Rosmarinic acid and thyroid autoimmunity

Rosmarinic acid is a molecule, first extracted from rosemary herb (since the similarity of the name) which is caffeic acid derivative, present in a number of herbs of mint (family Lamiaceae) such as Mentha spp (garden mint, spearmint), Origanum vulgare (oregano), Melissa officinalis (lemon balm), Rosmarinus officinalis (rosemary), Prunella vulgaris, Coleus spp, Ocimum spp (basil, holy basil), Origanum majorana (marjoram), thyme, Salvia officinalis (sage) and even small amounts in Lavandula angustifolia (English lavender). It is also present in some members of Boraginaceae family, including Lithospermum. Rosemarinic acid acts as a protective molecule in these plants. In a comparative study Mentha spicata (garden mint), Salvia officinalis and Melissa officinalis were shown to contain highest amounts of rosmarinic acid. The content of rosmarinic acid in rosemary was much lower but may vary in plants in different countries (12).

I will talk about studies regarding rosmarinic acid for thyroid autoimmunity and the herbs which contain it. Some herbs containing rosmarinic acid are beneficial for Graves’ disease (GD) and others for Hashimoto’s thyroiditis (HT) and hypothyroidism as they contain other different active components which may affect thyroid hormone levels and how they work in body cells.

The majority of studies on rosmarinic acid are in vitro (in the lab). There are some positive human studies on herbs containing rosmarinic acid for Graves’ disease (see my previous blogs). Melissa officinalis and Lycopus virginicus bugleweed (Lamiaceae) have been used in treatment of mild hyperthyroidism and GD. Generally herbs of the mint family (but not all) are thyro-suppressive possibly due to phenolic and cinnamic acid-flavonoid-type plant components. Bugleweed extract was found to reduce peripheral T4 to T3 conversion and thus it may lower the levels of T3 thyroid hormone levels in rat liver (23).  

There is no specific scientific human research (that I could find) in regards to rosmarinic acid molecule and HT. However, there are laboratory studies  indicating that it can indeed be a beneficial anti-inflammatory agent for thyroid autoimmunity (both GD and HT) as I will discuss in this blog.

The herbs containing rosmarinic acid, such as rosemary and sage may be beneficial for HT and hypothyroidism. They contain rosmarinic acid but also high amounts of carnosic acid, among other components, which improve thyroid hormone sensitivity within body cells. They have many minerals and vitamins. It has been shown in laboratory studies that carnosic acid in rosemary improves thyroid hormone action on DNA level by improving the signalling of thyroid receptor. Carnosic acid helps to promote the function of Retinoid-X- receptors and improve thyroid receptor coupling and expression of target genes thus increasing sensitivity to thyroid hormones. Another component of rosemary herb, carnosol, supports thyroid hormone metabolism and production of active thyroid hormone T3. Rosemary also improves learning and memory. Sage is believed to “heal” a memory.

Generally, many thyroid support supplements contain rosemary herb extracts and powders as it has been observed by naturopaths and herbalists that they improve thyroid function.

Let’s then discuss rosmarinic acid. It is a natural molecule which may be helpful in pharmaceutical therapy for some autoimmune disorders (rheumatoid arthritis, SLE, MS) and thyroid autoimmunity.

Here is why:

It is a potent antioxidant, anti-inflammatory agent, antimicrobial, anti-carcinogenic agent with tissue healing and protective abilities. It may help with allergies.

Rosmarinic acid is anti-inflammatory and helps with balancing of the immune system. There are a number of laboratory studies indicating that rosmarinic acid may disrupt the cascade of thyroid damage in thyroid autoimmunity by interfering with complement molecules of the immune system.

When too much free radicals are produced in the thyroid (for example when selenium levels are too low), they affect the TPO enzyme which is the enzyme involved in thyroid hormone synthesis. TPO enzyme was found to bind specific molecules of immune system called complement C4 (11). This then may start inflammatory responses cascade, formation of complement C5 and other complement components resulting in thyroid tissue destruction. A study (11) reported over-expression of C4 and all the subsequent components in the complement cascade by Hashimoto’s thyroiditis (HT) tissue thyrocytes.

Rosmarinic acid has been found (10) to inhibit a molecule called Complement 5 convertase which generates complement component C5. This molecule is a dominant inflammatory mediator in the development of many inflammatory and some organ specific autoimmune diseases, such as rheumatoid arthritis, SLE and thyroid autoimmune disease. It is involved in generation of other complement molecules and eventual tissue damage. Study on complement expression in GD disease and HT showed that C5 and C6 complements were over expressed in thyroid tissue from people with Graves’ disease compared to normal tissue. People with HT over expressed all complement components. In a study (10) Rosmarinic acid inhibited C5 convertase and covalent attachment of C3b to cells which indicated that it may stop the formation of complement cascade molecules in the thyroid that damage thyroid in autoimmunity.

Rosmarinic acid also has other actions (1). It promotes death of aberrant T lymphocytes and balances the immune system by inhibiting a nuclear factor in these cells. It thus reduces autoimmune antibodies. Studies of herbs (3,4) containing rosmarinic such as Melissa officinalis showed that it inhibits the binding of thyroid stimulating hormone (TSH) and TSH specific antibodies to TSH receptors in Graves’ disease (3,4) thus blocking thyroid overstimulation and lowering the formation of excessive thyroid hormones Lithospermum officiale and Melissa inhibit Graves’ IgG (antibody) and the long-acting thyroid stimulator (LATS) response. In studies, the relative potency of the inhibition was greatest for Melissa which seem to help with the actions of anti-thyroid medications.

The Journal of Restorative Medicine (1) states: Rosmarinic acid also reduces gamma interferon driven T cell responses and reduces interleukin production following T cell stimulation. Furthermore, rosmarinic acid affects signal transduction inside T cells by affecting specific tyrosine kinase enzymes inside the cell. By direct effects on T cells as well as other anti-inflammatory and antioxidant effects, rosmarinic acid may be a safe and valuable tool for reducing autoimmune inflammation. It may also be safe and advantageous to use in tandem with pharmaceutical treatment of autoimmune diseases.”

Rosmarinic acid also modulates neuro- endocrine function. It has calming properties. Rosmarinic acid is helpful against hair loss (massaging scalp with rosemary oil or rinsing with rosemary tea) may be beneficial.

There are rosmarinic acid containing supplements on the market (extracted from rosemary). I have not seen human studies in regards to rosmarinic acid and thyroid autoimmunity although laboratory studies, as described above, look very promising for rosmarinic acid. I believe it is too early at the present time to take rosmarinic extract supplements for thyroid autoimmunity. It would be great to see more studies and human trials. Rosmarinic acid from rosemary is considered safe but you need to consult your doctor before considering using rosmarinic acid extracts or if you suffer any side effects while taking them.

Rosmarinic acid or rosemary extract powders extracts should not be used by children, pregnant, breastfeeding women and people taking specific med (heart or diabetic medications importantly), with specific medical conditions or if allergic to herbs from Lamiaceae family.

It is important to consult your doctor regarding any herbs containing rosmarinic acid.

Herbal teas can provide rosmarinic acid which it is water soluble. Since I have had my thyroid removed, I no longer have GD but there are still some autoimmunity markers in my body (ANA antibodies- the antinuclear antibodies) which are common in people who have had autoimmune issues. I try to reduce my ANA antibodies in a number of ways but one of them is by the use of rosemary and sage cooking herbs. I drink sage tea very often. I use rosemary and sage in cooking as much as possible. I like sage tea and it seems to make me feel better. Rosemary tea is more of an acquired taste for me but I have it occasionally. I find that adding some lemon slices and bit of honey to my rosemary leaf or sage in hot water infusion helps. I use fresh herbs or dried herbs. I grow rosemary in a pot and I have had the same plant for years now. I have roughly calculated that 2tbl of dried rosemary leaves would roughly contain standard daily dose of rosmarinic acid but do not quote me on that calculation…

This blog is for educational purposes only.

References:

1. Stansbury, Jill; Saunders, Paul; Winston, David; Zampieron, Eugene R. Rosmarinic acid as a novel agent in the treatment of autoimmune disease. Journal of Restorative Medicine. 2012(1):115, pp. 112-116(5).
2. Kennedy DO, LittleW, Schley AB. Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm). Psychosom Med. 2004 Jul-Aug; 66(4):607-13.
3. Francis Brinker. Inhibition of Endocrine Function by Botanical Agents. I Boraginaceae and Labiatae. Journal of Naturopathic Medicine. 1990 (1):10-19.
4. Auf’mkolk, M. Ingbar, J.C., Kubota, K., Amir, S.M., Ingbar, S.H. Extracts and auto-oxidized constituents of certain plants inhibit the receptor-binding and biological activity of Graves’ disease Immunoglobulins. Endocrinology. 1985 May; 116(5):1687-93.
5. Kang MA, Yun SY, Won J. Rosmarinic acid inhibits Ca2+-dependent pathways of T-cell antigen receptor-mediated signaling by inhibiting the PLC-gamma 1 and Itk activity: M.A. Kang, et al.; Blood 2003:101(9): 3534-42.
6. Won J, Hur YG, Hur EM. Park SH, Kang MA,Choi Y,Park C, Lee KH, Yun Y. Rosmarinic acid inhibits TCR-induced T cell activation and proliferation in an Lck-dependent  European Journal Immunol. 2003 Apr 33(4): 870–9.
7. Anshita Gupta, Suchita Wamankar, Bina Gidwani, Chanchal Deep Kaur. Herbal drugs for thyroid treatment. Shri Rawatpura Sarkar Institute of Pharmacy. India. 2016 Jan-Mar; 6(1):62-70. URL: https://ijpbs.com/ijpbsadmin/upload/ijpbs_572a3e8ca4615.pdf
8. Peake PW, Pussell BA, Martyn P, Timmermans V, Charlesworth JA. The inhibitory effect of rosmarinic acid on complement involves the C5 convertase. Int. J Immunopharmacol. 1991. 13 (7):853-7.
9. Potluková E1, Limanová Z. [The role of complement in autoimmune thyroid disorders]. [Article in Czech]. Cas Lek Cesk. 2007; 146(3):210-4.
10. Sahu A, Rawal N, Pangburn MK. Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b. Biochem Pharmacol. 1999 Jun 15; 57(12):1439-46.
11. Stephanie Blanchin, Valerie Estienne, Josee-Martine Durand-Gorde, Pierre Carayon, Jean Ruf. Complement activation by direct C4 binding to thyroperoxidase in Hashimoto’s thyroiditis. Endocrinology. 2003 Dec. 144(12). Url: https://academic.oup.com/endo/article/144/12/5422/2880991
12. Maryam Shekarchi, Homa Hajimehdipoor, Soodabeh Saeidnia, Ahmad Reza Gohari and Morteza Pirali Hamedani. Comparative study of rosmarinic acid content in some plants of Labiatae family. Pharmacogn Mag. 2012 Jan-Mar; 8(29): 37–41.
13. Auf’mkolk M, Amir S, Kubota K, Ingbar S. The active principles of plant extracts with antithyrotropic activity: oxidation products of derivatives of 3,4-dihydroxycinnamic acid. Endocrinology. 1985; 116(5):1677-1686.
14. Rosmarinic acid. https://www.sciencedirect.com/topics/medicine-and-dentistry/rosmarinic-acid.
15. Naturopathic doctor news and reviews. All about autoimmune thyroiditis. http://ndnr.com/autoimmuneallergy-medicine/all-about-autoimmune-thyroiditis/
16. Aim for women. Advancing Integrative medicine. URL: https://www.aimforwomen.com/top-herbs-for-hashimotos/
17. URL: https://www.yourhormones.com/content/ThyroMend-Professional-Guide_A4.pdf
18. Thyroid Support. URL: https://www.yourhormones.com/thyroid-support/
19. Farr SA, Niehoff ML, Ceddia MA, Herrlinger KA, Lewis BJ, Feng S, Welleford A, Butterfield DA, Morley JE. Effect of botanical extracts containing carnosic acid or rosmarinic acid on learning and memory in SAMP8 mice. Physiol Behav. 2016 Oct 15; 165:328-38.
20. Panahi Y, Taghizadeh M, Marzony ET, Sahebkar A. Rosemary oil vs minoxidil 2% for the treatment of androgenetic alopecia: a randomized comparative trial. Skinmed. 2015 Jan-Feb; 13(1):15-21.
21. Steiner M, Priel I, Giat J, Levy J, Sharoni Y, Danilenko M. Carnosic acid inhibits proliferation and augments differentiation of human leukemic cells induced by 1,25-dihydroxyvitamin D3 and retinoic acid. Nutr Cancer. 2001; 41(1-2):135-44. [PMID: 12094616]
22. Danilenko M, Wang X, Studzinski GP. Carnosic acid and promotion of monocytic differentiation of HL60-G cells initiated by other agents. J Natl Cancer Inst. 2001 Aug 15; 93(16):1224-33.
23. Aufmkolk M, Köhrle J, Gumbinger H, et al. Antihormonal effects of plant extracts: iodothyronine deiodinase of rat liver is inhibited by extracts and secondary metabolites of plants. Horm Metab Res. 1984; 16(4):188-92.
24. Rosmarinic- acid.com. URL: https://www.rosmarinic-acid.com/

Bugleweed- primary herb for hyperthyroidism

Bugleweed (Lycopus virginicus or Lycopus europaeus-gypsywort)

It is a primary herb for Graves’ disease and a member of the mint family. It might help in mild forms of hyperthyroidism. Bugleweed has been approved by German Commission E for use in mild hyperthyroidism. It is used in Europe for a mildly overactive thyroid, usually in the early stages and often with combination of Melissa. The herb is considered safe for long term administration. It is traditionally used to stop iodine conversion in the thyroid gland.  Bugleweed also inhibits the conversion of T4 into T3 in peripheral tissues. It might also inhibit the action of thyroid-stimulating antibodies. Bugleweed is helpful for symptoms such as palpitations and convulsions; it can lower heart rate and help with insomnia. It helps with relaxation. There has been a human study of Bugleweed for use in hyperthyroidism. The study involved 62 patients and its findings confirmed positive effects of Bugleweed (Lycopus europaeus) in mild forms of hyperthyroidism (1) without adverse reactions. German Bugleweed europaeus preparation is called Thyreogutt mono tablets or drops. Scientific studies of this preparation showed statistically significant improvements for mild hyperthyroidism for over 300 patients without side effects. Best results were seen in people receiving more than a 4 week course of preparation (2). Other German preparation is Mutellon (Lycopus Europaeus, Motherwort and Valerian).

Aqueous extracts of Bugleweed are also commonly used as well as alcohol extracts (prescribed by naturopathic professionals). Tea can be prepared by infusing 2-3 teaspoons of air-dried herb in a cup of hot water drank three times daily.

Talk to your doctor before using Bugleweed. It is not indicated with iodine supplements or iodine I-125 (used for Iodine Uptake Test) and with certain medical conditions. Bugleweed should not be taken in condition of osteoporosis. It is not advisable in pregnancy or lactation.

This post is for educational purposes only.

References:

1. Beer AM, Wiebelitz KR, Schmidt-Gayk H. Lycopus europaeus (Gypsywort): effects on the thyroidal parameters and symptoms associated with thyroid function. Phytomedicine 2008 Jan; 15(1-2):16-22.
2. Eiling R, Wieland V, Niestroj M. Improvement of symptoms in mild hyperthyroidism with an extract of Lycopus europaeus (Thyreogutt® mono). [Article in German]. Wien Med Wochenschr. 2013 Feb; 163(3-4):95-101.

Lemon balm (Melissa officinalis) and Graves’ disease- overview

Lemon Balm is one of herbs which may be useful for Grave’s disease. I had talked about many other herbs in my book: ’Thyroid and Graves’ disease unmasked’. Lemon balm is a relaxing, gentle, anxiety reducing herb from the mint family.

It has been approved by the German Commission E for sleep disturbance and nervousness. It has been used in the past to treat baby’s colic and viral infections. Many people use it as a calming remedy in times of stress and to help them sleep better. Fresh leaves are often put into salads.

There are no clinical human studies of Lemon balm effectiveness in relation to Graves’ disease. However laboratory studies have shown that freeze dried extracts of lemon balm had decreased the binding of Graves’ disease thyroid stimulating antibody to the receptors on thyroid cells in a dose dependent manner (1). Lemon balm also blocks the stimulation of thyroid by thyroid stimulating hormone (3). Therefore the herb may reduce the symptoms of hyperthyroidism. A study in rats has shown that lemon balm extract had inhibited the generation of T3 hormone (2). Another study had demonstrated a reduction of cardiac rate in isolated rat hearts with extracts of lemon balm. A human clinical study showed that lemon balm had reduced heart palpitations and anxiety in patients (6). Therefore, it is possible that lemon balm may improve the symptoms and thyroid hormone levels in Graves’ disease.

There was a human trial showing lemon balm effectiveness for better sleep.  Lemon balm was also shown to increase mood and significantly increase  calmness. A scientific study has shown that it was effective in treating laboratory induced stress (4).

Lemon balm has anti-oxidant properties. The active ingredients in lemon balm include caffeic acid, protocatechuic acid (also found in green tea, acai berries and onion skin), luteolin-7-glucoside (also found in dandelion, coffee and artichoke) and rhamnazin rosmarinic acid (also present in rosemary, sage and mint).

No serious adverse effects have been reported with the use of this herb. Overall it is considered safe when used as a leaf, fresh or dried. No interaction with other drugs is known. However due to its sedative effects, take care if you are also taking sedatives or barbiturates. Lemon balm has been used safely for thousands of years, however it is not recommended for pregnant/breastfeeding women unless under doctors consultation. It has a prolactin depressing effect. As with any new herbal remedies, it is important to watch out for any side effects. Consult with your physician before using Lemon balm.

I grow it in my garden and hang branches in a cool place or dry some leaves on towel paper for few weeks and store it in a glass container for use. It has a nice citrus, aromatic taste. The lemon balm is usually not used alone to treat hyperthyroidism.

The recommended dose, suggested by German Commission E monographs is 1.5-4.5g /day prepared as tea (or 0.5 g-1.5g/3times daily). It is sold in a tea bag form in many continental shops.

References:

1. Auf’mkolk M, Ingbar JC, Kubota K, Amir SM, Ingbar SH. Extracts and auto-oxidized constituents of certain plants inhibit the receptor-binding and the biological activity of Graves’ immunoglobulins. Endocrinology. 1985 May;116 (5):1687-93.
2. Auf’mkolk, M., Kohrle, J., Gumbinger, H., Winterhoff, H., and Hesch, R. D. Antihormonal effects of plant extracts: iodothyronine deiodinase of rat liver is inhibited by extracts and secondary metabolites of plants. Horm Metab Res 1984;16(4):188-192.
3. Auf’mkolk, M., Ingbar, J. C., Amir, S. M., Winterhoff, H., Sourgens, H., Hesch, R. D., and Ingbar, S. H. Inhibition by certain plant extracts of the binding and adenylate cyclase stimulatory effect of bovine thyrotropin in human thyroid membranes. Endocrinology 1984; 115(2):527-534.
4. Kennedy DO, LittleW, Schley AB. Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm). Psychosom Med. 2004 Jul-Aug; 66(4):607-13.
5. Zahra Akhondali, Mahin Dianat and Maryam Radan. Negative Chronotropic and Antidysrhythmic Effects of Hydroalcoholic Extract of Lemon Balm (Melissa Officinalis L.) on CaCl2-Induced Arrhythmias in Rats. Electron Physician. 2015 Jan-Mar; 7(1): 971–976.
6. Alijaniha F, Naseri M, Afsharypuor S, Fallahi F, Noorbala A, Mosaddegh M, Faghihzadeh S, Sadrai S. 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
7. Inhibition of Endocrine Function by Botanical Agents, Review Article; Journal of Naturopathic Medicine; Francis Brinker, N.D.URL: http://webhome.idirect.com/~wolfnowl/thyroid3.htm
8. http://cms.herbalgram.org/expandedE/LemonBalm.html?ts=1497694750&signature=31609c0f561bf152ad019c6304583eeb
9. http://buecher.heilpflanzen-welt.de/BGA-Commission-E-Monographs/0225.htm