Handbook of Vitamin C Research

250Jun Yang, Jiaren Liu and John Parryinduction of apoptosis. Nucleic acid oxidation by free radicals can have seriousconsequences. It is possible to oxidize DNA with free radicals that can change the DNAsequence altering genes associated with normal cell cycle control including oncogenes and/ortumor suppressor genes which can lead to the development of cancer.The most publicized study on the prooxidant activity of ascorbic acid was performed byPodmore et al, 1998 and published in Nature. The research group found that volunteerssupplemented with 500 milligrams of ascorbic acid had significant increases, compared tobaseline, placebo, and the washout phases, in their levels of the oxidized nucleic acid,adenine, which was converted to 8-oxoadenine. In a 2005 study by Hininger et al, it wasfound that the removal of ascorbic acid (5 grams) from the standard cocktail used in EDTAchelation therapy significantly improved oxidative stress markers including reduced plasmamalondialdehyde, increased total blood glutathione, increased red blood cell glutathioneperoxidase, increased red blood cell superoxide dismutase, and decreased DNA scission. Theresearchers proposed that the mechanism for the higher levels of the oxidative stress markerswere the prooxidant effects caused by the high concentration of ascorbic acid in the standardcocktail. In a another study, it was found that the addition of ascorbic acid enhanced DNAsingle strand breakage and toxicity in U937 human myeloid leukemia cells exposed toperoxynitrite (Guidarelli et al, 2001). Yen et al, 2002 found that human lymphocytes treatedwith ascorbic acid in vitro had increased damage to DNA. The concentration of ascorbic acidthat caused the greatest damage was 0.82 millimolar which damaged approximately 9.4 %more compared to control. In three higher concentrations of ascorbic acid, up to 4.25millimolar, there was a reduction in DNA damage; however, the DNA damage in the threeconcentrations were still higher than the control (Yen et al, 2002). A study by Lee et al, 2001found that ascorbic acid induced lipid hydroperoxide decomposition to DNA reactivecompounds including 4,5-epoxy-2(E)-decenal which is a precursor to etheno-2‘-deoxyadenosine which is an extremely mutagenic compound. Oxidative stress is increasedsignificantly following liver transplant, and it is thought to be caused by reperfusion of bloodflow. In a recent investigation of the ability of ascorbic acid to attenuate oxidative stressmarkers in rat liver during cold ischemia/reperfusion it was found that 0.25 and 0.5millimolar ascorbic acid increased the level of reduced/oxidized glutathione, decreased lipidperoxidation, and decreased mitochondrial swelling compared to control and was ascribed ashaving an antioxidant effect; however, at 2 millimolar, ascorbic acid augmented the markerssuggesting the higher concentration had a prooxidant effect (Park and Lee, 2008).Ascorbic Acid and Vitamin B 12 DeficiencySome early studies suggested that megadoses of ascorbic acid may degrade vitamin B 12in food systems, which in turn may lead to decreased bioavailability and ultimatelydeficiency with all of the complex health afflictions associated. Doses of ascorbic acid of 500mg or more may reduce the availability of vitamin B 12 from food, and doses of 1 gram ormore may lead to the development of vitamin B 12 deficiency (Mix, 1999). The mechanismsuggested is that redox reactions of ascorbic acid, iron, and other antioxidants convertvitamin B 12 into a biologically unusable analog. A study by Herbert et al, 1976 investigated