Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Communication
  • Published:

Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR(C677T) genotype. Inter99 (7)

Abstract

Objective: To examine the associations between various lifestyle factors—smoking habits, physical activity, dietary habits, coffee, tea, and alcohol consumption—and homocysteine (tHcy) in relation to MTHFR(C677T) genotype.

Design: Cross-sectional population-based study.

Setting: Residents of Copenhagen County, Denmark.

Subjects: A random sample of 6457 men and women aged 30–60 years drawn from the Civil Registration System and invited to a health examination in 1999–2001. A total of 2788 participants were included in the statistical analysis.

Main outcome measures: tHcy was measured using a Fluorescent Polarization Immuno Assay. MTHFR-genotype was determined by PCR and RFLP analysis. Information about lifestyle factors was obtained from a self-administered questionnaire.

Results: Daily smoking, less healthy dietary habits, and coffee drinking were associated with elevated tHcy concentrations independent of other determinants. Wine consumption was related to tHcy in a J-shaped manner, whereas beer consumption was negatively associated with tHcy after multiple adjustments. Interaction was observed between smoking status and MTHFR-genotype, smoking status and sex, and beer consumption and age. The effect of smoking was more pronounced in persons with the TT genotype and in women. The effect of beer consumption was more pronounced at younger than at older ages.

Conclusions: Smoking status, dietary habits, coffee intake, wine, and beer consumption were major lifestyle determinants of tHcy. Changes in these lifestyle factors may reduce tHcy concentrations, thereby lowering cardiovascular risk in the general population.

Sponsorship: Danish Medical Research Council, Danish Centre for Evaluation and Health Technology Assessment, and Danish Heart Foundation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  • Bleich S, Bleich K, Kropp S, Bittermann HJ, Degner D, Sperling W, Ruther E & Kornhuber J (2001): Moderate alcohol consumption in social drinkers raises plasma homocysteine levels: a contradiction to the ‘French Paradox’? Alcohol 36, 189–192.

    Article  CAS  Google Scholar 

  • 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 intakes. JAMA 274, 1049–1057.

    Article  CAS  PubMed  Google Scholar 

  • Brattstrom L, Wilcken DE, Ohrvik J & Brudin L (1998): Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis. Circulation 98, 2520–2526.

    Article  CAS  PubMed  Google Scholar 

  • Cafolla A, Dragoni F, Girelli G, Tosti ME, Costante A, Pastorelli D, Bedogni G & Scott S (2000): Folate status in Italian blood donors: relation to gender and smoking. Haematologica 85, 694–698.

    CAS  PubMed  Google Scholar 

  • Christensen B, Mosdol A, Retterstol L, Landaas S & Thelle DS (2001): Abstention from filtered coffee reduces the concentrations of plasma homocysteine and serum cholesterol—a randomized controlled trial. Am. J. Clin. Nutr. 74, 302–307.

    Article  CAS  PubMed  Google Scholar 

  • Clarke R & Armitage J (2000): Vitamin supplements and cardiovascular risk: review of the randomized trials of homocysteine-lowering vitamin supplements. Semin. Thromb. Hemost. 26, 341–348.

    Article  CAS  PubMed  Google Scholar 

  • Cravo ML, Gloria LM, Selhub J, Nadeau MR, Camilo ME, Resende MP, Cardoso JN, Leitao CN & Mira FC (1996): Hyperhomocysteinemia in chronic alcoholism: correlation with folate, vitamin B-12, and vitamin B-6 status. Am. J. Clin. Nutr. 63, 220–224.

    Article  CAS  PubMed  Google Scholar 

  • De Bree A, Verschuren WM, Blom HJ & Kromhout D (2001a): Lifestyle factors and plasma homocysteine concentrations in a general population sample. Am. J. Epidemiol. 154, 150–154.

    Article  CAS  PubMed  Google Scholar 

  • De Bree A, Verschuren WM, Blom HJ & Kromhout D (2001b): Association between B vitamin intake and plasma homocysteine concentration in the general Dutch population aged 20-65 y. Am. J. Clin. Nutr. 73, 1027–1033.

    Article  CAS  PubMed  Google Scholar 

  • De Bree A, Verschuren WM, Blom HJ & Kromhout D (2001c): Alcohol consumption and plasma homocysteine: what's brewing? Atherosclerosis 30, 626–627.

    CAS  Google Scholar 

  • De Bree A, Verschuren WM, Kromhout D, Kluijtmans LA & Blom HJ (2002): Homocysteine determinants and the evidence to what extent homocysteine determines the risk of coronary heart disease. Pharmacol. Rev. 54, 599–618.

    Article  CAS  PubMed  Google Scholar 

  • Dekou V, Gudnason V, Hawe E, Miller GJ, Stansbie D & Humphries SE (2001): Gene–environment and gene–gene interaction in the determination of plasma homocysteine levels in healthy middle-aged men. Thromb. Haemost. 85, 67–74.

    Article  CAS  PubMed  Google Scholar 

  • Dixon JB, Dixon ME & O'Brien PE (2002): Reduced plasma homocysteine in obese red wine consumers: a potential contributor to reduced cardiovascular risk status. Eur. J. Clin. Nutr. 56, 608–614.

    Article  CAS  PubMed  Google Scholar 

  • Ford ES, Smith SJ, Stroup DF, Steinberg KK, Mueller PW & Thacker SB (2002): Homocyst(e)ine and cardiovascular disease: a systematic review of the evidence with special emphasis on case–control studies and nested case–control studies. Atherosclerosis 31, 59–70.

    Google Scholar 

  • Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP & Rozen R (1995): A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat. Genet. 10, 111–113.

    Article  CAS  PubMed  Google Scholar 

  • Giles WH, Kittner SJ, Croft JB, Wozniak MA, Wityk RJ, Stern BJ, Sloan MA, Price TR, McCarter RJ, Macko RF, Johnson CJ, Feeser BR, Earley CJ, Buchholz DW & Stolley PD (1999): Distribution and correlates of elevated total homocyst(e)ine: the Stroke Prevention in Young Women Study. Ann. Epidemiol. 9, 307–313.

    Article  CAS  PubMed  Google Scholar 

  • Girelli D, Friso S, Trabetti E, Olivieri O, Russo C, Pessotto R, Faccini G, Pignatti PF, Mazzucco A & Corrocher R (1998): Methylenetetrahydrofolate reductase C677T mutation, plasma homocysteine, and folate in subjects from northern Italy with or without angiographically documented severe coronary atherosclerotic disease: evidence for an important genetic–environmental interaction. Blood 91, 4158–4163.

    CAS  PubMed  Google Scholar 

  • 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, Evans AE, Medrano MJ & Candito M (1998): Plasma homocysteine as a risk factor for vascular disease. The European Conserted Action Project. JAMA 22, 1775–1781.

    Google Scholar 

  • Grubben MJ, Boers GH, Blom HJ, Broekhuizen R, de Jong R, van Rijt L, de Ruijter E, Swinkels DW, Nagengast FM & Katan MB (2000): Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial. Am. J. Clin. Nutr. 71, 480–484.

    Article  CAS  PubMed  Google Scholar 

  • Gudnason V, Stansbie D, Scott J, Bowron A, Nicaud V & Humphries S (1998): C677T (thermolabile alanine/valine) polymorphism in methylenetetrahydrofolate reductase (MTHFR): its frequency and impact on plasma homocysteine concentration in different European populations. EARS group. Atherosclerosis 136, 347–354.

    Article  CAS  PubMed  Google Scholar 

  • Halsted CH (2001): Lifestyle effects on homocysteine and an alcohol paradox. Am. J. Clin. Nutr. 73, 501–502.

    Article  CAS  PubMed  Google Scholar 

  • Homocysteine Studies Collaboration (2002): Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 288, 2015–2022.

    Article  Google Scholar 

  • Husemoen LLN, Thomsen TF, Fenger M, Jørgensen HL & Jørgensen T (2003): Contribution of the thermolabile methylenetetrahydrofolate reductase variant to total plasma homocysteine levels in healthy men and women. Inter99(2) Genet. Epidemiol. 24, 322–330.

    Article  PubMed  Google Scholar 

  • Hustad S, Ueland PM, Vollset SE, Zhang Y, Bjorke-Monsen AL & Schneede J (2000): Riboflavin as a determinant of plasma total homocysteine: effect modification by the methylenetetrahydrofolate reductase C677T polymorphism. Clin. Chem. 46, 1065–1071.

    CAS  PubMed  Google Scholar 

  • Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, Selhub J & Rozen R (1996a): Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 93, 7–9.

    Article  CAS  PubMed  Google Scholar 

  • Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, Selhub J & Rozen R (1996b): Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 93, 7–9.

    Article  CAS  PubMed  Google Scholar 

  • Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH & Selhub J (2001): Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am. J. Clin. Nutr. 73, 613–621.

    Article  CAS  PubMed  Google Scholar 

  • Jacques PF, Kalmbach R, Bagley PJ, Russo GT, Rogers G, Wilson PW, Rosenberg IH & Selhub J (2002): The relationship between riboflavin and plasma total homocysteine in the Framingham Offspring cohort is influenced by folate status and the C677T transition in the methylenetetrahydrofolate reductase gene. J. Nutr. 132, 283–288.

    Article  CAS  PubMed  Google Scholar 

  • Jørgensen HL, Madsen JS, Saleh MMA, Abrahamsen B, Fenger M & Lauritzen JB (2002): Association of a common allelic polymorphism (C677T) in the methylene tetrahydrofolate reductase gene with reduced risk of osteoporotic fractures. A case control study in Danish postmenopausal women. Calcif. Tissue Int. 71, 386–392.

    Article  PubMed  Google Scholar 

  • Jørgensen T, Borch-Johnsen K, Thomsen TF, Ibsen H, Glümer C & Pisinger C (2003): A randomised non-pharmacological intervention study for prevention of ischemic heart disease., Baseline results. Inter99 (1), Eur. J. Cardiovasc. Prevention Rehab. 10, 377–386.

    Article  Google Scholar 

  • Knudsen VK, Rasmussen LB, Haraldsdottir J, Ovesen L, Bülow I, Knudsen N, Jørgensen T, Lauerberg P & Perrild H (2001): Use of dietary supplements in Denmark is associated with health and former smoking. Public Health Nutr. 5, 1–6.

    Google Scholar 

  • Koehler KM, Baumgartner RN, Garry PJ, Allen RH, Stabler SP & Rimm EB (2001): Association of folate intake and serum homocysteine in elderly persons according to vitamin supplementation and alcohol use. Am. J. Clin. Nutr. 73, 628–637.

    Article  CAS  PubMed  Google Scholar 

  • Mayer Jr O, Simon J & Rosolova H (2001): A population study of the influence of beer consumption on folate and homocysteine concentrations. Eur. J. Clin. Nutr. 55, 605–609.

    Article  CAS  PubMed  Google Scholar 

  • McQuillan BM, Beilby JP, Nidorf M, Thompson PL & Hung J (1999): Hyperhomocysteinemia but not the C677T mutation of methylenetetrahydrofolate reductase is an independent risk determinant of carotid wall thickening. The Perth Carotid Ultrasound Disease Assessment Study (CUDAS). Circulation 99, 2383–2388.

    Article  CAS  PubMed  Google Scholar 

  • Meleady R, Ueland PM, Blom H, Whitehead AS, Refsum H, Daly LE, Vollset SE, Donohue C, Giesendorf B, Graham IM, Ulvik A, Zhang Y & Bjorke Monsen AL; EC Concerted Avtion Project: Homocysteine Vascular Disease (2003): Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: the European Concerted Action Project. Am. J. Clin. Nutr. 1, 63–70.

    Article  Google Scholar 

  • Moat SJ, Ashfield-Watt PA, Powers HJ, Newcombe RG & McDowell IF (2003): Effect of riboflavin status on the homocysteine-lowering effect of folate in relation to the MTHFR(C677T) genotype. Clin. Chem. 49, 295–302.

    Article  CAS  PubMed  Google Scholar 

  • National Consumer Agency (Forbrugerstyrelsen) (1995): De syv kostråd. (in Danish). Copenhagen: Forbrugerstyrelsen.

  • Nygard O, Refsum H, Ueland PM, Stensvold I, Nordrehaug JE, Kvale G & Vollset SE (1997): Coffee consumption and plasma total homocysteine: The Hordaland Homocysteine Study. Am. J. Clin. Nutr. 65, 136–143.

    Article  CAS  PubMed  Google Scholar 

  • 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, 263–270.

    Article  CAS  PubMed  Google Scholar 

  • Nygard O, Vollset SE, Refsum H, Stensvold I, Tverdal A, Nordrehaug JE, Ueland M & Kvale G (1995): Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. JAMA 274, 1526–1533.

    Article  CAS  PubMed  Google Scholar 

  • O'Callaghan P, Meleady R, Fitzgerald T, Graham I & European COMAC group (2002): Smoking and plasma homocysteine. Eur. Heart J. 20, 1559–1560.

    Google Scholar 

  • Olthof MR, Hollman PC, Zock PL & Katan MB (2001): Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans. Am. J. Clin. Nutr. 73, 532–538.

    Article  CAS  PubMed  Google Scholar 

  • Piyathilake CJ, Macaluso M, Hine RJ, Richards EW & Krumdieck CL (1994): Local and systemic effects of cigarette smoking on folate and vitamin B-12. Am. J. Clin. Nutr. 60, 559–566.

    Article  CAS  PubMed  Google Scholar 

  • Rasmussen LB, Ovesen L, Bulow I, Knudsen N, Laurberg P & Perrild H (2000): Folate intake, lifestyle factors, and homocysteine concentrations in younger and older women. Am. J. Clin. Nutr. 72, 1156–1163.

    Article  CAS  PubMed  Google Scholar 

  • Rosengren A & Wilhelmsen L (1997): Physical activity protects against coronary death and deaths from all causes in middle-aged men. Evidence from a 20-year follow-up of the primary prevention study in Goteborg. Ann. Epidemiol. 7, 69–75.

    Article  CAS  PubMed  Google Scholar 

  • Saw SM, Yuan JM, Ong CN, Arakawa K, Lee HP, Coetzee GA & Yu MC (2001): Genetic, dietary, and other lifestyle determinants of plasma homocysteine concentrations in middle-aged and older Chinese men and women in Singapore. Am. J. Clin. Nutr. 73, 232–239.

    Article  CAS  PubMed  Google Scholar 

  • 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, 2693–2698.

    Article  CAS  PubMed  Google Scholar 

  • Stein JH, Bushara M, Bushara K, McBride PE, Jorenby DE & Fiore MC (2002): Smoking cessation, but not smoking reduction, reduces plasma homocysteine levels. Clin. Cardiol. 25, 23–26.

    Article  PubMed  Google Scholar 

  • Stolzenberg-Solomon RZ, Miller ER, III, Maguire MG, Selhub J & Appel LJ (1999): Association of dietary protein intake and coffee consumption with serum homocysteine concentrations in an older population. Am. J. Clin. Nutr. 69, 467–475.

    Article  CAS  PubMed  Google Scholar 

  • Tonstad S & Urdal P (2002): Does short-term smoking cessation reduce plasma total homocysteine concentrations? Scand. J. Clin. Lab. Invest. 62, 279–284.

    Article  CAS  PubMed  Google Scholar 

  • Ubbink JB, Fehily AM, Pickering J, Elwood PC & Vermaak WJ (1998): Homocysteine and ischaemic heart disease in the Caerphilly cohort. Atherosclerosis 140, 349–356.

    Article  CAS  PubMed  Google Scholar 

  • Urgert R, Van Vliet T, Zock PL & Katan MB (2000): Heavy coffee consumption and plasma homocysteine: a randomized controlled trial in healthy volunteers. Am. J. Clin. Nutr. 72, 1107–1110.

    Article  CAS  PubMed  Google Scholar 

  • van der Gaag MS, Ubbink JB, Sillanaukee P, Nikkari S & Hendriks HF (2000): Effect of consumption of red wine, spirits, and beer on serum homocysteine. Lancet 355, 1522.

    Article  CAS  PubMed  Google Scholar 

  • Verhoef P, Pasman WJ, Van Vliet T, Urgert R & Katan MB (2002): Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans. Am. J. Clin. Nutr. 76, 1244–1248.

    Article  CAS  PubMed  Google Scholar 

  • Wright M, Francis K & Cornwell P (1998): Effect of acute exercise on plasma homocysteine. J. Sports Med. Phys. Fitness 38, 262–265.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The Danish Medical Research Council, The Danish Centre for Evaluation and Health Technology Assessment, and the Danish Heart Foundation financially supported this study.

Author information

Authors and Affiliations

Authors

Contributions

Contributors: LLNH: design of the study, analysis of data, interpretation of results, writing of the manuscript. TFT: design of the study, interpretation of results. MF: interpretation of results. TJ: design of the study, interpretation of results.

Corresponding author

Correspondence to L L N Husemoen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Husemoen, L., Thomsen, T., Fenger, M. et al. Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR(C677T) genotype. Inter99 (7). Eur J Clin Nutr 58, 1142–1150 (2004). https://doi.org/10.1038/sj.ejcn.1601942

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1601942

Keywords

This article is cited by

Search

Quick links