Efficacy, Safety, and Dose-response Effects of Calcifediol Supplementation on 25-hydroxyvitamin D, Parathyroid Hormone, and 1,25-dihydroxyvitamin D Levels in Healthy Adults: An Open-label, Interventional Pilot Study

Overview

Journal Indian J Pharmacol

Specialty Pharmacology

Date 2023 Nov 6

PMID 37929406

Authors

Liza Das

Michael F Holick

Naresh Sachdeva

Sanjay Kumar Bhadada

Shallu Singhmar

Neetika Thakur

Pinaki Dutta

Raman Kumar Marwaha

Affiliations

Soon will be listed here.

Abstract

Background: Vitamin D deficiency (VDD) is highly prevalent across the globe. Cholecalciferol (Vitamin D3) fails to attain sufficient serum concentrations of 25-hydroxyvitamin D (25(OH)D) in a significant proportion of supplemented individuals. Calcifediol (25-hydroxyvitamin D3) is less studied in healthy adults and its effects on 25(OH)D, parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D (1,25(OH)2D) at higher doses are not well known.

Materials And Methods: The study was an open-label, interventional trial recruiting consecutive participants with VDD who were allocated to receive either 2 capsules (50 μg-group) or 1 capsule (25 μg-group) daily doses of calcifediol. Baseline assessment included clinicodemographic parameters, dietary calcium, calcemic (calcium, inorganic phosphate, albumin, alkaline phosphatase, urine spot calcium/creatinine), and hormonal parameters (25(OH)D, PTH, and 1,25(OH)2D). Participants were followed up at 4 and 8 weeks with repeat assessments of calcemic and hormonal parameters.

Results: There were 64 participants, 35 (50 μg-group) and 29 (25 μg-group), without any significant difference in any of the baseline parameters. 97.1% participants in the 50 μg-group (at 4 and 8 weeks) and 93.1% (at 4 weeks) and 96.5% (at 8 weeks) in the 25 μg-group attained 25(OH)D sufficiency (≥30 ng/ml) with calcifediol. The mean serum 25(OH)D was 84.0 ± 27.7 ng/ml in the 50 μg-group and 58.0 ± 23.6 ng/ml in the 25 μg-group group at 4 weeks, which later rose to 94.3 ± 21.8 ng/ml and 76.0 ± 16.4 ng/ml, respectively, at 8 weeks. PTH levels decreased in both groups at both time points. 1,25(OH)2D rose significantly in both groups at 4 and 8 weeks but was not significantly different between both groups. There was no case of incident hypercalcemia or symptomatic nephrolithiasis.

Conclusion: Calcifediol is a safe and efficacious alternative for oral Vitamin D supplementation in young adults. Increment in 25(OH)D levels is rapid and dose-dependent.

References

Cesareo R, Falchetti A, Attanasio R, Tabacco G, Naciu A, Palermo A . Hypovitaminosis D: Is It Time to Consider the Use of Calcifediol?. Nutrients. 2019; 11(5). PMC: 6566727. DOI: 10.3390/nu11051016. View

Gallagher J, Yalamanchili V, Smith L . The effect of vitamin D supplementation on serum 25(OH)D in thin and obese women. J Steroid Biochem Mol Biol. 2012; 136:195-200. PMC: 3686842. DOI: 10.1016/j.jsbmb.2012.12.003. View

Zhao L, Zhou Y, Bu F, Travers-Gustafson D, Ye A, Xu X . Factors predicting vitamin D response variation in non-Hispanic white postmenopausal women. J Clin Endocrinol Metab. 2012; 97(8):2699-705. PMC: 3410260. DOI: 10.1210/jc.2011-3401. View

Jetter A, Egli A, Dawson-Hughes B, Staehelin H, Stoecklin E, Goessl R . Pharmacokinetics of oral vitamin D(3) and calcifediol. Bone. 2014; 59:14-9. View

Wimalawansa S . Non-musculoskeletal benefits of vitamin D. J Steroid Biochem Mol Biol. 2016; 175:60-81. DOI: 10.1016/j.jsbmb.2016.09.016. View

Gozdzik A, Zhu J, Wong B, Fu L, Cole D, Parra E . Association of vitamin D binding protein (VDBP) polymorphisms and serum 25(OH)D concentrations in a sample of young Canadian adults of different ancestry. J Steroid Biochem Mol Biol. 2011; 127(3-5):405-12. DOI: 10.1016/j.jsbmb.2011.05.009. View

Marino R, Misra M . Extra-Skeletal Effects of Vitamin D. Nutrients. 2019; 11(7). PMC: 6683065. DOI: 10.3390/nu11071460. View

Mazess R, Bischoff-Ferrari H, Dawson-Hughes B . Vitamin D: Bolus Is Bogus-A Narrative Review. JBMR Plus. 2021; 5(12):e10567. PMC: 8674779. DOI: 10.1002/jbm4.10567. View

Bischoff-Ferrari H, Dawson-Hughes B, Stocklin E, Sidelnikov E, Willett W, Edel J . Oral supplementation with 25(OH)D3 versus vitamin D3: effects on 25(OH)D levels, lower extremity function, blood pressure, and markers of innate immunity. J Bone Miner Res. 2011; 27(1):160-9. DOI: 10.1002/jbmr.551. View

10.

Bouillon R, Manousaki D, Rosen C, Trajanoska K, Rivadeneira F, Richards J . The health effects of vitamin D supplementation: evidence from human studies. Nat Rev Endocrinol. 2021; 18(2):96-110. PMC: 8609267. DOI: 10.1038/s41574-021-00593-z. View

11.

Quesada-Gomez J, Bouillon R . Is calcifediol better than cholecalciferol for vitamin D supplementation?. Osteoporos Int. 2018; 29(8):1697-1711. DOI: 10.1007/s00198-018-4520-y. View

12.

Richter K, Breitner S, Webb A, Huth C, Thorand B, Kift R . Influence of external, intrinsic and individual behaviour variables on serum 25(OH)D in a German survey. J Photochem Photobiol B. 2014; 140:120-9. DOI: 10.1016/j.jphotobiol.2014.07.018. View

13.

Yao P, Sun L, Lu L, Ding H, Chen X, Tang L . Effects of Genetic and Nongenetic Factors on Total and Bioavailable 25(OH)D Responses to Vitamin D Supplementation. J Clin Endocrinol Metab. 2016; 102(1):100-110. DOI: 10.1210/jc.2016-2930. View

14.

Bischoff-Ferrari H, Shao A, Dawson-Hughes B, Hathcock J, Giovannucci E, Willett W . Benefit-risk assessment of vitamin D supplementation. Osteoporos Int. 2009; 21(7):1121-32. PMC: 3062161. DOI: 10.1007/s00198-009-1119-3. View

15.

Shab-Bidar S, Bours S, Geusens P, Kessels A, van den Bergh J . Serum 25(OH)D response to vitamin D3 supplementation: a meta-regression analysis. Nutrition. 2014; 30(9):975-85. DOI: 10.1016/j.nut.2013.12.020. View

16.

Bouillon R, Antonio L, Olarte O . Calcifediol (25OH Vitamin D) Deficiency: A Risk Factor from Early to Old Age. Nutrients. 2022; 14(6). PMC: 8949915. DOI: 10.3390/nu14061168. View

17.

Vaes A, Tieland M, de Regt M, Wittwer J, van Loon L, de Groot L . Dose-response effects of supplementation with calcifediol on serum 25-hydroxyvitamin D status and its metabolites: A randomized controlled trial in older adults. Clin Nutr. 2017; 37(3):808-814. DOI: 10.1016/j.clnu.2017.03.029. View

18.

Garg M, Marwaha R, Khadgawat R, Ramot R, Obroi A, Mehan N . Efficacy of vitamin D loading doses on serum 25-hydroxy vitamin D levels in school going adolescents: an open label non-randomized prospective trial. J Pediatr Endocrinol Metab. 2013; 26(5-6):515-23. DOI: 10.1515/jpem-2012-0390. View

19.

Marwaha R, Garg M, Dang N, Mithal A, Narang A, Chadha A . Reference range of random urinary calcium creatinine ratio in North Indian children and adolescents. Ann Pediatr Endocrinol Metab. 2019; 24(1):34-40. PMC: 6449613. DOI: 10.6065/apem.2019.24.1.34. View

20.

Vieth R . Vitamin D supplementation: cholecalciferol, calcifediol, and calcitriol. Eur J Clin Nutr. 2020; 74(11):1493-1497. DOI: 10.1038/s41430-020-0697-1. View