Международный эндокринологический журнал Том 21, №1, 2025

Вітамін B6 — це загальний термін для шести взаємоперетворюваних водорозчинних вітамерів: піридоксалю, піридоксину і піридоксаміну, а також їх 5-фосфорильованих форм: піридоксаль-5’-фосфату (pyri­doxal 5’-phosphate, PLP), піридоксин-5’-фосфату і піридоксамін-5’-фосфату. PLP, біологічно активна форма вітаміну B6, діє як кофермент у різних ферментативних процесах, які каталізують найважливіші метаболічні реакції, зокрема синтез, перетворення та деградацію амінів і амінокислот, постачання одновуглецевих одиниць, транс­сульфування, синтез тетрапіролових сполук та поліамінів. PLP також чинить значний вплив на метаболізм гомоцистеїну, біосинтез різноманітних нейромедіаторів; пригнічує утворення активних форм кисню (АФК) і кінцевих продуктів глікування, генотоксичних сполук, пов’язаних зі старінням і цукровим діабетом (ЦД), отже, виконує функцію антиоксидантної молекули. Крім того, PLP функціонує як модулятор факторів транскрипції, впливає на активність низки ферментів і може зв’язуватися з рецепторами стероїдних гормонів, відіграючи певну роль у мембранному транспорті. Повідомляється, що у хворих на ЦД 2-го типу з серцево-судинними захворюваннями (ССЗ) відзначається нижчий рівень вітаміну B6, тоді як прийом лікарських препаратів вітаміну B6 знижує ризик виникнення діабету та його судинних ускладнень. Механізми, що лежать в основі взаємозв’язку між вітаміном В6 і ЦД, остаточно не з’ясовані. Натомість все більше даних вказує на те, що вітамін В6 може захищати від ускладнень ЦД завдяки його ролі поглинача АФК. Дефіцит вітаміну B6 пов’язують із низкою клінічно значущих захворювань, як-от аутизм, шизофренія, хвороба Альцгеймера, хвороба Паркінсона, епілепсія, синдром Дауна, ЦД і рак, хоча процеси, що лежать в їх основі, здебільшого залишаються нез’ясованими. Метою цього огляду було обговорити роль і особливості взаємозв’язків вітаміну B6 з ССЗ та цукровим діабетом, а також проаналізувати нові тенденції й напрямки майбутніх досліджень. Особливу увагу приділено аналізу особливостей біологічної ролі вітаміну B6, метаболізму триптофану, взаємозв’язків між вітаміном В6, ССЗ, ЦД та пошкодженнями ДНК при діабеті. Пошук проводився в Scopus, Science Direct (від Elsevier) і PubMed, разом з базами даних Medline. Використані ключові слова «вітамін B6», «серцево-судинні захворювання», «цукровий діабет». Для виявлення результатів дослідження, які не вдалося знайти під час онлайн-пошуку, використовувався ручний пошук бібліографії публікацій.

Vitamin B6 is a broad term for six water-soluble vitamins that can change forms. These include pyridoxal, pyridoxine, pyridoxamine, and their 5-phosphorylated forms, which are pyridoxal 5’-phosphate (PLP), pyridoxine 5’-phosphate, and pyridoxamine 5’-phosphate. PLP is the biologically active form of vitamin B6. It works as a coenzyme in many enzymatic processes that speed up the body’s most important metabolic reactions, including the synthesis, conversion and degradation of amines and amino acids, the supply of one-carbon units, transsulfuration, the synthesis of tetrapyrrole compounds and polyamines. PLP also has a big impact on the metabolism of homocysteine and the biosynthesis of different neurotransmitters. It inhibits the production of reactive oxygen species and advanced glycation end products, which are genotoxic compounds linked to aging and diabetes mellitus (DM), so it works as an antioxidant. In addition, PLP functions as a modulator of transcription factors, affects the activity of a number of enzymes, and can bind to steroid hormone receptors, playing a role in membrane transport. Researchers have reported that patients with type 2 DM and cardiovascular disease (CVD) exhibit lower levels of vitamin B6, whereas taking vitamin B6 supplements lowers the risk of diabetes and its vascular complications. We still don’t fully understand the mechanisms underlying the relationship between vitamin B6 and DM. Instead, a growing body of evidence suggests that vitamin B6 may protect against diabetes complications through its role as a scavenger of reactive oxygen species. Vitamin B6 deficiency has been linked to a number of clinically significant diseases, including autism, schizophrenia, Alzheimer’s disease, Parkinson’s disease, epilepsy, Down syndrome, DM, and cancer, although the underlying processes remain largely unclear. The purpose of this review was to discuss the role and specifics of the relationship between vitamin B6 and CVD and diabetes mellitus, as well as to analyze new trends and directions for future research. The analysis focused on the biological role of vitamin B6, tryptophan metabolism, and the correlation between vitamin B6, CVD, diabetes, and DNA damage in diabetes. The search was conducted in Scopus, Science Direct (from Elsevier) and PubMed, including MEDLINE databases. The keywords used were “vitamin B6”, “cardiovascular disease”, and “diabetes mellitus”. A manual search of the bibliography of publications was used to identify study results that could not be found during the online search.

вітамін В6; серцево-судинні захворювання; цукровий діабет; огляд

vitamin B6; cardiovascular diseases; diabetes mellitus; review

1. Zhang B, Dong H, Xu Y, Xu D, Sun H, Han L. Associations of dietary folate, vitamin B6 and B12 intake with cardiovascular outcomes in 115664 participants: a large UK population-based cohort. Eur J Clin Nutr. 2023 Mar;77(3):299-307. doi: 10.1038/s41430-022-01206-2.
2. Azzini E, Ruggeri S, Polito A. Homocysteine: its possible emerging role in at-risk population groups. Int J Mol Sci. 2020 Feb 20;21(4):1421. doi: 10.3390/ijms21041421.
3. Bajic Z, Sobot T, Skrbic R, et al. Homocysteine, vitamins B6 and folic acid in experimental models of myocardial infarction and heart failure-how strong is that link? Biomolecules. 2022 Apr 1;12(4):536. doi: 10.3390/biom12040536.
4. Kumrungsee T, Peipei Zhang, Yanaka N, Suda T, Kato N. Emerging cardioprotective mechanisms of vitamin B6: a narrative review. Eur J Nutr. 2022 Mar;61(2):605-613. doi: 10.1007/s00394-021-02665-2.
5. Smith AD, Refsum H. Homocysteine — from disease biomarker to disease prevention. J Intern Med. 2021 Oct;290(4):826-854. doi: 10.1111/joim.13279.
6. Stach K, Stach W, Augoff K. Vitamin B6 in health and disease. Nutrients. 2021 Sep 17;13(9):3229. doi: 10.3390/nu13093229.
7. Qian B, Shen S, Zhang J, Jing P. Effects of vitamin B6 deficiency on the composition and functional potential of T cell populations. J Immunol Res. 2017;2017:2197975. doi: 10.1155/2017/2197975.
8. Kumrungsee T, Zhang P, Chartkul M, Yanaka N, Kato N. Potential role of vitamin B6 in ameliorating the severity of COVID-19 and its complications. Front Nutr. 2020 Oct 29;7:562051. doi: 10.3389/fnut.2020.562051.
9. Baviera-Muñoz R, Buigues-Lafuente A, Campins-Romeu M, Garcés-Sánchez M, Martinez-Torres I. Refractory status epilepticus due to vitamin B6 deficit in a Parkinson’s disease patient in treatment with levodopa/carbidopa intestinal gel. Neurologia (Engl Ed). 2022 Sep;37(7):608-609. doi: 10.1016/j.nrleng.2021.10.002.
10. Ito T, Ogawa H, Hemmi H, Downs DM, Yoshimura T. Mechanism of pyridoxine 5’-phosphate accumulation in pyrido–xal 5’-phosphate-binding protein deficiency. J Bacteriol. 2022 Mar 15;204(3):e0052121. doi: 10.1128/JB.00521-21.
11. Hossain KS, Amarasena S, Mayengbam S. B vitamins and their roles in gut health. Microorganisms. 2022 Jun 7;10(6):1168. doi: 10.3390/microorganisms10061168.
12. Vernì F. Vitamin B6 and diabetes and its role in counteracting advanced glycation end products. Vitam Horm. 2024;125:401-438. doi: 10.1016/bs.vh.2024.02.005.
13. Mascolo E, Vernì F. Vitamin B6 and diabetes: relationship and molecular mechanisms. Int J Mol Sci. 2020 May 23;21(10):3669. doi: 10.3390/ijms21103669.
14. Islam Z, Aldous N, Choi S, et al. Flavin adenine dinucleotide (FAD) and pyridoxal 5’-phosphate (PLP) bind to Sox9 and alter the expression of key pancreatic progenitor transcription factors. Int J Mol Sci. 2022 Nov 14;23(22):14051. doi: 10.3390/ijms232214051.
15. Moreno-Navarrete JM, Jove M, Ortega F, et al. Metabolomics uncovers the role of adipose tissue PDXK in adipogenesis and systemic insulin sensitivity. Diabetologia. 2016 Apr;59(4):822-32. doi: 10.1007/s00125-016-3863-1.
16. Sharma V, Patial V. Peroxisome proliferator-activated receptor gamma and its natural agonists in the treatment of kidney diseases. Front Pharmacol. 2022 Oct 21;13:991059. doi: 10.3389/fphar.2022.991059.
17. Bird RP. The emerging role of vitamin B6 in inflammation and carcinogenesis. Adv Food Nutr Res. 2018;83:151-194. doi: 10.1016/bs.afnr.2017.11.004.
18. Serhiyenko VA, Oliinyk AYu, Pavlovskiy YaI, Kruk OS, Serhiyenko AA. Post-traumatic stress disorder and metabolic syndrome: the role of some antioxidants in treatment. Mìžnarodnij endokrinologìčnij žurnal. 2024;20(6):470-480. doi: 10.22141/2224-0721.20.6.2024.1445.
19. Baca P, Barajas-Olmos F, Mirzaeicheshmeh E, et al. DNA methylation and gene expression analysis in adipose tissue to identify new loci associated with T2D development in obesity. Nutr Diabetes. 2022 Dec 19;12(1):50. doi: 10.1038/s41387-022-00228-w.
20. Liu Z, Li P, Zhao ZH, Zhang Y, Ma ZM, Wang SX. Vitamin B6 prevents endothelial dysfunction, insulin resistance, and hepatic lipid accumulation in Apoe (-/-) mice fed with high-fat diet. J Diabetes Res. 2016;2016:1748065. doi: 10.1155/2016/1748065.
21. Ala OA, Akintunde AA, Ikem RT, Kolawole BA, Ala OO, Adedeji TA. Association between insulin resistance and total plasma homocysteine levels in type 2 diabetes mellitus patients in south west Nigeria. Diabetes Metab Syndr. 2017 Dec;11 Suppl 2:S803-S809. doi: 10.1016/j.dsx.2017.06.002.
22. Li FJ, Zheng SR, Wang DM. Adrenomedullin: an impor–tant participant in neurological diseases. Neural Regen Res. 2020 Jul;15(7):1199-1207. doi: 10.4103/1673-5374.272567.
23. Serhiyenko VA, Serhiyenko LM, Serhiyenko AA. Omega-3 polyunsaturated fatty acids in the treatment of diabetic cardiovascular autonomic neuropathy: A review. In: Moore SJ, editor. Omega-3: Dietary sources, biochemistry and impact on human health. New York, NY: Nova Science Publishers; 2017. 79-154 pp.
24. Calder PC, Carr AC, Gombart AF, Eggersdorfer M. Optimal nutritional status for a well-functioning immune system is an important factor to protect against viral infections. Nutrients. 2020 Apr 23;12(4):1181. doi: 10.3390/nu12041181.
25. Serhiyenko VA, Sehin VB, Serhiyenko LM, Serhiyenko AA. Post-traumatic stress disorder, metabolic syndrome, and chronic low-grade inflammation: A narrative review. Problemi Endocrinnoi Patologii. 2024 Mar 14;81(1):77-83. doi: 10.21856/j-PEP.2024.1.10.
26. Yoshii K, Hosomi K, Sawane K, Kunisawa J. Metabolism of dietary and microbial vitamin B family in the regulation of host immunity. Front Nutr. 2019 Apr 17;6:48. doi: 10.3389/fnut.2019.00048.
27. Elmadfa I, Meyer AL. The role of the status of selected micronutrients in shaping the immune function. Endocr Metab Immune Disord Drug Targets. 2019;19(8):1100-1115. doi: 10.2174/1871530319666190529101816.
28. Gombart AF, Pierre A, Maggini S. A Review of micronutrients and the immune system-working in harmony to reduce the risk of infection. Nutrients. 2020 Jan 16;12(1):236. doi: 10.3390/nu12010236.
29. Wang P, Huang J, Xue F, Abuduaini M, Tao Y, Liu H. Associations of serum vitamin B6 status with the risks of cardiovascular, cancer, and all-cause mortality in the elderly. Front Immunol. 2024 Apr 18;15:1354958. doi: 10.3389/fimmu.2024.1354958.
30. Badawy AA. Kynurenine pathway of tryptophan metabolism: regulatory and functional aspects. Int J Tryptophan Res. 2017 Mar 15;10:1178646917691938. doi: 10.1177/1178646917691938.
31. Muneer A. Kynurenine pathway of tryptophan metabolism in neuropsychiatric disorders: pathophysiologic and therapeutic conside–rations. Clin Psychopharmacol Neurosci. 2020 Nov 30;18(4):507-526. doi: 10.9758/cpn.2020.18.4.507.
32. Hajsl M, Hlavackova A, Broulikova K, et al. Tryptophan metabolism, inflammation, and oxidative stress in patients with neurovascular disease. Metabolites. 2020 May 19;10(5):208. doi: 10.3390/metabo10050208.
33. Cervenka I, Agudelo LZ, Ruas JL. Kynurenines: Tryptophan’s metabolites in exercise, inflammation, and mental health. Science. 2017 Jul 28;357(6349):eaaf9794. doi: 10.1126/science.aaf9794.
34. Zhang P, Tsuchiya K, Kinoshita T, et al. Vitamin B6 prevents IL-1β protein production by inhibiting NLRP3 inflammasome activation. J Biol Chem. 2016 Nov 18;291(47):24517-24527. doi: 10.1074/jbc.M116.743815.
35. Walden M, Tian L, Ross RL, et al. Metabolic control of BRISC-SHMT2 assembly regulates immune signalling. Nature. 2019 Jun;570(7760):194-199. doi: 10.1038/s41586-019-1232-1.
36. Jayedi A, Zargar MS. Intake of vitamin B6, folate, and vitamin B12 and risk of coronary heart disease: a systematic review and dose-response meta-analysis of prospective cohort studies. Crit Rev Food Sci Nutr. 2019;59(16):2697-2707. doi: 10.1080/–10408398.2018.1511967.
37. Wu S, Feng P, Li W, et al. Dietary folate, vitamin B6, and vitamin B12 and risk of cardiovascular diseases among individuals with type 2 diabetes: A case-control study. Ann Nutr Metab. 2023;79(1):5-15. doi: 10.1159/000527529.
38. Chen L, Li Q, Fang X, Wang X, Min J, Wang F. dietary intake of homocysteine metabolism-related B-vitamins and the risk of stroke: A dose-response meta-analysis of prospective studies. Adv Nutr. 2020 Nov 16;11(6):1510-1528. doi: 10.1093/advances/nmaa061.
39. Stone KL, Lui LY, Christen WG, et al. Effect of combination folic acid, vitamin B6, and vitamin B12 supplementation on fracture risk in women: A randomized, controlled trial. J Bone Miner Res. 2017 Dec;32(12):2331-2338. doi: 10.1002/jbmr.3229.
40. Lyon P, Strippoli V, Fang B, Cimmino L. B vitamins and one-carbon metabolism: implications in human health and disease. Nutrients. 2020 Sep 19;12(9):2867. doi: 10.3390/nu12092867.
41. McCaddon A, Miller JW. Homocysteine — a retrospective and prospective appraisal. Front Nutr. 2023 Jun 13;10:1179807. doi: 10.3389/fnut.2023.1179807.
42. Dhalla NS, Shah AK, Tappia PS. Role of oxidative stress in metabolic and subcellular abnormalities in diabetic cardiomyopathy. Int J Mol Sci. 2020 Mar 31;21(7):2413. doi: 10.3390/ijms21072413.
43. Serhiyenko VA, Sehin VB, Serhiyenko AA. Questionnaire “Composite assessment of autonomic symptoms 31” (COMPASS 31): validation and possibilities of application in the diagnostics of autonomic dysfunction in patients with type 2 diabetes mellitus. Endokrynologia. 2024;29(4):338-346. doi: 10.31793/1680-1466.2024.29-4.338.
44. Liu Y, Bao C, Wang H, Wei D, Zhang Z. Appraising the role of circulating concentrations of micronutrients in hypertension: A two-sample, multivariable Mendelian randomization study. Glob Heart. 2024 Oct 29;19(1):81. doi: 10.5334/gh.1367.
45. Tappia PS, Shah AK, Dhalla NS. The efficacy of vitamins in the prevention and treatment of cardiovascular disease. Int J Mol Sci. 2024 Sep 10;25(18):9761. doi: 10.3390/ijms25189761.
46. Toriumi K, Miyashita M, Suzuki K, et al. Vitamin B6 deficiency hyperactivates the noradrenergic system, leading to social deficits and cognitive impairment. Transl Psychiatry. 2021 May 3;11(1):262. doi: 10.1038/s41398-021-01381-z.
47. Serhiyenko VA, Sehin VB, Serhiyenko LM, Serhiyenko AA. Post-traumatic stress disorder, metabolic syndrome, and the autono–mic nervous system. Endokrynologia. 2023 Dec;28(4):377-392. doi: 10.31793/1680-1466.2023.28-4.377.
48. Dakshinamurti K, Dakshinamurti S, Czubryt MP. Vitamin B6: effects of deficiency, and metabolic and therapeutic functions. In: Preedy V, Patel V, editors. Handbook of Famine, Starvation, and Nutrient Deprivation. Basel: Springer, Cham. 2017. P. 1-23. doi: 10.1007/978-3-319-40007-5_81-1.
49. Wang Q, Zhao J, Chang H, Liu X, Zhu R. Homocysteine and folic acid: risk factors for Alzheimer’s disease-An updated meta-ana–lysis. Front Aging Neurosci. 2021 May 26;13:665114. doi: 10.3389/fnagi.2021.665114.
50. Haesen S, Jager MM, Brillouet A, et al. Pyridoxamine limits cardiac dysfunction in a rat model of doxorubicin-induced cardiotoxicity. Antioxidants (Basel). 2024 Jan 17;13(1):112. doi: 10.3390/antiox13010112.
51. Hu L, Li Y, Liu Z, et al. Association of plasma vitamin B6 with coronary heart disease in patients undergoing diagnostic coronary angiography: new insight on sex differences. Front Cardiovasc Med. 2021 Dec 15;8:789669. doi: 10.3389/fcvm.2021.789669.
52. Karadeniz M, Sarak T, Duran M, et al. Hyperhomocysteinemia predicts the severity of coronary artery disease as determined by the SYNTAX score in patients with acute coronary syndrome. Acta Cardiol Sin. 2018 Nov;34(6):458-463. doi: 10.6515/ACS.201811_34(6).20180528B.
53. Kataria N, Yadav P, Kumar R, et al. Effect of Vitamin B6, B9, and B12 supplementation on homocysteine level and cardiovascular outcomes in stroke patients: A meta-analysis of randomized controlled –trials. Cureus. 2021 May 11;13(5):e14958. doi: 10.7759/cureus.14958.
54. Dugué PA, Hodge AM, Ulvik A, et al. Association of markers of inflammation, the kynurenine pathway and B vitamins with age and mortality, and a signature of inflammaging. J Gerontol A Biol Sci Med Sci. 2022 Apr 1;77(4):826-836. doi: 10.1093/gerona/glab163.
55. Pusceddu I, Herrmann W, Kleber ME, et al. Subclinical inflammation, telomere shortening, homocysteine, vitamin B6, and mortality: the Ludwigshafen Risk and Cardiovascular Health Study. Eur J Nutr. 2020 Jun;59(4):1399-1411. doi: 10.1007/s00394-019-01993-8.
56. Chaturvedi S, Hoffman RM, Bertino JR. Exploiting methionine restriction for cancer treatment. Biochem Pharmacol. 2018 Aug;154:170-173. doi: 10.1016/j.bcp.2018.05.003.
57. Fezeu LK, Ducros V, Guéant JL, et al. MTHFR 677C → T genotype modulates the effect of a 5-year supplementation with B-vitamins on homocysteine concentration: The SU.FOL.OM3 rando–mized controlled trial. PLoS One. 2018 May 29;13(5):e0193352. doi: 10.1371/journal.pone.0193352.
58. Maruyama K, Eshak E, Kinuta M, et al. Association between vitamin B group supplementation with changes in % flow-mediated dila–tation and plasma homocysteine levels: a randomized controlled trial. J Clin Biochem Nutr. 2019 May;64(3):243-249. doi: 10.3164/jcbn.17-56.
59. Moretti R, Caruso P. The controversial role of homocysteine in neurology: from labs to clinical practice. Int J Mol Sci. 2019 Jan 8;20(1):231. doi: 10.3390/ijms20010231.
60. Yuan D, Chu J, Lin H, et al. Mechanism of homocysteine-–mediated endothelial injury and its consequences for atherosclerosis. Front Cardiovasc Med. 2023 Jan 16;9:1109445. doi: 10.3389/fcvm.2022.1109445.
61. Wang J, Zhang Y, Ren K, Li Y, Ying K. Hyperhomocysteinemia is associated with the risk of venous thromboembolism in patients with mental illness: a case-control study. Front Psychiatry. 2024 May 17;15:1340138. doi: 10.3389/fpsyt.2024.1340138.
62. Christen WG, Cook NR, Van Denburgh M, Zaharris E, Albert CM, Manson JE. Effect of combined treatment with folic acid, vitamin B6, and vitamin B12 on plasma biomarkers of inflammation and endothelial dysfunction in women. J Am Heart Assoc. 2018 May 18;7(11):e008517. doi: 10.1161/JAHA.117.008517.
63. Serhiyenko V, Serhiyenko A. Diabetic Cardiac Autonomic Neuropathy. In: Rodriguez-Saldana J.R., editors. The Diabetes Textbook: Clinical Principles, Patient Management and Public Health Issues. 2nd ed. Basel: Springer, Cham: Springer Nature Switzerland AG; 2023. 939-966 pp. doi: 10.1007/978-3-031-25519-9_57
64. González P, Lozano P, Ros G, Solano F. Hyperglycemia and oxidative stress: An integral, updated and critical overview of their metabolic interconnections. Int J Mol Sci. 2023 May 27;24(11):9352. doi: 10.3390/ijms24119352.
65. Zhu Y, Ying T, Xu M, Chen Q, Wu M, Liu Y, He G. Joint B vitamin intake and type 2 diabetes risk: the mediating role of inflammation in a prospective Shanghai Cohort. Nutrients. 2024 Jun 16;16(12):1901. doi: 10.3390/nu16121901.
66. Serhiyenko VA, Serhiyenko AA. Diabetes mellitus and congestive heart failure. Mìžnarodnij endokrinologìčnij žurnal. 2022;18(1):57-69. doi: 10.22141/2224-0721.18.1.2022.1146.
67. Pellegrini V, La Grotta R, Carreras F, et al. Inflammatory trajectory of type 2 diabetes: novel opportunities for early and late treatment. Cells. 2024 Oct 8;13(19):1662. doi: 10.3390/cells13191662.
68. Mutavdzin S, Gopcevic K, Stankovic S, Jakovljevic Uzelac J, Labudovic Borovic M, Djuric D. The effects of folic acid administration on cardiac oxidative stress and cardiovascular biomarkers in diabetic rats. Oxid Med Cell Longev. 2019 Jun 11;2019:1342549. doi: 10.1155/2019/1342549.
69. Serhiyenko VA, Serhiyenko LM, Serhiyenko AA. Features of Circadian Rhythms of Heart Rate Variability, Arterial Stiffness and Outpatient Monitoring of Blood Pressure in Diabetes Mellitus: Data, Mechanisms and Consequences. In: Sinha R.P., editors. Circadian Rhythms and Their Importance. New York, NY: Nova Science Publishers; 2022. 279-341 pp. doi: 10.52305/GXME8274
70. Dawood MH, Abdulridha MK, Qasim HS. Assessing pyrido–xine adjuvant therapy effects on blood glucose levels in type 2 diabetes: A randomized clinical trial. J Med Life. 2023 Oct;16(10):1474-1481. doi: 10.25122/jml-2023-0178.
71. Yilgor A, Demir C. Determination of oxidative stress level and some antioxidant activities in refractory epilepsy patients. Sci Rep. 2024 Mar 20;14(1):6688. doi: 10.1038/s41598-024-57224-6.
72. Mutavdzin Krneta S, Gopcevic K, Stankovic S, et al. Insights into the cardioprotective effects of pyridoxine treatment in diabetic rats: A study on cardiac oxidative stress, cardiometabolic status, and cardiovascular biomarkers. Diagnostics (Basel). 2024 Jul 12;14(14):1507. doi: 10.3390/diagnostics14141507.
73. Chen X, Zhang Y, Yu W, Zhang W, Tang H, Yuan WE. In situ forming ROS-scavenging hybrid hydrogel loaded with polydopamine-modified fullerene nanocomposites for promoting skin wound healing. J Nanobiotechnology. 2023 Apr 13;21(1):129. doi: 10.1186/s12951-023-01879-2.
74. Hu Y, Xu Y, Wang G. Homocysteine levels are associated with endothelial function in newly diagnosed type 2 diabetes mellitus patients. Metab Syndr Relat Disord. 2019 Jul/Aug;17(6):323-327. doi: 10.1089/met.2019.0011.
75. Muzurović E, Kraljević I, Solak M, Dragnić S, Mikhai–lidis DP. Homocysteine and diabetes: role in macrovascular and microvascular complications. J Diabetes Complications. 2021 Mar;35(3):107834. doi: 10.1016/j.jdiacomp.2020.107834.
76. Nix WA, Zirwes R, Bangert V, et al. Vitamin B status in patients with type 2 diabetes mellitus with and without incipient nephropathy. Diabetes Res Clin Pract. 2015 Jan;107(1):157-65. doi: 10.1016/j.diabres.2014.09.058.
77. Khobrani M, Kandasamy G, Vasudevan R, et al. Impact of vitamin B6 deficiency on the severity of diabetic peripheral neuropathy — A cross sectional study. Saudi Pharm J. 2023 May;31(5):655-658. doi: 10.1016/j.jsps.2023.03.005.
78. Essa NS, Mohammed I. Aladul MI. Role of neurotropic B vitamins in the treatment of diabetic neuropathy: narrative review. Irq J Pharm. 2022;19(1):98-111. doi: 10.33899/iphr.2022.174805.
79. Muhamad R, Akrivaki A, Papagiannopoulou G, Zavridis P, Zis P. The role of vitamin B6 in peripheral neuropathy: A systematic review. Nutrients. 2023 Jun 21;15(13):2823. doi: 10.3390/nu15132823.
80. Elbarbary NS, Ismail EAR, Zaki MA, Darwish YW, Ibrahim MZ, El-Hamamsy M. Vitamin B complex supplementation as a homocysteine-lowering therapy for early stage diabetic nephropathy in pediatric patients with type 1 diabetes: A randomized controlled trial. Clin Nutr. 2020 Jan;39(1):49-56. doi: 10.1016/j.clnu.2019.01.006.
81. Wu HHL, McDonnell T, Chinnadurai R. Physiological associations between vitamin B deficiency and diabetic kidney disease. Biomedi–cines. 2023 Apr 11;11(4):1153. doi: 10.3390/biomedicines11041153.
82. Horikawa C, Aida R, Kamada C, et al.; Japan Diabetes Complications Study Group. Vitamin B6 intake and incidence of diabetic retinopathy in Japanese patients with type 2 diabetes: analysis of data from the Japan Diabetes Complications Study (JDCS). Eur J Nutr. 2020 Jun;59(4):1585-1594. doi: 10.1007/s00394-019-02014-4.
83. Chiazza F, Cento AS, Collotta D, et al. Protective effects of pyridoxamine supplementation in the early stages of diet-induced kidney dysfunction. Biomed Res Int. 2017;2017:2682861. doi: 10.1155/2017/2682861.
84. Mascolo E, Amoroso N, Saggio I, Merigliano C, Vernì F. Pyri–doxine/pyridoxamine 5’-phosphate oxidase (Sgll/PNPO) is important for DNA integrity and glucose homeostasis maintenance in Drosophila. J Cell Physiol. 2020 Jan;235(1):504-512. doi: 10.1002/jcp.28990.
85. Baltrusch S. The Role of neurotropic B vitamins in nerve regeneration. Biomed Res Int. 2021 Jul 13;2021:9968228. doi: 10.1155/2021/9968228.
86. Kim HH, Kang YR, Lee JY, Chang HB, Lee KW, Apostoli–dis E, Kwon YI. The postprandial anti-hyperglycemic effect of pyridoxine and its derivatives using in vitro and in vivo animal models. Nutrients. 2018 Feb 28;10(3):285. doi: 10.3390/nu10030285.
87. Abdullah KM, Abul Qais F, Hasan H, Naseem I. Anti-diabetic study of vitamin B6 on hyperglycaemia induced protein carbonylation, DNA damage and ROS production in alloxan induced diabetic rats. Toxicol Res (Camb). 2019 Jun 11;8(4):568-579. doi: 10.1039/c9tx00089e.
88. Ramis R, Ortega-Castro J, Caballero C, et al. How does pyri–doxamine inhibit the formation of advanced glycation end products? The role of its primary antioxidant activity. Antioxidants (Basel). 2019 Sep 1;8(9):344. doi: 10.3390/antiox8090344.
89. Zhong A, Chang M, Yu T, et al. Aberrant DNA damage response and DNA repair pathway in high glucose conditions. J Can Res Updates. 2018;7(3):64-74. PMID: 30498558; PMCID: PMC6258084.
90. Liu J, Qin L, Zheng J, et al. Research progress on the relationship between vitamins and diabetes: systematic review. Int J Mol Sci. 2023 Nov 15;24(22):16371. doi: 10.3390/ijms242216371.
91. Serhiyenko A, Baitsar M, Sehin V, Serhiyenko L, Kuznets V, Serhiyenko V. Post-traumatic stress disorder, insomnia, heart rate varia–bility and metabolic syndrome (narrative review). Proc Shevchenko Sci Soc Med Sci. 2024 Jun;73(1):1-10. doi: 10.25040/ntsh2024.01.07.
92. Tay VSY, Devaraj S, Koh T, Ke G, Crasta KC, Ali Y. Increased double strand breaks in diabetic β-cells with a p21 response that limits apoptosis. Sci Rep. 2019 Dec 18;9(1):19341. doi: 10.1038/s41598-019-54554-8.
93. Giri B, Dey S, Das T, Sarkar M, Banerjee J, Dash SK. Chronic hyperglycemia mediated physiological alteration and metabolic distortion leads to organ dysfunction, infection, cancer progression and other pathophysiological consequences: An update on glucose toxicity. Biomed Pharmacother. 2018 Nov;107:306-328. doi: 10.1016/j.biopha.2018.07.157.
94. Pappuswamy M, Rajesh N, Philip AM. Analysis of chromosomal aberrations and micronuclei in type 2 diabetes mellitus patients. Asian Pac J Cancer Biol. 2020;5(1):15-18. doi: 10.31557/apjcb.2020.5.1.15-18.
95. Nersesyan A, Mišík M, Cherkas A, et al. Use of micronucleus experiments for the detection of human cancer risks: A brief overview. Proc Shevchenko Sci Soc Med Sci. 2021;65(2):50-58. doi: 10.25040/ntsh2021.02.05.
96. Smail HO. Identification of micronuclei in the lymphocytes of the type 2 diabetes mellitus according to the period of diagnosis as a biomarker. Polytechnic Journal 2023;13(2):1-6. doi: 10.59341/2707-7799.1720.
97. Mascolo E, Liguori F, Merigliano C, et al. Vitamin B6 rescues insulin resistance and glucose-induced DNA damage caused by reduced activity of Drosophila PI3K. J Cell Physiol. 2022 Sep;237(9):3578-3586. doi: 10.1002/jcp.30812. 
98. Pilesi E, Tesoriere G, Ferriero A, et al. Vitamin B6 deficiency cooperates with oncogenic RAS to induce malignant tumors in Drosophila. Cell Death Dis. 2024 Jun 3;15(6):388. doi: 10.1038/s41419-024-06787-3.
99. Merigliano C, Mascolo E, La Torre M, Saggio I, Vernì F. Protective role of vitamin B6 (PLP) against DNA damage in Droso–phila models of type 2 diabetes. Sci Rep. 2018 Jul 30;8(1):11432. doi: 10.1038/s41598-018-29801-z.
100. Serhiyenko VA, Serhiyenko LM, Sehin VB, Serhiyenko AA. Effect of alpha-lipoic acid on arterial stiffness parameters in type 2 diabetes mellitus patients with cardiac autonomic neuropathy. Endocr Regul. 2021;55(4):224-233. doi: 10.2478/enr-2021-0024.
101. Mascolo E, Barile A, Mecarelli LS, et al. The expression of four pyridoxal kinase (PDXK) human variants in Drosophila impacts on genome integrity. Sci Rep. 2019 Oct 2;9(1):14188. doi: 10.1038/s41598-019-50673-4.