Abstract
Background: Hyperhomocysteinemia (Hhcy) is considered an independent risk factor for vascular diseases and, more recently, for dementia. The methionine loading test (MLT) is useful for diagnosing additional subjects with moderate Hhcy. However, it is a complex and time-consuming procedure. A noninvasive test for the diagnosis of moderate Hhcy is desirable.
Methods: The study protocol consisted of three consecutive visits. During the first visit, we performed an MLT to characterize the Hhcy status of 75 healthy adult subjects. For the breath test protocol, we selected a subsample and assigned to the control group 17 subjects with fasting and post-loading homocysteine (Hcy) ≤12 and <42.3 μmol/L, respectively, and to the Hhcy group 16 subjects with fasting Hcy ≤12 and >42.3 μmol/L after loading. Selected subjects were requested to have a second visit to perform a breath test within 1–4 weeks following the MLT test and received an oral dose of 2.5 mg/kg of 1-13C-methionine dissolved in water. Breath samples were collected at basal, 20, 40, 60, 80, 100 and 120 min (test 1). The same procedure was repeated within 1 week (test 2).
Results: MLT was useful for diagnosing almost twice the number of individuals with Hhcy (24%) in comparison with the fasting determination alone (13.3%). The 13C-methionine breath test reported a sensitivity of 81.3% and a specificity of 64.7% against the MLT. The coefficient of variation between breath test 1 and breath test 2 was 9.0±5.4%.
Conclusions: The 13C-methionine breath test is a valid and reliable method for identifying subjects with moderate Hhcy.
Acknowledgments
We are grateful to the volunteers for their participation in this study. This study was supported by grants from Consejo Nacional de Ciencia y Tecnología (CONACYT: 86648-SALUD 2008-1) and from Fondo de Investigación en Salud (FIS/IMSS/PROT/623) and (FIS/IMSS/PROT/119).
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research support played no role in thestudy design; in the collection, analysis, and interpretationof data; in the writing of the report; or in the decision tosubmit the report for publication.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
References
1. Cattaneo M. Hyperhomocysteinemia, atherosclerosis and thrombosis. Thromb Haemost 1999;81:165–76.10.1055/s-0037-1614438Suche in Google Scholar
2. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. Br Med J 2002;325:1202–8.10.1136/bmj.325.7374.1202Suche in Google Scholar PubMed PubMed Central
3. Sacco RL, Anand K, Lee HS, Boden-Albala B, Stabler S, Allen R, et al. Homocysteine and the risk of ischemic stroke in a triethnic cohort: The Northern Manhattan Study. Stroke 2004;35:2263–9.10.1161/01.STR.0000142374.33919.92Suche in Google Scholar PubMed
4. Galimberti G, Conti E, Zini M, Piazza F, Fenaroli F, Isella V, et al. Post-methionine load test: A more sensitive tool to reveal hyperhomocysteinemia in Alzheimer patients? Clin Biochem 2008;41:914–6.10.1016/j.clinbiochem.2008.03.015Suche in Google Scholar PubMed
5. Haan MN, Miller JW, Aiello AE, Whitemer RA, Jagust WJ, Mungas DM, et al. Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the Sacramento Area Latino Study on Aging. Am J Clin Nutr 2007;85:511–7.10.1093/ajcn/85.2.511Suche in Google Scholar PubMed PubMed Central
6. MacCoss M, Fukagawa N, Matthews D. Measurement of intracellular sulfur amino acid metabolism in humans. Am J Physiol Endocrinol Metab 2001;280:947–55.10.1152/ajpendo.2001.280.6.E947Suche in Google Scholar PubMed
7. Maron BA, Loscalzo J. The treatment of hyperhomocysteinemia. Annu Rev Med 2009;60:39–54.10.1146/annurev.med.60.041807.123308Suche in Google Scholar PubMed PubMed Central
8. Friedman AN, Bostom AG, Selhub J, Levey AS, Rosenberg IH. The kidney and homocysteine metabolism. J Am Soc Nephrol 2001;122:181–9.10.1681/ASN.V12102181Suche in Google Scholar PubMed
9. Ubbink J, van der Merwe A, Delport R, Allen R, Stabler S, Riezer R. The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J Clin Invest 1996;98:177–84.10.1172/JCI118763Suche in Google Scholar PubMed PubMed Central
10. Guéant-Rodríguez R, Guéant JL, Debrad R, Thirion S, Hong LX, Bronowicki JA, et al. Prevalence of methylenetetrahydrofolate reductase 677T and 1298C alleles and folate status: a comparative study in Mexican, West African, and European populations. Am J Clin Nutr 2006;83:701–7.10.1093/ajcn.83.3.701Suche in Google Scholar PubMed
11. Van der Griend R, Haas FJ, Duran M, Biesma DH, Meuwissen OJ, Banga JD. Methionine loading test is necessary for detection of hyperhomocysteinemia. J Lab Clin Med 1998;132:67–7210.1016/S0022-2143(98)90027-0Suche in Google Scholar
12. Van de Laak MF, Grobbee DE, Van der Griend R, De Valk HW, Algra A, Banga JD, et al. A 2-step strategy to reduce the need for methionine loading tests to diagnose hyperhomocysteinemia. J Lab Clin Med 2003;142:121–7.10.1016/S0022-2143(03)00103-3Suche in Google Scholar
13. De Jonge R, Griffioen PH, Van Zelst B, Brouns RM, Visser W, Lindemans J. Evaluation of a shorter methionine test. Clin Chem Lab Med 2004;910:27–31.Suche in Google Scholar
14. Dunkelgrun M, Hoeks SE, Schouten O, Feringa HH, Welten GM, Vidakovic R, et al. Methionine loading does not enhance the predictive value of homocysteine serum testing for all-cause mortality or major adverse cardiac events. Int Med J 2009;39:13–8.10.1111/j.1445-5994.2007.01596.xSuche in Google Scholar PubMed
15. Keijzer M, Verhoef P, Borm GF, Blom HJ, den Heijer M. No added value of the methionine loading test in assessment for venous thrombosis and cardiovascular risk. Thromb Haemost 2006;95:380–5.10.1160/TH05-07-0498Suche in Google Scholar
16. Zepeda GS, Montano LA, Zapata CJ, Vargas VF, Majluf CA, Uscanga L. Oral challenge with methionine load in patients with inflammatory bowel disease: a better test to identify hyperhomocysteinemia. Inflamm Bowel Dis 2008;14:383–8.10.1002/ibd.20307Suche in Google Scholar PubMed
17. Colucci M, Cattaneo M, Martinelli I, Semerano F, Binnetti BM, Semerano N. Mild hyperhomocysteinemia is associated with increased TAFI levels and reduced plasma fibrinolytic potential. J Thromb Haemost 2008;6:1571–7.10.1111/j.1538-7836.2008.03070.xSuche in Google Scholar PubMed
18. Eleftheriadou I, Grigoropoulou P, Moyssakis A, Perrea D, Toutouzas K, Katsilambros N, et al. The effect of hyperhomocysteinemia on aortic distensibility in healthy individuals. Nutrition 2013;29:876–80.10.1016/j.nut.2012.12.026Suche in Google Scholar PubMed
19. Marongiu F, Fenu L, Pisu G, Contu Paolo, Barcellona D. Hyperhomocysteinemia: could the post-methionine oral loading test sometimes be avoided? Haematologica 2003;88:186–91.Suche in Google Scholar
20. O’Dochartaigh C, Ong H, Lovell S, Donelly R, Hanratty C, Riley M, et al. Changes in pulmonary vascular function after acute methionine loading in normal men. Clin Sci 2004;106:413–9.10.1042/CS20030383Suche in Google Scholar PubMed
21. Milazzo L, Piazza M, Sangaletti O, Gatti N, Cappelletti A, Adorni F, et al. [13C] methionine breath test: a novel method to detect antiretroviral drug-related mitochondrial toxicity. J Antimicrob Chemother 2005;55:84–9.10.1093/jac/dkh497Suche in Google Scholar PubMed
22. Spahr L, Negro F, Leandro G, Marinescu O, Goodman KJ, Brandt LR, et al. Impaired hepatic mitochondrial oxidation using the 13C-methionine breath test in patients with macrovesicular steatosis and patients with cirrhosis. Med Sci Monit 2003;9:6–11.Suche in Google Scholar
23. Armuzzi A, Marcoccia S, Zocco M, De Lorenzo A, Grieco A, Tondi P, et al. Non-invasive assessment of human mitochondrial function through the 13C-methionine breath test. Scand J Gastroenterol 2000;6:650–3.10.1080/003655200750023633Suche in Google Scholar PubMed
24. Bleie Ø, Refsum H, Ueland P, Vollset SE, Guttormsen AB, Nexo E, et al. Changes in basal and postmethionine load concentrations of total homocysteine and cystathionine after B vitamin intervention. Am J Clin Nutr 2004;80:641–8.10.1093/ajcn/80.3.641Suche in Google Scholar PubMed
25. Ueland P, Refsum H, Stabler S, Malinow R, Anderson A, Allen R. Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem 1993;39:1764–79.10.1093/clinchem/39.9.1764Suche in Google Scholar
©2014 by Walter de Gruyter Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Editorial
- Potential application of fetal epigenetic markers on the non-invasive prenatal detection of chromosomal abnormality
- Review
- Epigenetic mechanisms in bone
- Opinion Papers
- Circulating fetal cell-free DNA and prenatal molecular diagnostics: are we ready for consensus?
- Hepcidin levels in chronic hemodialysis patients: a critical evaluation
- D-dimer testing for suspected venous thromboembolism in the emergency department. Consensus document of AcEMC, CISMEL, SIBioC, and SIMeL
- General Clinical Chemistry and Laboratory Medicine
- Effect of biobanking conditions on short-term stability of biomarkers in human serum and plasma
- Non-invasive detection of fetal trisomy 21 using fetal epigenetic biomarkers with a high CpG density
- Development and validation of dried matrix spot sampling for the quantitative determination of amyloid β peptides in cerebrospinal fluid
- Instability of cerebrospinal fluid after delayed storage and repeated freezing: a holistic study by drop coating deposition Raman spectroscopy
- Analysis of patients with γ-heavy chain disease by the heavy/light chain and free light chain assays
- Performance of urinary NGAL and L-FABP in predicting acute kidney injury and subsequent renal recovery: a cohort study based on major surgeries
- Rapid extraction, identification and quantification of drugs of abuse in hair by immunoassay and ultra-performance liquid chromatography tandem mass spectrometry
- Validity and reliability of the 13C-methionine breath test for the detection of moderate hyperhomocysteinemia in Mexican adults
- Quantitative detection of target cells using unghosted cells (UGCs) of DxH 800 (Beckman Coulter)
- Evaluation of different sized blood sampling tubes for thromboelastometry, platelet function, and platelet count
- Cancer Diagnostics
- Routine use of the Ion Torrent AmpliSeq™ Cancer Hotspot Panel for identification of clinically actionable somatic mutations
- Analytical performance of a new one-step quantitative prostate-specific antigen assay, the FREND™ PSA Plus
- Relationship between prostate-specific antigen kinetics and detection rate of radiolabelled choline PET/CT in restaging prostate cancer patients: a meta-analysis
- Methylation of OPCML promoter in ovarian cancer tissues predicts poor patient survival
- Cardiovascular Diseases
- Red blood cell distribution width predicts survival in patients with Eisenmenger syndrome
- Low serum adropin is associated with coronary atherosclerosis in type 2 diabetic and non-diabetic patients
- Corrigendum
- Standardization and analytical goals for glycated hemoglobin measurement
- Letter to the Editors
- Do we need to worry about contamination by circulating fetal DNA?
- Stat testing utilization in clinical laboratories. National survey of Italian Society of Clinical Biochemistry and Molecular Biology (SIBioC)
- Aldosterone measurement with LiaisonXL automated system: remarks about reference range
- Better blood collection tubes for plasma glucose: ready for prime time?
- Upregulation of cytokines and IL-17 in patients with hereditary angioedema
- Underestimation of platelet count on magnesium salt-anticoagulated samples
- Extensive elevation of BNP but not NT-ProBNP in a patient with advanced urothelial carcinoma in absence of cardiac failure and volume overload
Artikel in diesem Heft
- Frontmatter
- Editorial
- Potential application of fetal epigenetic markers on the non-invasive prenatal detection of chromosomal abnormality
- Review
- Epigenetic mechanisms in bone
- Opinion Papers
- Circulating fetal cell-free DNA and prenatal molecular diagnostics: are we ready for consensus?
- Hepcidin levels in chronic hemodialysis patients: a critical evaluation
- D-dimer testing for suspected venous thromboembolism in the emergency department. Consensus document of AcEMC, CISMEL, SIBioC, and SIMeL
- General Clinical Chemistry and Laboratory Medicine
- Effect of biobanking conditions on short-term stability of biomarkers in human serum and plasma
- Non-invasive detection of fetal trisomy 21 using fetal epigenetic biomarkers with a high CpG density
- Development and validation of dried matrix spot sampling for the quantitative determination of amyloid β peptides in cerebrospinal fluid
- Instability of cerebrospinal fluid after delayed storage and repeated freezing: a holistic study by drop coating deposition Raman spectroscopy
- Analysis of patients with γ-heavy chain disease by the heavy/light chain and free light chain assays
- Performance of urinary NGAL and L-FABP in predicting acute kidney injury and subsequent renal recovery: a cohort study based on major surgeries
- Rapid extraction, identification and quantification of drugs of abuse in hair by immunoassay and ultra-performance liquid chromatography tandem mass spectrometry
- Validity and reliability of the 13C-methionine breath test for the detection of moderate hyperhomocysteinemia in Mexican adults
- Quantitative detection of target cells using unghosted cells (UGCs) of DxH 800 (Beckman Coulter)
- Evaluation of different sized blood sampling tubes for thromboelastometry, platelet function, and platelet count
- Cancer Diagnostics
- Routine use of the Ion Torrent AmpliSeq™ Cancer Hotspot Panel for identification of clinically actionable somatic mutations
- Analytical performance of a new one-step quantitative prostate-specific antigen assay, the FREND™ PSA Plus
- Relationship between prostate-specific antigen kinetics and detection rate of radiolabelled choline PET/CT in restaging prostate cancer patients: a meta-analysis
- Methylation of OPCML promoter in ovarian cancer tissues predicts poor patient survival
- Cardiovascular Diseases
- Red blood cell distribution width predicts survival in patients with Eisenmenger syndrome
- Low serum adropin is associated with coronary atherosclerosis in type 2 diabetic and non-diabetic patients
- Corrigendum
- Standardization and analytical goals for glycated hemoglobin measurement
- Letter to the Editors
- Do we need to worry about contamination by circulating fetal DNA?
- Stat testing utilization in clinical laboratories. National survey of Italian Society of Clinical Biochemistry and Molecular Biology (SIBioC)
- Aldosterone measurement with LiaisonXL automated system: remarks about reference range
- Better blood collection tubes for plasma glucose: ready for prime time?
- Upregulation of cytokines and IL-17 in patients with hereditary angioedema
- Underestimation of platelet count on magnesium salt-anticoagulated samples
- Extensive elevation of BNP but not NT-ProBNP in a patient with advanced urothelial carcinoma in absence of cardiac failure and volume overload