α-Tocopherol Pharmacokinetics in Adults with Cystic Fibrosis: Benefits of Supplemental Vitamin C Administration

Abstract

Background: Numerous abnormalities in cystic fibrosis (CF) could influence tocopherol absorption, transportation, storage, metabolism and excretion. We hypothesized that the oxidative distress due to inflammation in CF increases vitamin E utilization, which could be positively influenced by supplemental vitamin C administration.

Methods: Immediately before and after receiving vitamin C (500 mg) twice daily for 3.5 weeks, adult CF patients (n = 6) with moderately advanced respiratory tract (RT) disease consumed a standardized breakfast with 30% fat and a capsule containing 50 mg each hexadeuterium (d₆)-α- and dideuterium (d₂)-γ-tocopheryl acetates. Blood samples were taken frequently up to 72 h; plasma tocopherol pharmacokinetics were determined. During both trials, d₆-α- and d₂-γ-tocopherols were similarly absorbed and reached similar maximal plasma concentrations ~18-20 h. As predicted, during vitamin C supplementation, the rates of plasma d₆-α-tocopherol decline were significantly slower.

Conclusions: The vitamin C-induced decrease in the plasma disappearance rate of α-tocopherol suggests that vitamin C recycled α-tocopherol, thereby augmenting its concentrations. We conclude that some attention should be paid to plasma ascorbic acid concentrations in CF patients, particularly to those individuals with more advanced RT inflammatory disease and including those with severe exacerbations.

Keywords: carboxyethyl hydroxy chromanol (CEHC); stable isotope-labeled vitamin E; vitamin E.

Figure 1

The efficacy of vitamin C supplementation in CF participants. Plasma concentrations of ascorbic acid (a) and malondialdehyde (b) during pharmacokinetic trials. Shown are the means (±SD, n = 6) of the average concentrations measured from plasma samples collected at 0, 3, 6, 9, 12, 24, 48, 72 h from each participant.

Figure 2

The plasma d₆-α- (a) and d₂-γ-tocopherol (b) concentrations at baseline and after vitamin C supplementation (representative participant, #3). Plasma-labeled and unlabeled tocopherols were measured by LC/MS from blood samples periodically collected up to 72 h. Filled symbols denote baseline, open symbols denote vitamin C pharmacokinetics trial. Lines indicate post-peak exponential decay curves. The d₂-γ-tocopherol rates of disappearance were so fast that the slopes were no longer linear after 36 h; thus, a second curve was fit to the data. Neither slope was altered by vitamin C status; only the slope from Tmax is reported.

Figure 3

The plasma half-lives in hours for d₆-α- and d₂-γ tocopherols and d₂-γ CEHC. Half-lives indicate the length of time for half of the indicated compound to leave the plasma compartment (a). Individual data shows disappearance rates (pools per day) by person (b) d₆-α tocopherol; (c) d₂-γ tocopherols). The rates shown are based on the percentage labeled to demonstrate that the baseline tocopherol concentrations did not impact the outcomes.