High-dose intravenous vitamin C is not associated with an increase of pro-oxidative biomarkers.
OBJECTIVE
High-dose vitamin C therapy might mediate beneficial clinical effects by counteracting reactive oxygen species. However, concerns are raised whether this approach might provoke diametrical (ie pro-oxidative) effects. The objective was to determine ascorbyl free radical (AFR) concentrations and potential variables of pro-oxidative damage.


METHODS
Crossover study; six healthy males received daily infusions of 750 or 7500 mg vitamin C for six consecutive days. Fasting concentrations of vitamin C and AFR were determined daily. On day 1, concentrations of vitamin C and AFR were measured at 0.25, 0.5, 1, 2, 4 and 8 h post infusion. Plasma concentrations of thiobarbituric acid-reactive substances (TBARS), tocopherol and urine concentrations of 8-oxoguanosine were determined on days 1 and 6.


RESULTS
Kinetic studies on day 1 showed that concentrations of vitamin C and AFR displayed parallel dose- and time-dependent kinetics and elimination was highly efficient. Vitamin C and AFR fasting concentrations on days 2-6 were slightly above the baseline, suggesting new, stable steady states. TBARS decreased in both groups, whereas tocopherol and 8-oxoguanosine concentrations remained unchanged.


CONCLUSIONS
Kinetics of AFR largely depend on plasma vitamin C concentrations and AFR is eliminated efficiently. Our data do not support induction of pro-oxidative effects in healthy volunteers given intravenous high-dose vitamin C.


BACKGROUND
Pascoe Pharmazeutische Präparate GmbH, Giessen, Germany.
Mühlhöfer
A
A
Division of Gastroenterology at Katharinenhospital, Stuttgart, Germany.
Mrosek
S
S
Schlegel
B
B
Trommer
W
W
Rozario
F
F
Böhles
H
H
Schremmer
D
D
Zoller
W G
WG
Biesalski
H K
HK
D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D005609:Free Radicals / Q000097:blood*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000652:urine; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D000975:Antioxidants; D016166:Free Radical Scavengers; D005609:Free Radicals; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D006151:Guanosine; C046215:8-hydroxyguanosine; D001205:Ascorbic Acid