Questionable Reliability Of Homocysteine As The Metabolic Marker For Folate And Vitamin B12 Deficiency In Patients With Chronic Obstructive Pulmonary Disease

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Background: An increased homocysteine (Hcy) concentration may represent a metabolic marker of folate and vitamin B12 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hcy concentration in predicting folate or vitamin B12 deficiency in these patients.

Methods: A group of 50 COPD patients (28 males/22 females, age (x¯±SD=49.0±14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and χ2 tests, Spearman’s correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05.

Results: Average (SD) concentrations of folate and vitamin B12 were 4.13 (2.16) μg/L and 463.6 (271.0) ng/L, whereas only vitamin B12 correlated with the Hcy level (P=−0.310 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R=0.279 (P=0.047)). The incidence of folate and vitamin B12 deficiency differed significantly (P=0.000 and P<0.000 for folate and vitamin B12 respectively), depending on the cut-off used for classification (4.4, 6.6 and 8.0 μg/L – folate; 203 and 473 ng/L – vitamin B12). ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B12 deficiency.

Conclusion: Reliability of the Hcy concentration as a biomarker of folate or vitamin B12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy.

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  • 1. Nazki FH Sameer AS Ganaie BA. Folate: metabolism genes polymorphisms and the associated diseases. Gene 2014; 533: 11–20.

  • 2. Burtsi CA Ashwood ER Bruns DE eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th ed. St. Louis MO: Elsevier Saunders 2006. pp. 1100–5.

  • 3. Green R. Indicators for assessing folate and vitamin B-12 status and for monitoring the efficacy of intervention strategies. Am J Clin Nutr 2011; 94: Suppl 2: 666–72.

  • 4. Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies. Food and Nutrition Bulletin 2008; 29: Suppl 2: 238–44.

  • 5. McNulty H Scott JM. Intake and status of folate and related B-vitamins: considerations and challenges in achieving optimal status. British Journal of Nutrition 2008; 99: Suppl 3: 48–54.

  • 6. WHO. Serum and red blood cell folate concentrations for assessing folate status in populations. Vitamin and Mineral Nutrition Information System. Geneva World Health Organization 2012. Available at: Accessed April 10th 2014.

  • 7. Jiang B Ding C Yao G Yao C Zhang Y Ge J et al. Intervention effect of folic acid and vitamin B12 on vascular cognitive impairment complicated with hyperhomocysteinemia. J Med Biochem 2014; 33: 169–74.

  • 8. Guéant JL Alpers DH. Vitamin B12 a fascinating micronutrient which influences human health in the very early and later stages of life. Biochimie 2013; 95: 967–9.

  • 9. Dhonukshe-Rutten RA de Vries JH de Bree A van der Put N van Staveren WA de Groot LC. Dietary intake and status of folate and vitamin B12 and their association with homocysteine and cardiovascular disease in European populations. Eur J Clin Nutr 2009; 63: 18–30.

  • 10. Zappacosta B Persichilli S Iacoviello L Di Castelnuovo A Graziano M Gervasoni J et al. Folate vitamin B12 and homocysteine status in an Italian blood donor population. Nutr Metab Cardiovasc Dis 2013; 23: 473–80.

  • 11. De Bruyn E Gulbis B Cotton F. Serum and red blood cell folate testing for folate deficiency: new features? Eur J Haematol 2014; 92: 354–9.

  • 12. Andersson I Grönberg A Slinde F Bosaeus I Larsson S. Vitamin and mineral status in elderly patients with chronic obstructive pulmonary disease. Clin Respir J 2007; 1: 23–9.

  • 13. Hirayama F Lee AH Terasawa K Kagawa Y. Folate intake associated with lung function breathlessness and the prevalence of chronic obstructive pulmonary disease. Asia Pac J Clin Nutr 2010; 19: 103–9.

  • 14. Seemungal TA Cho Fook Lun J Davis G Neblett C Chinyepi N Dookhan C et al. Plasma homocysteine is elevated in COPD patients and is related to COPD severity. Int J Chron Obstruct Pulmon Dis 2007; 2: 313–21.

  • 15. Fimognari FL Loffredo L Di Simone S Sampietro F Pastorelli R Monaldo M et al. Hyperhomocysteinaemia and poor vitamin B status in chronic obstructive pulmonary disease. Nutr Metab Cardiovasc Dis 2009; 19: 654–9.

  • 16. Refsum H Smith AD Ueland PM Nexo E Clarke R McPartlin J et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 2004; 50: 3–32.

  • 17. GOLD. Global Strategy for Diagnosis Management and Prevention of COPD. Report 2013_pdf. Available at: Accessed: January 9th 2014.

  • 18. Nikolac N Supak-Smolčić V [imundić AM Celap I. Croatian Society of Medical Biochemistry and Laboratory Medicine: National recommendations for venous blood sampling. Biochem Med 2013; 23: 242–54.

  • 19. Wald DS Law M Morris JK. Homocysteine and cardiovascular disease: evidence on causality from meta-analysis. BMJ 2002; 325: 1202–6.

  • 20. Veeranki S Tyagi SC. Defective homocysteine metabolism: potential implications for skeletal muscle malfunction. Int J Mol Sci 2013; 14: 15074–91.

  • 21. Hoffman M. Hypothesis: hyperhomocysteinemia is an indicator of oxidant stress. Med Hypotheses 2011; 77: 1088–93.

  • 22. Stanojković I Kotur-Stevuljević J Milenković B Spasić S Vujić T Stefanović A et al. Pulmonary function oxidative stress and inflammatory markers in severe COPD exacerbation. Respir Med 2011; 105: Suppl 3: 31–7.

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