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Vitamin C: Prevention of Chronic Diseases and Optimal Doses

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Vitamin C: Prevention of Chronic Diseases and Optimal Doses NFT 9-2010 s. 20-27 08.09.10 13.00 Side 20 Vitenskap Review Vitamin C: Prevention of Chronic Diseases and Optimal Doses TEXT: Purusotam Basnet, Department of Pharmacy, Faculty of Health Sciences, University of Tromsø, e-mail: [email protected] INTRODUCTION acid because of its anti-scorbutic property ABSTRACT It has been known for a long time that (Latin word scorbutus = scurvy). In absence of fresh fruit and vegetables in the solution, it releases a proton to give an The role of vitamin C in prevention and human diet leads to scurvy, a fatal disease anion called ascorbate. Ascorbate easily treatment of scurvy is well accepted. In widely described throughout written transfers one electron and one additional spite of having long history as the candidate of alternative therapy for the history (Lind, 1753). Later, it was dis - proton and can remains in the stable prevention and treatment of cancer, still covered that ascorbic acid in fresh fruits radical form as semidehydroascorbate there is no common conclusion on the and vegetables prevents scurvy and that is (SDA), a state in between dehydroa- topic. However, its biochemical reaction why it is a vitamin for humans and must be scorbic acid (DHA) and ascorbate in the as an antioxidant and its immuno- a part of human diet (Mandl et al., 2009). physiological condition (figure 1). stimulating effects drew further Among the long list of people who Because of the unique electron trans- attention towards its health beneficial contributed to the knowledge regarding ferring capability, ascorbate plays a vital effects. Current official recommended vitamin C, three Nobel prize-winners are in role in living cells. Our body synthesizes dietary allowance in most of the the fore front. Albert Szent-Györgyi discov- collagen to strengthen connective tissue. countries is higher than what is needed ered vitamin C as an anti-scorbutic factor For this, prolyl residue must be for the prevention of scurvy, but (Svirbely and Szent-Györgyi, 1932). hydroxylated and the reaction is carried research result suggested that it is far Walter Norman Haworth used the material out by the enzyme prolyl hydroxylase with less to obtain optimum health. from Szent-Györgyi and elucidated the the support of vitamin C (figure 2). The Therefore, especially for the prevention structure and synthesized vitamin C hindrance of this biochemical reaction is of chronic illness such as cancer, (Haworth and Hirst, 1933). For their contri- the cause of scurvy. In spite of having its hypertension, Alzheimer’s diseases etc., it is recommended to consume more butions, Szent-Györgyi and Haworth were vital role in physiology, human is unable to fruits and vegetables together with the rewarded with Nobel prizes in medicine synthesize ascorbate due to the absence of vitamin C supplements. Evaluating the and chemistry in 1937, respectively. The the enzyme, gulonolactone oxidase (GLO) vitamin C efficiency and safety with third person, Linus Pauling is perhaps the as found in most animals and those current literature, up to 1 g/day supple- most renowned advocate of vitamin C. animals including human unable to pro- ment of vitamin C has been suggested to Pauling believed that high doses of vitamin duce GLO, need external supplement of be needed for optimal health. In C can cure or prevent several mental ill- ascorbate as vitamin to carry out normal addition, male population compared to nesses, chronic diseases such as heart dise- physiological functions (Linster and Van female population, older population ases and cancer, including common cold Schaftingen, 2007). compared to younger population, (Pauling, 1970; Cameron and Pauling, Besides acting as a cofactor in several smoking population compared to non- 1973; Cameron and Campbell, 1974; metabolic reactions, it serves primarily as smoking population and stressed Pauling, 1974; Cameron and Pauling, a biologic antioxidant and free radical population compared to non-stressed 1979; Cameron and Pauling, 1993). The scavenger in aqueous environment. Free population need larger amounts of vita- knowledge contributed by these three great radicals produced by enzymatic and non- min C to obtain health beneficial effects. scientists and many others led to the found- enzymatic reactions inside and outside ation for research on vitamin C. cells have been suggested as a major Although the role of vitamin C in the pre- cause of aging process (Harman, 1956; vention and treatment of scurvy is well Harman, 1994). This theory was further accepted, immunomodulatory effect of supported by the discovery of superoxide MAIN MESSAGE vitamin C, its role as an antioxidant to dismutase (SOD) (McCord and Fridovich, Vitamin C (ascorbic acid) is one of the prevent or treat chronic illness and official 1969). Since then, a great deal of essential components in human physio- recommended dietary allowance (RDA) evidences has been accumulated impli- logy working as a water-soluble antioxi- are under critical discussion (Deruelle and cating free radical reactive oxygen and dant and enzyme cofactor. Humans do Baron, 2008; Mandl, 2009). In this review, nitrogen species in the pathology of a not synthesize ascorbate, therefore we need to administer it through diet or the effect of vitamin C on cancer and other number of chronic diseases and age supplements. We must assure a sufficient diseases and optimal doses are discussed. associated functional decline (Knight, intake of vitamin C in order to define its 1998, Ratten 2006; Viña et al., 2007; role for the prevention or treatment of UNIQUE CHEMICAL FEATURE AND Gruber et al., 2008; Ljubunic and Reznick various diseases. BIOLOGICAL FUNCTION OF VITAMIN C 2009). Ascorbate readily scavenges many Vitamin C (C6H8O6) is named as ascorbic physiologically relevant reactive oxygen 20 NORSK FARMACEUTISK TIDSSKRIFT 9/2010 NFT 9-2010 s. 20-27 08.09.10 13.00 Side 21 CH OH 2 CH2OH CH2OH CH2OH CH2OH H C OH H C OH H C OH H C OH H C OH O O O O O O O O O O H e, H e H H H H H H e, H e HO OH O OH O OH O O O O Ascorbic acid Semidehydroascorbate Dehydroascorbic Ascorbate (ASC) acid (DHA) radical (SDA) Figure 1. Structure of ascorbic acid and its fates during physiological reactions. and nitrogen species and is the most effective endogenous aqueous phase COO H O antioxidant in human plasma under many different oxidizing conditions (Frei et al., NCC CH2 1989). Although other endogenous CH2 antioxidants are able to decrease the rate + O2 + of lipid and protein oxidation in plasma, C O only ascorbate is reactive enough to H H intercept oxidants before they can cause COO Prolyl residue Prolyl hydroxylase detectable oxidative damage. Due to its +Ascorbate α−Ketoglutarate role as an antioxidant and by having +Fe+++/Fe++ immunomodulatory functions, vitamin C is H O COO one of the most promising molecules of NCC health beneficial effects. For this purpose, CH2 more than 86,000 metric tons of vitamin C + CO2 + was consumed only in 2003 which is more CH2 than 50 % of all the other vitamins. In C O addition, consumption rate is expected to H OH increase by more than 2000 metric tons 4-Hydroxyprolyl residue O per year (Asard et al., 2004). Succinate RECOMMENDED DIETARY ALLOWANCE FOR VITAMIN C Figure 2. Hydroxylation of a prolyl residue with the enzyme prolyl hydroxylase. In this The US Food and Nutrition Board has pre- reaction, vitamin C acts as an antioxidant by reducing ferric ion which activates prolyl pared RDAs for vitamin C since 1941. hydroxylase. Hydroxyprolyl residue stabilizes the collagen triple helix by forming interstrand hydrogen bonds. Initially, the RDA was based on the amount needed to prevent people from getting scurvy with a safety margin but numerous research results suggested that lactating period. Pauling suggested the for chronic diseases such as heart disease this may not be sufficient for optimal daily intake of vitamin C of 250–4000 mg and certain types of cancer (Hathcock, health (Pauling 1974; Levine et al., 1996; (Pauling, 1970; Pauling 1974). Challem 1997; Ames 2004; Ames 2005; Ames Food and Nutrition Board, 2000). concluded that the RDAs might be 2006). In this connection, two studies Moreover, the RDA for vitamin C is based seriously inadequate guidelines for health demonstrated that current RDA for vitamin on estimates of rates of absorption, (Challem, 1999). However, high doses of C should be re-evaluated and increased to depletion, turnover and catabolism (Levine vitamin C, as proposed by previous aut- 200 mg daily (Levine, 1996; Graumlich et et al., 1999; Food and Nutrition Board, hors, are not supported by all literature. A al., 1997). 2000). For vitamin C, however, the meta-analysis on a potential effect of information is unavailable, incomplete, or vitamin C on the common cold showed ROLE OF VITAMIN C IN CANCER flawed. Currently, RDA requirements for that there seems no justification for routine THERAPY vitamin C differ among countries, with the mega dose vitamin C supplementation, For the prevention of cancer, the US highest value being 110 mg/day (Food 1–3 g/day, in the normal population department of Agriculture and the and Nutrition Board 2000; Levine et al., (Hemilä et al., 2007a). Moreover, without National Cancer Institute has recom- 2001). According to Norwegian Social reaching the mega doses of vitamin C mended five servings of fruits and and Health Affair, the RDA for vitamin C consumption, numerous reviews suggest vegetables daily. Further analyses have are 75 mg per day for the adult and 100 that intakes of vitamin C much higher than suggested that this consumption should be mg per day for the women during the RDA may reduce the risk or risk factors even higher (Lachance and Langseth, NORSK FARMACEUTISK TIDSSKRIFT 9/2010 21 NFT 9-2010 s.
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