Patients with cystic fibrosis (CF) commonly have lower circulating concentrations of 25-hydroxyvitamin D (25(OH)D) than healthy populations. We comprehensively compared measures of vitamin D metabolism among individuals with CF and healthy control subjects. In a cross-sectional study, serum from participants with CF (N = 83) and frequency-matched healthy control subjects by age and race (N = 82) were analyzed for: 25(OH)D 2 and 25(OH)D 3 , 1α,25-dihydroxyvitamins D 2 and D 3 (1α,25(OH) 2 D 2 and 1α,25(OH) 2 D 3 ), 24,25-dihydroxyvitamin D 3 (24,25(OH) 2 D 3 ), 4β,25-dihydroxyvitamin D 3 (4β,25(OH) 2 D 3 ), 25-hydroxyvitamin D 3 -3-sulfate (25(OH)D 3 -S), and 25-hydroxyvitamin D 3 -3-glucuronide (25(OH)D 3 -G). In a 56-day prospective pharmacokinetic study, ∼25 μg deuterium-labeled 25(OH)D 3 (d 6 -25(OH)D 3 ) was administered intravenously to participants (N = 5 with CF, N = 5 control subjects). Serum was analyzed for d 6 -25(OH)D 3 and d 6 -24,25(OH) 2 D 3 , and pharmacokinetic parameters were estimated. In the cross-sectional study, participants with CF had similar mean (SD) total 25(OH)D concentrations as control subjects (26.7 [12.3] vs. 27.7 [9.9] ng/mL) and had higher vitamin D supplement use (53% vs. 22%). However, participants with CF had lower total 1α,25(OH) 2 D (43.6 [12.7] vs. 50.7 [13.0] pg/mL), 4β,25(OH) 2 D 3 (52.1 [38.9] vs. 79.9 [60.2] pg/mL), and 25(OH)D 3 -S (17.7 [11.6] vs. 30.1 [12.3] ng/mL) (p < 0.001 for all). The pharmacokinetics of d 6 -25(OH)D 3 and d 6 -24,25(OH)D 3 did not differ between groups. In summary, although 25(OH)D concentrations were comparable, participants with CF had lower 1α,25(OH) 2 D, 4β,25(OH) 2 D 3 , and 25(OH)D 3 -S concentrations than healthy controls. Neither 25(OH)D 3 clearance, nor formation of 24,25(OH) 2 D 3 , appears to account for these differences and alternative mechanisms for low 25(OH)D in CF (i.e., decreased formation, altered enterohepatic recirculation) should be explored.
Competing Interests: Declarations of Competing Interest None.
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