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Прием метформина провоцирует нарушения гомеостаза витамина В12
Прием метформина провоцирует нарушения гомеостаза витамина В12
Громова О.А., Стаховская Л.В., Торшин И.Ю., Томилова И.К. Прием метформина провоцирует нарушения гомеостаза витамина В12. Consilium Medicum. 2017; 19 (4): 58–64.
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Аннотация
Метформин является одним из наиболее широко используемых гипогликемических средств для приема внутрь. Нежелательным побочным эффектом лечения метформином и другими бигуанидами является нарушение обмена витамина В12, ассоциированное со снижением уровней витамеров В12 в сыворотке крови, особенно на фоне дефицита кальция. Возникающий при этом гиповитаминоз B12 сопровождается периферической полинейропатией, астенией и при достаточно длительном приеме может приводить к мегалобластной анемии, повышению риска депрессии, цереброваскулярных и нейродегенеративных заболеваний. Клинические исследования и метаанализы многократно подтвердили взаимосвязь приема метформина и гиповитаминоза В12. Показано, в частности, что повышение уровней кобаламина на каждые 25 пмоль/л было ассоциировано с 6% снижением риска нейропатии. Дотации цианокобаламина способствуют компенсации вызываемых метформином нарушений обмена витамина В12.
Ключевые слова: диабет, метформин, цианокобаламин, гиповитаминоз В12, витамины группы В, Нейромультивит.
Key words: diabetes mellitus, metformin, cyanocobalamin, vitamin B12 hypovitaminosis, B vitamins, Neuromultivit.
Ключевые слова: диабет, метформин, цианокобаламин, гиповитаминоз В12, витамины группы В, Нейромультивит.
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Key words: diabetes mellitus, metformin, cyanocobalamin, vitamin B12 hypovitaminosis, B vitamins, Neuromultivit.
Полный текст
Список литературы
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24. Callaghan TS, Hadden DR, Tomkin GH. Megaloblastic anaemia due to vitamin B12 malabsorption associated with long-term metformin treatment. Br Med J 1980; 280 (6225): 1214–5.
25. Biemans E, Hart HE, Rutten GE et al. Cobalamin status and its relation with depression, cognition and neuropathy in patients with type 2 diabetes mellitus using metformin. Acta Diabetol 2015; 52 (2): 383–93.
26. Ahmed MA, Muntingh G, Rheeder P. Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy. BMC Pharmacol Toxicol 2016; 17 (1): 44.
27. Damiao CP, Rodrigues AO, Pinheiro MF et al. Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study. Sao Paulo Med J 2016; Sao Paulo: S1516-318020160050.
28. Wulffele MG, Kooy A, Lehert P et al. Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med 2003; 254 (5): 455–63.
29. Kancherla V, Garn JV, Zakai NA et al. Multivitamin Use and Serum Vitamin B12 Concentrations in Older-Adult Metformin Users in REGARDS, 2003–2007. PLoS One 2016; 11 (8): e0160802.
30. Chapman LE, Darling AL, Brown JE. Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab 2016; 42 (5): 316–27.
31. Holmes D. Diabetes: Metformin linked to vitamin B12 deficiency. Nat Rev Endocrinol 2016; 12 (6): 312.
32. Aroda VR, Edelstein SL, Goldberg RB et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab 2016; 101 (4): 1754–61.
33. Liu Q, Li S, Quan H, Li J. Vitamin B12 status in metformin treated patients: systematic review. PLoS One 2014; 9 (6): e100379.
34. Niafar M, Hai F, Porhomayon J, Nader ND. The role of metformin on vitamin B12 deficiency: a meta-analysis review. Intern Emerg Med 2015; 10 (1): 93–102.
35. Parry-Strong A, Langdana F, Haeusler S et al. Sublingual vitamin B12 compared to intramuscular injection in patients with type 2 diabetes treated with metformin: a randomised trial. N Z Med J 2016; 129 (1436): 67–75.
36. Beulens JW, Hart HE, Kuijs R et al. Influence of duration and dose of metformin on cobalamin deficiency in type 2 diabetes patients using metformin. Acta Diabetol 2015; 52 (1): 47–53.
37. Доскина Е.В. Диабетическая полинейропатия и В12-дефицитные состояния: основы патогенеза, пути лечения и профилактики. Фарматека. 2011; 20: 38–43. / Doskina E.V. Diabeticheskaia polineiropatiia i B12-defitsitnye sostoianiia: osnovy patogeneza, puti lecheniia i profilaktiki. Farmateka. 2011; 20: 38–43. [in Russian]
38. Панкратова Ю.В. Длительное лечение метформином пациентов с сахарным диабетом 2 типа и витамин В12: рандомизированное плацебо-контролируемое исследование. Ожирение и метаболизм. 2012; 4: 56–7. / Pankratova Yu.V. Dlitel'noe lechenie metforminom patsientov s sakharnym diabetom 2 tipa i vitamin В12: randomizirovannoe platsebo-kontroliruemoe issledovanie. Ozhirenie i metabolizm. 2012; 4: 56–7. [in Russian]
39. Новиков В.И., Новиков К.Ю. Осложнения сахарного диабета: терапия от А до… В1, В6, В12. Справочник поликлинического врача. 2015; 6–7: 56–9. / Novikov V.I., Novikov K.Yu. Oslozhneniia sakharnogo diabeta: terapiia ot A do… B1, B6, B12. Handbook for Practitioners Doctors. 2015; 6–7: 56–9. [in Russian]
2. Xu L, Huang Z, He X et al. Adverse effect of metformin therapy on serum vitamin B12 and folate: short-term treatment causes disadvantages? Med Hypotheses 2013; 81 (2): 149–51.
3. Buvat DR. Use of metformin is a cause of vitamin B12 deficiency. Am Fam Physician 2004; 69 (2): 264; author reply 26.
4. Gromova O.A., Torshin I.Yu., Prokopovich O.A. Synergistic neuroprotective effects of thiamine, pyridoxine and cyanocobalamin within the human proteome. Neurology and Rheumatology (Suppl. Consilium Medicum). 2016; 2: 76–84. [in Russian]
5. Adams JF, Clark JS, Ireland JT et al. Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy. Diabetologia 1983; 24 (1): 16–8.
6. Muller P, Fischer H, Sorger D. Vitamin B12-level in serum of diabetics receiving long-term buformin therapy. Z Gesamte Inn Med 1981; 36 (6): 226–8.
7. Caspary WF, Zavada I, Reimold W et al. Alteration of bile acid metabolism and vitamin-B12-absorption in diabetics on biguanides. Diabetologia 1977; 13 (3): 187–93.
8. Maev I.V., Samsonov A.A. Bolezni dvenadtsatiperstnoi kishki. M.: MEDpress-inform, 2005. [in Russian]
9. Kapadia CR, Essandoh LK. Active absorption of vitamin B12 and conjugated bile salts by guinea pig ileum occurs in villous and not crypt cells. Dig Dis Sci 1988; 33 (11): 1377–82.
10. Tomkin GH. Comparison of the effect of parenteral with oral biguanide therapy on vitamin B12 and bile acid absorption. Ir J Med Sci 1976; 145 (1): 340.
11. Greibe E, Miller JW, Foutouhi SH et al. Metformin increases liver accumulation of vitamin B12 – an experimental study in rats. Biochimie 2013; 95 (5): 1062–5.
12. Obeid R, Jung J, Falk J et al. Serum vitamin B12 not reflecting vitamin B12 status in patients with type 2 diabetes. Biochimie 2013; 95 (5): 1056–61.
13. Novelle M, Ali A, Diéguez C et al. Metformin: A Hopeful Promise in Aging Research. Cold Spring Harb Perspect Med 2016; 6 (3): a025932. DOI: 10.1101/cshperspect.a025932
14. Sahin M, Tutuncu NB, Ertugrul D et al. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. J Diabetes Complications 2007; 21 (2): 118–23.
15. Bauman WA, Shaw S, Jayatilleke E et al. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000; 23 (9): 1227–31.
16. Rufenacht P, Mach-Pascual S, Iten A. Vitamin B12 deficiency: a challenging diagnosis and treatment. Rev Med Suisse 2008; 4 (175): 2212–4, 2216–7.
17. Zdilla MJ. Metformin With Either Histamine H2-Receptor Antagonists or Proton Pump Inhibitors: A Polypharmacy Recipe for Neuropathy via Vitamin B12 Depletion. Clin Diabetes 2015; 33 (2): 90–5.
18. Damiao CP, Rodrigues AO, Pinheiro MF et al. Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study. Sao Paulo Med J 2016; 134 (6): 473–9.
19. Roy RP, Ghosh K, Ghosh M et al. Study of Vitamin B12 deficiency and peripheral neuropathy in metformin-treated early Type 2 diabetes mellitus. Indian J Endocrinol Metab 2016; 20 (5): 631–7.
20. Andres E, Perrin AE, Demangeat C et al. The syndrome of food-cobalamin malabsorption revisited in a department of internal medicine. A monocentric cohort study of 80 patients. Eur J Intern Med 2003; 14 (4): 221–6.
21. Hansen CS, Jensen JS, Ridderstrale M et al. Vitamin B12 deficiency is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes. J Diabetes Complications 2017; 31 (1): 202–8.
22. Moore E, Mander A, Ames D et al. Cognitive impairment and vitamin B12: a review. Int Psychogeriatr 2012; 24 (4): 541–56.
23. Mourits-Andersen T, Ditzel J. Megaloblastic anemia caused by malabsorption of vitamin B12 during long-term metformin therapy. Ugeskr Laeger 1983; 145 (1): 25–6.
24. Callaghan TS, Hadden DR, Tomkin GH. Megaloblastic anaemia due to vitamin B12 malabsorption associated with long-term metformin treatment. Br Med J 1980; 280 (6225): 1214–5.
25. Biemans E, Hart HE, Rutten GE et al. Cobalamin status and its relation with depression, cognition and neuropathy in patients with type 2 diabetes mellitus using metformin. Acta Diabetol 2015; 52 (2): 383–93.
26. Ahmed MA, Muntingh G, Rheeder P. Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy. BMC Pharmacol Toxicol 2016; 17 (1): 44.
27. Damiao CP, Rodrigues AO, Pinheiro MF et al. Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study. Sao Paulo Med J 2016; Sao Paulo: S1516-318020160050.
28. Wulffele MG, Kooy A, Lehert P et al. Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med 2003; 254 (5): 455–63.
29. Kancherla V, Garn JV, Zakai NA et al. Multivitamin Use and Serum Vitamin B12 Concentrations in Older-Adult Metformin Users in REGARDS, 2003–2007. PLoS One 2016; 11 (8): e0160802.
30. Chapman LE, Darling AL, Brown JE. Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab 2016; 42 (5): 316–27.
31. Holmes D. Diabetes: Metformin linked to vitamin B12 deficiency. Nat Rev Endocrinol 2016; 12 (6): 312.
32. Aroda VR, Edelstein SL, Goldberg RB et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab 2016; 101 (4): 1754–61.
33. Liu Q, Li S, Quan H, Li J. Vitamin B12 status in metformin treated patients: systematic review. PLoS One 2014; 9 (6): e100379.
34. Niafar M, Hai F, Porhomayon J, Nader ND. The role of metformin on vitamin B12 deficiency: a meta-analysis review. Intern Emerg Med 2015; 10 (1): 93–102.
35. Parry-Strong A, Langdana F, Haeusler S et al. Sublingual vitamin B12 compared to intramuscular injection in patients with type 2 diabetes treated with metformin: a randomised trial. N Z Med J 2016; 129 (1436): 67–75.
36. Beulens JW, Hart HE, Kuijs R et al. Influence of duration and dose of metformin on cobalamin deficiency in type 2 diabetes patients using metformin. Acta Diabetol 2015; 52 (1): 47–53.
37. Doskina E.V. Diabeticheskaia polineiropatiia i B12-defitsitnye sostoianiia: osnovy patogeneza, puti lecheniia i profilaktiki. Farmateka. 2011; 20: 38–43. [in Russian]
38. Pankratova Yu.V. Dlitel'noe lechenie metforminom patsientov s sakharnym diabetom 2 tipa i vitamin В12: randomizirovannoe platsebo-kontroliruemoe issledovanie. Ozhirenie i metabolizm. 2012; 4: 56–7. [in Russian]
39. Novikov V.I., Novikov K.Yu. Oslozhneniia sakharnogo diabeta: terapiia ot A do… B1, B6, B12. Handbook for Practitioners Doctors. 2015; 6–7: 56–9. [in Russian]
2. Xu L, Huang Z, He X et al. Adverse effect of metformin therapy on serum vitamin B12 and folate: short-term treatment causes disadvantages? Med Hypotheses 2013; 81 (2): 149–51.
3. Buvat DR. Use of metformin is a cause of vitamin B12 deficiency. Am Fam Physician 2004; 69 (2): 264; author reply 26.
4. Громова О.А., Торшин И.Ю., Прокопович О.А. Синергидные нейропротекторные эффекты тиамина, пиридоксина и цианокобаламина в рамках протеома человека. Неврология и Ревматология (Прил. к журн. Consilium Medicum). 2016; 2: 76–84. / Gromova O.A., Torshin I.Yu., Prokopovich O.A. Synergistic neuroprotective effects of thiamine, pyridoxine and cyanocobalamin within the human proteome. Neurology and Rheumatology (Suppl. Consilium Medicum). 2016; 2: 76–84. [in Russian]
5. Adams JF, Clark JS, Ireland JT et al. Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy. Diabetologia 1983; 24 (1): 16–8.
6. Muller P, Fischer H, Sorger D. Vitamin B12-level in serum of diabetics receiving long-term buformin therapy. Z Gesamte Inn Med 1981; 36 (6): 226–8.
7. Caspary WF, Zavada I, Reimold W et al. Alteration of bile acid metabolism and vitamin-B12-absorption in diabetics on biguanides. Diabetologia 1977; 13 (3): 187–93.
8. Маев И.В., Самсонов А.А. Болезни двенадцатиперстной кишки. М.: МЕДпресс-информ, 2005. / Maev I.V., Samsonov A.A. Bolezni dvenadtsatiperstnoi kishki. M.: MEDpress-inform, 2005. [in Russian]
9. Kapadia CR, Essandoh LK. Active absorption of vitamin B12 and conjugated bile salts by guinea pig ileum occurs in villous and not crypt cells. Dig Dis Sci 1988; 33 (11): 1377–82.
10. Tomkin GH. Comparison of the effect of parenteral with oral biguanide therapy on vitamin B12 and bile acid absorption. Ir J Med Sci 1976; 145 (1): 340.
11. Greibe E, Miller JW, Foutouhi SH et al. Metformin increases liver accumulation of vitamin B12 – an experimental study in rats. Biochimie 2013; 95 (5): 1062–5.
12. Obeid R, Jung J, Falk J et al. Serum vitamin B12 not reflecting vitamin B12 status in patients with type 2 diabetes. Biochimie 2013; 95 (5): 1056–61.
13. Novelle M, Ali A, Diéguez C et al. Metformin: A Hopeful Promise in Aging Research. Cold Spring Harb Perspect Med 2016; 6 (3): a025932. DOI: 10.1101/cshperspect.a025932
14. Sahin M, Tutuncu NB, Ertugrul D et al. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. J Diabetes Complications 2007; 21 (2): 118–23.
15. Bauman WA, Shaw S, Jayatilleke E et al. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000; 23 (9): 1227–31.
16. Rufenacht P, Mach-Pascual S, Iten A. Vitamin B12 deficiency: a challenging diagnosis and treatment. Rev Med Suisse 2008; 4 (175): 2212–4, 2216–7.
17. Zdilla MJ. Metformin With Either Histamine H2-Receptor Antagonists or Proton Pump Inhibitors: A Polypharmacy Recipe for Neuropathy via Vitamin B12 Depletion. Clin Diabetes 2015; 33 (2): 90–5.
18. Damiao CP, Rodrigues AO, Pinheiro MF et al. Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study. Sao Paulo Med J 2016; 134 (6): 473–9.
19. Roy RP, Ghosh K, Ghosh M et al. Study of Vitamin B12 deficiency and peripheral neuropathy in metformin-treated early Type 2 diabetes mellitus. Indian J Endocrinol Metab 2016; 20 (5): 631–7.
20. Andres E, Perrin AE, Demangeat C et al. The syndrome of food-cobalamin malabsorption revisited in a department of internal medicine. A monocentric cohort study of 80 patients. Eur J Intern Med 2003; 14 (4): 221–6.
21. Hansen CS, Jensen JS, Ridderstrale M et al. Vitamin B12 deficiency is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes. J Diabetes Complications 2017; 31 (1): 202–8.
22. Moore E, Mander A, Ames D et al. Cognitive impairment and vitamin B12: a review. Int Psychogeriatr 2012; 24 (4): 541–56.
23. Mourits-Andersen T, Ditzel J. Megaloblastic anemia caused by malabsorption of vitamin B12 during long-term metformin therapy. Ugeskr Laeger 1983; 145 (1): 25–6.
24. Callaghan TS, Hadden DR, Tomkin GH. Megaloblastic anaemia due to vitamin B12 malabsorption associated with long-term metformin treatment. Br Med J 1980; 280 (6225): 1214–5.
25. Biemans E, Hart HE, Rutten GE et al. Cobalamin status and its relation with depression, cognition and neuropathy in patients with type 2 diabetes mellitus using metformin. Acta Diabetol 2015; 52 (2): 383–93.
26. Ahmed MA, Muntingh G, Rheeder P. Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy. BMC Pharmacol Toxicol 2016; 17 (1): 44.
27. Damiao CP, Rodrigues AO, Pinheiro MF et al. Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study. Sao Paulo Med J 2016; Sao Paulo: S1516-318020160050.
28. Wulffele MG, Kooy A, Lehert P et al. Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med 2003; 254 (5): 455–63.
29. Kancherla V, Garn JV, Zakai NA et al. Multivitamin Use and Serum Vitamin B12 Concentrations in Older-Adult Metformin Users in REGARDS, 2003–2007. PLoS One 2016; 11 (8): e0160802.
30. Chapman LE, Darling AL, Brown JE. Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab 2016; 42 (5): 316–27.
31. Holmes D. Diabetes: Metformin linked to vitamin B12 deficiency. Nat Rev Endocrinol 2016; 12 (6): 312.
32. Aroda VR, Edelstein SL, Goldberg RB et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab 2016; 101 (4): 1754–61.
33. Liu Q, Li S, Quan H, Li J. Vitamin B12 status in metformin treated patients: systematic review. PLoS One 2014; 9 (6): e100379.
34. Niafar M, Hai F, Porhomayon J, Nader ND. The role of metformin on vitamin B12 deficiency: a meta-analysis review. Intern Emerg Med 2015; 10 (1): 93–102.
35. Parry-Strong A, Langdana F, Haeusler S et al. Sublingual vitamin B12 compared to intramuscular injection in patients with type 2 diabetes treated with metformin: a randomised trial. N Z Med J 2016; 129 (1436): 67–75.
36. Beulens JW, Hart HE, Kuijs R et al. Influence of duration and dose of metformin on cobalamin deficiency in type 2 diabetes patients using metformin. Acta Diabetol 2015; 52 (1): 47–53.
37. Доскина Е.В. Диабетическая полинейропатия и В12-дефицитные состояния: основы патогенеза, пути лечения и профилактики. Фарматека. 2011; 20: 38–43. / Doskina E.V. Diabeticheskaia polineiropatiia i B12-defitsitnye sostoianiia: osnovy patogeneza, puti lecheniia i profilaktiki. Farmateka. 2011; 20: 38–43. [in Russian]
38. Панкратова Ю.В. Длительное лечение метформином пациентов с сахарным диабетом 2 типа и витамин В12: рандомизированное плацебо-контролируемое исследование. Ожирение и метаболизм. 2012; 4: 56–7. / Pankratova Yu.V. Dlitel'noe lechenie metforminom patsientov s sakharnym diabetom 2 tipa i vitamin В12: randomizirovannoe platsebo-kontroliruemoe issledovanie. Ozhirenie i metabolizm. 2012; 4: 56–7. [in Russian]
39. Новиков В.И., Новиков К.Ю. Осложнения сахарного диабета: терапия от А до… В1, В6, В12. Справочник поликлинического врача. 2015; 6–7: 56–9. / Novikov V.I., Novikov K.Yu. Oslozhneniia sakharnogo diabeta: terapiia ot A do… B1, B6, B12. Handbook for Practitioners Doctors. 2015; 6–7: 56–9. [in Russian]
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Авторы
О.А.Громова*1,2, Л.В.Стаховская3, И.Ю.Торшин2,4, И.К.Томилова1
1 ФГБОУ ВО «Ивановская государственная медицинская академия» Минздрава России. 153462, Россия, Иваново, пр. Шереметевский, д. 8;
2 Российский сотрудничающий центр Института микроэлементов под эгидой ЮНЕСКО при ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И.Пирогова» Минздрава России. 117997, Россия, Москва, Островитянова, д. 1А;
3 ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И.Пирогова» Минздрава России. 117997, Россия, Москва, ул. Островитянова, д. 1;
4 ФГАОУ ВО «Московский физико-технический институт (государственный университет)» Минобороны России. 141700, Россия, Долгопрудный, Институтский пер., д. 9
*unesco.gromova@gmail.com
1 Ivanovo State Medical Academy of the Ministry of Health of the Russian Federation. 153462, Russian Federation, Ivanovo, pr. Sheremetevskii, d. 8;
2 Moscow branch of Trace Element Institute for UNESCO at N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1А;
3 N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1;
4 Moscow Institute of Physics and Technology of the Ministry of Defence of the Russian Federation. 141700, Russian Federation, Dolgoprudnyi, Institutskii per., d. 9
*unesco.gromova@gmail.com
1 ФГБОУ ВО «Ивановская государственная медицинская академия» Минздрава России. 153462, Россия, Иваново, пр. Шереметевский, д. 8;
2 Российский сотрудничающий центр Института микроэлементов под эгидой ЮНЕСКО при ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И.Пирогова» Минздрава России. 117997, Россия, Москва, Островитянова, д. 1А;
3 ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И.Пирогова» Минздрава России. 117997, Россия, Москва, ул. Островитянова, д. 1;
4 ФГАОУ ВО «Московский физико-технический институт (государственный университет)» Минобороны России. 141700, Россия, Долгопрудный, Институтский пер., д. 9
*unesco.gromova@gmail.com
________________________________________________
1 Ivanovo State Medical Academy of the Ministry of Health of the Russian Federation. 153462, Russian Federation, Ivanovo, pr. Sheremetevskii, d. 8;
2 Moscow branch of Trace Element Institute for UNESCO at N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1А;
3 N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1;
4 Moscow Institute of Physics and Technology of the Ministry of Defence of the Russian Federation. 141700, Russian Federation, Dolgoprudnyi, Institutskii per., d. 9
*unesco.gromova@gmail.com
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