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 Article
  • Published:

Nutritional determinants of plasma total homocysteine distribution in the Canary Islands

Abstract

Objective:

We sought to define plasma homocysteine reference values in healthy individuals in the Canary Islands and to determine its relations to folate and vitamin B12 intakes and concentrations.

Design:

Cross-sectional study.

Setting:

Population-based representative sample of 557 participants, aged 18–65 years, from the Canary Islands Nutrition Survey (ENCA).

Subjects:

All participants completed two 24-h dietary recalls and a general questionnaire collecting socio-demographic and health-related lifestyle information.

Interventions:

Plasma homocysteine and serum vitamin B12 levels were measured by immunoassay, whereas folate levels through an automated ionic capturing method.

Results:

Median plasma homocysteine was 11.9 μmol/l, higher in men (13.1 μmol/l) than in women (10.9 μmol/l) (P<0.001) and positively associated with age in both sexes (P<0.001). The prevalence of hyperhomocysteinaemia (15 μmol/l), 21.4%, was also greater in men (32.2%) than in women (13.4%). There were significant negative correlations between plasma homocysteine and serum (r=−0.32, P<0.001) and erythrocyte (r=−0.26, P<0.001) folate, as well as serum vitamin B12 (r=−0.28, P<0.001) concentrations. When divided in quartiles of vitamin intakes or concentrations, men with the lowest vitamin B12 and folate serum values had significantly higher plasma homocysteine concentrations than those in the other three quartiles. In women, hyperhomocysteinaemia was higher in the lowest quartiles of folate intake and serum and erythrocyte folate concentrations.

Conclusions:

These data provide further evidence that hyperhomocysteinaemia is a sensitive marker of inadequate folate and vitamin B12 status, allowing for the identification of those with greatest need for nutritional interventions.

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

  • Alfthan G, Laurinen MS, Valsta LM, Pastinen T, Aro A (2003). Folate intake, plasma folate and homocysteine status in a random Finnish population. Eur J Clin Nutr 57, 81–88.

    Article  CAS  Google Scholar 

  • Bostom A, Brosnan JT, Hall B, Nadeau MR, Selhub J (1995). Net uptake of plasma homocysteine by the rat kidney in vivo. Atherosclerosis 116, 59–62.

    Article  CAS  Google Scholar 

  • Brattström L, Wilcken DEL (2000). Homocysteine and cardiovascular disease: cause or effect? Am J Clin Nutr 72, 315–323.

    Article  Google Scholar 

  • Brouwer IA, van Dusseldorp M, Thomas CM, Duran M, Hautvast JG, Eskes TK et al. (1999). Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial. Am J Clin Nutr 69, 99–104.

    Article  CAS  Google Scholar 

  • Catarino PA (1992). Is there a safe level of drinking? A student's view. Alcohol Alcoholism 27, 465–470.

    CAS  PubMed  Google Scholar 

  • Chait A, Malinow MR, Nevin DN, Morris CD, Eastgard RL, Kris-Etherton P et al. (1999). Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease. Am J Clin Nutr 70, 881–887.

    Article  CAS  Google Scholar 

  • Cravo ML, Camilo ME (2000). Hyperhomocysteinemia in chronic alcoholism: relations to folic acid and vitamins B6 and B12 status. Nutrition 16, 296–302.

    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, 150–154.

    Article  CAS  Google Scholar 

  • Eikelboom JW, Lonn E, Genest Jr J, Hankey G, Yusuf S (1999). Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med 131, 363–375.

    Article  CAS  Google Scholar 

  • Favier JC, Ireland-Ripert J, Toque C, Feinberg M (1995). Répertoire Général des Aliments. Table de composition, 2e éd. Institut National de la Recherche Agronomique: Versailles.

    Google Scholar 

  • Fernández-Miranda C, de la Calle M, Manuel-Bris J, Muelas M, Gómez P, Díaz-Rubio P (2001). Influencia de la menopausia en la concentración plasmática de la homocisteína. Med Clin (Barcelona) 116, 206–208.

    Article  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, 826–833.

    Article  CAS  Google Scholar 

  • Graham I (1999). Homocysteine in health and disease. Ann Intern Med 131, 387–388.

    Article  CAS  Google Scholar 

  • Haslam DW, James WP (2005). Obesity. Lancet 366, 1197–1209.

    Article  Google Scholar 

  • Henríquez P, Doreste J, Díaz-Cremades J, López-Blanco F, Álvarez-León E, Serra-Majem L (2004). Folate status of adults living in the Canary Islands (Spain). Int J Vitam Nutr Res 74, 187–192.

    Article  Google Scholar 

  • Jacob RA, Wu MM, Henning SM, Swendseid ME (1994). Homocysteine increases as folate decreases in plasma of healthy men during short-term dietary folate and methyl group restriction. J Nutr 124, 1072–1080.

    Article  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, 613–621.

    Article  CAS  Google Scholar 

  • Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH (1999). The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 340, 1449–1454.

    Article  CAS  Google Scholar 

  • Kato I, Dnistrian AM, Schwartz M, Toniolo P, Koenig K, Shore RE et al. (1999). Epidemiologic correlates of serum folate and homocysteine levels among users and non-users of vitamin supplement. Int J Vitam Nutr Res 69, 322–329.

    Article  CAS  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  Google Scholar 

  • Liu K, Stamler J, Dyer A, McKeever J, McKeever P (1978). Statistical methods to assess and minimize the role of intra-individual variability in obscuring the relationship between dietary lipids and serum cholesterol. J Chron Dis 31, 399–418.

    Article  CAS  Google Scholar 

  • Lussier-Cacan S, Xhignesse M, Piolot A, Selhub J, Davignon J, Genest Jr J (1996). Plasma total homocysteine in healthy subjects: sex-specific relation with biological traits. Am J Clin Nutr 64, 587–593.

    Article  CAS  Google Scholar 

  • Mann NJ, Li D, Sinclair AJ, Dudman NP, Guo XW, Elsworth GR et al. (1999). The effect of diet on plasma homocysteine concentrations in healthy male subjects. Eur J Clin Nutr 53, 895–899.

    Article  CAS  Google Scholar 

  • Mataix J, Mañas M, Martínez de Vitoria E (1998). Tabla de composición de alimentos españoles, 3a ed. Universidad de Granada: Granada.

    Google Scholar 

  • Mayer Jr O, Simon J, Rosolová 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  Google Scholar 

  • Mennen LI, de Courcy GP, Guilland JC, Ducros V, Bertrais S, Nicolas JP et al. (2002). Homocysteine, cardiovascular disease risk factors, and habitual diet in the French Supplementation with Antioxidant Vitamins and Minerals Study. Am J Clin Nutr 76, 1279–1289.

    Article  CAS  Google Scholar 

  • Ministerio de Sanidad y Consumo (MSC) (1997). Encuesta Nacional de Salud. MSC: Madrid.

  • Morris MS, Jacques PF, Selhub J, Rosenberg IH (2000). Total homocysteine and estrogen status indicators in the third National Health and Nutrition Examination Survey. Am J Epidemiol 152, 140–148.

    Article  CAS  Google Scholar 

  • Nygård 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  Google Scholar 

  • Ortega RM, Redondo MR, Zamora MJ, López-Sobaler AM, Andrés P (1995). Eating behavior and energy and nutrient intake in overweight/obese and normal-weight Spanish elderly. Ann Nutr Metab 39, 371–378.

    Article  CAS  Google Scholar 

  • Osganian SK, Stampfer MJ, Spiegelman D, Rimm E, Cutler JA, Feldman HA et al. (1999). Distribution of and factors associated with serum homocysteine levels in children: Child and Adolescent Trial for Cardiovascular Health. JAMA 281, 1189–1196.

    Article  CAS  Google Scholar 

  • Pijoán-Zubizarreta JI, Irigoyen-Garbizu I, Aguirre-Errasti C (2001). Intervalos de referencia poblacional y determinantes de la homocisteína plasmática. Med Clin (Barcelona) 117, 487–491.

    Article  Google Scholar 

  • Quinlivan EP, Gregory III JF (2003). Effect of food fortification on folic acid intake in the United States. Am J Clin Nutr 77, 221–225.

    Article  CAS  Google Scholar 

  • Quinlivan EP, McPartlin J, McNulty H, Ward M, Strain JJ, Weir DG et al. (2002). Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease. Lancet 359, 227–228.

    Article  CAS  Google Scholar 

  • Rader JI (2002). Folic acid fortification, folate status and plasma homocysteine. J Nutr 132 (Suppl), 2466S–2470S.

    Article  CAS  Google Scholar 

  • Rasmussen LB, Ovesen L, Bülow 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  Google Scholar 

  • Riddell LJ, Chisholm A, Williams S, Mann JI (2000). Dietary strategies for lowering homocysteine concentrations. Am J Clin Nutr 71, 1448–1454.

    Article  CAS  Google Scholar 

  • Rodríguez-Esparragón F, Hernández-Perera O, Rodríguez-Pérez JC, Anabitarte A, Díaz-Cremades JM, Losada A et al. (2003). The effect of methylenetetrahydrofolate reductase C677T common variant on hypertensive risk is not solely explained by increased plasma homocysteine values. Clin Exp Hypertens 25, 209–220.

    Article  Google Scholar 

  • Saw SM, Yuan JM, Ong CN, Arakawa K, Lee HP, Coetzee GA 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, 232–239.

    Article  CAS  Google Scholar 

  • Selhub J, Jacques PF, Bostom AG, Wilson PW, Rosenberg IH (2000). Relationship between plasma homocysteine and vitamin status in the Framingham Study Population. Impact of folic acid fortification. Public Health Rev 28, 117–145.

    CAS  PubMed  Google Scholar 

  • Selhub J, Jacques PF, Rosenberg IH, Rogers G, Bowman BA, Gunter EW et al. (1999). Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey (1991–1994): population reference ranges and contribution of vitamin status to high serum concentrations. Ann Intern Med 131, 331–339.

    Article  CAS  Google Scholar 

  • Serra-Majem L, Ribas L, Armas-Navarro A, Álvarez-León E, Sierra A (2000). Ingesta de energía y nutrientes y riesgo de ingestas inadecuadas en Canarias (1997–98). Arch Latinoam Nutr 50 (Suppl 1), 7–22.

    CAS  PubMed  Google Scholar 

  • Stampfer MJ, Willett WC (1993). Homocysteine and marginal vitamin deficiency. The importance of adequate vitamin intake. JAMA 270, 2726–2727.

    Article  CAS  Google Scholar 

  • Stolzenberg-Solomon RZ, Miller III ER, 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  Google Scholar 

  • Verhoef P, Stampfer MJ, Buring JE, Gaziano JM, Allen RH, Stabler SP et al. (1996). Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12 and folate. Am J Epidemiol 143, 845–859.

    Article  CAS  Google Scholar 

  • Wald DS, Law M, Morris JK (2002). Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 325, 1202–1208.

    Article  Google Scholar 

  • Wilcken DEL, Wilcken B (2001). Historical overview and recent perspectives. In: Carmel R, Jacobsen DW (eds). Homocysteine in Health and Disease. Cambridge University Press: Cambridge, pp 1–6.

    Google Scholar 

Download references

Acknowledgements

This work was partially supported by the Research and Health Funding Agency of the Canary Islands Government (FUNCIS, Grant No. 10/00). The Canary Islands Nutrition Survey (ENCA 1997–1998) was supported by the Canarian Health Service. We also thank David Shea, lecturer, Department of Modern Languages, University of Las Palmas of Gran Canaria, for his assistance with the English version of this paper, and Lourdes Ribas Barba, Lluis Jover Armengol and Eva-Elisa Álvarez León for their comments. We have no conflicts of interest that are directly relevant to the content of this paper.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P Henríquez.

Additional information

Guarantor: L Serra-Majem.

Contributors: PHS is responsible for the study concept and design. RDP is responsible for homocysteine determinations. PHS, JDA and MDFP are responsible for statistical analysis. PHS and JDA are responsible for the acquisition of data and drafted the manuscript, which was critically revised by all other authors, contributing to the final version.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Henríquez, P., Doreste, J., Deulofeu, R. et al. Nutritional determinants of plasma total homocysteine distribution in the Canary Islands. Eur J Clin Nutr 61, 111–118 (2007). https://doi.org/10.1038/sj.ejcn.1602490

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1602490

Keywords

This article is cited by

Search

Quick links