AGE

, Volume 29, Issue 4, pp 219–227 | Cite as

Physical activity is inversely associated with total homocysteine levels, independent of C677T MTHFR genotype and plasma B vitamins

  • Rachel Dankner
  • Angela Chetrit
  • Gie Ken Dror
  • Ben-Ami Sela
Article

Abstract

The homocysteine level is considered to be a product of genetic and lifestyle interactions, mainly mutated methylenetetrahydrofolate reductase (MTHFR) and the intake of folate, vitamin B12 and pyridoxine, and their blood levels. Physical activity has been associated with lower homocysteine levels in some population studies, especially among elderly subjects. To further elucidate the observed association between homocysteine and physical activity, while accounting for the effect of the MTHFR C677T genotype, and of plasma levels of folate and B12 vitamins, a cross-sectional study of 620 males and females, aged 70.5 ± 6.8 years, was carried out. Information on lifestyle habits was collected and laboratory examinations of 12-h fasting total plasma homocysteine, folate, and vitamin B12, as well as DNA analysis for MTHFR C677T variant, were performed. Median total homocysteine values were 11.4 μmol/l for males and 9.4 for females; p < 0.001. Smoking and ethnic origin were not found to be associated with homocysteine levels. Physically active subjects had significantly lower total homocysteine levels when adjusted for sex (p = 0.01). Significant inverse correlations were found between body mass index, plasma folate, B12 and homocysteine levels. Homocysteine levels of the CC, CT and TT genotypes were 9.7, 10.6 and 10.2 μmol/l, respectively (p = 0.002, controlling for sex). In a multiple linear regression model, a sedentary lifestyle increased homocysteine levels by 7% as compared to an active one (p = 0.03) controlling for sex, age, body mass index, folate, vitamin B12, and C677T genotype, all of which were also found to be significantly associated with homocysteine levels. Any level of physical activity was found to be independently associated with lower homocysteine levels in an elderly population, controlling for MTHFR genotype, plasma B-vitamins, age, sex, smoking and BMI. This study emphasizes the importance of maintaining a physically active lifestyle in the elderly.

Keywords

B vitamins Elderly Homocysteine Lifestyle MTHFR genotyping Physical activity 

Abbreviations

MTHFR

Methylenetetrahydrofolate Reductase

SNP

Single Nucleotide Polymorphism

PCR

Polymerase Chain Reaction

Hcy

Homocysteine

tHcy

Total homocysteine

BMI

Body Mass Index

CVD

Cardiovascular diseases

Notes

Acknowledgments

This work was supported by the Russell Berrie Foundation and D-Cure, Diabetes Care in Israel, and Israeli Ministry of Health.

References

  1. Bar On H, Kidron M, Friedlander Y, et al (2000) Plasma total homocysteine levels in subjects with hyperinsulinemia. J Intern Med 247:287–294PubMedCrossRefGoogle Scholar
  2. Bonaa KH, Njolstad I, Ueland PM et al (2006) NORVIT Trial Investigators. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 354(15):1578–88PubMedCrossRefGoogle Scholar
  3. Dankner R, Chetrit A, Lubin F, Sela BA (2004) Life-style habits and homocysteine levels in an elderly population. Aging Clin Exp Res 16(6):437–442PubMedGoogle Scholar
  4. de Bree A, Verschuren WM, Blom HJ, Kromhout D (2001) Lifestyle factors and plasma homocysteine concentrations in a general population sample. Am J Epidemiol 154:150–154PubMedCrossRefGoogle Scholar
  5. Engbersen AM, Franken DG, Boers GH, Stevens EM, Trijbels FJ, Blom HJ (1995) Thermolabile 5, 10-mthylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia. Am J Hum Genet 56:142–150PubMedGoogle Scholar
  6. 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 136:347–354PubMedCrossRefGoogle Scholar
  7. Guttormsen AB, Ueland PM, Nesthus I, Nygard O, Schneede J, Vollset SE (1996) Determinants and vitamin responsiveness of intermediate hyperhomocysteinemia (>40 μmol/liter). J Clin Invest 98:2174–2183PubMedGoogle Scholar
  8. Husemoen L, 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 58:1142–1150PubMedCrossRefGoogle Scholar
  9. Jacobsen DW, Gatautis VJ, Green R, et al (1994) Rapid HPLC determination of total homocysteine and other thiols in serum and plasma: sex differences and correlation with cobalamin and folate concentrations in healthy subjects. Clin Chem 40:873–881PubMedGoogle Scholar
  10. Jurinke C, Denissenko MF, Oeth P, Ehrich M, van den Boom D, Cantor CR (2005) A single nucleotide polymorphism based approach for the identification and characterization of gene expression modulation using MassARRAY. Mutat Res 573(1–2):83–95. Review, Jun 3PubMedGoogle Scholar
  11. Kang SS, Wong PW, Bock HG, Horwitz A, Grix A (1991) Intermediate hyperhomocysteinemia resulting from compound heterozygosity of methylenetetrahydrofolate reductase mutations. Am J Hum Genet 48(3):546–551PubMedGoogle Scholar
  12. 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 258:328–335PubMedCrossRefGoogle Scholar
  13. Lonn E, Yusuf S, Arnold MJ, Sheridan P, et al (2006) The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 354(15):1567–1570PubMedCrossRefGoogle Scholar
  14. Loscalzo J (2006) Homocysteine trials - clear outcomes for complex reasons. N Engl J Med 354:1–3CrossRefGoogle Scholar
  15. McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM (2006) Controlled trial of Homocysteine lowering and cognitive performans. N Engl J Med 354:2764–2772PubMedCrossRefGoogle Scholar
  16. Modan M, Halkin H, Almog S, et al (1985) Hyperinsulinemia: A link between hypertension obesity and glucose intolerance. J Clin Invest 75:809–817PubMedCrossRefGoogle Scholar
  17. Nurk E, Tell GS, Vollset SE et al (2004) Changes in lifestyle and plasma total Homocysteine: the Hordaland Homocysteine Study. Am J Clin Nutr 79:812–819PubMedGoogle Scholar
  18. Nygard O, Vollset SE, Refsum H, et al (1995) Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. JAMA 274:1526–1533PubMedCrossRefGoogle Scholar
  19. Nygard O, Refsum H, Ueland PM, et al (1997) Coffee consumption and plasma total homocysteine: the Hordaland Homocysteine Study. Am J Clin Nutr 65:136–143PubMedGoogle Scholar
  20. Refsum H, Nurk E, Smith D, et al (2006) The Hordaland Homocysteine Study: A community-based study of Homocysteine, its determinants, and associations with disease. J Nutr 136:1731S–1740SPubMedGoogle Scholar
  21. Saw SM, Yuan JM, Ong CN, et al (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 73:232–239PubMedGoogle Scholar
  22. Schneede J, Refsum H, Ueland PM (2000) Biological and environmental determinants of plasma Homocysteine. Semin Thromb Hemost 26(3):263–279PubMedCrossRefGoogle Scholar
  23. Simon J, Mayer O Jr, Rosolova H (1999) Effect of folates, vitamin B12 and life style factors on mild hyperhomocysteinemia in a population sample. Cas Lek Cesk 138:650–653PubMedGoogle Scholar
  24. Toole JF, Malinow MR, Chambless LE et al (2004) Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 291(5):565–575, Feb 4PubMedCrossRefGoogle Scholar
  25. Ward M, McNulty H, McPartlin J, Strain JJ, Weir DG, Scott JM (1997) Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid. Q J Med 90:519–524Google Scholar

Copyright information

© American Aging Association, Media, PA, USA 2007

Authors and Affiliations

  • Rachel Dankner
    • 1
    • 2
  • Angela Chetrit
    • 1
  • Gie Ken Dror
    • 2
  • Ben-Ami Sela
    • 2
    • 3
  1. 1.Unit for Cardiovascular EpidemiologyThe Gertner Institute for Epidemiology and Health Policy ResearchTel HashomerIsrael
  2. 2.Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.Institute of Chemical PathologySheba Medical CenterTel HashomerIsrael

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