Positive Association Between 25-Hydroxyvitamin D and C-Reactive Protein is Confounded by Hormonal Contraceptive Use

Abstract

Studies of the relationship between vitamin D and inflammation are equivocal. This may be due to unaccounted confounding. Hormonal contraceptive (HC) use is associated with elevated circulating 25-hydroxyvitamin D [25(OH)D] in Caucasians and African-Americans, but its effects on 25(OH)D in other ethnicities are unclear. HC use is associated with elevated C-reactive protein (CRP), an inflammatory biomarker. Our objectives were to assess the effect of HC use on 25(OH)D across ethnic groups, and to examine the association between HC, 25(OH)D and CRP in an ethnically diverse population of young adults. We recruited Caucasian, East Asian, and South Asian individuals (n=1,403) from Toronto, Canada. Fasting blood measures of 25(OH)D and CRP were obtained. Across ethnic groups, women HC users (n=280) had higher 25(OH)D and CRP than women HC non-users (n=695) and men (n=428) (p<0.008 and p<0.0001, respectively). Circulating 25(OH)D was positively associated with CRP in the entire population in models not accounting for HC use (β=0.010±0.003; p<0.0001). There was no association when men and women HC non-users were examined separately. Among women HC users, there was no association after accounting for hormone dose. A positive association between 25(OH)D and CRP among individuals above the median 25(OH)D (≥51.9 nmol/L) was not significant after adjustment for HC use. No association was observed among individuals below the median. HC use and 25(OH)D were positively associated across ethnic groups. We found no association between 25(OH)D and CRP when HC use was accounted for. HC use confounds the association between 25(OH)D and CRP.