TY - JOUR
T1 - Clinical and biomarker modifiers of vitamin D treatment response
T2 - The Multi-Ethnic Study of Atherosclerosis
AU - Hsu, Simon
AU - Prince, David K.
AU - Williams, Kayleen
AU - Allen, Norrina B.
AU - Burke, Gregory L.
AU - Hoofnagle, Andrew N.
AU - Li, Xiaohui
AU - Liu, Kiang J.
AU - McClelland, Robyn L.
AU - Michos, Erin D.
AU - Psaty, Bruce M.
AU - Shea, Steven J.
AU - Rice, Kenneth M.
AU - Rotter, Jerome I.
AU - Siscovick, David
AU - Tracy, Russell P.
AU - Watson, Karol E.
AU - Kestenbaum, Bryan R.
AU - De Boer, Ian H.
N1 - Publisher Copyright:
© 2022 The Author(s).
PY - 2022/3/1
Y1 - 2022/3/1
N2 - Background: Different 25-hydroxyvitamin D [25(OH)D] thresholds for treatment with vitamin D supplementation have been suggested and are derived almost exclusively from observational studies. Whether other characteristics, including race/ethnicity, BMI, and estimated glomerular filtration rate (eGFR), should also influence the threshold for treatment is unknown. Objectives: The aim was to identify clinical and biomarker characteristics that modify the response to vitamin D supplementation. Methods: A total of 666 older adults in the Multi-Ethnic Study of Atherosclerosis (MESA) were randomly assigned to 16 wk of oral vitamin D3 (2000 IU/d; n = 499) or placebo (n = 167). Primary outcomes were changes in serum parathyroid hormone (PTH) and 1, 25-dihydroxyvitamin D [1, 25(OH)2D] concentrations from baseline to 16 wk. Results: Among 666 participants randomly assigned (mean age: 72 y; 53% female; 66% racial/ethnic minority), 611 (92%) completed the study. The mean (SD) change in PTH was -3 (16) pg/mL with vitamin D3 compared with 2 (18) pg/mL with placebo (estimated mean difference: -5; 95% CI: -8, -2 pg/mL). Within the vitamin D3 group, lower baseline 25-hydroxyvitamin D [25(OH)D] was associated with a larger decline in PTH in a nonlinear fashion. With baseline 25(OH)D ≥30 ng/mL as the reference, 25(OH)D <20 ng/mL was associated with a larger decline in PTH with vitamin D3 supplementation (-10; 95% CI: -15, -6 pg/mL), whereas 25(OH)D of 20-30 ng/mL was not (-2; 95% CI: -6, 1 pg/mL). A segmented threshold model identified a baseline 25(OH)D concentration of 21 (95% CI: 13, 31) ng/mL as an inflection point for difference in change in PTH. Race/ethnicity, BMI, and eGFR did not modify vitamin D treatment response. There was no significant change in 1, 25(OH)2D in either treatment group. Conclusions: Of characteristics most commonly associated with vitamin D metabolism, only baseline 25(OH)D <20 ng/mL modified the PTH response to vitamin D supplementation, providing support from a clinical trial to use this threshold to define insufficiency.
AB - Background: Different 25-hydroxyvitamin D [25(OH)D] thresholds for treatment with vitamin D supplementation have been suggested and are derived almost exclusively from observational studies. Whether other characteristics, including race/ethnicity, BMI, and estimated glomerular filtration rate (eGFR), should also influence the threshold for treatment is unknown. Objectives: The aim was to identify clinical and biomarker characteristics that modify the response to vitamin D supplementation. Methods: A total of 666 older adults in the Multi-Ethnic Study of Atherosclerosis (MESA) were randomly assigned to 16 wk of oral vitamin D3 (2000 IU/d; n = 499) or placebo (n = 167). Primary outcomes were changes in serum parathyroid hormone (PTH) and 1, 25-dihydroxyvitamin D [1, 25(OH)2D] concentrations from baseline to 16 wk. Results: Among 666 participants randomly assigned (mean age: 72 y; 53% female; 66% racial/ethnic minority), 611 (92%) completed the study. The mean (SD) change in PTH was -3 (16) pg/mL with vitamin D3 compared with 2 (18) pg/mL with placebo (estimated mean difference: -5; 95% CI: -8, -2 pg/mL). Within the vitamin D3 group, lower baseline 25-hydroxyvitamin D [25(OH)D] was associated with a larger decline in PTH in a nonlinear fashion. With baseline 25(OH)D ≥30 ng/mL as the reference, 25(OH)D <20 ng/mL was associated with a larger decline in PTH with vitamin D3 supplementation (-10; 95% CI: -15, -6 pg/mL), whereas 25(OH)D of 20-30 ng/mL was not (-2; 95% CI: -6, 1 pg/mL). A segmented threshold model identified a baseline 25(OH)D concentration of 21 (95% CI: 13, 31) ng/mL as an inflection point for difference in change in PTH. Race/ethnicity, BMI, and eGFR did not modify vitamin D treatment response. There was no significant change in 1, 25(OH)2D in either treatment group. Conclusions: Of characteristics most commonly associated with vitamin D metabolism, only baseline 25(OH)D <20 ng/mL modified the PTH response to vitamin D supplementation, providing support from a clinical trial to use this threshold to define insufficiency.
KW - HbA1c harmonization program
KW - cholecalciferol
KW - randomized clinical trial
KW - standardization
KW - vitamin D
KW - vitamin D deficiency
KW - vitamin D insufficiency
KW - vitamin D standardization program
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U2 - 10.1093/ajcn/nqab390
DO - 10.1093/ajcn/nqab390
M3 - Article
C2 - 34849546
AN - SCOPUS:85122014898
SN - 0002-9165
VL - 115
SP - 914
EP - 924
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 3
ER -