Positive association between 25-hydroxyvitamin D and C-reactive protein is confounded by hormonal contraceptive use= May 2013
J Womens Health (Larchmt). 2013 May;22(5):417-25. doi: 10.1089/jwh.2012.4046.
García-Bailo B1, Josse AR, Jamnik J, Badawi A, El-Sohemy A.
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, M5S 3E2, Canada.
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.
Hormonal Contraceptive Use Is Associated With Higher Total but Unaltered Free 25-Hydroxyvitamin D Serum Concentrations
J Clin Endocrinol Metab. 2018 Jun 1;103(6):2385-2391. doi: 10.1210/jc.2018-00336.
.Pilz S1, Obeid R2, Schwetz V1, Trummer C1, Pandis M1, Lerchbaum E1, Pieber TR1,3, Obermayer-Pietsch B1,3, Wilhelm M4, Hahn A5, Schön C6.
CONTEXT: Intake of hormonal contraceptives (HC) is associated with higher total 25-hydroxyvitamin D 25(OH)D concentrations, but the effect of HC on free 25(OH)D is unclear.
OBJECTIVE: We investigated whether free 25(OH)D concentrations differ according to use of HC.
DESIGN: This is a post hoc analysis of a randomized open trial.
SETTING: This study was conducted from 13 January to 9 May, 2016, at a clinical research organization in Esslingen, Germany.
PARTICIPANTS: We included 201 apparently healthy women of childbearing age.
INTERVENTION: Participants were randomly assigned to receive a daily multimicronutrient supplement for 8 weeks; the supplement contained 200 IU (n =100) or 800 IU (n = 101) of vitamin D3.
MAIN OUTCOME MEASURES: Primary outcome was the difference in free 25(OH)D between users and nonusers of HC.
RESULTS: Overall, 176 participants median (25th to 75th percentiles) age: 25 (22 to 29) years with available free 25(OH)D were included in the present analysis. At baseline, total 25(OH)D was significantly higher in users (n = 110) than in nonusers (n = 66) of HC [49.2 (33.4 to 63.4) vs 39.1 (23.8 to 52.5) nmol/L; P < 0.001], whereas there was no difference in free 25(OH)D [7.87 (6.50 to 10.11) vs 7.88 (6.35 to 10.12) pmol/L; P = 0.923]. These results were confirmed after multimicronutrient supplementation and in subgroups according to treatment allocation.
CONCLUSIONS: Use of HC was associated with, on average, 26% higher total 25(OH)D, whereas free 25(OH)D values did not differ according to use of HC. These findings are relevant for epidemiological studies, but the physiological implications remain to be clarified.
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