Iodine deficiency in Russia: Current state of the problem, global practice and new approaches to therapy

Iodine performs a number of important functions in the body, participating in the synthesis of thyroid hormones, which creates the need for constant replenishment of the element in adequate amounts. Continuous monitoring of micronutrient deficiency in the Russian Federation reveals low average daily iodine intake and an increase in the number of cases of thyroid diseases in the period from 2010 to 2020. This actualizes the need to develop new therapeutic and preventive approaches to replenish iodine deficiency. The aim of the review is to analyze the problem of iodine deficiency in Russia and existing practices of its leveling in order to develop a new approach to the prevention and treatment of iodine deficiency conditions. The sample includes publications in Russian and English in the period from 2002 to 2023, using the resources of scientific metric databases Elibrary, Google Scholar, CyberLeninka, PubMed and ScienceDirect. The research work showed that the common practice of eliminating iodine deficiency is to increase the level of consumption of the trace element in the diet, the consequence of which is the availability of a wide range of iodized food supplements and products on the market. However, the analysis of the current functional nutrition sector has revealed a number of drawbacks associated with low bioavailability of the element and its resistance to technological factors in the production of food products. The article presents the key factors influencing the effectiveness of nutritional supplements being developed for nutritional correction of iodine deficiency. They are based on the evaluation of existing means of prevention. The study proposes the development of the technology of whey hydrolysates enriched with iodine and zinc. Application in food production of a food additive based on protein components of milk whey opens new opportunities for processing of secondary dairy raw materials and for full utilization of all milk components. The rich amino acid composition of the additive helps to increase the concentration of essential trace elements in products, as amino acid residues are able to bind iodine and chelate zinc.

1. Yashin, A. N., Petrov, A. N. (2023). The relevance of the development of food products enriched with trace elements for diet therapy in cardiovascular disease. Food Systems, 6(3), 272-278. (In Russian) https://doi.org/10.21323/2618-9771-2023-6-3-272-278

2. Kodentsova, V. M., Vrzhesinskaya, O. A., Risnik, D. V., Nikityuk, D. B., Tutelyan, V. A. (2017). Micronutrient status of population of the Russian Federation and possibility of its correction. State of the problem. Voprosy Pitaniia (Problems of Nutrition), 86(4), 113-124. (In Russian) https://doi.org/10.24411/0042-8833-2017-00067

3. Abdulhabirova, F. M., Bezlepkina, O. B., Brovin, D. N., Vadina, T. A., Melnichenko, G. A., Nagaeva, E. V. et al. (2021). Clinical practice guidelines “Management of iodine deficiency disorders”. Problems of Endocrinology, 67(3), 10-25. https://doi.org/10.14341/probl12750

4. Troshina, E. A. (2022). Elimination of iodine deficiency — care for the health of the nation. Elimination of iodine deficiency is a concern for the health of the nation. An excursion into the history, scientific aspects and the current state of the legal regulation of the problem in Russia. Problems of Endocrinology, 68(4), 4-12. (In Russian) https://doi.org/10.14341/probl13154

5. Mayurnikova, L. A., Koksharov, A. A., Krapiva, T. V., Novoselov, S. V. (2020). Food fortification as a preventive factor of micronutrient deficiency. Food Processing: Techniques and Technologies, 50(1), 124-139. (In Russian) http://doi.org/10.21603/2074-9414-2020-1-124-139

6. Troshina, E. A., Mazurina, N. V., Senyushkina, E. S., Makolina, N. P., Galieva, M. O., Nikankina, L. V. et al. (2021). Monitoring of iodine deficiency disorders in the Republic of Tyva. Problems of Endocrinology, 67(1), 60-68. (In Russian) https://doi.org/10.14341/probl12715

7. Blikra, M. J., Altintzoglou, T., L0vdal, T., Rognsa, G., Skipnes, D., Skara, T. et al. (2021). Seaweed products for the future: Using current tools to develop a sustainable food industry. Trends in Food Science and Technology, 118 (Part B), 765-776. https://doi.org/10.1016/j.tifs.2021.11.002

8. Popovicheva, N. N. (2021). Functional fortified fermented milk drink with iodized food composite. Food Systems, 4(3S), 228-231. (In Russian) https://doi.org/10.21323/2618-9771-2021-4-3S-228-231

9. Dydykin, A. S., Zubarev, Y. N., Logunova, E. I., Kuzlyakina, Y. A. (2023). Modern forms of iodine-containing food components. Theory and Practice of Meat Processing, 8(3), 172-182. https://doi.org/10.21323/2414-438X-2023-8-3-172-182

10. Szymandera-Buszka, K., Waszkowiak, K., Kaczmarek, A., Zaremba, A. (2021). Wheat dietary fibre and soy protein as new carriers of iodine compounds for food fortification — the effect of storage conditions on the stability of potassium iodide and potassium iodate. LWT, 137, Article 110424. https://doi.org/10.1016/j.lwt.2020.110424

11. Mamtsev, A. N., Kozlov, V. N., Dinyakova, M. V. (2016). Technology of production of fermented milk drink enriched with iodine. Milk Processing, 11(205), 42-45. (In Russian)

12. Groufh-Jacobsen, S., Hess, S. Y., Aakre, I., Gjengedal, E. L. F., Pettersen, K.B., Henjum, S. (2020). Vegans, vegetarians and pescatarians are at risk of iodine deficiency in Norway. Nutrients, 12(11), Article 3555. https://doi.org/10.3390/nu12113555

13. Tattari, S., Gavaravarapu, S. M., Pullakhandam, R., Bhatia, N., Kaur, S., Sarwal, R. et al. (2022). Nutritional requirements for the elderly in India: A status paper. Indian Journal of Medical Research, 156(3), 411-420. https://doi.org/10.4103/ijmr.ijmr_2784_21

14. Popova, A. Yu., Tutelyan, V. A., Nikityuk, D. B. (2021). On the new (2021) Norms of physiological requirements in energy and nutrients of various groups of the population of the Russian Federation. Voprosy Pitaniia (Problems of Nutrition), 90(4), 6-19. In Russian) https://doi.org/10.33029/0042-8833-2021-90-4-6-19

15. Torres-Sánchez, L., Gamboa, R., Bassol-Mayagoitia, S., Huesca-Gómez, C., Nava, M. P., Vázquez-Potisek, J. I. et al. (2019). Para-occupational exposure to pesticides, PON1 polymorphisms and hypothyroxinemia during the first half of pregnancy in women living in a Mexican floricultural area. Environmental Health, 18(1), Article 33. https://doi.org/10.1186/s12940-019-0470-x

16. Bertinato, J. (2021). Iodine nutrition: Disorders, monitoring and policies. Chapter in the book: Advances in Food and Nutrition Research. Academic Press, 2021. https://doi.org/10.1016/bs.afnr.2021.01.004

17. Krela-Kaźmierczak, I., Czarnywojtek, A., Skoracka, K., Rychter, A. M., Ratajczak, A. E., Szymczak-Tomczak, A. et al. (2021). Is there an ideal diet to protect against iodine deficiency? Nutrients, 13(2), Article 513. https://doi.org/10.3390/nu13020513

18. Censi, S., Watutantrige-Fernando, S., Groccia, G., Manso, J., Plebani, M., Faggian, D. et al. (2019). The effects of iodine supplementation in pregnancy on iodine status, thyroglobulin levels and thyroid function parameters: Results from a randomized controlled clinical trial in a mild-to-moderate iodine deficiency area. Nutrients, 11(11), Article 2639. https://doi.org/10.3390/nu11112639

19. Mokhort, T. V. (2021). Iodine deficiency and pregnancy: Problem and solutions. Reproductive Health. Eastern Europe, 11(4), 410-421. (In Russian)] http://doi.org/10.34883/PI.2021.11.4.003

20. Hatch-McChesney, A., Lieberman, H. R. (2022). Iodine and iodine deficiency: A comprehensive review of a re-emerging issue. Nutrients, 14(17), Article 3474. https://doi.org/10.3390/nu14173474

21. Dedov I. I., Troshina E. A., Platonova N. M., Makolina N. P., Belovalova I. M., Senyushkina E. S. et al. (2022). Prevention of iodine deficiency diseases: Focus on regional targeted programs. Problems of Endocrinology, 68(3), 16-20. (In Russian) https://doi.org/10.14341/probl13119

22. Drakina, S. A., Perevoschikova, N. K., Burmistrova, E. Yu., Zinchuk, S. F. (2022). Health status of young children depending on their iodine level. Opportunities for correction. Clinical Practice in Pediatrics, 17(1), 128-134. (In Russian) https://doi.org/10.20953/1817-7646-2022-1-128-134

23. Cesar, А. J., Santos, S. I., Black, E. R., Chrestani, D. M. A., Duarte, A. F., Nilson, F. E. A. (2020). Iodine status of Brazilian school-age children: A national cross-sectional survey. Nutrients, 12(4), Article 1077. https://doi.org/10.3390/nu12041077

24. Tsukareva, E. A., Avchinnikova, D. A. (2021). Comparative characteristics of the actual nutrition of younger schoolchildren with different indices of nutritional status. Hygiene and Sanitation, 100(5), 512-518. (In Russian) https://doi.org/10.47470/0016-9900-2021-100-5-512-518

25. Manousou, S., Andersson, M., Eggertsen, R., Hunziker, S., Hulthen, L., Nystrom, H. F. (2020). Iodine deficiency in pregnant women in Sweden: a national cross-sectional study. European Journal of Nutrition, 59, 2535-2545. https://doi.org/10.1007/s00394-019-02102-5

26. Lisco, G., De Tullio, A., Triggiani, D., Zupo, R., Giagulli, V. A., De Pergola, G. et al. (2023). Iodine Deficiency and Iodine Prophylaxis: An Overview and Update. Nutrients, 15(4), Article 1004. https://doi.org/10.3390/nu15041004

27. Zimmermann, M. B. (2019). Iodine deficiency. Chapter in the book: The thyroid and its diseases: A comprehensive guide for the clinician. Springer, Cham, 2019. https://doi.org/10.1007/978-3-319-72102-6_8

28. Karbownik-Lewińska, M., Stępniak, J., Iwan, P., Lewiński, A. (2022). Iodine as a potential endocrine disruptor — a role of oxidative stress. Endocrine, 78(2), 219-240. https://doi.org/10.1007/s12020-022-03107-7

29. Saha, A., Mukherjee, S., Bhattacharjee, A., Sarkar, D., Chakraborty, A., Banerjee, A. et al. (2019). Excess iodine-induced lymphocytic impairment in adult rats. Toxicology Mechanisms and Methods, 29(2), 110-118. https://doi.org/10.1080/15376516.2018.1528647

30. Bolshakova, L. S., Lukin, D. E. (2020). Absorption of iodotyrosine from iodized milk protein in animals. Foods and Raw Materials, 8(1), 60-66. http://doi.org/10.21603/2308-4057-2020-1-60-66

31. Bolshakova, L. S., Lisitsyn, A. B., Chernukha, I. M., Zubtsov, Y. N., Lukin, D. E., Lyublinsky, S. L. (2018). The study of the metabolism of iodotyrosines included in the iodized milk protein in rats. Voprosy pitaniia (Problems of Nutrition), 87(3), 12-17. (In Russian) https://doi.org/10.24411/0042-8833-2018-10026

32. Zimmermann, M. B. (2020). Iodine and the iodine deficiency disorders. Chapter in the book: Present Knowledge in Nutrition: Basic Nutrition and Metabolism. Academic Press, 2020.

33. Barbaro, D., Orru, B., Unfer, V. (2019). Iodine and myo-inositol: A novel promising combination for iodine deficiency. Frontiers in Endocrinology, 10, Article 457. https://doi.org/10.3389/fendo.2019.00457

34. Winder, M., Kosztyia, Z., Boral, A., Koceiak, P., Chudek, J. (2022). The impact of iodine concentration disorders on health and cancer. Nutrients, 14(11), Article 2209. https://doi.org/10.3390/nu14112209

35. Rayman, M. P. (2019). Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease. Proceedings of the Nutrition Society, 78(1), 34-44. https://doi.org/10.1017/S0029665118001192

36. Bonofiglio, D., Catalano, S. (2020). Effects of iodine intake and nutraceuticals in thyroidology: Update and prospects. Nutrients, 12(5), Article 1491. https://doi.org/10.3390/nu12051491

37. Gharibzahedi, S. М. T., Jafari, S. M. (2017). The importance of minerals in human nutrition: Bioavailability, food fortification, processing effects and nanoencapsulation. Trends in Food Science and Technology, 62, 119-132. https://doi.org/10.1016/j.tifs.2017.02.017

38. Arias-Borrego, A., Velasco, I., Gómez-Ariza, J. L., García-Barrera, T. (2022). Iodine deficiency disturbs the metabolic profile and elemental composition of human breast milk. Food Chemistry, 371, Article 131329. https://doi.org/10.1016/j.foodchem.2021.131329

39. Shaaban, E. S., Yamamah, G. A. N., Bassuoni, R. A., Hussien, L., Mohamed, M. S., Gad, M. (2022). Iodine deficiency and anemia levels of urban and rural Egyptian children; Follow up study. Advances in Public Health Communication and Tropical Medicine, 2022(6), 1-7. https://doi.org/10.37722/APHCTM.2022601

40. Suplotova, L. A., Makarova, O. B., Troshina, E. A. (2022). Neonatal thyrotropin — indicatior of monitoring of iodine deficiency severity. What's level is considered a «cutoff point»? Problems of Endocrinology, 68(6), 12-21. (In Russian) https://doi.org/10.14341/probl12892

41. Turcan, L., Gerasimov, G. A., Parvanta, I., Timmer, A. (2021). Progress in Iodine Deficiency Disorders (IDD) Control and Elimination in Europe and Central Asia Region (ECAR) in 2010-2020. Clinical and Experimental Thyroidology, 17(4), 4-16. (In Russian) https://doi.org/10.14341/ket12713

42. Liu, P., Fan, L., Meng, F., Su, X., Liu, S., Shen, H. et al. (2020). Prevention and control of iodine deficiency disorders — China, 1995-2020. China CDC Weekly, 2(20), 345-349. https://doi.org/10.46234/ccdcw2020.090

43. Mathiaparanam, S., de Macedo, A. N., Mente, A., Poirier, P., Lear, S. A., Wielgosz, A. et al. (2022). The prevalence and risk factors associated with iodine deficiency in Canadian adults. Nutrients, 14(13), Article 2570. https://doi.org/10.3390/nu14132570

44. Randremanana, R. V., Bastaraud, A., Rabarijaona, L. P., Piola, P., Rakotonirina, D., Razafinimanana, J. O. et al. (2019). First national iodine survey in Madagascar demonstrates iodine deficiency. Maternal and Child Nutrition, 15(2), Article e12717. https://doi.org/10.1111/mcn.12717

45. World Health Organization. (2024). Microelements Data Base. Retrieved from https://platform.who.int/nutrition/micronutrients-database/search-by-micronutrient Accessed January 28, 2024

46. Zimmermann, M. B. (2023). The remarkable impact of iodisation programmes on global public health. Proceedings of the Nutrition Society, 82(2), 113-119. https://doi.org/10.1017/S0029665122002762

47. Adelmurzina, A. I., Viktorov, V. V., Bilalov, F. S., Timofeeva, E. A. (2023). Screening results for congenital hypothyroisis and transitional forms of hypothyroisis in newborn in iodine-deficient region of the Republic of Bashkortostan. Medicine. Sociology. Philosophy. Applied Research, 2, 9-13. (In Russian)

48. Henjum, S., Brantsæter, A. L., Kurniasari, A., Dahl, L., Aadland, E. K., Gjengedal, E. L. F. et al. (2018). Suboptimal iodine status and low iodine knowledge in young Norwegian women. Nutrients, 10(7), Article 941. https://doi.org/10.3390/nu10070941

49. Vasiljev, V., Subotic, A., Glavic, M. M., Juraga, D., Bilajac, L., Jelakovic, B. et al. (2022). Overview of iodine intake. Southeastern European Medical Journal, 6(1), 12-20. https://doi.org/10.26332/seemedj.v6i1.241

50. Gerasimov, G. A., Tsurkan, L., Aslanian, H., Salaru, I., Demiscan, D. (2021). Modeling of iodine consumption with industrial processed foods made with iodized salt in the adults and pregnant in Armenia and Moldova. Voprosy Pitaniia (Problems of Nutrition), 90(1), 49-56. (In Russian) https://doi.org/10.33029/0042-8833-2021-90-1-49-56

51. Koukkou, E. K., Roupas, N. D., Markou, K. B. (2017). Effect of excess iodine intake on thyroid on human health. Minerva Medica, 108(2), 136-146. https://doi.org/10.23736/S0026-4806.17.04923-0

52. Troshina, E. A., Dedov, I. I., Platonova, N. M., Makolina, N. P., Belovalova, I. M., Senyushkina, E. S. et al. (2022). Regional target program «Prevention of iodine deficiency diseases for 202X-202X» (Draft). Problems of Endocrinology, 68(3), 21-29. (In Russian) https://doi.org/10.14341/probl13120

53. Bespalov, V. G., Tumanyan, I. A. (2019). Iodine deficiency in the diet as a multidisciplinary problem. Lechaschi Vrach, 3, 8-13 (In Russian)

54. Zobkova, Z. S. (2020). Implementation and commercialization of the investigations results in whole milk branch. Current Issues in the Dairy Industry, Intersectoral Technologies and Quality Management Systems, 1(1), 199-204. (In Russian) https://doi.org/10.37442/978-5-6043854-1-8-2020-1-199-204

55. Trofimiuk-Muldner, M., Konopka, J., Sokolowski, G., Dubiel, A., Kiec-Klimczak, M., Kluczynski, E. et al. (2020). Current iodine nutrition status in Poland (2017): Is the Polish model of obligatory iodine prophylaxis able to eliminate iodine deficiency in the population? Public Health Nutrition, 23(14), 2467-2477. https://doi.org/10.1017/S1368980020000403

56. Rodriguez-Diaz, E., Pearce, E. N. (2020). Iodine status and supplementation before, during, and after pregnancy. Best Practice and Research Clinical Endocrinology and Metabolism, 34(4), Article 101430. https://doi.org/10.1016/j.beem.2020.101430

57. Antipova, L. V., Chubirko, M. I., Kulneva, N. G., Storublyovtsev, S. A. (2018). Ensuring the safety of food systems based on the sorption properties of collagen proteins Hygiene and Sanitation, 97(8), 772-777. (In Russian) http://doi.org/10.18821/0016-9900-2018-97-8-772-777

58. Kulikovskiy, A. V., Lisitsyn, A. B., Kuznetsova, O. A., Vostrikova, N. L., Gorlov, I. F. (2016). Methodological aspects of determining organic iodine (iodotyrosines) in food products. Voprosy Pitaniia (Problems of Nutrition), 85(4), 91-97. (In Russian)

59. Savlukova, Y. O., Kovaleva, E. G. (2023). Production of functional yogurt enriched with iodine in a bioavailable form. Bulletin of the South Ural State University. Series: Food and Biotechnology, 11(2), 83-92. (In Russian)

60. Khotimchenko, S. A., Sharafetdinov, Kh. Kh. (2020). On the prevention of iodine deficiency. Message 2. Voprosy Pitaniia (Problems of Nutrition), 89(3), 126-128. (In Russian) https://doi.org/10.24411/0042-8833-2020-10037

61. Kobzeva, S. Yu., Zhmurina, N. D., Podkopaeva, Z. P., Ashikhina, L. A., Tikhoykina, I. M. (2016). Application of the kelp powder to increase quality of culinary products. Voprosy Pitaniia (Problems of Nutrition), 85(S2), 193-193. (In Russian)

62. Tabatorovich, A. N., Reznichenko, I. Yu. (2016). Technology and quality estimation of marshmallow enriched with organic iodine. Food Processing: Techniques and Technology, 1(40), 61-67. (In Russian)

63. Slavyanskiy, A. A., Gribkova, V. A., Nikolaeva, N. V., Mitroshina, D. P. (2021). Granulated sugar-containing functional products in jelly fillings. Food Processing: Techniques and Technology, 51(4), 859-868. (In Russian) https://doi.org/10.21603/2074-9414-2021-4-859-868

64. Giro, T. M., Kulikovsky, A. V., Andreeva, S. V., Gorlov, I. F., Giro, A. V. (2020). Production of enriched lamb in biodegradable packaging. Foods and Raw Materials, 8(2), 312-320. http://doi.org/10.21603/2308-4057-2020-2-312-320

65. Kruchinin, A. G., Bigaeva, A. V., Turovskaya, S. N., Illarionova, E. E. (2022). Current state of the market of secondary raw material resources of the dairy industry. Polzunovskiy Vestnik, 4(1), 140-148. (In Russian) https://doi.org/10.25712/ASTU.2072-8921.2022.04.018

66. Kruchinin, A. G., Bolshakova, E. I. (2022). Hybrid strategy of bioinformatics modeling (in silico): Biologically active peptides of milk protein. Food Processing: Techniques and Technology, 52(1), 46-57. https://doi.org/10.21603/2074-9414-2022-1-46-57

67. Sirimulla, S., Bailey, J. B., Vegesna, R., Narayan, M. (2013). Halogen interactions in protein-ligand complexes: Implications of halogen bonding for rational drug design. Journal of Chemical Information and Modeling, 53(11), 2781-2791. https://doi.org/10.1021/ci400257k

68. Shinada, N. K., de Brevern, A. G., Schmidtke, P. (2019). Halogens in protein-ligand binding mechanism: A structural perspective. Journal of Medicinal Chemistry, 62(21), 9341-9356. https://doi.org/10.1021/acs.jmedchem.8b01453

69. Costa, P. J., Nunes, R., Vila-Viçosa, D. (2019). Halogen bonding in halocarbon-protein complexes and computational tools for rational drug design. Expert Opinion on Drug Discovery, 14(8), 805-820. https://doi.org/10.1080/17460441.2019.1619692

70. Nunes, R. S., Vila-Viçosa, D., Costa, P. J. (2021). Halogen bonding: An underestimated player in membrane-ligand interactions. Journal of the American Chemical Society, 143(11), 4253-4267. https://doi.org/10.1021/jacs.0c12470

71. Ibragimova, Z. R., Baerova, F. S. (2007). Iodine enrichment of semi-finished products from freshwater fish. Food Industry, 3, 59-60. (In Russian)

72. Lukin, D. E., Utyanov, D. A., Milushev, R. K., Vostrikova, N. L., Knyazeva, A. S. (2023). Effect of organically bound iodine in cattle feed on health indicators. Theory and Practice of Meat Processing, 8(1), 26-33. https://doi.org/10.21323/2414-438X-2023-8-1-26-33

73. Sordonova, E. V., Zhamsaranova, S. D., Lygdenov, D. V. (2018). Development and characterization of organic iodine and zinc derivatives. ESSUTM Bulletin, 2(69), 73-79. (In Russian)

74. Leskova, S. Yu., Danilov, M. B., Gombozhapova, N. I. (2016). Creaton of enriched protein-and-fat emulsion for meat products. Food Processing: Techniques and Technology, 2(41), 55-61. (In Russian)

75. Mavlonov, G. T., Rustamov, N. F., Sharipov, A. T., Aminov, S. N. (November 19, 2019). Zinc-activated betonite — a natural inorganic sorbent for histidine-containing peptides. Proceedings of the International scientific-practical conference (67th annual) dedicated to the 80th anniversary of Avicenna Tajik State Medical University and “Years of the development of rural areas, tourism and folk crafts (2019-2021)”, Dushanbe, Tajikistan. Retrieved from https://www.researchgate.net/profile/Ruslan-Aminov/publication/337843573_IMMUNE_SYSTEM_OF_MALE_RAT_AFTER_HIRUDOLOGICAL_INTERVENTION/links/5dee94af92851c8364704b3c/IMMUNE-SYSTEM-OF-MALE-RAT-AFTER-HIRUDOLOGICAL-INTERVENTION.pdf#page=186 Accessed March 10, 2024 (In Russian)]

76. Keltsieva, O. A., Gladilovich, V. D., Podolskaya, E. P. (2013). Immobilized metal ion affinity chromatography (imac). principle and applications. Scientific Instrumentation, 23(1), 74-85. (In Russian)

77. Kutyakov, V. A., Salmina, A. B. (2014). Metallothioneins as sensors and controls exchange of metals in the cells. Bulletin of Siberian Medicine, 13(3), 91-99. (In Russian)

78. Popov I. A., Indeikina M. I., Kononikhin A. S., Starodubtseva N. L., Nikolaev E. N., Kozin S. A. et al. (2013). ESI-MS identification of the minimal zinc-binding center in natural isoforms of в-amyloid domain 1-16. Molecular Biology, 47(3), 440-445. https://doi.org/10.1134/S002689331302012X

79. Pinto, L. D., Puppin, P. A., Behring, V. M., Alves, O. C., Rey, N. A., Felcman, J. (2012). Solution and solid state study of copper (II) ternary complexes containing amino acids of interest for brain biochemistry-2: Homocysteine with aspartate, glutamate or methionine. Inorganica Chimica Acta, 386, 60-67. https://doi. org/10.1016/j.ica.2012.01.025

80. Skugoreva, S. G., Ashihmina, T. Y., Fokina, A. I., Lyalina, E. I. (2016). Chemical grouns of toxic effect of heavy metals (review). Theoretical and Applied Ecology, 1, 4-13. (In Russian)

81. Jamsaranova, S. D., Lygdenov, D. V., Sokolov, D. V., Bolkhonov, B. A. (2019). Creation of a hypothetical computer model of organic forms of microelements. ESSUTM Bulletin, 3(74), 26-34. (In Russian)

82. Shishkova, V. N., Narcissov, Y. R., Titova, V. Y., Sheshegova, E. V. (2022). Molecular mechanisms defining application of glycine and zinc combinationin correction of stress and anxiety main manifestations. Pharmacy and Pharmacology, 10(5), 404-415. (In Russian) https://doi.org/10.19163/2307-9266-2022-10-5-404-415

83. Cheknyov, S. B. (2021). The proteins of ү-globulin fraction binding metal ions, in physiological immune regulation. Mutual action of copper and zinc. Immunologiya, 42(5), 546-551. (In Russian) https://doi.org/10.33029/0206-4952-2021-42-5-546-551

84. Tsib, A. F., Tutelyan, V. A., Onishchenko, G. G., Shakhtarin, V. V., Silaev, A. V., Rozyev, R. A. et al. (2004). A new approach to settling the problem of liquidation Iodium deficit. Food Industry, 11, 84-86. (In Russian)