DOI QR코드

DOI QR Code

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

제2형 당뇨병 환자에게 엽산과 아스코르브산 보충이 혈장 호모시스테인 농도와 산화 스트레스에 미치는 영향

  • 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)
  • 황미리 (전남대학교 생활과학대학 식품영양학과) ;
  • 소주련 (전북대학교 생활과학대학 식품영양학과) ;
  • 임현숙 (전남대학교 생활과학연구소)
  • Published : 2009.03.31

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

References

  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 https://doi.org/10.1111/j.1464-5491.1995.tb00544.x
  2. 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 https://doi.org/10.1007/s001250050023
  3. 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 https://doi.org/10.1056/NEJM199807233390404
  4. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969; 56(1): 111-128
  5. 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 https://doi.org/10.1001/archinte.157.20.2299
  6. van Guldener C, Stehouwer CD. Hyperhomocysteinemia, vascular pathology, and endothelial dysfunction. Semin Thromb Hemost 2000; 26(3): 281-289 https://doi.org/10.1055/s-2000-8472
  7. McCully KS. Chemical pathology of homocysteine I. Atherogenesis. Ann Clin Lab Sci 1993; 23(6): 477-493
  8. 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 https://doi.org/10.1046/j.1365-2362.1997.18807328.x
  9. 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 https://doi.org/10.1111/j.1365-2362.1995.tb01541.x
  10. 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 https://doi.org/10.1093/ajcn/57.5.650
  11. 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 https://doi.org/10.1161/01.ATV.17.7.1438
  12. 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 https://doi.org/10.1016/S0735-1097(00)00820-2
  13. Medina MA, Amores-Snchez MI. Homocysteine: an emergent cardiovascular risk factor? Eur J Clin Invest 2000; 30(9): 754-762 https://doi.org/10.1046/j.1365-2362.2000.00691.x
  14. 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 https://doi.org/10.1093/ajcn/67.2.263
  15. 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 https://doi.org/10.1172/JCI118763
  16. Davie SJ, Gould BJ, Yudkin JS. Effect of Vitamin C on glycosylation of protein. Diabetes 1992; 41(2): 167-173 https://doi.org/10.2337/diabetes.41.2.167
  17. Sies H, Stahl W. Vitamin E and vitamin C and carotenoid as antioxidants. Am J Clin Nutr 1995; 62(6): 1315s-1321s https://doi.org/10.1093/ajcn/62.6.1315S
  18. Rinkins LE. Effects of alloxan diabetes on rat river ascorbic acid. Horm Metab Res 1981; 13(2): 123-129 https://doi.org/10.1055/s-2007-1019193
  19. Som S, Basu S, Mukherjee D, Deb S, Choudhury PR, Mukherjee S. Ascorbic acid metabolism in diabetes mellitus. Metabolism 1981; 30(6): 572-577 https://doi.org/10.1016/0026-0495(81)90133-5
  20. 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
  21. 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
  22. 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
  23. 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 https://doi.org/10.1016/0009-8981(80)90144-8
  24. Lim HS. Folate status in pregnant and lactating women. J Korean Soc Food Sci Nutr 1997; 26(5): 983-992
  25. 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
  26. Dipolack AT. Safety of antioxidation vitamins and beta-carotene. Am J Clin Nutr 1995; 62(6): 1510s-1516s https://doi.org/10.1093/ajcn/62.6.1510S
  27. 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 https://doi.org/10.4040/jkan.2003.33.2.170
  28. 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 https://doi.org/10.1097/00007611-199709000-00008
  29. 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
  30. 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 https://doi.org/10.1007/BF00251831
  31. 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 https://doi.org/10.1111/j.1365-2362.1992.tb01940.x
  32. Brattstrom L. Vitamins as homocysteine-lowering agents. J Nutr 1996; 126(4): 1276s-1280s https://doi.org/10.1093/jn/126.suppl_4.1276S
  33. 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 https://doi.org/10.1056/NEJM199905133401901
  34. 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 https://doi.org/10.2337/diacare.23.4.524
  35. 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
  36. 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 https://doi.org/10.1161/01.CIR.101.13.1506
  37. 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 https://doi.org/10.1161/01.ATV.21.1.74
  38. 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 https://doi.org/10.1016/0021-9150(93)90258-V
  39. 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 https://doi.org/10.2337/diacare.23.12.1816
  40. 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 https://doi.org/10.1161/01.ATV.18.1.133
  41. 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 https://doi.org/10.1001/jama.274.19.1526
  42. 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
  43. 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 https://doi.org/10.1001/jama.281.22.2113
  44. 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 https://doi.org/10.1016/0891-5849(94)00202-U
  45. 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
  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 https://doi.org/10.1161/01.CIR.99.9.1156
  47. Shukla N, Angelini GD, Jeremy JY. The administration of folic acid reduces intravascular oxidative stress in diabetic rabbits. Metabolism 2008; 57(6): 774-781 https://doi.org/10.1016/j.metabol.2008.01.017

Cited by

  1. Effect of Folic Acid Supplementation on Homocysteine, Serum Total Antioxidant Capacity, and Malondialdehyde in Patients with Type 2 Diabetes Mellitus vol.30, pp.3, 2011, https://doi.org/10.1080/07315724.2011.10719962
  2. Effect of Dietary Supplementation of β-Carotene on Hepatic Antioxidant Enzyme Activities and Glutathione Concentration in Diabetic Rats vol.40, pp.8, 2011, https://doi.org/10.3746/jkfn.2011.40.8.1092