Analysis of some homocysteine contradictions
The existence of contradictory data in the literature and the lack of convincing evidence of the causes of hyperhomocysteinemia syndrome (HHC) associated with the disease give opposing views to the practical significance of high levels of homocysteine (HC) in plasma in patients. The article is written for the aim of having theoretical analysis of ambiguous, sometimes paradoxical data, on the problem of HHC, on the example of its association with cardiovascular pathology (CVP). The following paradoxes are formulated. The first paradox: in the part of clinical work, there was no link between moderate HHC and the risk of CVP. The second paradox: the prescription of vitamin B6, B9, B12 to patients for the prevention and treatment of CVP is usually accompanied by a significant reduction in the level of HC in plasma, but is not always realized by a decrease in the number of cardiovascular events. The third paradox: the mechanisms of the occurrence of HHC have not yet been identified in people with CVP or other diseases that correlate with the level of HC. Exceptions are only cases of these people having insufficient vitamins B6, B9, B12 taking part in the exchange of HC, or congenital defects of enzymes metabolism HC. The fourth paradox: in contrast to controversial clinical research, the results of experimental work are virtually unequivocal - artificial HHC pathogenetically associated with the development of CVP and other types of associated pathology. Thus, analysis of literary sources suggests the existence of opposing opinions, especially clinicians, about the role of HHC in the formation of cardiovascular pathology and the benefits of hypohomocysteinemic therapy. We believe that a definite value for the explanation of the contradictions will be focused research in the following areas: a) whether an increased level of HC is a cause, marker or consequence of cardiovascular disease; and b) whether HC is only a passive intermediate catabolism product of methionine or a biologically active compound with specific metabolic functions, the violation of which may take place both in the HHC, as well as due to hypohomocysteinemic therapy.
2. Lutsiuk, M. B., Zaichko, N. V., Hryhorieva, H. S., Konakhovych, N. F., Artemchuk, M. A., Pentiuk, N. O. … Shtatko, O. I. (2013). Syndrom hi perhomotsysteinemii : prychyny vynyknenni a, sposoby profi laktyky ta l ikuvanni a. [Hyperhomocysteinemia syndrome: causes, methods of prevention and treatment]. Racionalnaya farmakoterapiya - Rational pharmacotherapy, 4 (29), 55-60.
3. Lutsiuk, M. B., Artemchuk, M. A., Tertyshna, O. V., Kachula, S. O. & Balytska, O. P. (2015). Kharchuvannia ta syndrom hiperhomotsysteinemii. [Nutriti on and hyperhomocysteinemia syndrome]. Biomedical and biosocial anthropology, 24, 201-206.
4. Lutsiuk, M. B., Zaichko, N. V., Artemchuk, M. A. & Nekrut, D. O. (2016). Homotsysteinovi paradoksy. Aktualni pytannia patolohii za umov dii nadzvychainykh faktoriv na orhanizm, Materialy IX Naukovo-praktychnoi konferentsii. [Homocysteine paradoxes. Topical issues of pathology under the conditions of extraordinary factors on the organism, Materials of the IX Scientific and Practical Conference]. Ternopil: (b.v.) - Ternopil: (w.p.h.).
5. Pentiuk, O. O., Lutsiuk, M. B., Andrushko, I. I. & Postovitenko, K. P. (2003). Metaboli zm homotsysteinu ta yoho rol v patolohii. [Metaboli sm of homocysteine and its role in pathology]. Ukrainskyi biokhimichnyi zhurnal - Ukrainian Biochemical Journal, 75 (1), 5-17.
6. Abraham, J. M. & Cho, L. (2010). The homocystei ne hypothesis: still relevant to the prevention and treatment of cardiovascular disease? Cleve. Clin. J. Med., 77 (12), 911-918. doi: 10.3949/ccjm.77a.10036.
7. Armitage, J. M., Bowman, L., Clarke, R. J., Wallendszus, K., Bulbulia, R., Rahimi, K., & Collins, R. (2010). Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH). Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and maj or morbi dity in myocardi al i nfarction survivors: a randomized trial. JAMA, 303 (24), 2486-2494. doi: 10.1001/ jama.2010.840.
8. Clarke, R., Halsey, J., Lewington, S., Lonn, E., Armitage, J., Manson, J. E. … Collins, R. (2010). Effects of lowering homocysteine levels with B vitamins on cardi ovascular disease, cancer, and cause-specific mortality. Meta-analysis of 8 randomized trials involving 37 485 individuals. Arch. Intern. Med., 170, 1622-1631. doi: 10.1001/archinternmed.2010.348.
9. Clarke, R., Bennett, D. A., Parish, S., Verhoef, P., Detsch- Klerk, M., Lathrop, M. … Anand, S. S. (2012). Homocysteine and Coronary Heart Disease: Meta-analysis of MTHFR Case- Control Studies, Avoiding Publication Bias. PLoS Med., 9 (2), e1001177. doi:10.1371/journal.pmed.1001177.
10. Gibson, J. B., Carson, N. A. & Neill, D.W. (1964). Pathological findings in homocystinuria. J. Clin. Pathol., 17, 427-437.
11. Homocysteine Studies Collaboration. (2002). Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA, 288 (16), 2015-2022. Retri eved from https:// www.ncbi.nlm.nih.gov/pubmed/12387654.
12. Kothek ar, M. A. (2007). Homocysteine in cardiovascular disease: a culprit or an innocent bystander? Indian J. Med. Sci., 61 (6), 361-371. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/17558103.
13. Marti-Carvajal, A. J., Sola, I., Lathyris, D., Karakitsiou, D. E. & Simancas-Racines, D. (2013). Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst. Rev., 1, CD006612. doi :10.1002/ 14651858.CD006612.pub3.
14. McCully, K. S. (1996). Homocysteine and vascular disease. Nat. Med., 2, 386.
15. Rajneesh Tripathi, Satyendra Tewari, Prabhat Kumar Singh, & Sarita Agarwal.. (2010). Association of homocysteine and methylene tetrahydrofolate reductase (MTHFR C677T) gene polymorphism with coronary artery disease (CAD) in the population of North India. Genet. Mol. Biol., 33 (2), 224- 22 8.
16. Renzhe Cui, Hiroyasu Iso, Chigusa Date, Shogo Kikuchi, Akiko Tamakoshi. (2010). Dietary Folate and Vitamin B6 and B12 Intake in Relation to Mortality From Cardiovascular Diseases. Japan Collaborative Cohort Study. Stroke, 41, 1285-1289. https://doi.org/10.1161/ ST ROKEAHA.110.578906.
17. Smulders, Y. M. & Blom, H. J. (2011). The homocysteine controversy. J. Inheri. Metab. Dis., 34 (1), 93-99.
18. Gong, T., Wang, J., Yang, M., Shao, Y., Liu, J., Wu, Q. … Wang, Y. (2016). Serum homocysteine level and gestational diabetes mellitus: A meta analysis. J. Diabetes Investig., 7 (4), 622-628. doi: 10.1111/jdi.12460.
19. Wald, D. S., Morris, J. K. & Wald, N. J. (2011). Reconciling the evidence on serum homocysteine and ischaemic heart disease: a meta-analysis. PLoS ONE, 6, e16473. https:// doi.org/10.1371/journal.pone.0016473.
This work is licensed under a Creative Commons Attribution 4.0 International License.