Handbook of Vitamin C Research

164Borut Poljsak and John G. Ionescuit to a form that is more easily absorbed (Bendich and Cohen 1990). Individuals with ironoverload generally have low plasma levels of vitamin C, possibly due to interaction with theelevated levels of ‗catalytic‘ iron in these individuals, and therefore vitamin C administrationhas been proposed to be harmful in these people (Halliwell 1996; Herbert 1994). Accordingto Herbert (1994) for consumer protection, every advertisement and label for vitamin Cand/or iron supplements should warn: ―Do not take this product until your blood iron statushas been determined‖. Six percent of Americans are in negative iron balance, and thisproduct may help them. Twelve percent of Americans are in positive iron balance and thisproduct may hurt them.‖Intravenous administration of large doses of ascorbate (20g) in metal-sensitive atopiceczema patients resulted in a 24-48 hours of worsening of their clinical symptoms, withincreased erythema and itching. The simultaneous monitoring of the evolution of free radicalgeneration in whole blood and serum showed a dramatic increase of superoxide and hydrogenperoxide in serum, and a moderate ROS increase in whole blood (Figure 6, Ionescu 2002).Carr and Frei (1999) analyzed 44 in vivo studies done on vitamin C, 38 of them showeda reduction in markers of oxidative DNA, lipid, and protein damage, 14 showed no changeand only 6 showed an increase in oxidative damage after supplementation with vitamin C.According to Carr and Frei (1999) the answer to the question: ―Does vitamin C act as a prooxidantunder physiological conditions?‖ appears to be ‗no‘. However, there is still debate onwhether supplements of vitamin C could act as pro-oxidants in vivo. Vitamin supplementstaken by millions of people do not increase life expectancy and some of them, such as betacarotene, vitamin A, and vitamin E may raise the risk of a premature death, according to alatest review of 67 studies with more than 230,000 subjects (Bjelakovic et al. 2007). On theother hand, the same study concludes that ―vitamin C and selenium had no significant effect onmortality‖.3.1 Vitamin C and Epidemiological StudiesEpidemiological data in humans is confused although some minor benefits to overallmortality risk, coronary heart disease and subsequent risk of stroke, in particular, appearassociated with vitamin C supplementation (Enstrom, et al. 1992; Gale et al. 1995; Osganianet al. 2003), despite markers of oxidative damage generally being unaffected (Prieme et al.1997). A large majority of 26 examined epidemiological studies by Enstrom (2008) show amodest decrease in mortality from all causes, cancer, and cardiovascular diseases with anincrease of vitamin C intake, particularly for levels of vitamin C intake around the currentU.S. RDA of 75-90 mg per day per adults (Enstrom 2008). However, several other studiesshow no significant relationship after controlling for confounding variables. According toEnstrom (2008) there does not appear to be a relation between mortality and vitamin Csupplement intake per se. The strongest inverse relation has been observed in those studiesthat have analyzed serum vitamin C and total mortality. In the same line, low levels ofvitamin C in plasma and leucocytes are closely related to an increased myocardial infarct andstroke risk (Gey et al., 1993; Ramirez and Flowers 1980; Nyyssönen et al., 1997; Myint et al.,2008). The potential roles of vitamin C and selenium on mortality need further study