Graves’ disease is a common autoimmune disease characterised by loss of immune tolerance to thyroid antigens and the development of stimulating autoantibodies directed at the thyrotrophin (thyroid stimulating hormone) receptors in the thyroid, orbital fibroblasts and adipocytes, and the skin.¹

Antibodies cause overproduction of thyroid hormone, leading to classic symptoms of hyperthyroidism.¹ These include an enlarged and overactive thyroid gland, fatigue, palpitations and tachycardia, nervous tension, insomnia, and other symptoms (see Figure 1). Thyroid hormones regulate metabolism in all body cells, therefore excessive levels have systemic effects.

Figure 1. Symptoms of Hyperthyroidism

Abnormal activation of T cells and B cells, imbalance between Th17-lymphocytes and regulatory T cell (Treg) lymphocytes, and abnormal production of pro-inflammatory cytokines have a significant influence on autoimmune progression.^2,3 The high metabolic rate also increases oxidative stress. 

Herbal Management of Graves’ Disease

In the naturopathic management of Graves’ disease, treatment aims may include:⁴

- reducing thyroxine (T4) output from the thyroid gland

- modulating immune function and reducing production of thyroid antibodies

- reducing inflammation and oxidative damage, and

- managing associated symptoms including heart palpitations, nervous agitation,
   and sleep disturbance.

Bugleweed (Lycopus spp.), Lemon balm (Melissa officinalis) and Hemidesmus (Hemidesmus indicus) are key herbs that may support patients with Graves’ disease.

Bugleweed

Bugleweed is specific for hyperthyroidism. Traditional Western herbal medicine uses include nervous tachycardia, Graves’ disease with cardiac involvement, thyrotoxicosis with difficult breathing, tremor, and exophthalmic goitre.⁵ Bugleweed possesses antithyroid and TSH antagonist actions, reduces heart rate and is a mild sedative.^5,6

Bugleweed has been shown to attach to and block the TSH receptor in the thyroid, thereby reducing the binding of TSH receptor-stimulating antibodies. This in turn reduces T4 output, reduces conversion of T4 to triiodothyronine (T3) and inhibits peripheral T3 formation.⁴

Lemon Balm

Data indicates that Lemon Balm acts upon both the TSH hormone and the receptor itself.⁷ In vitro studies have demonstrated Lemon Balm’s TSH antagonist actions. In vitro, constituents of Lemon Balm extract significantly inhibit TSH binding to its receptor, and of antibody binding to TSH.⁷  In animal studies, Lemon Balm extract has been shown to decrease levels of circulating TSH and inhibit thyroid secretion.⁸

As a nervine tonic, mild sedative and spasmolytic, Lemon Balm may help ease nervous tension and support restful sleep. In patients with mild-moderate anxiety and sleep disturbance, Lemon Balm (300 mg BID for 15 days) reduced anxiety (agitation, hyperactivity, and tension) by 18% (p<0.01), and lowered insomnia by 42% (p<0.01).⁹

In patients with benign palpitations (not specifically thyroid-related), Lemon Balm (4.8 g/day for 14 days) significantly reduced the frequency of palpitation episodes compared to placebo. The number of patients with anxiety and insomnia disorder decreased significantly after Lemon Balm treatment (from 75% to 42.8%; p=0.004). These results represented an improvement from mild to moderate anxiety symptoms and difficulty falling asleep, to minimal or no symptoms. ¹⁰

Hemidesmus

Commonly known as Indian Sarsaparilla, Hemidesmus root is used in Ayurvedic medicine for the management of autoimmune disease.¹¹ One its main actions is the depression of immune function. In a series of tests, oral administration of Hemidesmus extract decreased both the cell-mediated and humoral components of the immune system in mice.⁶ Hemisdesmus is a depurative, diaphoretic and tonic herb. It also demonstrates anti-inflammatory and analgesic effects.¹²

Nutritional Interventions for Hyperthyroidism

Nutrients including vitamin A, vitamin D, selenium and zinc may be deficient in thyroid disorders. These antioxidant nutrients also provide much needed support in reducing the high oxidative load in Graves’ disease patients.⁴ Selenium deficiency is theorised to influence the generation of free radicals, the conversion of T4 to T3 and the thyroidal autoimmune process.⁴

Patients with active Graves’ had lower mean vitamin D levels compared to those in remission and significantly higher prevalence of deficiency. A negative correlation between serum vitamin D levels and serum free T4 levels was also observed.¹³

Newly diagnosed Grave’s disease patients with insufficient vitamin D and selenium levels received either standard treatment (Methimazole) alone or combined with selenomethionine and colecalciferol (intervention). Results show those in the intervention group had a significantly greater improvement in hyperthyroidism and quality of life scores.¹⁴

The addition of vitamin D and selenium may help restore immune homeostasis by modulating Treg and natural killer (NK) cell frequency, favouring a more pronounced reduction of NK cells and an increase of Treg cells. Low numbers or defective suppressive activity of Treg cells has been reported in Graves’ disease. Treg cells help keep autoreactive immune cells under control, thus preventing the development of autoimmune diseases.³

Modulating the Gut Microbiota with Probiotics and Diet

Studies suggest that the gut microbiota plays a key role in the pathogenesis of Graves’ disease. Significant differences exist in the microbiota composition between Graves’ patients and healthy controls, and antithyroid and other medication further disrupt the milieu. Probiotics can promote the differentiation of Treg cells, thus modifying intestinal immune homeostasis. Probiotics and fibre-rich diets that modulate the gut microbiota are important strategies for Graves’ disease management.¹⁵

Interestingly, the Paleo diet has been shown to improve antibodies and thyroid hormones in autoimmune thyroid disease including Graves’ disease and can provide a natural source of beneficial nutrients.¹⁶ 

In Summary

Targeted herbal medicines and nutrients may improve clinical outcomes for patients with Graves’ disease by reducing the thyroid overactivity, modulating immune function, reducing oxidative damage and aiding symptom management.

References

1. Jo Kamimoto JL, Flood JJ. Systemic thyroid dysfunction in Graves disease. Int
Ophthalmol Clin. 2023 Apr 1;63(2):55-63. doi: 10.1097/IIO.0000000000000463. 

2. Kravchenko V, Zakharchenko T. Thyroid hormones and minerals in immunocorrection of disorders in autoimmune thyroid diseases. Front Endocrinol (Lausanne). 2023 Aug 30;14:1225494. doi: 10.3389/fendo.2023.1225494.

3. Gallo D, Bruno A, Gallazzi M, Cattaneo SAM, Veronesi G, Genoni A, et al. Immunomodulatory role of vitamin D and selenium supplementation in newly diagnosed Graves' disease patients during methimazole treatment. Front Endocrinol (Lausanne). 2023 Apr 14;14:1145811. doi: 10.3389/fendo.2023.1145811.

4. Hechtman L. Clinical naturopathic medicine. 2nd ed. Chatswood NSW: Elsevier Australia; 2019. p. 1168-82.

5. Bone K, Mills S. Principles and practice of phytotherapy: modern herbal medicine. 2^nd ed. Edinburgh: Elsevier Health Sciences; 2013. p. 454-9.

6. Bone K. A Clinical Guide to Blending Liquid Herbs: Herbal Formulations for the Individual Patient, Churchill Livingstone, 2003.

7. Santini F, Vitti P, Ceccarini G, Mammoli C, Rosellini V, Pelosini C, et al. In vitro assay of thyroid disruptors affecting TSH-stimulated adenylate cyclase activity. J Endocrinol Invest. 2003 Oct;26(10):950-955. DOI: 10.1007/BF03348190

8. Natural Medicines Database [Internet]. Denver CO: TRC Healthcare; 2022. Lemon balm; 2021 Sep [cited 2022 May 11]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=437

9. Cases J, Ibarra A, Feuillère N, Roller M, Sukkar SG. Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances. Med J Nutrition Metab. 2011 Dec;4(3):211-218. DOI: 10.1007/ s12349-010-0045-4

10. Alijaniha F, Naseri M, Afsharypuor S, Fallahi F, Noorbala A, Mosaddegh M, et al. Heart palpitation relief with Melissa officinalis leaf extract: double blind, randomized, placebo controlled trial of efficacy and safety. J Ethnopharmacol. 2015 Apr 22;164:378-84.

11. Pansare T, Khandekar SB, Satpudke SS. Ayurvedic and modern aspects of Sariva (Hemidesmum Indicus R. Br): an overview. Int J Ayurv Herb Med. 2018;8(1):3133-4.

12. Moorthy H, Kumar V. Hemidesmus indicus (L.) R. BR. An overview. Plant Archives. 2021;21(1):2132-43.

13. Rattanamusik N, Uitrakul S, Charoenpiriya A. Vitamin D levels in patients with active and remission Graves' disease. Medicines (Basel). 2023 Jul 6;10(7):41. doi: 10.3390/medicines10070041. 

14. Gallo D, Mortara L, Veronesi G, Cattaneo SA, Genoni A, Gallazzi M, et al. Add-on effect of selenium and vitamin d combined supplementation in early control of Graves' disease hyperthyroidism during methimazole treatment. Front Endocrinol (Lausanne). 2022 Jun 15;13:886451.

15. Hou J, Tang Y, Chen Y, Chen D. the role of the microbiota in Graves' disease and Graves' orbitopathy. Front Cell Infect Microbiol. 2021 Dec 22;11:739707. doi: 10.3389/fcimb.2021.739707.

16. 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 Jan 4:1-10. doi: 10.1080/27697061.2022.2159570.