Augmentation of Respiratory Tract Lining Fluid Ascorbate Concentrations Through Supplementation with Vitamin C

Abstract

Low molecular weight antioxidants within human respiratory tract lining fluids (RTLFs) have been proposed to confer protection against the damaging action of inhaled oxidant gases. There is therefore considerable interest in augmenting the concentrations of these moieties at the airlung interface to protect against injury to the airway epithelium, the induction of inflammation, and declines in lung function. To determine whether RTLF ascorbate concentrations could be augmented through vitamin C supplementation, 24 healthy subjects with low plasma ascorbate (<50 µM) were recruited into a double-blinded study. Subjects were divided into two groups, one receiving 60 mg/day of vitamin C for 14 days, the other placebo. On days 8 and 15 of this protocol, plasma, urine, and nasal lavage were obtained for ascorbate determination. After a 7-14-day non-intervention period, subjects previously on placebo received supplements containing 125 mg ascorbate, whilst the group previously on supplements received the placebo compound. This "switching" protocol was repeated three more times utilizing 250, 500, and 1000 mg/day ascorbate dosage regimens. Plasma ascorbate increased incrementally with vitamin C dose, as did its urinary excretion. Despite this, nasal lavage concentrations remained unaltered 24 h after the final supplement at all doses. Closer examination of this issue demonstrated that nasal lavage ascorbate concentrations increased acutely after ingestion of a high dose (1000 mg) supplement, peaking at 2-4 h (p < 0.05) before returning to baseline concentrations 24 h post-supplement. In the absence of a quantitative association between plasma and lavage ascorbate concentrations we 250 Inhalation Toxicology Downloaded from informahealthcare.com by Universitat de Girona on 11/17/14For personal use only. VITAMIN C SUPPLEMENTATION IN HEALTHY SUBJECTS 251contend that this response does not simply reflect ascorbate transudation from the plasma and interstitial space into the lavage medium. We therefore conclude that RTLF ascorbate can be augmented, albeit transiently, by oral vitamin C supplementation, with the transient nature of this response likely reflecting oxidative losses within the RTLF or its sequestration into airway cells.

Allantoin in Human Plasma, Serum, and Nasal-Lining Fluids as a Biomarker of Oxidative Stress: Avoiding Artifacts and Establishing Realin vivoConcentrations

“…When [1,[3][4][5][6][7][8][9][10][11][12][13][14][15] N 2 ] urate-spiked plasma samples were subjected to the alkaline SPE procedure, we found that the corrected ion ratio increased nonlinearly with the concentration of spiked [1,[3][4][5][6][7][8][9][10][11][12][13][14][15] N 2 ] urate (Fig. 2).…”

“…When plasma was spiked with high, but physiologically relevant levels of [1,3-15 N 2 ] urate (equivalent to 400 mM plasma urate), the corrected 400-398 m=z ion ratio was *1.3. This indicates that under these conditions, the amount of 15 N-labelled allantoin produced by artifactual conversion of [1,[3][4][5][6][7][8][9][10][11][12][13][14][15] (Fig. 2).…”

“…The SI-isotope-corrected 400-398 m=z ion ratio is calculated by subtracting 0.1523 from the experimentally observed ion ratio (8,29). A corrected 400-398-m=z ion ratio larger than zero indicates conversion of the spiked [1,[3][4][5][6][7][8][9][10][11][12][13][14][15] …”

“…Heavy isotope-labeled allantoin for use as internal standard was prepared by digesting [1,[3][4][5][6][7][8][9][10][11][12][13][14][15] …”

Vitamin C: Overview and Update

“…44,45 Furthermore, acute vitamin C supplementation (1 g) is associated with a rapid, but transient, rise in vitamin C concentrations in respiratory tract lining fluids, which could provide immediate antioxidant protection to lung tissues and temporarily attenuate oxidative stress in airways. 46 In elderly patients hospitalized with acute respiratory infections, patients randomized to receive 200 mg of vitamin C daily recovered more rapidly than patients receiving placebo, and the vitamin C supplemented patients experienced lower death rates compared with the placebo group (4% vs 17%). 47 In a Japanese population (439 patients with atrophic gastritis), chronic vitamin C supplementation (500 mg/d) reduced the number of common colds by 20% over a 3-year period compared with placebo ingestion.…”