Ergothioneine

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms

  • 1-Carboxy-2-[2-mercaptoimidazole-4-(or 5)-yl]ethyl]-trimethyl-ammonium hydroxide, 2-mercaptohistidine trimethylbetaine, erythrothioneine, ET, ETT, L-Ergo, L-ergothioneine, OCTN1, S-alpha-carboxy-2,3-dihydro-N,N-N,-trimethyl-thioxo-1H-imidazole-4-eth-anaminium hydroxide, SLC22A4, sympectothion, thiasine, thiazine, thiolhistidinebetaine, thioneine, thiozine.

Background

  • Ergothioneine is a naturally occurring, water-soluble amino acid of plant origin that accumulates in animal tissues. Dietary sources of ergothioneine include various types of mushrooms (king bolete, oyster mushroom), chicken liver, pork liver, pork kidney, oat bran, and beans (black turtle bean, red kidney bean).

  • Ergothioneine is a water-soluble thiol compound that is of interest to scientists and consumers for its potential beneficial effects as an antioxidant, which may protect against oxidative stress, as well as its anti-inflammatory, neuroprotective, and antiaging properties. Due to its potential benefits for the skin, it is found in some skin care products.

  • Ergothioneine cannot cross the plasma membrane of cells unless they express the ergothioneine transporter ETT (originally designated as OCTN1; human gene symbol SLC22A4). Ergothioneine specifically accumulates to millimolar concentrations in cell types that are normally subjected to high levels of oxidative stress (including erythrocytes and plasma). In humans, abnormal ETT and ergothioneine levels have been implicated in rheumatoid arthritis and Crohn’s disease.

Scientific Evidence

Uses

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Hyperpigmentation

Limited evidence supports the use of a combination of hydroquinone and ergothioneine to treat hyperpigmentation. Further research is needed.

*Key to grades:

Tradition

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

  • Antiaging, anti-inflammatory, antioxidant, cancer, chelating agent (heavy metals), chronic obstructive pulmonary disease (COPD), congenital methemoglobinemia, hyperthyroid, immune disorders, photoprotection, skin conditions.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

  • There is no proven safe or effective dose for ergothioneine in adults.

Children (under 18 years old)

  • There is no proven safe or effective dose for ergothioneine in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid with known allergy or hypersensitivity to ergothioneine.

Side Effects and Warnings

  • Use cautiously in patients with certain autoimmune disorders, such as rheumatoid arthritis and Crohn’s disease, as unexplained high levels of ergothioneine have been discovered in their red blood cells.

  • Use cautiously in pre-eclamptic patients, as they have higher concentrations of ergothioneine in erythrocytes.

  • Use cautiously in combination with verapamil, as this medication may inhibit the ergothioneine transporter ETT.

  • Use cautiously in diabetic patients, as certain diabetic patients have markedly elevated levels of ergothioneine compared to nondiabetic individuals.

  • Use cautiously in patients with immune disorders or in those using immunosuppressants, as ergothioneine may have immunomodulatory effects.

  • Ergothioneine may also cause liver damage, cataracts, Alzheimer’s disease, diabetes, and heart disease.

  • Avoid in children, and in patients who are pregnant or breastfeeding, due to a lack of sufficient data.

  • Avoid with known allergy or hypersensitivity to ergothioneine.

Pregnancy and Breastfeeding

  • Avoid in patients who are pregnant or breastfeeding, due to a lack of sufficient data.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

  • Ergothioneine may interact with drugs that may affect blood sugar, anti-inflammatory agents, immune system suppressants, lithium, agents that increase light sensitivity, and verapamil.

Interactions with Herbs and Dietary Supplements

  • Ergothioneine may interact with anti-inflammatory herbs and supplements, antioxidants, immune system suppressants, herbs and supplements that may affect blood sugar, agents that increase light sensitivity, and vitamin C.

Author Information

  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Bacher, P., Giersiefer, S., Bach, M., Fork, C., Schomig, E., and Grundemann, D. Substrate discrimination by ergothioneine transporter SLC22A4 and carnitine transporter SLC22A5: gain-of-function by interchange of selected amino acids. Biochim.Biophys Acta 2009;1788(12):2594-2602. View Abstract
  2. Botta, C., Di, Giorgio C., Sabatier, A. S., and De, Meo M. Genotoxicity of visible light (400-800 nm) and photoprotection assessment of ectoin, L-ergothioneine and mannitol and four sunscreens. J Photochem.Photobiol.B 4-25-2008;91(1):24-34. View Abstract
  3. Dong, K. K., Damaghi, N., Kibitel, J., Canning, M. T., Smiles, K. A., and Yarosh, D. B. A comparison of the relative antioxidant potency of L-ergothioneine and idebenone. J Cosmet.Dermatol 2007;6(3):183-188. View Abstract
  4. Ey, J., Schomig, E., and Taubert, D. Dietary sources and antioxidant effects of ergothioneine. J Agric Food Chem 8-8-2007;55(16):6466-6474. View Abstract
  5. Kato, Y., Kubo, Y., Iwata, D., Kato, S., Sudo, T., Sugiura, T., Kagaya, T., Wakayama, T., Hirayama, A., Sugimoto, M., Sugihara, K., Kaneko, S., Soga, T., Asano, M., Tomita, M., Matsui, T., Wada, M., and Tsuji, A. Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1. Pharm Res 2010;27(5):832-840. View Abstract
  6. Markova, N. G., Karaman-Jurukovska, N., Dong, K. K., Damaghi, N., Smiles, K. A., and Yarosh, D. B. Skin cells and tissue are capable of using L-ergothioneine as an integral component of their antioxidant defense system. Free Radic.Biol Med 4-15-2009;46(8):1168-1176. View Abstract
  7. Nakamura, T., Sugiura, S., Kobayashi, D., Yoshida, K., Yabuuchi, H., Aizawa, S., Maeda, T., and Tamai, I. Decreased proliferation and erythroid differentiation of K562 cells by siRNA-induced depression of OCTN1 (SLC22A4) transporter gene. Pharm Res 2007;24(9):1628-1635. View Abstract
  8. Smiles, K. A., Dong, K. K., Canning, M. T., Grimson, R., Walfield, A. M., and Yarosh, D. B. A hydroquinone formulation with increased stability and decreased potential for irritation. J Cosmet.Dermatol 2007;6(2):83-88. View Abstract
  9. Tahara, H., Yee, S. W., Urban, T. J., Hesselson, S., Castro, R. A., Kawamoto, M., Stryke, D., Johns, S. J., Ferrin, T. E., Kwok, P. Y., and Giacomini, K. M. Functional genetic variation in the basal promoter of the organic cation/carnitine transporters OCTN1 (SLC22A4) and OCTN2 (SLC22A5). J Pharmacol Exp Ther 2009;329(1):262-271. View Abstract
  10. Taubert, D., Jung, N., Goeser, T., and Schomig, E. Increased ergothioneine tissue concentrations in carriers of the Crohn’s disease risk-associated 503F variant of the organic cation transporter OCTN1. Gut 2009;58(2):312-314. View Abstract
  11. Taubert, D., Lazar, A., Grimberg, G., Jung, N., Rubbert, A., Delank, K. S., Perniok, A., Erdmann, E., and Schomig, E. Association of rheumatoid arthritis with ergothioneine levels in red blood cells: a case control study. J Rheumatol 2006;33(11):2139-2145. View Abstract
  12. Toh, D. S., Koo, S. H., Limenta, L. M., Yee, J. Y., Murray, M., and Lee, E. J. Genetic variations of the SLC22A4 gene in Chinese and Indian populations of Singapore. Drug Metab Pharmacokinet. 2009;24(5):475-481. View Abstract
  13. Turner, E., Brewster, J. A., Simpson, N. A., Walker, J. J., and Fisher, J. Imidazole-based erythrocyte markers of oxidative stress in preeclampsia–an NMR investigation. Reprod.Sci 2009;16(11):1040-1051. View Abstract
  14. Urban, T. J., Yang, C., Lagpacan, L. L., Brown, C., Castro, R. A., Taylor, T. R., Huang, C. C., Stryke, D., Johns, S. J., Kawamoto, M., Carlson, E. J., Ferrin, T. E., Burchard, E. G., and Giacomini, K. M. Functional effects of protein sequence polymorphisms in the organic cation/ergothioneine transporter OCTN1 (SLC22A4). Pharmacogenet.Genomics 2007;17(9):773-782. View Abstract
  15. Xiao, L., Zhao, L., Li, T., Hartle, D. K., Aruoma, O. I., and Taylor, E. W. Activity of the dietary antioxidant ergothioneine in a virus gene-based assay for inhibitors of HIV transcription. Biofactors 2006;27(1-4):157-165. View Abstract

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.