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Mechanisms of action for the biological differences in vitamin D2 and vitamin D3: further analysis of the D2-D3 study cohort

Published online by Cambridge University Press:  05 October 2018

H. Sanders
Affiliation:
Department of Nutritional Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH
L. Wilson
Affiliation:
Department of Nutritional Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH Yakult UK Ltd, Odyssey Business Park, South Ruislip, HA4 6QQ
L. Tripkovic
Affiliation:
Department of Nutritional Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH
K. Hart
Affiliation:
Department of Nutritional Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH
R.E. Elliott
Affiliation:
Department of Nutritional Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH
C.P. Smith
Affiliation:
School of Pharmacy and Biomolecular Sciences, University of Brighton. BN2 5GJ.
S.A. Lanham-New
Affiliation:
Department of Nutritional Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH
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Abstract

Type
Abstract
Copyright
Copyright © The Authors 2018 

Vitamin D plays an important role in musculoskeletal health due to its involvement in the regulation of calcium and phosphorus(Reference Holick1). The two forms of vitamin D – vitamin D2 and vitamin D3 – are both metabolised into 25-hydroxyvitamin D (25OHD) in the liver(Reference Henry2), which is the marker of vitamin D status. 25OHD is then transported to the kidney via the serum, bound to vitamin D binding protein (VDBP)(Reference Bikle3), where 25OHD is converted to 1,25-dihydroxyvitamin D (1,25(OH)2D) which is the active form of vitamin D(Reference Tripkovic, Wilson and Hart4). VDBP has a greater affinity for vitamin D3 than vitamin D2 due to the differences in their side chains(Reference Tripkovic, Wilson and Hart4). The aims of this analysis were to examine the effect of vitamin D supplementation on VDBP & 1,25(OH)2D and to assess differences in VDBP & 1,25(OH)2D in those with suboptimal (<50 nmol/L) vitamin D status compared to those with optimal (>50 nmol/L) vitamin D status.

Healthy Caucasian (CA) and South Asian (SA) women, aged 20–64yrs, were recruited from the county of Surrey onto the D2-D3 study(Reference Tripkovic, Wilson and Hart4). The D2-D3 study was run over two consecutive winters and the participants took 15μg vitamin D2, 15μg vitamin D3 or a placebo daily for 12 weeks. A sub-set of participants (n73: n54 CA and n19 SA) were used in this analysis to explore the effects on VDBP and 1,25(OH)2D. Anthropometric measurements and blood samples were taken at baseline, week 6 and week 12. Serum 25OHD was measured using liquid chromatography tandem mass spectrophotometry (ANSciex 5500 tandem mass spectrophotometer and MassChrom® 25OHD3/D2 kit), serum 1,25(OH)2D was measured using an in vitro chemiluminescent immunoassay (DiaSorin Liaison XL 1,25-dihydroxyvitamin D), and VDBP was measured using a monoclonal Human VDBP Immunoassay Quantikine ELISA (R&D Systems Europe). Statistical analysis was carried out using IMB SPSS24® (2016).

There were no significant differences in VDBP or 1,25(OH)2D between CA or SA women at baseline (p > 0·5), therefore CA and SA were combined for these analyses. The data are presented in Table 1. In a mixed between-within analysis of variance, a significant interaction was found between time and intervention group on 1,25(OH)2D (p < 0·001, partial eta squared = 0·26). There was a significant main effect of time on 1,25(OH)2D (p = 0·007, partial eta squared = 0·14). No significant interaction was found between time and intervention group on VDBP (p = 0·295). Within the placebo group, there was no significant interaction between time and baseline vitamin D status (categorised as suboptimal <50 nmol/L or sufficient >50 nmol/L) on VDBP or 1,25(OH)2D (p = 0·275, p = 0·766 respectively).

Table 1. VDBP and 1,25(OH)2D concentrations at each visit (mean ± SD)

In conclusion, the 12-week vitamin D supplementation intervention had a significant effect on 1,25(OH)2D concentrations, with concentrations increasing in those taking vitamin D2 or D3. There was no significant effect on VDBP concentrations, However there is some debate as to the reliability of the kit that was used to measure VDBP, which is important to consider(Reference Bouillon, Jones and Schoenmakers5) and further analysis is certainly warranted.

References

1.Holick, MF (2007) N Engl J Med 357, 266281.Google Scholar
2.Henry, HL (2011) Best Pract Res Clin Endocrinol Metab 25, 531541.Google Scholar
3.Bikle, DD (2014) Chem Bol 21(3), 319329.Google Scholar
4.Tripkovic, L, Wilson, LR, Hart, K, et al. (2017) Am J Clin Nutr 116, 1386–93.Google Scholar
5.Bouillon, R, Jones, K & Schoenmakers, I (2014) N Engl J Med 370, 879.Google Scholar
Figure 0

Table 1. VDBP and 1,25(OH)2D concentrations at each visit (mean ± SD)