Skip to main content
SpringerLink
Log in

Associations among objectively measured physical activity, fasting plasma homocysteine concentration, and MTHFR C677T genotype

  • Original Article
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

Elevated fasting plasma homocysteine (Hcy) level is a vascular disease risk factor. Plasma Hcy is affected by 5,10-methylenetetrahydofolate reductase (MTHFR) genotype and dietary folate intake. This cross-sectional study in 434 Japanese adults examined the associations among objectively measured physical activity (PA), plasma Hcy adjusting for dietary folate intake, and MTHFR C677T genotype. Daily PA was measured by triaxial accelerometry and all subjects completed a questionnaire about their dietary habits. Plasma Hcy and MTHFR C677T genotype were determined. Plasma Hcy in subjects with the TT genotype was significantly higher than in those with CC or CT genotype (p < 0.001). Plasma Hcy was significantly different between ≥200 (7.6 ± 0.2 nmol/mL) and <200 µg/day (8.3 ± 0.3 nmol/mL) folate intake groups (p = 0.003). There were no differences in plasma Hcy adjusting for age, sex, and folate intake between groups according to PA category in all subjects. However, there were significant interactions between time spent in light PA (p = 0.003), vigorous PA (p = 0.001), or inactivity (p = 0.004), and MTHFR genotype. In only the TT genotype, shorter time spent in light PA was associated with higher plasma Hcy than a longer time spent in light PA (11.5 ± 3.3 nmol/mL vs. 8.5 ± 3.3 nmol/mL, p < 0.001), and longer time spent in vigorous PA and inactivity were associated with higher plasma Hcy (11.8 ± 3.3 nmol/mL vs. 8.4 ± 3.2 nmol/mL, 11.6 ± 3.3 nmol/mL vs. 8.4 ± 3.3 nmol/mL, respectively, p < 0.001). In conclusion, light and vigorous PA were associated with plasma Hcy only in the TT genotype, but there were no such associations in all genotypes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Bathum L, Petersen I, Christiansen L, Konieczna A, Sorensen TI, Kyvik KO (2007) Genetic and environmental influences on plasma homocysteine: results from a danish twin study. Clin Chem 53(5):971–979

    Article  PubMed  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(13):1049–1057

    Article  PubMed  CAS  Google Scholar 

  • Castro R, Rivera I, Blom HJ, Jakobs C, Tavares de Almeida I (2006) Homocysteine metabolism, hyperhomocysteinaemia and vascular disease: an overview. J Inherit Metab Dis 29(1):3–20

    Article  PubMed  CAS  Google Scholar 

  • Dankner R, Chetrit A, Ken Dror G, Sela BA (2007) Physical activity is inversely associated with total homocysteine levels, independent of c677t mthfr genotype and plasma b vitamins. Age (Dordr) 29(4):219–227

    Article  CAS  Google Scholar 

  • de Bree A, Verschuren WM, Blom HJ, Kromhout D (2001) Lifestyle factors and plasma homocysteine concentrations in a general population sample. Am J Epidemiol 154(2):150–154

    Article  PubMed  Google Scholar 

  • Freedson PS, Melanson E, Sirard J (1998) Calibration of the computer science and applications, inc. Accelerometer. Med Sci Sports Exerc 30(13):777–781

    PubMed  CAS  Google Scholar 

  • Gando Y, Kawano H, Yamamoto K, Sanada K, Tanimoto M, Oh T, Ohmori Y, Miyatani M, Usui C, Takahashi E, Tabata I, Higuchi M, Miyachi M (2009) Age and cardiorespiratory fitness are associated with arterial stiffening and left ventricular remodelling. J Hum Hypertens 24(3):197–206

    Article  PubMed  Google Scholar 

  • Ganji V, Kafai MR (2003) Demographic, health, lifestyle, and blood vitamin determinants of serum total homocysteine concentrations in the third national health and nutrition examination survey, 1988–1994. Am J Clin Nutr 77(4):826–833

    PubMed  CAS  Google Scholar 

  • Holm PI, Bleie O, Ueland PM, Lien EA, Refsum H, Nordrehaug JE, Nygard O (2004) Betaine as a determinant of postmethionine load total plasma homocysteine before and after b-vitamin supplementation. Arterioscler Thromb Vasc Biol 24(2):301–307

    Article  PubMed  CAS  Google Scholar 

  • Homosysteine Studies Collaboration (2002) Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. Jama 288(16):2015–2022

    Article  Google Scholar 

  • Husemoen LL, Thomsen TF, Fenger M, Jorgensen T (2004) Effect of lifestyle factors on plasma total homocysteine concentrations in relation to mthfr(c677t) genotype. Inter99 (7). Eur J Clin Nutr 58(8):1142–1150

    Article  PubMed  CAS  Google Scholar 

  • Hustad S, Midttun O, Schneede J, Vollset SE, Grotmol T, Ueland PM (2007) The methylenetetrahydrofolate reductase 677c– > t polymorphism as a modulator of a b vitamin network with major effects on homocysteine metabolism. Am J Hum Genet 80(5):846–855

    Article  PubMed  CAS  Google Scholar 

  • Iemitsu M, Maeda S, Otsuki T, Sugawara J, Tanabe T, Jesmin S, Kuno S, Ajisaka R, Miyauchi T, Matsuda M (2006) Polymorphism in endothelin-related genes limits exercise-induced decreases in arterial stiffness in older subjects. Hypertension 47(5):928–936

    Article  PubMed  CAS  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(3):613–621

    PubMed  CAS  Google Scholar 

  • Joubert LM, Manore MM (2008) The role of physical activity level and b-vitamin status on blood homocysteine levels. Med Sci Sports Exerc 40(11):1923–1931

    Article  PubMed  CAS  Google Scholar 

  • Konstantinova SV, Tell GS, Vollset SE, Nygard O, Bleie O, Ueland PM (2008) Divergent associations of plasma choline and betaine with components of metabolic syndrome in middle age and elderly men and women. J Nutr 138(5):914–920

    PubMed  CAS  Google Scholar 

  • Kuo HK, Yen CJ, Bean JF (2005) Levels of homocysteine are inversely associated with cardiovascular fitness in women, but not in men: data from the national health and nutrition examination survey 1999–2002. J Intern Med 258(4):328–335

    Article  PubMed  CAS  Google Scholar 

  • Labayen I, Olsson LA, Ortega FB, Nilsson TK, Sjostrom M, Lucia A, Ruiz JR (2010) Cardiorespiratory fitness modifies the association between the ucp3-55>t (rs1800849) polymorphism and plasma homocysteine in swedish youth. Atherosclerosis 210(1):183–187

    Article  PubMed  CAS  Google Scholar 

  • Lange LA, Croteau-Chonka DC, Marvelle AF, Qin L, Gaulton KJ, Kuzawa CW, McDade TW, Wang Y, Li Y, Levy S, Borja JB, Lange EM, Adair LS, Molke KL (2010) Genome-wide association study of homocysteine levels in Filipinos provides evidence for CPS1 in women and a stronger MTHFR effect in young adults. Hum Mol Genet 19(10):2050–2058

    Article  PubMed  CAS  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 (2003) Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: the European concerted action project. Am J Clin Nutr 77(1):63–70

    PubMed  CAS  Google Scholar 

  • Misono M, Maeda S, Iemitsu M, Nakata Y, Otsuki T, Sugawara J, Zempo H, Yoshizawa M, Miyaki A, Kuno S, Matsuda M, Ajisaka R (2009) Combination of polymorphisms in the beta2-adrenergic receptor and nitric oxide synthase 3 genes increases the risk for hypertension. J Hypertens 27(7):1377–1383

    Article  PubMed  CAS  Google Scholar 

  • Mudd SH, Poole JR (1975) Labile methyl balances for normal humans on various dietary regimens. Metabolism 24(6):721–735

    Article  PubMed  CAS  Google Scholar 

  • Mudd SH, Ebert MH, Scriver CR (1980) Labile methyl group balances in the human: the role of sarcosine. Metabolism 29(8):707–720

    Article  PubMed  CAS  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(19):1526–1533

    Article  PubMed  CAS  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(2):263–270

    PubMed  CAS  Google Scholar 

  • Okubo H, Sasaki S, Rafamantanantsoa HH, Ishikawa-Takata K, Okazaki H, Tabata I (2008) Validation of self-reported energy intake by a self-administered diet history questionnaire using the doubly labeled water method in 140 japanese adults. Eur J Clin Nutr 62(11):1343–1350

    Article  PubMed  CAS  Google Scholar 

  • Olthof MR, Verhoef P (2005) Effects of betaine intake on plasma homocysteine concentrations and consequences for health. Curr Drug Metab 6(1):15–22

    Article  PubMed  CAS  Google Scholar 

  • Rowe DA, Mahar MT, Raedeke TD, Lore J (2004) Measuring physical activity in children with pedometers: reliability, reactivity, and replacement of missing data. Pediatric Exerc Sci 16:343–354

    Google Scholar 

  • Ruiz JR, Hurtig-Wennlof A, Ortega FB, Patterson E, Nilsson TK, Castillo MJ, Sjostrom M (2007a) Homocysteine levels in children and adolescents are associated with the methylenetetrahydrofolate reductase 677c-->t genotype, but not with physical activity, fitness or fatness: the European youth heart study. Br J Nutr 97(2):255–262

    Article  PubMed  CAS  Google Scholar 

  • Ruiz JR, Sola R, Gonzalez-Gross M, Ortega FB, Vicente-Rodriguez G, Garcia-Fuentes M, Gutierrez A, Sjostrom M, Pietrzik K, Castillo MJ (2007b) Cardiovascular fitness is negatively associated with homocysteine levels in female adolescents. Arch Pediatr Adolesc Med 161(2):166–171

    Article  PubMed  Google Scholar 

  • Sasaki S, Ushio F, Amano K, Morihara M, Todoriki O, Uehara Y, Toyooka E (2000) Serum biomarker-based validation of a self-administered diet history questionnaire for Japanese subjects. J Nutr Sci Vitaminol (Tokyo) 46(6):285–296

    Article  CAS  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(2):232–239

    PubMed  CAS  Google Scholar 

  • Wyss M, Kaddurah-Daouk R (2000) Creatine and creatinine metabolism. Physiol Rev 80(3):1107–1213

    PubMed  CAS  Google Scholar 

  • Yamada Y, Yokoyama K, Noriyasu R, Osaki T, Adachi T, Itoi A, Naito Y, Morimoto T, Kimura M, Oda S (2009) Light-intensity activities are important for estimating physical activity energy expenditure using uniaxial and triaxial accelerometers. Eur J Appl Physiol 105(1):141–152

    Article  PubMed  Google Scholar 

  • Yang QH, Botto LD, Gallagher M, Friedman JM, Sanders CL, Koontz D, Nikolova S, Erickson JD, Steinberg K (2008) Prevalence and effects of gene-gene and gene-nutrient interactions on serum folate and serum total homocysteine concentrations in the united states: findings from the third national health and nutrition examination survey DNA bank. Am J Clin Nutr 88(1):232–246

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to express their appreciation to the participants in this study. This study was supported by a Grant-in-Aid for Scientific Research (#20300231, M. Miyachi, #18200041, H. Shibayama, #22700708, H. Murakami) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan and a Grant-in-Aid for Scientific Research from the Ministry of Health, Labor, and Welfare of Japan (M. Miyachi). The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Health Promotion and Exercise Program, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku, Tokyo, 162-8636, Japan

    Haruka Murakami, Yuko Gando, Yumi Ohmori, Ryoko Kawakami, Izumi Tabata & Motohiko Miyachi

  2. Faculty of Sport and Health Science, Ritsumeikan University, Shiga, Japan

    Motoyuki Iemitsu, Kiyoshi Sanada & Izumi Tabata

  3. Department of Social and Preventive Epidemiology, School of Public Health, The University of Tokyo, Tokyo, Japan

    Satoshi Sasaki

Authors
  1. Haruka Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Motoyuki Iemitsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kiyoshi Sanada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuko Gando
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yumi Ohmori
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ryoko Kawakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Satoshi Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Izumi Tabata
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Motohiko Miyachi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Haruka Murakami.

Additional information

Communicated by Klaas R Westerterp.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Murakami, H., Iemitsu, M., Sanada, K. et al. Associations among objectively measured physical activity, fasting plasma homocysteine concentration, and MTHFR C677T genotype. Eur J Appl Physiol 111, 2997–3005 (2011). https://doi.org/10.1007/s00421-011-1926-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-011-1926-z

Keywords

Search

Navigation