Lifestyle and Other Factors Explain One-Half of the Variability in the Serum 25-Hydroxyvitamin D Response to Cholecalciferol Supplementation in Healthy Adults.
BACKGROUND
Many factors have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentrations in observational studies, with variable consistency. However, less information is available on factors affecting the magnitude of changes in serum 25(OH)D resulting from vitamin D supplementation.


OBJECTIVE
This study aimed to identify factors associated with the serum 25(OH)D response to supplementation with 1000 IU cholecalciferol/d during the first year of a large, multicenter, randomized, placebo-controlled colorectal adenoma chemoprevention trial.


METHODS
Eligible older adults who were not vitamin D-deficient [serum 25(OH)D ≥12 ng/mL] were randomly assigned in a modified 2 × 2 factorial design to 1 of 4 groups: daily 1000 IU cholecalciferol, 1200 mg Ca as carbonate, both, or placebo. Women could elect 2-group (calcium ± cholecalciferol) random assignment. In secondary analyses, we used multivariable models to assess factors associated with serum 25(OH)D concentrations in all enrollees (n = 2753) and with relative changes in serum 25(OH)D after 1 y cholecalciferol supplementation among those randomly assigned (n = 2187).


RESULTS
In multivariable models, 8 factors accounted for 50% of the variability of proportional change in serum 25(OH)D after cholecalciferol supplementation. Larger increases were associated with being female (34.5% compared with 20.5%; P < 0.001) and with lower baseline serum 25(OH)D (P < 0.0001), optimal adherence to study pill intake (P = 0.0002), wearing long pants and sleeves during sun exposure (P = 0.0002), moderate activity level (P = 0.01), use of extra vitamin D-containing supplements during the trial (P = 0.03), and seasons of blood draw (P ≤ 0.002). Several genetic polymorphisms were associated with baseline serum 25(OH)D and/or serum response, but these did not substantially increase the models' R2values. Other factors, including body mass index, were associated with serum 25(OH)D at baseline but not with its response to supplemental cholecalciferol.


CONCLUSIONS
The factors that most affected changes in serum 25(OH)D concentrations in response to cholecalciferol supplementation included sex, baseline serum 25(OH)D, supplement intake adherence, skin-covering clothes, physical activity, and season. Genetic factors did not play a major role. This trial was registered at www.clinicaltrials.gov as NCT00153816.
Departments of Epidemiology and judith.r.rees@dartmouth.edu.
Judy R
JR
Rees
Departments of Epidemiology and.
Leila A
LA
Mott
Departments of Epidemiology and.
Elizabeth L
EL
Barry
Departments of Epidemiology and.|Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC.
John A
JA
Baron
Department of Epidemiology, Rollins School of Public Health.|Winship Cancer Institute, Emory University, Atlanta, GA.
Roberd M
RM
Bostick
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center.|Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Jane C
JC
Figueiredo
Department of Gastroenterology, Hepatology and Nutrition, the University of Texas MD Anderson Cancer Center, Houston, TX.
Robert S
RS
Bresalier
Medicine, Geisel School of Medicine at Dartmouth, Lebanon, NH.|VA Medical Center, White River Junction, VT; and.
Douglas J
DJ
Robertson
Departments of Epidemiology and.|Division of Health and Social Care Research, King's College London, London, United Kingdom.
Janet L
JL
Peacock
D000368:Aged; D000369:Aged, 80 and over; D002762:Cholecalciferol / Q000008:administration & dosage / Q000494:pharmacology*; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics / Q000378:metabolism; D000072467:Cytochrome P450 Family 2 / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase
25-hydroxyvitamin D; calcium; cholecalciferol; dose response; randomized controlled trial; vitamin D3
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