JOURNAL OF INTEGRATIVE NUTRITION
TREATMENT STRATEGY
Conquering Epigenetic Influences in Autoimmune Thyroid Disease with Nutritional Dietary Protocols: A Nutrigenomic Outlook
Hollywood, JB
FIRST PUBLISHED
2025-02-01
Article:
-
Can be printed.
-
Can be downloaded.
-
Can NOT be distributed.
ABSTRACT
Background: Autoimmune thyroid diseases (AITD), Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), surface from complicated interactions between genetic and environmental factors. There’s new emerging evidence coming from genetic and nutritional studies demonstrating solid proof of nutrigenomic factors having a strong influence over the occurrence of AITD. Case reports have documented Ancestral dietary interventions in the reduction of AITD antibodies (Ab). This review summarizes the findings.
Methods: Thyroid and immune system genes as well as their structures and nutritional components were researched to include candidate gene analysis, whole- genome linkage screening, genome-wide association studies, and whole-genome sequencing.
Results: Twelve (12) genes were identified as conferring to genetic susceptibility in patients with AITD. Diet modalities were considered based on findings. Zinc was found to have a close relation with thyroid disease, increased genetic susceptibility to the development of AITD, the ability to reduce AITD Ab, and increase thyroid hormones. Amino acids were found to play a critical role in gene structure, mutation, and cell relationship. Vitamin C was found to be a key player involved in antioxidant processes and ability to decrease AITD Ab, while other nutrients (niacin) supported these mechanisms of genetic influence on AITD. Calorie restrictive diets were found to have a positive influence on AITD and reduce Ab.
Conclusion: Nutrients such as zinc, amino acids, vitamin C, and niacin influence gene expression, mutation, and cellular function in AITD. These findings suggest that targeted nutritional and dietary interventions may modulate genetic susceptibility and Ab levels associated with AITD.
COI STATEMENT
The authors declare no competing financial interests.
REFERENCES
1. Franco JS, Amaya-Amaya J, Anaya JM. Thyroid disease and autoimmune diseases. In: Autoimmunity: From Bench to Bedside. Bogotá: El Rosario University Press; 2013. Chapter 30. scs
2. Heuck, Claus C, Kallner, Anders, Kanagasabapathy, A. S, Riesen, W & World Health Organization. Diagnostic Imaging and Laboratory Technology. (2000). Diagnosis and monitoring of diseases of the thyroid. World Health Organization. scs
3. Mincer DL, Jialal I. Hashimoto Thyroiditis. StatPearls Publishing LLC: Treasure Island (FL). 2022.
4. Tomer Y. Genetic susceptibility to autoimmune thyroid disease: past, present, and future. Thyroid. 2010;20(7):715-725. doi:10.1089/thy.2010.1644
5. Day KJ, Adamski MM, Dordevic AL, Murgia C. Genetic Variations as Modifying Factors to Dietary Zinc Requirements—A Systematic Review. Nutrients. 2017; 9(2):148. scs
6. National Center for Biotechnology Information. Gene Expression Omnibus: Dataset GSE145958. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE145958.
7. Núñez Miguel R, Sanders J, Furmaniak J, Smith BR. Structure and activation of the TSH receptor transmembrane domain. Autoimmun Highlights. 2017;8(1):2. doi:10.1007/s13317-016-0090-1
8. Miller-Gallacher J, Sanders P, Young S, et al. Crystal structure of a ligand-free stable TSH receptor leucine-rich repeat domain. J Mol Endocrinol. 2019;62(3):117-128. doi:10.1530/JME-18-0213
9. National Center for Biotechnology Information. ClinVar: NM_004972.3(TSHR):c.769G>A (p.Arg257Gln). Updated March 21, 2023. https://www.ncbi.nlm.nih.gov/clinvar/variation/314693/?new_evidence=true.
10. Pang AL-Y, Chan W-Y. Molecular Basis of Diseases of the Endocrine System. In: Essential Concepts in Molecular Pathology. Academic Press; 2010:361-391
11. Williams DE, Le SN, Hoke DE, et al. Structural studies of thyroid peroxidase show the monomer interacting with autoantibodies in thyroid autoimmune disease. Endocrinology. doi:10.1210/endocr/bqaa016
12. National Center for Biotechnology Information. Tg Gene: thyroglobulin. Updated September 30, 2023. https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=DetailsSearch&Term=7038.
13. National Center for Biotechnology Information. ClinVar: RCV000022790. Updated May 19, 2023. https://www.ncbi.nlm.nih.gov/clinvar/RCV000022790
14. Fröhlich E, Wahl R. Thyroid autoimmunity: Role of anti-thyroid antibodies in thyroid and extra-thyroidal diseases. Front Immunol. 2017;8:521. doi:10.3389/fimmu.2017.00521
15. Coscia F, Taler-Verčič A, Chang VT, et al. The structure of human thyroglobulin. Nature. 2020;578(7796):627-630. doi:10.1038/s41586-020-1995-4
16. National Center for Biotechnology Information. DUOX2 Gene: Dual oxidase 2. Updated October 15, 2023. https://www.ncbi.nlm.nih.gov/gtr/genes/50506/.
17. National Center for Biotechnology Information. IL2RA Gene: interleukin 2 receptor subunit alpha. Updated November 2, 2023. https://www.ncbi.nlm.nih.gov/gene/3559
18. Li CW, Concepcion E, Tomer Y. Dissecting the role of the FOXP3 gene in the joint genetic susceptibility to autoimmune thyroiditis and diabetes: A genetic and functional analysis. Gene. 2015;556(2):142-148. doi:10.1016/j.gene.2014.11.064
19. Kalantar K, Khansalar S, Eshkevar Vakili M, et al. Association of FOXP3 gene variants with risk of Hashimoto’s thyroiditis and correlation with anti-TPO antibody levels. Acta Endocrinol (Buchar). 2019;15(4):423-429. doi:10.4183/aeb.2019.423
20. Frommer L, Kahaly GJ. Type 1 diabetes and autoimmune thyroid disease—the genetic link. Front Endocrinol (Lausanne). 2021;12:618213. doi:10.3389/fendo.2021.618213
21. Lee AH, Dixit VD. Dietary regulation of immunity. Immunity. 2020;53(3):510-523. doi:10.1016/j.immuni.2020.08.013
22. Djilali-Saiah I, Schmitz J, Harfouch-Hammoud E, Mougenot JF, Bach JF, Caillat-Zucman S. CTLA-4 gene polymorphism is associated with predisposition to coeliac disease. Gut. 1998;43(2):187-189. doi:10.1136/gut.43.2.187
23. National Center for Biotechnology Information. CD40 Gene: cluster differentiation 40. Updated November 2, 2023. scs
24. Graham, R., Ortmann, W., Rodine, P. et al. Specific combinations of HLA-DR2 and DR3 class II haplotypes contribute graded risk for disease susceptibility and autoantibodies in human SLE. Eur J Hum Genet 15, 823–830 (2007). https://doi.org/10.1038/sj.ejhg.5201827
25. Brand OJ, Gough SCL. Genetics of thyroid diseases. Mol Cell Endocrinol. 2010;322(1-2):1-4. doi:10.1016/j.mce.2010.03.022. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0303720710000158?via%3Dihub
26. National Center for Biotechnology Information. FCRL3 Gene: Fc receptor like 3. https://www.ncbi.nlm.nih.gov/gene
27. National Center for Biotechnology Information. SLC30A1 Gene: solute carrier family 30 member 1. https://www.ncbi.nlm.nih.gov/gene/7779
28. Severo JS, Morais JBS, de Freitas TEC, et al. The Role of Zinc in Thyroid Hormones Metabolism. Int J Vitam Nutr Res. 2019;89(1-2):80-88. doi:10.1024/0300-9831/a000262
29. Dai H, Wang L, Li L, Huang Z and Ye L (2021) Metallothionein 1: A New Spotlight on Inflammatory Diseases. Front. Immunol. 12:739918. doi: 10.3389/fimmu.2021.739918
30. Haase H, Rink L. The immune system and the impact of zinc during aging. Immun Ageing. 2009;6:9. Published 2009 Jun 12. doi:10.1186/1742-4933-6-9
31. Stefan M, Faustino LC. Genetics of Thyroid-Stimulating Hormone Receptor- Relevance for Autoimmune Thyroid Disease. Front Endocrinol. 2017;8:57. doi:10.3389/fendo.2017.00057
32. Stefan M, Wei C, Lombardi A, et al. Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity. Proc Natl Acad Sci U S A. 2014;111(34):12562-12567. doi:10.1073/pnas.1408821111
33. Ban Y. Genetic factors of autoimmune thyroid diseases in Japanese. Autoimmune Dis. 2012;2012:236981. doi:10.1155/2012/236981
34. Chistiakov DA. Immunogenetics of Hashimoto's thyroiditis. J Autoimmune Dis. 2005;2(1):1. doi:10.1186/1740-2557-2-1
35. Ertek S, Cicero AF, Caglar O, Erdogan G. Relationship between serum zinc levels, thyroid hormones, and thyroid volume following successful iodine supplementation. Hormones (Athens). 2010;9(3):263-268. doi:10.14310/horm.2002.1276
36. Nishi Y, Kawate R, Usui T. Zinc metabolism in thyroid disease. Postgrad Med J. 1980;56(662):833-837. doi:10.1136/pgmj.56.662.833
37. Zhou Q, Xue S, Zhang L, Chen G. Trace elements and the thyroid. Front Endocrinol (Lausanne). 2022;13:904889. Published 2022 Oct 24. doi:10.3389/fendo.2022.904889
38. National Center for Biotechnology Information. PubChem Compound Summary for CID 853, DL-Thyroxine. https://pubchem.ncbi.nlm.nih.gov/compound/DL-Thyroxine.
39. Hollywood JB, Hutchinson D, Feehery-Alpuerto N, Whitfield M, Davis K, Johnson LM. The Effects of the Paleo Diet on Autoimmune Thyroid Disease: A Mixed Methods Review. J Am Nutr Assoc. 2023;42(8):727-736. doi:10.1080/27697061.2022.2159570
40. Tourkochristou E, Triantos C, Mouzaki A. The Influence of Nutritional Factors on Immunological Outcomes. Front Immunol. 2021;12:665968. doi:10.3389/fimmu.2021.665968
41. Ihnatowicz P, Wątor P, Gębski J, Frąckiewicz J, Drywień ME. Are nutritional patterns among Polish Hashimoto thyroiditis patients differentiated internally and related to ailments and other diseases? Nutrients. 2021;13(11):3675. doi:10.3390/nu13113675