Handbook of Vitamin C Research

348Alin StirbanVitamin C and Lipid Induced EDBy measuring FMD before and hourly for 6 hours following a high-fat meal (900kcalories, 50 g of fat) in twenty healthy, normocholesterolemic subjects, Plotnick andcoworkers demonstrated that a decrease in endothelial function for up to 4 hours occurs andthat this effect can be prevented by oral pretreatment with the antioxidant vitamins C (1 g)and E (800 IU) [50]. In another study performed in 10 healthy volunteers, vasculardysfunction due to increased free fatty acid concentration induced by Intralipid/heparininfusion could be reversed by concomitant intraarterial infusion of ascorbic acid (24 mg/min)[51].Recently it has been suggested that high-dose vitamin C improves endothelial function ofharvested saphenous vein segments in an ex vivo model, providing evidence that not only thearterial segment, but also the venous one can benefit from ascorbic acid replacement [52].Endpoint Data to Oral Vitamin C SubstitutionThe Physicians' Health Study II was a randomized, double-blind, placebo-controlledfactorial trial of vitamin E and vitamin C completed between 1997 and 2007 [53]. A numberof 14,641 US male physicians aged 50 years and above were enrolled, including 754 men(5.1%) with CAD at randomization. The intervention consisted of supplements of 400 IUvitamin E every other day and 500 mg vitamin C daily. Results showed that neither vitamin Enor vitamin C supplementation reduced the risk of major cardiovascular events in middleagedand older men. These data are in line with previous studies showing that a combinationof vitamin E and vitamin C provides no cardiovascular benefits in postmenopausal womenwith CAD and a potential for harm was even suggested [54].In contrast, 500 mg/d of vitamin C reduced restenosis rates in patients after percutaneoustransluminal coronary angioplasty [55]. A combination of 136 IU of vitamin E plus 250 mgof slow-release vitamin C twice daily administered for 6 years reduced the progression ofintima media thickness in hypercholesterolemic subjects [56].Vitamin C in Critically Ill PatientsWhile oral, prophylactic approaches of treatment with vitamin C are controversial, alarge body of evidence proves beneficial effects of parenteral administration in critically illpatients. Extensive data on this topic have been reviewed [57,24,58].Oxidative stress implies a depletion of vitamin C and therefore ascorbatesupplementation might play a clinical role in the treatment of diseases characterized byincreased oxidative stress. Supraphysiologic levels of ascorbate may facilitate the restorationof vascular function in patients after severe burns and other major traumas. This translatesclinically into reduced circulatory shock, fluid requirements and oedema [57]. The effects onthe microcirculation seem to be of particular interest since microcirculation is verysusceptible to oxidative stress that acts pathogenically to cause multiple organ failure. High-