Effects of Folic Acid or Ascorbate Supplementation on Plasma Homocysteine Levels and Oxidative Stress in Korean Adults with Impaired Fasting Glucose

공복혈당장애 성인에서 엽산 또는 아스코르브산의 보충급여가 혈장 호모시스테인 수준과 산화 스트레스에 미치는 영향

  • Hwang, Mir-Ri (Department of Food and Nutrition, Chonnam National University) ;
  • Shin, Min-Ho (Department of Preventive Medicine, Chonnam National University, Medical School) ;
  • Rhee, Jung-Ae (Department of Preventive Medicine, Chonnam National University, Medical School) ;
  • Kweon, Sun-Seog (Jeonnam Regional Cancer Center, Hwasun Chonnam National University Hospital) ;
  • Lim, Hyeon-Sook (Department of Food and Nutrition, Chonnam National University)
  • 황미리 (전남대학교 생활과학대학 식품영양학과) ;
  • 신민호 (전남대학교 의과대학 예방의학교실) ;
  • 이정애 (전남대학교 의과대학 예방의학교실) ;
  • 권순석 (화순전남대학교병원 전남지역암센터) ;
  • 임현숙 (전남대학교 생활과학대학 식품영양학과)
  • Published : 2008.04.30

Abstract

Impaired fasting glucose (IFG) is one of significant risk factors of developing diabetes. The persons with IFG are, thus, an important target group for primary prevention of diabetes. It is well known that plasma homocysteine concentration may be increased in poor folate nutritional status. Elevated level of plasma homocysteine is considered as a marker of enhanced oxidative stress. In addition, the protective effect against oxidative stress may be diminished in poor antioxidative nutrient status as vitamin C. It is, therefore, important to maintain adequate nutritional status of folate and vitamin C in the patients with type 2 diabetes or IFG. This study was performed to determine the effects of supplementation of folic acid or vitamin C on plasma concentrations of homocysteine, oxidized LDL, and lipids and on the activity of plasma anti-oxidative enzyme in patients with IFG. A total of 97 patients with IFG were participated voluntarily with written consents. They were divided into one of the four experimental groups; Control (C), Folatesupplemented (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 were received 1,000 mg of vitamin C, and those in FA were given 1 mg of folate plus 1,000 mg of vitamin C daily for 4 weeks. No change in plasma concentrations of vitamin C, lipids, and oxidized LDL and the activity of GSH-Px were observed in vitamin C-supplemented group (A + FA) and folate-supplemented group (F + FA) compared to the placebo group (C + A). Only the folate-supplemented group (F + FA) had significantly increased average serum folate concentration and lowered plasma homocysteine concentration compared to the placebo group (C + A). Thus, it should be recommended the patients with IFG to increase folate intake through diets and, if it is not sufficient, to take folic acid supplements to prevent the development of complications induced by hyperhomocysteinemia as well as oxidative stress.

Keywords

References

  1. Al-Obaidi MK, Stubbs PJ, Collinson P, Conroy R, Graham I, Noble MI (2000): Elevated homocysteine levels are associated with increased ischemic myocardial injury in acute coronary syndromes. J Am Coll Cardiol 36(4): 1217-1222 https://doi.org/10.1016/S0735-1097(00)00820-2
  2. Asayama K, Nakane T, Uchida N, Hayashibe H, Dobashi K, Nakazawa S (1994): Serum antioxidant states in streptozotocininduced diabetic rat. Horm metab Res 26(7): 313-315 https://doi.org/10.1055/s-2007-1001693
  3. Aukrus P, Berge RK, Müller F, Ueland PM, Svardal AM, Froland SS (1997): Elevated plasma levels of reduced homocysteine in common variable immunodeficiency-a marker of enhanced oxidative stress. Eur J Clin Invest 27(10): 723-730 https://doi.org/10.1046/j.1365-2362.1997.18807328.x
  4. Bennett PH (1990): Epidemiology of diabetes mellitus. In: Rifkin H, Porte D, eds: Diabetes Mellitus Theory and Practice, 4th Ed. pp. 357-377, Elsevier, New York
  5. Blom HJ, Kleinveld HA, Boers GH, Demacker PN, Hak-Lemmers HL, Te Poele-Pothoff MT, Trijbels JM (1995): Lipid peroxidation and susceptibility of low-density lipoprotein to in vitro oxidation in hyperhomocysteinemia. Eur J Clin Invest 25(3): 149-154 https://doi.org/10.1111/j.1365-2362.1995.tb01541.x
  6. Brattstrom L (1996): Vitamins as homocysteine-lowering agents. J Nutr 126(4): 1276S-1280S https://doi.org/10.1093/jn/126.suppl_4.1276S
  7. Breskins MW, Thrahms CM, Worthington-Roberts B, Label RF, Kosolwski B (1985): Supplement use: vitamin intakes and biochemical indexes in 40 to 108 month-old children. J Am Diet Assoc 85(1): 49-59
  8. Capes S, Anand S (2001): What is type 2 diabetes? In: Gerstein HC, Haynes RB, eds: Evidence-Based Diabetes Care. pp. 151-163, Hamilton, Ont. Decker
  9. Chanarin I (1979): Folate in blood, cerebrospinal fluid and tissues. In: Chanarin I. ed: The Megablastic Anemias. p. 187, Oxford: Blackwell Scientific Publications
  10. Chang NS, Kim JM, Park SW, Cho YW, Kwon OO (2000): Folate intake and plasma homocysteine levels in the elderly patients with NIDDM. Korean J Nutr 33(3): 250-256
  11. Chauveau P, Chadefaux B, Coude M, Aupetit J, Kamoun P, Jungers P (1996): Long-term folic acid (but not pyridoxine) supplementation lowers elevated plasma homocysteine level in chronic renal failure. Miner Electrolyte Metab 22(1-3): 106-109
  12. Clarke R, Frost C, Leroy V, Collins R (1998): Homocysteine lowering trialist's collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomized trials. Br Med J 316(7135): 894-898 https://doi.org/10.1136/bmj.316.7135.894
  13. Daniel Bunout, MD, Argelia Garrido, MSc, Myriam Auazo, BQ, Ronald Kauffman, MD. Paz Venegas, RD, Pia de la Maza, MD, MSc, Margarita Petermann, MSc, and Sandra Hirsch, MD, MSc (2000): Effects of supplementation with Folic acid and antioxidant vitamins on homocysteine levels and LDL oxidation in coronary patients. Nutr 16(2): 107-110 https://doi.org/10.1016/S0899-9007(99)00248-8
  14. Davie SJ, Gould BJ, Yudkin (1992): Effect of Vitamin C on glycosylation of protein. Diabetes 41(2): 167-73 https://doi.org/10.2337/diabetes.41.2.167
  15. Edelstein SL, Knowler WC, Bain RP, Andres R, Barrett-Connor EL, Dowse GK, Haffner SM (1997): Predictors of progression from impaired glucose tolerance to NIDDM: An analysis of six prospective studies. Diabetes 46(4): 701-710 https://doi.org/10.2337/diabetes.46.4.701
  16. Fonseca VA, Stone A, Munshi M, Baliga BS, Aljada A, Thusu K, Fink L, Dandona P (1997): Oxidative stress in diabetic macrovascular disease: does homocysteine play a role? South Med J 90(9): 903-906 https://doi.org/10.1097/00007611-199709000-00008
  17. Friedwald WT, Levy RI (1972): Fredrickson DS. Estimation of the concentration of low density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 18(6): 499-502
  18. Frosst P, Blom HJ, Milos R, Goyette P, heppard CA, Matthews RG, Boers GJH, den Heijer M, Kluijtmans LAJ, van den Heuvel LP, Rozen R (1995): A candidate genetic risk factors for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10(1): 111-113 https://doi.org/10.1038/ng0595-111
  19. Gibson RS (1990): Principles of Nutritional Assessment. pp. 378- 379, Oxford University Press, New York
  20. Ha AW, Kim HM (1999): The study of lipid-peroxidation, antioxidant enzymes, and the antioxidant vitamins in NIDDM patients with microvascular-diabetic complications. Korean J Nutr 32(1): 17-23
  21. Herbert V (1987): The 1986 Herman Award Lecture. Nutrition science as a continually unfolding: the folate and vitamin B-12 paradigm. Am J Clin Nutr 46(3): 387-402 https://doi.org/10.1093/ajcn/46.3.387
  22. Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH (1999): The effect of Folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 340(19): 1449-1454 https://doi.org/10.1056/NEJM199905133401901
  23. Kang NE, Kim WK (1999): Effects of antioxidant Vitamins supplementation on antioxidative status and plasma lipid profiles in Korean NIDDM patients. Korean J Nutr 32(7): 775-780
  24. Kown SJ, Kim EK (2002): Anthropometry, blood pressure, serum lipid levels and nutrient intakes in people with impaired fasting glucose and with diabetes. Korean J Nutr 35(3): 303-313
  25. Koh ET (1984): Effects of vitamin C on blood parameters of hypertensive subjects. J Oklahoma State Med Assoc 77(6): 177- 182
  26. Kedziora-Kornatowska KZ, Luciak M, Blaszczyk J, Pawlak W (1998): Lipid peroxidation and activity of antioxidant enzymes in erythrocyte of patients with NIDDM with or without diabetic nephropathy. Nephrol Dial Transplant 13(11): 2829-2832 https://doi.org/10.1093/ndt/13.11.2829
  27. Lauer RM, Clarke WP, Lee J (1998): Factors affecting the relationship between childhood and adult cholesterol levels. The Muscatine study. Pediatrics 82(3): 309-318
  28. Lee MH, Lee DS, Ihm SH, YU JM (1996): Level of plasma lipid hydroperoxides in NIDDM patients. Korean J Diabetes 20(2): 124-133
  29. Lim JY, Kim OH, Kim JH (2006): Effects of antioxidant supplementation on lipid profiles in elderly women. Korean J Community Nutr 11(1): 133-142
  30. Lu J, Pan C, Tian H (1996): Study of insulin sensitivity and its related factors in patients with non-insulin dependent diabetes mellitus and impaird glucose tolerance. Chinese J Intern Med 35(10): 678-681
  31. McCully KS (1993): Chemical pathology of homocysteine I. Atherogenesis. Ann Clin Lab Sci 23(6): 477-493
  32. McCully KS (1969): Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 56(1): 111-128
  33. McKinley MC (2000): Nutritional aspects and possible pathological mechanisms of hyperhomocysteinaemia: an independent risk factor for vascular disease. Proc Nutr Soc 59(2): 221-237
  34. Medina MA, Amores-Sanchez MI (2000): Homocysteine: an emergent cardiovascular risk factor? Eur J Clin Invest 30(9): 754-762
  35. Min HS (2001): Folate status and plasma homocysteine concentration of Korean adults. Korean J Nutr 34(4): 393-400
  36. Nappo F, De Rosa N, Marfella R, De Lucia D, Ingrosso D, Perna AF, Farzati B, Giugliano D (1999): Impairment of endothelial functions by acute hyperhomocysteinemia and reversal by antioxidant vitamins. JAMA 281(22): 2113-2118 https://doi.org/10.1001/jama.281.22.2113
  37. Nygard O, Refsum H, Ueland PM, Vollset SE (1998): Major lifestyle determinants of plasma total homocysteine distribution: The Hordaland homocysteine study. Am J Clin Nutr 67(2): 263-270 https://doi.org/10.1093/ajcn/67.2.263
  38. Oiao Q, Rajala U, Keinanen-Kiukaanniemi S (1998): Hypertension, hyperinsulinaemia and obesity in middle-aged Finns with Impaired glucose tolerance. J Hypertension 12(4): 265-269 https://doi.org/10.1038/sj.jhh.1000602
  39. Okamura M (1980): An improved method for determination of Lascorbic acid and L-dehydroascorbic acid in blood plasma. Clinica Chimica Acta 103(3): 259-268 https://doi.org/10.1016/0009-8981(80)90144-8
  40. Park, HS, Lee, YM (2003): Effects of vitamin C supplementation on blood sugar and antioxidative status in type 2 diabetes mellitus patients. J Korean Acad Nurs 33(2): 170-178 https://doi.org/10.4040/jkan.2003.33.2.170
  41. Racek J, Rusnakova H, Trefil L, Siala KK (2005): The Influence of folate and antioxidants on homocysteine levels and oxidative stress in patients with hyperlipidemia and hyperhomocysteinemia. Physiol Res 54(1): 87-95
  42. Reaven PD, Khouw A, Beltz WF, Parthasarathy S, Witztum JL (1993): Effect of dietary antioxidant combinations in human. Protection of LDL by vitamine E but not by beta carotene. Arterioscler Thromb Vasc Biol 13(4): 590-600 https://doi.org/10.1161/01.ATV.13.4.590
  43. Ross R (1986): The pathogenesis of atherosclerosis an update. N Engl J Med 314(8): 488-500 https://doi.org/10.1056/NEJM198602203140806
  44. Rydlewicz A, Simpson JA, Taylor RJ, Bond CM, Golden MHN (2002): The effect of Folic acid supplementation on plasma homocysteine in an elderly population. QJM 95(1): 27-35 https://doi.org/10.1093/qjmed/95.1.27
  45. Sargeant LA, Wareham NJ, Bingham S, Day NE, Luben R, Oakes S, Welch A, Khaw KT (2000): Vitamin C and hyperglycemia in the European prospective investigation into Cancer Norfolk (EPIC - Norfolk) study: a population-based study. Diabetes Care 23(6): 726-732 https://doi.org/10.2337/diacare.23.6.726
  46. Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH (1993): Vitamin status and intakes as primary determinants of homocystenemia in an elderly population. JAMA 270(22): 2693- 2698 https://doi.org/10.1001/jama.270.22.2693
  47. Sies H, Stahl W (1995): Vitamin E and Vitamin C and carotenoid as antioxidants. Am J Clin Nutr 62(6): 1315s-1321s https://doi.org/10.1093/ajcn/62.6.1315S
  48. Som S, Basu S, Mukherjee D, Deb S, Choudhury PR, Mukherjee S (1981): Chatterjee SN, Chatterjee IB. Ascorbic acid metabolism in diabetes mellitus. Metabolism 30(6): 572-577 https://doi.org/10.1016/0026-0495(81)90133-5
  49. Stevens MJ, Feldman EL, Greene DA (1995): The etiology of diabetic neuropathy: The combined roles of metabolic and vascular defect. Diabetic Med 12(7): 1566-1579 1995
  50. Targher G, Bertolini L, Zenari L, Cacciatori V, Muggeo M, Faccini G, Zoppini G (2000): Cigarette smoking and plasma total homocysteine levels in young adults with type 1 diabetes. Diabetes Care 23(4): 524-528 https://doi.org/10.2337/diacare.23.4.524
  51. The Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003): Report of the Expert Committee on the Diagnosis and Classification of Diabetes Melllitus. Diabetes Care 26(1): S5-S20 https://doi.org/10.2337/diacare.26.2007.S5
  52. The Expert Committee on Diagnosis and Classification of Diabetes Melllitus (1997): Report of the Expert Committee on the Diagnosis and Classification of Diabetes Melllitus. Diabetes Care 20(1): 1183-1197 https://doi.org/10.2337/diacare.20.7.1183
  53. The Korean Nutrition Society (2005): CAN-Pro 3.0. Seoul
  54. The Korean Nutrition Society (2005): Dietary Reference Intake For Korean. Seoul
  55. Ueland PM, Refsum H, Stabler SP, Malinow MR, Andersson A, Allen RH (1993): Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem 39(9): 1764-1779
  56. Van Guldener C, Stehouwer CD (2000): Hyperhomocysteinemia, vascular pathology, and endothelial dysfunction. Semin Thromb Hemos 26(3): 281-289 https://doi.org/10.1055/s-2000-8472
  57. Varillo AR, Ade T, Golia R, Nunziata V (1983): The relationship between glycosylated haemoglobin levels and various degrees of glucose intolerance. Diabetologia 24(5): 391-393 https://doi.org/10.1007/BF00251831
  58. Witium TL, Lancet (1994): The oxidation hypothesis of atherosclerosis. Lancet 344(8925): 793-795 https://doi.org/10.1016/S0140-6736(94)92346-9
  59. Woo HO (1999): Vitamin C concentration in whole blood and plasma among residents living in southern central part of Korea. Thesis of Gyeongsang National University
  60. World Health Organization (1985): WHO Study Group on Diabetes mellitus. Technical Report Series 727. Geneva
  61. World Health Organization Regional Office for the Western Pacific (WPRO), the International Association for the Study of Obesity (IASO) and the International Obesity Task Force (IOTF) (2000): The Asia-Pacific Perspective: Redefining Obesity and Its Treatment. Geneva
  62. World Health Organization (2003): The Expert Committee on Diabetes mellitus. Technical Report Series 646. Geneva
  63. Yang YJ, Kim JY (2000): The nutritional status of middle aged Korean men exhibiting impaired glucose tolerance and their blood lipid profile. Korean J Nutr 33(1): 59-67
  64. Yishai L, Haya Z, Ami BA, Yoram K, Michael A (1999): $\beta$-Carotene affects antioxidant status in non-insulin-dependent diabetes mellitus. Pathophysiology 6(3): 157-161 https://doi.org/10.1016/S0928-4680(99)00013-9
  65. Yoshida H, Ishikawa T, Nakamura H (1997): Vitamin E/lipid peroxide ratio and susceptibility of LDL to oxidative modification in NIDDM. Arterioscler Throm Vasc Biol 17(7): 1438-1446 https://doi.org/10.1161/01.ATV.17.7.1438
  66. Yudkin JS, Alberti KG, McLarty DG, Swai AB. Impaired glucose tolerance (1990): Br Med J 301(6749): 397-402 https://doi.org/10.1136/bmj.301.6749.397
  67. Yu BJ, Bae HY, Lee BR (1993): The activity of erythrocyte antioxidant enzymes in diabetes mellitus, Korean J Intern Med 44(6): 766-774