Skip to main content
Top
Published in: European Journal of Nutrition 8/2008

01-12-2008 | ORIGINAL CONTRIBUTION

B-vitamins, homocysteine and gene polymorphism in adults with fasting or post-methionine loading hyperhomocysteinemia

Authors: Chien-Hsiung Cheng, Yi-Chia Huang, Feng-Pan Chen, Ming-Chih Chou, Tsung-Po Tsai

Published in: European Journal of Nutrition | Issue 8/2008

Login to get access

Abstract

Background

Although fasting and post-methionine loading (PML) homocysteine concentrations are not necessarily related, a high percentage of hyperhomocysteinemia cases would be missed if methionine loading was not performed.

Aim of the study

The influences of B-vitamins and genetic polymorphism (methylenetetrahydrofolate reductase 677C → T, MTHFR 677C → T) on fasting and PML homocysteine concentrations and the relationship between fasting and PML homocysteine were studied.

Methods

This study was a cross-sectional study. Healthy subjects were divided into either fasting hyper-homocysteinemia (≥12.2 µmol/l) (fasting hyper-hcy, n = 51), PML hyper-homocysteinemia (fasting homocysteine <12.2 µmol/l but PML homocysteine ≥25.6 µmol/l) (PML hyper-hcy, n = 29), or normo-homocysteinemia (fasting homocysteine <12.2 µmol/l and PML homocysteine <25.6 µmol/l) (normo-hcy, n = 118) group based on elevated fasting and PML homocysteine levels of the 75th percentile of the population. The concentrations of plasma fasting and PML homocysteine, serum folate, vitamin B-12, plasma pyridoxal 5′- phosphate (PLP) were measured. The genetic polymorphisms were determined.

Results

Fasting homocysteine, but not PML homocysteine and MTHFR 677C → T genotype, was significantly and inversely affected by serum folate concentration after adjusting for potential confounders (β = −0.062, P < 0.01). Fasting and PML homocysteine were highly associated in the fasting hyper-hcy and pooled groups (P < 0.01) but not in the PML hyper-hcy and normo-hcy groups. PML homocysteine did not interact with either serum folate (P = 0.302), vitamin B-12 (P = 0.465), plasma PLP (P = 0.996) or MTHFR 677C → T genotype (P = 0.136) to affect fasting homocysteine concentration.

Conclusions

Approximately one-third (36.3%) of hyperhomocysteinemia cases would be missed if methionine loading were not performed. Even though subjects may have a normal fasting homocysteine concentration, they need further screening for their PML homocysteine.
Literature
1.
go back to reference Araki A, Sako Y (1987) Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr 422: 43–52CrossRef Araki A, Sako Y (1987) Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr 422: 43–52CrossRef
2.
go back to reference Bates CJ, Pentieva KD, Matthews N, Macdonald A (1999) A simple, sensitive and reproducible assay for pyridoxal 5′-phosphate and 4-pyridoxic acid in human plasma. Chin Chim Acta 280:101–111CrossRef Bates CJ, Pentieva KD, Matthews N, Macdonald A (1999) A simple, sensitive and reproducible assay for pyridoxal 5′-phosphate and 4-pyridoxic acid in human plasma. Chin Chim Acta 280:101–111CrossRef
3.
go back to reference Bostom AG, Jacques PF, Nadeau MR, Williams RR, Ellison RC, Selhub J (1995) Post-methionine load hyperhomocysteinemia in persons with normal fasting total plasma homocysteine: initial results from the NHLBI Family Heart Study. Atherosclerosis 116:147–51CrossRef Bostom AG, Jacques PF, Nadeau MR, Williams RR, Ellison RC, Selhub J (1995) Post-methionine load hyperhomocysteinemia in persons with normal fasting total plasma homocysteine: initial results from the NHLBI Family Heart Study. Atherosclerosis 116:147–51CrossRef
4.
go back to reference Boushey CJ, Beresford SA, Omenn GS, Motulsky AG (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intake. JAMA 274:1049–1057CrossRef Boushey CJ, Beresford SA, Omenn GS, Motulsky AG (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intake. JAMA 274:1049–1057CrossRef
5.
go back to reference Brattström L, Israelsson B, Norrving B, Bergqvist D, Thorne J, Hultberg B, Hamfelt A (1990) Impaired homocysteine metabolism in early-onset cerebral and peripheral occlusive arterial disease. Effects of pyridoxine and folic acid treatment. Atherosclerosis 81:51–60CrossRef Brattström L, Israelsson B, Norrving B, Bergqvist D, Thorne J, Hultberg B, Hamfelt A (1990) Impaired homocysteine metabolism in early-onset cerebral and peripheral occlusive arterial disease. Effects of pyridoxine and folic acid treatment. Atherosclerosis 81:51–60CrossRef
6.
go back to reference Clarke R, Armitage J (2000) Vitamin supplements and cardiovascular risk: review of the randomized trials of homocysteine-lowering vitamin supplements. Semin Thromb Hemost 26:341–348CrossRef Clarke R, Armitage J (2000) Vitamin supplements and cardiovascular risk: review of the randomized trials of homocysteine-lowering vitamin supplements. Semin Thromb Hemost 26:341–348CrossRef
7.
go back to reference Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, Graham I (1991) Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 324:1149–1155 Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, Graham I (1991) Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 324:1149–1155
8.
go back to reference Dudman NP, Wilcken DE, Wang J, Lynch JF, Macey D, Lundberg P (1993) Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology. Arterioscler Thromb 13:1253–1260 Dudman NP, Wilcken DE, Wang J, Lynch JF, Macey D, Lundberg P (1993) Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology. Arterioscler Thromb 13:1253–1260
9.
go back to reference Dunkelgrun M, Hoeks SE, Schouten O, Feringa HHH, Welten GMJM, Vidakovic R, van Gestel YRBM, van Domburg RT, Goei D, de Jonge R, Lindemans J, Poldermans D (2008) Methionine loading does not enhance the predictive value of homocysteine serum testing for all-cause mortality or major adverse cardiac events. Intern Med J (in press) Dunkelgrun M, Hoeks SE, Schouten O, Feringa HHH, Welten GMJM, Vidakovic R, van Gestel YRBM, van Domburg RT, Goei D, de Jonge R, Lindemans J, Poldermans D (2008) Methionine loading does not enhance the predictive value of homocysteine serum testing for all-cause mortality or major adverse cardiac events. Intern Med J (in press)
10.
go back to reference Durand P, Prost M, Loreau N, Lussier-Cacan S, Blache D (2001) Impaired homocysteine metabolism and atherothrombotic disease. Lab Invest 81:645–672CrossRef Durand P, Prost M, Loreau N, Lussier-Cacan S, Blache D (2001) Impaired homocysteine metabolism and atherothrombotic disease. Lab Invest 81:645–672CrossRef
11.
go back to reference Girelli D, Martinelli N, Olivieri O, Pizzolo F, Friso S, Faccini G, Bozzini C, Tenuti I, LottoV Villa G, Guarini P, Trabetti E, Pignatti PF, Mazzucco A, Corrocher R (2006) Hyperhomocysteinemia and mortality after coronary artery bypass grafting. Plos One 1:e83CrossRef Girelli D, Martinelli N, Olivieri O, Pizzolo F, Friso S, Faccini G, Bozzini C, Tenuti I, LottoV Villa G, Guarini P, Trabetti E, Pignatti PF, Mazzucco A, Corrocher R (2006) Hyperhomocysteinemia and mortality after coronary artery bypass grafting. Plos One 1:e83CrossRef
12.
go back to reference Giusti B, Camacho-Vanegas O, Attanosio M, Comeglio P, Gori AM, Brunelli T, Prisco D, Gensini GF, Abbate R, Pepe G (1999) Microheterogeneity in the distribution of the 844ins68 in the cystathionine β-synthase gene in Italy. Thromb Res 94:249–254CrossRef Giusti B, Camacho-Vanegas O, Attanosio M, Comeglio P, Gori AM, Brunelli T, Prisco D, Gensini GF, Abbate R, Pepe G (1999) Microheterogeneity in the distribution of the 844ins68 in the cystathionine β-synthase gene in Italy. Thromb Res 94:249–254CrossRef
13.
go back to reference Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, Boers GH, Sheahan RG, Israelsson B, Uiterwaal CS, Meleady R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht JC, de Valk HW, Sales Luis AC, Parrot-Rouland FM, Tan KS, Higgins I, Garcon D, Andria G (1997) Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA 277:1775–1781CrossRef Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, Boers GH, Sheahan RG, Israelsson B, Uiterwaal CS, Meleady R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht JC, de Valk HW, Sales Luis AC, Parrot-Rouland FM, Tan KS, Higgins I, Garcon D, Andria G (1997) Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA 277:1775–1781CrossRef
14.
go back to reference Hart SR, Mangoni AA, Swift CG, Jackson SH (2006) Effect of methionine loading on pulse wave analysis in elderly volunteers. Postgrad Med J 82:524–527CrossRef Hart SR, Mangoni AA, Swift CG, Jackson SH (2006) Effect of methionine loading on pulse wave analysis in elderly volunteers. Postgrad Med J 82:524–527CrossRef
15.
go back to reference Hart SR, Mangoni AA, Swift CG, Jackson SHD (2006) Lack of significant effects of methionine loading on endothelial function in elderly volunteers. Heat Lung Circ 15:358–361CrossRef Hart SR, Mangoni AA, Swift CG, Jackson SHD (2006) Lack of significant effects of methionine loading on endothelial function in elderly volunteers. Heat Lung Circ 15:358–361CrossRef
16.
go back to reference Lee BJ, Lin PT, Liaw YP, Chang SJ, Cheng CH, Huang YC (2003) Homocysteine and risk of coronary artery disease: folate is the important determinant of plasma homocysteine concentration. Nutrition 19:577–583CrossRef Lee BJ, Lin PT, Liaw YP, Chang SJ, Cheng CH, Huang YC (2003) Homocysteine and risk of coronary artery disease: folate is the important determinant of plasma homocysteine concentration. Nutrition 19:577–583CrossRef
17.
go back to reference Lee BJ, Huang MC, Chung LJ, Cheng CH, Lin KL, Su KH, Huang YC (2004) Folic acid and vitamin B-12 are more effective than vitamin B-6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease. Eur J Clin Nutr 58:481–487CrossRef Lee BJ, Huang MC, Chung LJ, Cheng CH, Lin KL, Su KH, Huang YC (2004) Folic acid and vitamin B-12 are more effective than vitamin B-6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease. Eur J Clin Nutr 58:481–487CrossRef
18.
go back to reference Ma J, Stampfer MJ, Hennekens CH, Frosst P, Selhub J, Horsford J, Malinow MR, Willett WC, Rozen R (1996) Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US physicians. Circulation 94:2410–2416 Ma J, Stampfer MJ, Hennekens CH, Frosst P, Selhub J, Horsford J, Malinow MR, Willett WC, Rozen R (1996) Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US physicians. Circulation 94:2410–2416
19.
go back to reference Malinow MR, Bostom AG, Krauss RM (1999) Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 99:178–82 Malinow MR, Bostom AG, Krauss RM (1999) Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 99:178–82
20.
go back to reference Marcucci R, Giusti B, Betti I, Evangelisti L, Fedi S, Sodi A, Cappelli S, Menchini U, Abbate R, Prisco D (2003) Genetic determinants of fasting and post-methionine hyperhomocysteinemia in patients with retinal vein occlusion. Thromb Res 11:7–12CrossRef Marcucci R, Giusti B, Betti I, Evangelisti L, Fedi S, Sodi A, Cappelli S, Menchini U, Abbate R, Prisco D (2003) Genetic determinants of fasting and post-methionine hyperhomocysteinemia in patients with retinal vein occlusion. Thromb Res 11:7–12CrossRef
21.
go back to reference Miller JW, Nadeau MR, Smith D, Selhub J (1994) Vitamin B–6 deficiency vs folate deficiency: comparison of responses to methionine loading in rats. Am J Clin Nutr 59:1033–1039 Miller JW, Nadeau MR, Smith D, Selhub J (1994) Vitamin B–6 deficiency vs folate deficiency: comparison of responses to methionine loading in rats. Am J Clin Nutr 59:1033–1039
22.
go back to reference Qujeq D, Omran TS, Hosini L (2001) Correlation between total homocysteine, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in the serum of patients with myocardial infarction. Clin Biochem 34:97–101CrossRef Qujeq D, Omran TS, Hosini L (2001) Correlation between total homocysteine, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in the serum of patients with myocardial infarction. Clin Biochem 34:97–101CrossRef
23.
go back to reference Refsum H, Ueland PM (1998) Recent data are not in conflict with homocysteine as a cardiovascular risk factor. Curr Opin Lipidol 9:533–539CrossRef Refsum H, Ueland PM (1998) Recent data are not in conflict with homocysteine as a cardiovascular risk factor. Curr Opin Lipidol 9:533–539CrossRef
24.
go back to reference Refsum H, Ueland PM, Nygrd O, Vollset SE (1998) Homocysteine and cardiovascular disease. Annu Rev Med 49:31–62CrossRef Refsum H, Ueland PM, Nygrd O, Vollset SE (1998) Homocysteine and cardiovascular disease. Annu Rev Med 49:31–62CrossRef
25.
go back to reference Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH (1993) Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 270:2693–2698CrossRef Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH (1993) Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 270:2693–2698CrossRef
26.
go back to reference Selhub J, Miller JW (1992) Hypothesis—the pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr 55:131–138 Selhub J, Miller JW (1992) Hypothesis—the pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr 55:131–138
27.
go back to reference Stampfer MJ, Malinow MR, Willett WC, Newcomer LM, Upson B, Ullmann D, Tishler PV, Hennekens CH (1992) A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 268:877–881CrossRef Stampfer MJ, Malinow MR, Willett WC, Newcomer LM, Upson B, Ullmann D, Tishler PV, Hennekens CH (1992) A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 268:877–881CrossRef
28.
go back to reference Tsai MY, Welge BG, Hanson NQ, Bignell MK, Vessey J, Schwichtenberg K, Yang F, Bullemer FE, Rasmussen R, Graham KJ (1999) Genetic causes of mild hyperhomocysteinemia in patients with premature occlusive coronary artery diseases. Atherosclerosis 143:163–170CrossRef Tsai MY, Welge BG, Hanson NQ, Bignell MK, Vessey J, Schwichtenberg K, Yang F, Bullemer FE, Rasmussen R, Graham KJ (1999) Genetic causes of mild hyperhomocysteinemia in patients with premature occlusive coronary artery diseases. Atherosclerosis 143:163–170CrossRef
29.
go back to reference Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP, Riezler R, Vermaak WJ (1996) The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J Clin Invest 98:177–184CrossRef Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP, Riezler R, Vermaak WJ (1996) The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J Clin Invest 98:177–184CrossRef
30.
go back to reference Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ, Delport R, Potgieter HC (1994) Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 124:1927–1933 Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ, Delport R, Potgieter HC (1994) Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 124:1927–1933
31.
go back to reference van den Berg M, de Jong SC, Devillé W, Rauwerda JA, Jakobs C, Pals G, Boers GH, Stehouwer CD (1999) Variability of fasting and post-methionine plasma homocysteine levels in normo- and hyperhomocysteinemia individuals. Neth J Med 55:29–38CrossRef van den Berg M, de Jong SC, Devillé W, Rauwerda JA, Jakobs C, Pals G, Boers GH, Stehouwer CD (1999) Variability of fasting and post-methionine plasma homocysteine levels in normo- and hyperhomocysteinemia individuals. Neth J Med 55:29–38CrossRef
32.
go back to reference van der Griend R, Haas FJLM, Duran M, Biesma DH, Th Meuwissen OJA, Banga JD (1998) Methionine loading test is necessary for detection of hyperhomocysteinemia. J Lab Clin Med 132:67–72CrossRef van der Griend R, Haas FJLM, Duran M, Biesma DH, Th Meuwissen OJA, Banga JD (1998) Methionine loading test is necessary for detection of hyperhomocysteinemia. J Lab Clin Med 132:67–72CrossRef
33.
go back to reference Ventura P, Panini R, Verlato C, Scarpetta G, Salvioli G (2000) Peroxidation indices and total antioxidant capacity in plasma during hyperhomocysteinemia induced by methionine oral loading. Metab Clin Exp 49:225–228 Ventura P, Panini R, Verlato C, Scarpetta G, Salvioli G (2000) Peroxidation indices and total antioxidant capacity in plasma during hyperhomocysteinemia induced by methionine oral loading. Metab Clin Exp 49:225–228
34.
go back to reference Verhoef P, Kok FJ, Kluijtmans LA, Blom HJ, Refsum H, Ueland PM, Kruyssen DA (1997) The 677C → T mutation in the methylenetetrahydrofolate reductase gene: associations with plasma total homocysteine levels and risk of coronary atherosclerotic disease. Atherosclerosis 132:105–113CrossRef Verhoef P, Kok FJ, Kluijtmans LA, Blom HJ, Refsum H, Ueland PM, Kruyssen DA (1997) The 677C → T mutation in the methylenetetrahydrofolate reductase gene: associations with plasma total homocysteine levels and risk of coronary atherosclerotic disease. Atherosclerosis 132:105–113CrossRef
35.
go back to reference Verhoef P, Stampfer MJ, Buring JE, Gaziano JM, Allen RH, Stabler SP, Reynolds RD, Kok FJ, Hennekens CH, Willett WC (1996) Homocysteine metabolism and risk of myocardial infarction: relation with vitamin B6, B12, and folate. Am J Epidemiol 143:845–859 Verhoef P, Stampfer MJ, Buring JE, Gaziano JM, Allen RH, Stabler SP, Reynolds RD, Kok FJ, Hennekens CH, Willett WC (1996) Homocysteine metabolism and risk of myocardial infarction: relation with vitamin B6, B12, and folate. Am J Epidemiol 143:845–859
36.
go back to reference Zhang G, Dai C (2001) Gene polymorphism of homocysteine metabolism-related enzymes in Chinese patients with occlusive coronary artery or cerebral vascular disease. Thromb Res 104:187–195CrossRef Zhang G, Dai C (2001) Gene polymorphism of homocysteine metabolism-related enzymes in Chinese patients with occlusive coronary artery or cerebral vascular disease. Thromb Res 104:187–195CrossRef
Metadata
Title
B-vitamins, homocysteine and gene polymorphism in adults with fasting or post-methionine loading hyperhomocysteinemia
Authors
Chien-Hsiung Cheng
Yi-Chia Huang
Feng-Pan Chen
Ming-Chih Chou
Tsung-Po Tsai
Publication date
01-12-2008
Publisher
D. Steinkopff-Verlag
Published in
European Journal of Nutrition / Issue 8/2008
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-008-0752-5

Other articles of this Issue 8/2008

European Journal of Nutrition 8/2008 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.