Determinants of plasma 25-hydroxyvitamin D and development of prediction models in three US cohorts

Epidemiological and other evidence suggests that vitamin D may be protective against several chronic diseases. Assessing vitamin D status in epidemiological studies, however, is challenging given finite resources and limitations of commonly used approaches. Using multivariable linear regression, we derived predicted 25-hydroxyvitamin D (25(OH) D) scores based on known determinants of circulating 25(OH) D, including age, race, UV-B radiation flux at residence, dietary and supplementary vitamin D intakes, BMI, physical activity, alcohol intake, post-menopausal hormone use (women only) and season of blood draw, in three nationwide cohorts: the Nurses' Health Study, Nurses' Health Study II and the Health Professionals Follow-up Study. The model r(2) for each cohort ranged from 0.25 to 0.33. We validated the prediction models in independent samples of participants from these studies. Mean measured 25(OH) D levels rose with increasing decile of predicted 25(OH) D score, such that the differences in mean measured 25(OH) D between the extreme deciles of predicted 25(OH) D were in the range 8.7-12.3 ng/ml. Substituting predicted 25(OH) D scores for measured 25(OH) D in a previously published case-control analysis of colorectal cancer yielded similar effect estimates with OR of approximately 0.8 for a 10 ng/ml difference in either plasma or predicted 25(OH) D. We conclude that these data provide reasonable evidence that a predicted 25(OH) D score is an acceptable marker for ranking individuals by long-term vitamin D status and may be particularly useful in research settings where biomarkers are not available for the majority of a study population.