Christine A Simpson1, Jane H Zhang2, Dirk Vanderschueren3, Lei Fu4,5, Teresita C Pennestri6, Roger Bouillon3, David E C Cole7, Thomas O Carpenter6. 1. Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. 2. Veterans Administration Cooperative Studies Program Coordinating Center, VA Connecticut Healthcare System, West Haven, Connecticut, USA. 3. Department of Chronic Diseases, Metabolism and Ageing, Laboratory of Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven, Belgium. 4. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. 5. Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. 6. Department of Pediatrics (Endocrinology), Yale University School of Medicine, New Haven, Connecticut, USA. 7. Departments of Laboratory Medicine and Pathobiology, Medicine, and Genetics, University of Toronto, and Sunnybrook Health Center, Toronto, Ontario, Canada.
Abstract
OBJECTIVE: GC/DBP effects on response to vitamin D supplementation have not been well-studied. Thus we assessed free and total 25-OHD after vitamin D treatment across the six common GC haplotypes. DESIGN: This double-blind, randomized study compared two vitamin D3 doses in healthy, urban-dwelling 6-month to 10-year-old children at-risk for vitamin D deficiency. Randomization was stratified by GC haplotype. METHODS: Children were randomized to receive 2800 or 7000 International Units of vitamin D3 weekly. 25-OHD and 1,25(OH)2D were sampled at baseline and after 1-6 months of supplementation. RESULTS AND CONCLUSIONS: One hundred ninety-two of 225 enrolled subjects completed the study. After one month, total 25-OHD increased with both doses and were higher with 7000 IU/week (85.5 ± 22.8 nmol/L) compared to 2800 IU/week (76.8 ± 18.0 nmol/L), despite equivalent baseline levels. No further significant increase occurred at 6 months (89.8 ± 35.5 and 74.3 ± 18.3 nmol/L, respectively). Free 25-OHD similarly changed. 25-OHD differed among GC groups at baseline. Although no significant effects of individual GC haplotypes on incremental changes were evident, a trend toward an effect of combined 'at risk' GC alleles on response was evident (P = 0.06). Total 1,25(OH)2D showed modest increases, moreso with the larger dose. In urban-dwelling children at-risk for vitamin D deficiency, 1 month of vitamin D3 2800 IU/week increased 25-OHD across all GC haplotype groups, and somewhat enhanced with 7000 IU/week with no further significant increases after 6 months of supplementation. Free 25-OHD measures offer no monitoring advantage over total 25-OHD.
OBJECTIVE: GC/DBP effects on response to vitamin D supplementation have not been well-studied. Thus we assessed free and total 25-OHD after vitamin D treatment across the six common GC haplotypes. DESIGN: This double-blind, randomized study compared two vitamin D3 doses in healthy, urban-dwelling 6-month to 10-year-old children at-risk for vitamin D deficiency. Randomization was stratified by GC haplotype. METHODS: Children were randomized to receive 2800 or 7000 International Units of vitamin D3 weekly. 25-OHD and 1,25(OH)2D were sampled at baseline and after 1-6 months of supplementation. RESULTS AND CONCLUSIONS: One hundred ninety-two of 225 enrolled subjects completed the study. After one month, total 25-OHD increased with both doses and were higher with 7000 IU/week (85.5 ± 22.8 nmol/L) compared to 2800 IU/week (76.8 ± 18.0 nmol/L), despite equivalent baseline levels. No further significant increase occurred at 6 months (89.8 ± 35.5 and 74.3 ± 18.3 nmol/L, respectively). Free 25-OHD similarly changed. 25-OHD differed among GC groups at baseline. Although no significant effects of individual GC haplotypes on incremental changes were evident, a trend toward an effect of combined 'at risk' GC alleles on response was evident (P = 0.06). Total 1,25(OH)2D showed modest increases, moreso with the larger dose. In urban-dwelling children at-risk for vitamin D deficiency, 1 month of vitamin D3 2800 IU/week increased 25-OHD across all GC haplotype groups, and somewhat enhanced with 7000 IU/week with no further significant increases after 6 months of supplementation. Free 25-OHD measures offer no monitoring advantage over total 25-OHD.
Authors: Christine A Simpson; Jane H Zhang; Dirk Vanderschueren; Lei Fu; Teresita C Pennestri; Roger Bouillon; David E C Cole; Thomas O Carpenter Journal: J Clin Endocrinol Metab Date: 2020-04-01 Impact factor: 5.958
Authors: Thomas O Carpenter; Francisca Herreros; Jane H Zhang; Bruce K Ellis; Christine Simpson; Esther Torrealba-Fox; Grace J Kim; Mary Savoye; Nancy A Held; David E C Cole Journal: Am J Clin Nutr Date: 2011-12-14 Impact factor: 7.045
Authors: Rene F Chun; Bradford E Peercy; Eric S Orwoll; Carrie M Nielson; John S Adams; Martin Hewison Journal: J Steroid Biochem Mol Biol Date: 2013-10-04 Impact factor: 4.292
Authors: Corinne D Engelman; Tasha E Fingerlin; Carl D Langefeld; Pamela J Hicks; Stephen S Rich; Lynne E Wagenknecht; Donald W Bowden; Jill M Norris Journal: J Clin Endocrinol Metab Date: 2008-07-01 Impact factor: 5.958