Handbook of Vitamin C Research

288E Tzagaraki, C Sofocleous, G Tounta, et al.Oxidative stress (OS) is a major contributor to endothelial cell dysfunction and animbalance between oxidants and antioxidants has been observed in women with establishedPE [85]. Altered release of placental debris may either cause this imbalance or be aconsequence of it [86, 87]. In pre-eclamptic placenta ROS production seems increased, asevidenced by increased peroxynitrite formation [88]. The concentration of anti-oxidants,including vitamin C, in the maternal circulation is decreased in women with PE, possibly dueto reduced anti-oxidant activity. Increased ROS combined with inadequate anti-oxidantcapacity could potentially lead to lipid peroxidation, leukocyte activation, platelet adhesion,and vasoconstriction [89]. Accordingly, OS seems to be the link connecting defectivetrophoblast invasion causing placental hypoperfusion, endothelial dysfunction, immunemaladaptation and inflammation [90].Vitamin C Supplementation and Pregnancy OutcomesOS in women with established PE is supported by increased plasma and placenta levelsof specific OS markers (8-epi-prostaglandin F 2a and lipid peroxide) combined with decreasedlevels of anti-oxidants such as vitamin C and E [91-93]. Maternal serum vitamin C levelsduring the second trimester in uncomplicated pregnancies are positively correlated with birthweight and length in full- term babies [47]. OS and free radicals have been implicated inseveral pregnancy related complications, including diabetic embryopathy, preterm labor,IUGR (Intrauterine Growth restriction) and luteal phase defect [94-97].In the majority of clinical trials studying the supplementation with antioxidants acombination of vitamins C and E was used as their ratio was assumed to be of greatimportance. Multiple studies suggested that vitamin C exerts a ―redox‖ recycling effect onoxidized vitamin E within lipoproteins and membranes, indicating that the combination of thetwo vitamins may be essential [98, 99].A Cochrane review evaluated the effects of vitamin C supplementation, alone orcombined with other supplements, on pregnancy outcomes, including PE. Five randomizedcontrolled trials, involving 766 pregnant women were evaluated. No significant differencewas found between women supplemented with vitamin C alone or combined with othersupplements compared with placebo for the risk of stillbirth, perinatal death, birth weight, orIUGR even though they were at increased risk of giving birth preterm. Women supplementedwith vitamin C combined with other supplements were at decreased risk for developing PEwhen using a fixed-effect model (RR 0.47, 95% CI 0.30-0.75), but the difference was notsignificant when using a random-effect model (RR 0.52, 95% CI 0.23-1.20). The authorsconsidered the data to be inadequate to establish if vitamin C supplementation is beneficialduring pregnancy [100].A large number of surveys in high-risk populations have shown that antioxidanttreatment lowered the prevalence of PE. In one of these randomized controlled trials, womenat high-risk for PE were supplemented with antioxidants or placebo, starting at 16-22 weeksof gestation, with a daily dosage of 1000 mg of vitamin C and 400 IU of vitamin E. Only 8%of women receiving antioxidant vitamins developed PE versus 17% of the control group. In