Korean J Nutr.  2009 Mar;42(2):107-118. 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

Affiliations
  • 1Department of Food & Nutrition, Chonnam National University, Gwangju 500-757, Korea. limhs@chonnam.ac.kr
  • 2Department of Food & Nutrition, Chonbuk National University, Jeonju 561-756, Korea.
  • 3Human Ecology Research Institute, Chonnam National University, Gwangju 500-757, Korea.

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 (HbA1c) 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.

Keyword

folate; ascorbate; diabetes; homocysteine; oxidative stress

MeSH Terms

Ascorbic Acid
Cholesterol
Diabetes Mellitus, Type 2
Folic Acid
Glutathione Peroxidase
Hemoglobins
Homocysteine
Humans
Lipoproteins, LDL
Oxidative Stress
Plasma
Ascorbic Acid
Cholesterol
Folic Acid
Glutathione Peroxidase
Hemoglobins
Homocysteine
Lipoproteins, LDL

Reference

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.
2. Lehto S, Rönnemaa T, Pyörälä 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.
Article
3. Haffner SM, Lehto S, Rönnemaa T, Pyörälä 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.
Article
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.
6. van Guldener C, Stehouwer CD. Hyperhomocysteinemia, vascular pathology, and endothelial dysfunction. Semin Thromb Hemost. 2000. 26(3):281–289.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
13. Medina MA, Amores-Snchez MI. Homocysteine: an emergent cardiovascular risk factor? Eur J Clin Invest. 2000. 30(9):754–762.
Article
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.
Article
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.
Article
16. Davie SJ, Gould BJ, Yudkin JS. Effect of Vitamin C on glycosylation of protein. Diabetes. 192. 41(2):167–173.
17. Sies H, Stahl W. Vitamin E and vitamin C and carotenoid as antioxidants. Am J Clin Nutr. 1995. 62(6):1315s–1321s.
18. Rinkins LE. Effects of alloxan diabetes on rat river ascorbic acid. Horm Metab Res. 1981. 13(2):123–129.
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.
Article
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.
Article
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.
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.
Article
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.
Article
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.
Article
31. Andersson A, Brattström 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.
32. Brattstrom L. Vitamins as homocysteine-lowering agents. J Nutr. 1996. 126(4):1276s–1280s.
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.
Article
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.
Article
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 follow-up of the Hoorn Study. Circulation. 2000. 101(13):1506–1511.
Article
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.
Article
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.
Article
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.
Article
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.
Article
41. Nygård 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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
Full Text Links
  • KJN
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr