Hostname: page-component-8448b6f56d-c4f8m Total loading time: 0 Render date: 2024-04-23T21:05:07.477Z Has data issue: false hasContentIssue false

Reference range of total serum homocysteine level and dietary indexes in healthy Greek schoolchildren aged 6–15 years

Published online by Cambridge University Press:  08 March 2007

D. Papandreou*
Affiliation:
2nd Department of Pediatrics, Aristotle University of Thessaloniki School of Medicine, Ahepa General Hospital, Greece
I. Mavromichalis
Affiliation:
2nd Department of Pediatrics, Aristotle University of Thessaloniki School of Medicine, Ahepa General Hospital, Greece
A. Makedou
Affiliation:
2nd Department of Pediatrics, Aristotle University of Thessaloniki School of Medicine, Ahepa General Hospital, Greece
I. Rousso
Affiliation:
2nd Department of Pediatrics, Aristotle University of Thessaloniki School of Medicine, Ahepa General Hospital, Greece
M. Arvanitidou
Affiliation:
2nd Department of Pediatrics, Aristotle University of Thessaloniki School of Medicine, Ahepa General Hospital, Greece
*
*Corresponding author: Dimitrios Papendreou, fax + 23 10994803, email vellada@otenet.gr
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Elevated total serum homocysteine (tHcy) may be a possible risk factor for CVD. A 5 μmol/l increase in tHcy is associated with an approximately 70 % increase in relative risk of CVD in adults. Data for children and adolescents are, however, limited. The purpose of the present study was to provide a reference range for tHcy and investigate any relationship between tHcy and nutritional indexes in a Greek paediatric population. tHcy, folate, vitamin B12 levels and dietary indexes were measured in 520 healthy schoolchildren (274 boys, 246 girls) aged 6–15 years. As in adults, the tHcy distribution skewed to the right, with a geometric mean for both genders of 7·4 (range 3·4–29 μmol/l). Concentrations were lower in young children and increased with age. No statistically significant difference in tHcy level was observed between gender. The 95th percentiles for the three age groups were as follows: 6–9 years, 9·98 μmol/l; 10–12 years, 10·62 μmol/l; 13–15 years, 14·4 μmol/l. Using Pearson's coefficient analysis, tHcy level was correlated with age, serum folate, BMI and systolic blood pressure. Dietary analysis showed that folate, vitamin B12 and fibre intake were inversely related with tHcy; conversely, sugar and fat were positively associated with tHcy. However, in multiple linear regression analysis, only age (odds ratio 0·246, P<0·05) and folate (odds ratio −0·346, P<0·05) were significantly and independently associated with tHcy. This study provides age-specific reference data regarding tHcy concentration in a Greek paediatric population. tHcy levels increased as a function of age. Serum folate levels were significantly and independently associated with tHcy levels.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2006

References

Bates, CJ, Mansoor, MA, Gregory, J, Pentiev, K & Prentice, A (2002) Correlates of plasma homocysteine, cysteine and cysteinyl-glycine in respondents in the British National Diet and Nutrition Survey of young people aged 4–18 years, and a comparison with the survey of people aged 65 years and over. Br J Nutr 87, 7179.Google Scholar
Bonna, KH, Njolstad, I & Ueland, PM (2006) Homocysteine lowering and cardiovascular events after acute myocardial infarction. New Engl J Med 345, 15781588.CrossRefGoogle 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 intake. J Am Med Assoc 274, 10491057.CrossRefGoogle Scholar
Brattstrom, L, Lindgreen, A, Israelsson, B, Anderrson, A & Hutelberg, B (1994) Homocysteine and cysteine: determinants of plasma levels in middle-aged and elderly subjects. J Intern Med 236, 633641.CrossRefGoogle ScholarPubMed
Canepa, A, Carrea, A, Caridi, G, Dertenois, L, Minniti, G, Cerone, R, Canini, S, Calevo, MG & Perfumo, F (2003) Homocysteine, folate, B12 levels and C677T MTHFR mutation in children with renal failure. Pediatr Nephrol 18 225229.CrossRefGoogle Scholar
Cardo, E, Vilaseca, MA, Campistol, J, Artuch, R, Colome, C & Pineda, M (1999) Evaluation of hyperhomocysteinemia in children with stroke. Eur J Paediatr Neurol 3, 112117.CrossRefGoogle ScholarPubMed
Chimonas, ET (2001) The treatment of coronary heart disease: an update. II. Mortality trends and main causes of death in the Greek population. Curr Med Res Opin 17, 2733.Google Scholar
de Laet, C, Wautrecht, JC, Brasseur, D, Dramaix, M, Boeynaems, J-M, Decuyper, J & Kahn, A (1999) Plasma homocysteine concentrations in a Belgian School-age population. Am J Clin Nutr 69, 968972.CrossRefGoogle Scholar
Diakoumopoulou, E, Tentolouris, N, Kirlaki, E, Perrea, D, Kitsou, E, Psallas, M, Doulgerakis, D & Katsilambros, N (2005) Plasma homocysteine levels in patients with type 2 diabetes in a Mediterranean population: relation with nutritional and other factors. Nutr Metab Cardiovasc Dis 15, 109117.Google Scholar
Erler, K (1998) Elecsys immunoassay systems using electrochemiluminescence detection. Wien Klin Wochenschr 110, 510.Google Scholar
Frantzen, F, Faaren, AL, Alfheim, I & Nordhei, AK (1998) Enzyme conversion immunoassay for determining total homocysteine in plasma or serum. Clin Chem 44, 311316.CrossRefGoogle ScholarPubMed
Ganji, V & Kafai, MR (2005) Population references for plasma total homocysteine concentrations for U.S. children and adolescents in the post-folic acid fortification era. J Nutr 135, 22532256.CrossRefGoogle ScholarPubMed
Gutierrez Revilla, JL, Perez Hernandez, F, Tamparillas Salvador, M, Calvo Martin, MT (2004) Influence of biochemical and genetic factors on homocysteine concentrations. An Pediatr (Barc) 60, 215221.Google ScholarPubMed
Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators (2006) Homocysteine lowering with folic acid and B vitamins in vascular disease. New Engl J Med 354, 15671577.Google Scholar
Institute of MedicineInstitute of Medicine (2002) Panel on Macronutrients, Panel on the Definition of Dietary Fiber, Subcommittee on Interpretation and uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty acids, Cholesterol, Protein, and Amino Acids. Washington, DC: National Academies PressGoogle 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 methylenetethrahydrofolate reductase gene. J Nutr 132, 283288.CrossRefGoogle Scholar
Kapantais, E, Haralambides, V, Tzotzas, T, Mortoglou, A, Bakatselos, S, Kaklamanou, M, Ioannidis, I, Lanaras, L & Kaklamanos, I (2004) First National Epidemiological Large Scale Survey on the Prevalence of Childhood and Adolescent Obesity in Greece. Int J Obes 28, Suppl. 1, 71Google Scholar
Kluijtmans, LA, Kluijtmans, LA & Young, IS (2003) Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults. Blood 101, 24832488.CrossRefGoogle ScholarPubMed
Koch, HG, Nabel, P, Junker, R, Auberger, K, Schohess, R, Homberger, A, Linnebank, M, Nowak-Gottl, U (1999) The 677T genotype of the common MTHFR thermolabile variant and fasting homocysteine in childhood venous thrombosis. Eur J Pediatr 158, Suppl. S113S116.CrossRefGoogle ScholarPubMed
Lasheras, C, Huerta, JM, González, S, Prada, M, Braga, S, Fernández, S & Patterson, AM (2003) A diet score is associated with plasma homocysteine in a healthy institutionalized elderly population. Nutr Metab Cardiovasc Dis 16, 384390.Google Scholar
Lindblad, B, Zaman, S, Malik, A, Martin, H, Ekstrom, AM, Amu, S, Holmgren, A & Norman, M (2005) Folate, vitamin B12, and homocysteine levels in South Asian women with growth-retarded fetuses. Acta Obstet Gynecol Scand 84, 10551061.Google ScholarPubMed
Magkos, F, Manios, Y, Christakis, G & Kafatos, AG (2005) Secular trends in cardiovascular risk factors among school-aged boys from Crete, 1982–2002. Eur J Clin Nutr 59, 17.Google Scholar
Mainou, CC, Garcia, GN, Vilaseca, BMFM, Ferrer, CI, Meco, LJF, Mainou, PA, Pinto, SX, Grinberg, VD & Balssells, CS (2002) Hyperhomocystinemia and 677C T methylenetetrahydrofolate reductase polymorphism as a cardiovascular risk factor in childhood. An Esp Pediatr 56, 402408.Google Scholar
Molloy, AM (2004) Folate and homocysteine interrelationships including genetics of the relevant enzymes. Curr Opin Lipidol 15, 4957.Google Scholar
Must, A, Jacques, PF, Rogers, G, Rosenberg, IH & Selhub, J (2003) Serum total homocysteine concentrations in children and adolescents: results from the Third National Health and Nutrition Examination Survey (NHANES III). J Nutr 133, 26432649.CrossRefGoogle ScholarPubMed
Narin, F, Atabek, ME, Karakukcu, M, Narin, N, Kurtoglu, S, Gumus, H, Coksevim, B & Erez, R (2005) The association of plasma homocysteine levels with serum leptin and apolipoprotein B levels in childhood obesity. Ann Saudi Med 25, 209214.CrossRefGoogle ScholarPubMed
Nygard, O, Vollset, SE & Refsum, HM (1995) Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. J Am Med Assoc 274, 15361543.CrossRefGoogle ScholarPubMed
Osganian, SK, Stampfer, MJ & Spiegelman, D (1999) Distribution of end factors associated with serum homocysteine levels in children: child and adolescent trial for cardiovascular health. J Am Med Assoc 281, 11891196.Google Scholar
Oshaug, A, Bugge, KH & Refsum, H (1998) Diet, an independent determinant for plasma total homocysteine. A cross sectional study of Norwegian workers on platforms in the North Sea. Eur J Clin Nutr 52, 711.CrossRefGoogle ScholarPubMed
Pancharuniti, N, Lewis, CA, Sauberlich, HE, Perkins, LL, Go, RC, Alvarez, JO, Macaluso, M, Acton, RT, Copeland, RB & Cousins, AL (1994) Plasma homocysteine, folate, and vitamin B-12 concentrations and risk for early-onset coronary artery disease. Am J Clin Nutr 59, 940948.CrossRefGoogle ScholarPubMed
Papoutsakis, C, Yiannakouris, N, Manios, Y, Papakonstantinou, E, Magkos, F, Schulpis, KH, Zampelas, A & Matalas, A (2005) Plasma homocysteine concentrations in Greek children are influenced by an interaction between the methylenetetrahydrofolate Redustase C677T genotype and folate status. J Nutr 135, 383388.CrossRefGoogle ScholarPubMed
Pernet, P, Lasnier, E & Vaubourdolle, M (2000) Evaluation of the AxSYM homocysteine assay and comparison with the IMx homocysteine assay. Clin Chem 46, 14401441.CrossRefGoogle ScholarPubMed
Rauh, M, Verwied, S, Knerr, I, Durr, IIG, Sonnichson, A & Koletzko, B (2001) Homocysteine concentrations in a German cohort of 500 individuals: reference ranges and determinants of plasma levels in healthy children and their parents. Amino Acids 20, 409418.CrossRefGoogle Scholar
Reddy, MN (1997) Reference ranges for total homocysteine in children. Clin Chim Acta 262, 153155.CrossRefGoogle ScholarPubMed
Refsum, H, Smith, AD, Ueland, PM, Nexo, E, Clarke, R, McPartlin, J, Johnston, C, Engbaek, F, Schneede, J, McPartlin, C & Scott, JM (2004) Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 50, 332.CrossRefGoogle ScholarPubMed
Schroder, H, Covas, MI, Marrugat, J, Vila, J, Pena, A, Alcantara, M & Masia, R (2001) Use of a three-day estimated food record, a 72-hour recall and a food-frequency questionnaire for dietary assessment in a Mediterranean Spanish population. Clin Nutr 20, 429437.Google Scholar
Selhub, J, Jacques, PF, Rosenberg, IH, Rogers, G, Bowman, BA, Gunter, EW, Wright, JD & Johnson, CL (1999) Serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey (1988–1994): population reference ranges and contribution of vitamin status to high homocysteine concentrations. Ann Intern Med 131, 331339.CrossRefGoogle Scholar
Selhub, J, Jacques, PF, Wilson, PWF, Rush, D & Rosenberg, IH (1993) Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. J Am Med Assoc 270, 26932698.CrossRefGoogle Scholar
Tonstad, S, Refsum, H, Sivertsen, M, Christophersen, B, Ose, L & Ueland, PM (1996) Relation of total homocysteine and lipid levels in children to premature cardiovascular death in male relatives. Pediatr Res 40, 4752.Google Scholar
Toole, JF, Malinow, MR, Chambless, LE, Spence, JD, Pettigrew, LC, Howard, VJ, Sides, EG, Wang, CH & Stampfer, M (2004) Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infraction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized control trial. J Am Med Assoc 291, 565575.CrossRefGoogle Scholar
Trichopoulou, A (1992) Food Composition Tables and Composition of Greek Cooked Food and Dishes Athens School of Public HealthGoogle Scholar
Ueland, PM, Refsum, H, Stabler, SP, Malinow, MR, Andersson, A & Allen, RH (1993) Total homocysteine in plasma or serum. Methods and clinical applications. Clin Chem 39, 17641779.Google Scholar
van Beynum, IM, de Heijer, M, Thomas, CMG, Afman, L, Oppenraay-van, Emmerzaal, D, Blom HJ (2005) Total homocysteine and its predictors in Dutch children. Am J Clin Nutr 81, 11101116.CrossRefGoogle ScholarPubMed
Vilaseca, MA, Moyano, D, Ferrer, I & Artuch, R (1997) Total homocysteine in pediatric patients. Clin Chem 43, 690692.Google Scholar