"However, large Phase III randomized placebo-controlled trials (RCTs) (see Definitions), currently considered the " gold standard " for establishing efficacy of dietary supplements in chronic disease prevention, have been disappointing , showing little or no beneficial effect of vitamin C supplementation on CVD or cancer incidence (Blot et al., 1993; Heart Protection Study, 2002; Hercberg et al., 2004; Cook et al., 2007; Sesso et al., 2008; Gaziano et al., 2009). However, we (Lykkesfeldt and Poulsen, 2010; Frei, 2004; Roberts et al., 2009) and others (Blumberg et al., 2010; Ames et al., 2007) have argued that current Phase III RCTs designed principally to test the safety and efficacy of pharmaceutical drugs in disease treatment are ill suited to demonstrate the efficacy in disease prevention of substances endogenously present in the human body and required for normal metabolism, such as vitamins and other essential nutrients. Even if study designs were improved, additional Phase III RCTs of vitamin C as primary intervention of CVD, cancer, and other chronic diseases will likely be cost-prohibitive and not be funded by federal agencies or private industry, and, hence, will not be conducted in the foreseeable future. "
[Show abstract][Hide abstract] ABSTRACT: The recommended dietary allowance (RDA) of vitamin C has traditionally been based on the prevention of the vitamin C deficiency disease, scurvy. While higher intakes of vitamin C may exert additional health benefits, the limited Phase III randomized placebo-controlled trials (RCTs) of vitamin C supplementation have not found consistent benefit with respect to chronic disease prevention. To date, this has precluded upward adjustments of the current RDA. Here we argue that Phase III RCTs-designed principally to test the safety and efficacy of pharmaceutical drugs-are ill suited to assess the health benefits of essential nutrients; and the currently available scientific evidence is sufficient to determine the optimum intake of vitamin C in humans. This evidence establishes biological plausibility and mechanisms of action for vitamin C in the primary prevention of coronary heart disease, stroke, and cancer; and is buttressed by consistent data from prospective cohort studies based on blood analysis or dietary intake and well-designed Phase II RCTs. These RCTs show that vitamin C supplementation lowers hypertension, endothelial dysfunction, chronic inflammation, and Helicobacter pylori infection, which are independent risk factors of cardiovascular diseases and certain cancers. Furthermore, vitamin C acts as a biological antioxidant that can lower elevated levels of oxidative stress, which also may contribute to chronic disease prevention. Based on the combined evidence from human metabolic, pharmacokinetic, and observational studies and Phase II RCTs, we conclude that 200 mg per day is the optimum dietary intake of vitamin C for the majority of the adult population to maximize the vitamin's potential health benefits with the least risk of inadequacy or adverse health effects.
Critical reviews in food science and nutrition 09/2012; 52(9):815-29. DOI:10.1080/10408398.2011.649149 · 5.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coal mining and incineration of solid residues of health services (SRHS) generate several contaminants that are delivered into the environment, such as heavy metals and dioxins. These xenobiotics can lead to oxidative stress overgeneration in organisms and cause different kinds of pathologies, including cancer. In the present study the concentrations of heavy metals such as lead, copper, iron, manganese and zinc in the urine, as well as several enzymatic and non-enzymatic biomarkers of oxidative stress in the blood (contents of lipoperoxidation = TBARS, protein carbonyls = PC, protein thiols = PT, α-tocopherol = AT, reduced glutathione = GSH, and the activities of glutathione S-transferase = GST, glutathione reductase = GR, glutathione peroxidase = GPx, catalase = CAT and superoxide dismutase = SOD), in the blood of six different groups (n = 20 each) of subjects exposed to airborne contamination related to coal mining as well as incineration of solid residues of health services (SRHS) after vitamin E (800 mg/day) and vitamin C (500 mg/day) supplementation during 6 months, which were compared to the situation before the antioxidant intervention (Ávila et al., Ecotoxicology 18:1150-1157, 2009; Possamai et al., Ecotoxicology 18:1158-1164, 2009). Except for the decreased manganese contents, heavy metal concentrations were elevated in all groups exposed to both sources of airborne contamination when compared to controls. TBARS and PC concentrations, which were elevated before the antioxidant intervention decreased after the antioxidant supplementation. Similarly, the contents of PC, AT and GSH, which were decreased before the antioxidant intervention, reached values near those found in controls, GPx activity was reestablished in underground miners, and SOD, CAT and GST activities were reestablished in all groups. The results showed that the oxidative stress condition detected previously to the antioxidant supplementation in both directly and indirectly subjects exposed to the airborne contamination from coal dusts and SRHS incineration, was attenuated after the antioxidant intervention.
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