,25(OH)2D2 in normal subjects. Acta Endocrinol. 1987;115:378–84.CrossRef
5.
go back to reference Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89(11):5387–91.CrossRef Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89(11):5387–91.CrossRef
6.
go back to reference Gallo S, Phan A, Vanstone CA, Rodd C, Weiler HA. The change in plasma 25-hydroxyvitamin D did not differ between breast-fed infants that received a daily supplement of ergocalciferol or cholecalciferol for mMonths. J Nutr. 2013;143(2):148–53.CrossRef Gallo S, Phan A, Vanstone CA, Rodd C, Weiler HA. The change in plasma 25-hydroxyvitamin D did not differ between breast-fed infants that received a daily supplement of ergocalciferol or cholecalciferol for mMonths. J Nutr. 2013;143(2):148–53.CrossRef
8.
go back to reference 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(4):854–8.CrossRef 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(4):854–8.CrossRef
12.
go back to reference Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006;84(4):694–7.CrossRef Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006;84(4):694–7.CrossRef
13.
go back to reference Romagnoli E, Mascia ML, Cipriani C, Fassino V, Mazzei F, D'Erasmo E, Carnevale V, Scillitani A, Minisola S. Short and long term variations in serum calciotropic hormones after single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab. 2008;93:3015–20.CrossRef Romagnoli E, Mascia ML, Cipriani C, Fassino V, Mazzei F, D'Erasmo E, Carnevale V, Scillitani A, Minisola S. Short and long term variations in serum calciotropic hormones after single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab. 2008;93:3015–20.CrossRef
17.
go back to reference Macdonald HM, Wood AD, Tang JCY, Fraser WD. Comparison of vitamin D2 and vitamin D3 supplementation in increasing serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. 2012;96(5):1152–3.CrossRef Macdonald HM, Wood AD, Tang JCY, Fraser WD. Comparison of vitamin D2 and vitamin D3 supplementation in increasing serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. 2012;96(5):1152–3.CrossRef
18.
go back to reference Cashman KD, Kiely M, Seamans KM, Urbain P. Effect of ultraviolet light–exposed mushrooms on vitamin D status: liquid chromatography–tandem mass spectrometry reanalysis of bio-banked sera from a randomized controlled trial and a systematic review plus meta-analysis. J Nutr. 2016;146(3):565–75.CrossRef Cashman KD, Kiely M, Seamans KM, Urbain P. Effect of ultraviolet light–exposed mushrooms on vitamin D status: liquid chromatography–tandem mass spectrometry reanalysis of bio-banked sera from a randomized controlled trial and a systematic review plus meta-analysis. J Nutr. 2016;146(3):565–75.CrossRef
20.
go back to reference 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(5):407–13.PubMed 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(5):407–13.PubMed
22.
go back to reference Waterhouse M, Tran B, Armstrong BK, Baxter C, Ebeling PR, English DR, Gebski V, Hill C, Kimlin MG, Lucas RM, Venn A, Webb PM, Whiteman DC, Neale RE. Environmental, personal, and genetic determinants of response to vitamin D supplementation in older adults. J Clin Endocrinol Metab. 2014;99(7):E1332–40. https://doi.org/10.1210/jc.2013-4101.CrossRefPubMed Waterhouse M, Tran B, Armstrong BK, Baxter C, Ebeling PR, English DR, Gebski V, Hill C, Kimlin MG, Lucas RM, Venn A, Webb PM, Whiteman DC, Neale RE. Environmental, personal, and genetic determinants of response to vitamin D supplementation in older adults. J Clin Endocrinol Metab. 2014;99(7):E1332–40. https://​doi.​org/​10.​1210/​jc.​2013-4101.CrossRefPubMed
23.
go back to reference Aterrado S, Ono G, Kanehira-Mar S, Meier J, Swislocki A. Evaluating vitamin D repletion regimens and effects in veteran patients. Ann Pharmacother. 2015;49(9):969–77.CrossRef Aterrado S, Ono G, Kanehira-Mar S, Meier J, Swislocki A. Evaluating vitamin D repletion regimens and effects in veteran patients. Ann Pharmacother. 2015;49(9):969–77.CrossRef
25.
26.
go back to reference Alvi SN, Yusuf A, Hammami MM. Simultaneous quantification of vitamin D-2, vitamin D-3, and their 25- hydroxy metabolites in human plasma by high performance liquid chromatography. J Bioequiv Availab. 2012;S14:1–5.CrossRef Alvi SN, Yusuf A, Hammami MM. Simultaneous quantification of vitamin D-2, vitamin D-3, and their 25- hydroxy metabolites in human plasma by high performance liquid chromatography. J Bioequiv Availab. 2012;S14:1–5.CrossRef
Metadata
Title
Vitamin-D2 treatment-associated decrease in 25(OH)D3 level is a reciprocal phenomenon: a randomized controlled trial
Authors
Muhammad M. Hammami
Kafa Abuhdeeb
Safa Hammami
Ahmed Yusuf
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2019
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-019-0337-8

Other articles of this Issue 1/2019

BMC Endocrine Disorders 1/2019 Go to the issue