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http://dx.doi.org/10.4163/kjn.2009.42.2.107

Effects of Folic Acid and Ascorbate Supplementation on Plasma Homocysteine and Oxidative Stress in Patients with Type 2 Diabetes Mellitus  

Hwang, Mi-Ri (Department of Food & Nutrition, Chonnam National University)
Soh, Ju-Ryoun (Department of Food & Nutrition, Chonbuk National University)
Lim, Hyeon-Sook (Human Ecology Research Institute, Chonnam National University)
Publication Information
Journal of Nutrition and Health / v.42, no.2, 2009 , pp. 107-118 More about this Journal
Abstract
In patients with type 2 diabetes, oxidative stress could be increased by their metabolic changes. Elevated plasma homocysteine is considered as one of markers of enhanced oxidative stress. Due to oxidative stress, some complications like cardiovascular or renal diseases may develop in type 2 diabetes patients. Plasma homocysteine concentration may be increased if folate status were inadequate. Protective effects against oxidative stress may be diminished if the status of anti-oxidative nutrient as vitamin C was poor. It is, therefore, important to maintain adequate status of folate and vitamin C in type 2 diabetes patients. Thus, this study was performed to determine the effects of supplementation of folate and/or ascorbate on blood glycated hemoglobin ($HbA_{1c}$) level, serum concentrations of homocysteine and cholesterol, plasma oxidized low density-lipoprotein (LDL), concentration and plasma glutathione peroxidase (GSH-Px) activity in the patients with type 2 diabetes. A total of 92 type 2 diabetes patients participated voluntarily with written consents. They were divided into one of the four experimental groups; Control (C), Folate-supplemented (F), Ascorbate-supplemented (A), and Folate plus ascorbate-supplemented (FA). The subjects in C were taken placebo, those in F were supplemented 1 mg of folate, those in A received 1,000 mg of ascorbate, and those in FA were given 1 mg of folate plus 1,000 mg of ascorbate daily for 4 weeks. Supplementation of folate or ascorbate resulted to increase serum folate level or plasma ascorbate concentration apparently, respectively. Folate supplementation not ascorbate seemed to decrease plasma concentrations of homocysteine and oxidized LDL and reduce plasma GSH-Px activity. There might not be synergic effect of the supplementation of folate plus ascorbate. The results indicate that oxidative stress in the patients with type 2 diabetes may lower mainly by folate supplementation.
Keywords
folate; ascorbate; diabetes; homocysteine; oxidative stress;
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Times Cited By KSCI : 3  (Citation Analysis)
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1 Stevens MJ, Feldman EL, Greene DA. The etiology of diabetic neuropathy: The combined roles of metabolic and vascular defect. Diabetic Med 1995; 12(7): 1566-1579   DOI   ScienceOn
2 McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969; 56(1): 111-128   PUBMED   ScienceOn
3 Paolisso G, D'Amore A, Giugliano D, Cereillo A, Varricchio M, D'Onofrio F. Pharmacological doses of vitamin E improve insulin action in healthy subjects and non-insulin dependent diabetic patients. Am J Clin Nutr 1993; 57(5): 650-656   DOI   PUBMED
4 Davie SJ, Gould BJ, Yudkin JS. Effect of Vitamin C on glycosylation of protein. Diabetes 1992; 41(2): 167-173   DOI   ScienceOn
5 Varillo AR, Ade T, Golia R, Nunziata V. The relationship between glycosylated haemoglobin levels and various degrees of glucose intolerance. Diabetologia 1983; 24(5): 391-393   DOI   PUBMED
6 Buysschaert M, Dramais AS, Wallemacq PE, Hermans MP. Hyperhomocysteinemia in type 2 diabetes: relationship to macroangiopathy, nephropathy, and insulin resistance. Diabetes Care 2000; 23(12): 1816-1822   DOI   ScienceOn
7 Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJ, Jakobs C, Bouter LM, Heine RJ, Stehouwer CD. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus: a population-based study. Arterioscler Thromb Vasc Biol 1998; 18(1): 133-138   DOI   PUBMED
8 Rinkins LE. Effects of alloxan diabetes on rat river ascorbic acid. Horm Metab Res 1981; 13(2): 123-129   DOI   PUBMED
9 Sies H, Stahl W. Vitamin E and vitamin C and carotenoid as antioxidants. Am J Clin Nutr 1995; 62(6): 1315s-1321s   DOI   PUBMED
10 Nappo F, De Rosa N, Marfella F, De Lucia D, Ingrosso D, Perna AF, Fazati B, Giugliano D. Impairment of endothelial functions by acute hyperhomocysteinemia and reversal by antioxidant vitamins. JAMA 1999; 281(22): 2113-2118   DOI   ScienceOn
11 Park HS, Lee YM. Effects of vitamin C supplementation on blood sugar and antioxidative status in type 2 diabetes mellitus patients. J Korean Acad Nurs 2003; 33(2): 170-178   DOI
12 Fonseca VA, Stone A, Munshi M, Baliga BS, Aljada A, Thusu K, Fink L, Candona P. Oxidative stress in diabetic macrovascular disease: does homocysteine play a role? South Med J 1997; 90(9): 903-906   DOI   PUBMED
13 Lehto S, Ronnemaa T, Pyorala K, Laakso M. Cardiovascular risk factors clustering with endogenous hyperinsulinemia predict death from coronary heart disease in patients with Type II diabetes. Diabetologia 2000; 43(2): 148-155   DOI   ScienceOn
14 Moghadasion MH, McManus BM, Frohlich JJ. Homocysteine and coronary heart disease; clinical evidence and genetic and metabolic background. Arch Intern Med 1997; 157(20): 2299-2308   DOI   ScienceOn
15 Nygard O, Vollset SE, Refsum H, Stensvold I, Tverdal A, Nordrehaug JE, Ueland M, Kvåle G. Total plasma homocysteine and cardiovascular risk profile: the Hordaland Homocysteine Study. JAMA 1995; 274(19): 1526-1533   DOI   ScienceOn
16 Young IS, Lightbody JH, McMaster D, Trimble ER. The effects of desferrioxamine and ascorbate on oxidative stress in the streptozotocin diabetic rat. Free Radic Biol Med 1995; 18(5): 833-840   DOI   ScienceOn
17 Medina MA, Amores-Snchez MI. Homocysteine: an emergent cardiovascular risk factor? Eur J Clin Invest 2000; 30(9): 754-762   DOI   ScienceOn
18 Hwang MR, Shin MH, Rhee JA, Kweon SS, Lim HS. Effects of folic acid or ascorbate supplemendation on plasma homocysteine levels and oxidative stress in Korean adults with impared fasting glucose. Korean J Community Nutrition 2008; 13(2):263-275
19 Shukla N, Angelini GD, Jeremy JY. The administration of folic acid reduces intravascular oxidative stress in diabetic rabbits. Metabolism 2008; 57(6): 774-781   DOI   ScienceOn
20 van Guldener C, Stehouwer CD. Hyperhomocysteinemia, vascular pathology, and endothelial dysfunction. Semin Thromb Hemost 2000; 26(3): 281-289   DOI   ScienceOn
21 Ha AW, Kim HM. The study of lipid-peroxidation, antioxidant enzymes, and the antioxidant vitamin in NIDDM patients with microvascular-diabetic complications. Korean J Nutr 1999; 32(1): 17-23
22 Andersson A, Brattstrom L, Israelsson B, Isaksson A, Hamfelt A, Hultberg B. Plasma homocysteine before and after methionine loading with regarding to age, gender, and menopausal status. Eur J Clin Invest 1992; 22(2): 74-87   DOI   ScienceOn
23 Lim HS. Folate status in pregnant and lactating women. J Korean Soc Food Sci Nutr 1997; 26(5): 983-992
24 Dipolack AT. Safety of antioxidation vitamins and beta-carotene. Am J Clin Nutr 1995; 62(6): 1510s-1516s   DOI   PUBMED
25 Kim NE, Kim WK. Effects of antioxidant vitamin supplementation on antioxidative status and plasma lipid profiles in Korean NIDDM patients. Korean J Nutr 1999; 32(7): 775-780
26 Brattstrom L. Vitamins as homocysteine-lowering agents. J Nutr 1996; 126(4): 1276s-1280s   DOI   PUBMED
27 Jager A, Kostense PJ, Nijpels G, Dekker JM, Heine RJ, Bouter LM, Donker AJ, Stehouwer CD. Serum Homocysteine levels are associated with the development of microalbuminuria: the Hoorn Study. Arterioscler Thromb Vasc Biol 2001; 21(1): 74-81   DOI   PUBMED
28 Araki A, Sako Y, Ito H. Plasma homocysteine concentrations in Japanese patients with non-insulin-dependent diabetes mellitus: effect of parenteral methylcobalamin treatment. Atherosclerosis 1993; 103(2): 149-157   DOI   ScienceOn
29 Aukrus P, Berge RK, Muller F, Ueland PM, Svardal AM, Froland SS. Elevated plasma levels of reduced homocysteine in common variable immunodeficiency-a marker of enhanced oxidative stress. Eur J Clin Invest 1997; 27(10): 723-730   DOI   ScienceOn
30 McCully KS. Chemical pathology of homocysteine I. Atherogenesis. Ann Clin Lab Sci 1993; 23(6): 477-493   PUBMED
31 Targher G, Bertolini L, Zenari L, Cacciatori V, Muggeo M, Faccini G, Zppini G. Cigarette smoking and plasma total homocysteine levels in young adults with type 1 diabetes. Diabetes Care 2000; 23(4): 524-528   DOI   ScienceOn
32 Chauvear P, Chadefaux B, Coud M, Aupetit J, Kamoun P, Jungers P. Long-term folic acid (but not pyridoxine) supplementation lowers elevated plasma homocysteine level in chronic renal failure. Miner Electrolyte Metab 1996; 22(1-3): 106-109   PUBMED
33 Al-Obaidi MK, Stubbs PJ, Collinson P, Conroy R, Graham I, Noble MI. Elevated homocysteine levels are associated with increased ischemic myocardial injury in acute coronary syndromes. J Am Coll Cardiol 2000; 36(4): 1217-1222   DOI   ScienceOn
34 Song IJ, Lee JA, Lim HS. Dietary and health-related lifestyle habits and blood parameters of non-insulin dependent diabetes patients. Nutr Sci 2005; 8(1): 35-41   과학기술학회마을
35 Blom HJ, Kleinveld HA, Boers GH, Demacker PN, Hak-Lemmers HL, Te Poele-Pothoff MT, Trijbels JM. Lipid peroxidation and susceptibility of low-density lipoprotein to in vitro oxidation in hyperhomocysteinemia. Eur J Clin Invest 1995; 25(3): 149-154   DOI   ScienceOn
36 Yoshida H, Ishikawa T, Nakamura H. Vitamin E/lipid peroxide ratio and susceptibility of LDL to oxidative modification in NIDDM. Arterioscler Throm Vasc Biol 1997; 17(7): 1438-1446   DOI
37 Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339(4): 229-234   DOI   ScienceOn
38 Nygard O, Refsum H, Ueland PM, Vollset SE. Major lifestyle determinants of plasma total homocysteine distribution: The Hordaland Homocysteine Study. Am J Clin Nutr 1998; 67(2): 263-270   DOI   PUBMED
39 Som S, Basu S, Mukherjee D, Deb S, Choudhury PR, Mukherjee S. Ascorbic acid metabolism in diabetes mellitus. Metabolism 1981; 30(6): 572-577   DOI   ScienceOn
40 Racek J, Rusnkov H, Trefil L, Siala KK. The Influence of folate and antioxidants on homocysteine levels and oxidative stress in patients with hyperlipidemia and hyperhomocysteinemia. Physiol Res 2005; 54(1): 87-95   PUBMED
41 Hoogeveen EK, Kostense PJ, Jakobs C, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD. Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes 5-year followup of the Hoorn Study. Circulation 2000; 101(13):1506-1511   DOI   PUBMED
42 Seo HY, Ha AW, Cho JS. The dietary intake, plasma lipid peroxidation and vitamin C in NIDDM patients. Korean J Nutr 2001; 34(8): 912-919
43 Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP, Riezler R, Vermaak WJ. The effect of a subnormal vitamin B6 status on homocysteine metabolism. J Clin Invest 1996; 98(1):177-184   DOI   ScienceOn
44 Okamura M. An improved method for determination of L-ascorbic acid and L-dehydroascorbic acid in blood plasma. Clin Chem Acta 1980; 103(3): 259-268   DOI   ScienceOn
45 Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999; 340(19):1449-1454   DOI   ScienceOn
46 Chambers JC, McGregor A, Jean-Marie J, Obeid OA, Kooner JS. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy. Circulation 1999; 99(9): 1156-1160   DOI   PUBMED
47 Chang NS, Kim JM, Park SW, Cho YW, Kwon OO. Folate intake and plasma homocysteine levels in the elderly patients with NIDDM. Korean J Nutr 2000; 33(3): 250-256