Ergothioneine

People with multiple sclerosis (MS) leave the workforce within 7 years of diagnosis because of low mood, disabling fatigue, and problems with brain fog. Disease-modifying drugs prescribed to those with MS are very good at reducing relapses and the number of new enhancing lesions seen on MRI imaging of the brain, but they are ineffective at improving mood, restoring energy, or reversing brain fog.

I want you to have tools you can use to improve your mood and lessen your anxiety and depression. I want you to have tools that will increase your energy and decrease memory problems and brain fog. I want you to be able to be an active participant in your family life, your work life, and your personal life. I want you to know everything you can do to support your cells so they can properly conduct the biology of life.

In this article I’ll review a terrific option for addressing the cellular dysfunction that drives low mood, severe fatigue, and/or brain fog problems in the setting of MS and autoimmunity. This strategy will help reduce excess inflammation and oxidative stress, which are key drivers of fatigue, anxiety, depression, and cognitive decline in the setting of MS.

One of the simplest things you can do to support your cells is eat mushrooms. I love mushrooms. They add a rich umami flavor to dishes and have tremendous health benefits. People who eat mushrooms more than once per week have less depression, anxiety, and cognitive decline than those who do not consume mushrooms!1-4

Mushrooms are potent antioxidants that have been used across multiple healing traditions for thousands of years to address mood disorders and neurodegenerative disorders.1 On the cellular level, science has identified over 80 bioactive compounds in mushrooms that have remarkable health benefits.1,2,5,6 One compound that has been studied more thoroughly and shown to have particularly significant health benefits is ergothioneine.

What is ergothioneine?

Ergothioneine is a sulfur-containing compound found in mushrooms. Humans and other mammals are unable to make this molecule. It must be consumed as part of our diet. Ergothioneine supports the health of the brain, eyes, immune, and reproductive systems.7,8 Scientists are beginning to study certain molecules found in mushrooms to understand the specific mechanisms by which mushrooms exert their powerful effects on human health.

What are the mechanisms by which ergothioneine impacts our cell biology?

Ergothioneine is a potent antioxidant that protects cells from free radicals and reduces the production of inflammation-producing cytokines.8,9 It can easily cross the blood-brain barrier to provide potent neuroprotective benefits, lowering production of inflammatory cytokines (molecules that drive up inflammation and cause adverse symptoms such as depression, anxiety, and fatigue) within the central nervous system.8,9 It has also been shown to boost the production of nerve growth factors, including brain-derived neurotrophic factors.10,11 In an animal model of Alzheimer’s disease, ergothioneine improved clearance of beta-amyloid plaque and improved health and function of the immune cells in the central nervous system (microglia and astrocytes).12 All of these functions have a major impact on anxiety, depression, fatigue, memory, and verbal and non-verbal reasoning in humans and animal models of neurodegenerative disease states.

What symptoms have been helped in animal models of anxiety, depression, and dementia?

Scientists are now studying the effect of ergothioneine in animal models of anxiety, depression, and Alzheimer’s. That research shows ergothioneine reduced depressive behaviors and anxiety behaviors in animal models of depression and anxiety.7 It has also improved memory and cognition in animal models of cognitive decline.13-16

Who could benefit from taking ergothioneine?

These findings suggest that those with anxiety and depression may benefit from additional ergothioneine, as well as people with autoimmune issues and excess inflammation-producing cytokines. Those who are worried about their memory or risk of developing Alzheimer’s may also benefit from adding more ergothioneine to their diet.

Where do you get ergothioneine?

We cannot make ergothioneine. You can get it from a supplement or food. The best food source is mushrooms, particularly bolete and oyster mushrooms. If you are a mushroom collector, be sure to correctly identify what you find so you don’t accidentally consume a toxic bolete mushroom.

Conclusion

Ergothioneine is a powerful antioxidant, anti-inflammatory, immune-modulating, and neuroprotective compound found in mushrooms. It can help reduce inflammation, improve clearance of beta-amyloid, and support nerve growth factor production in the brain, making it an ideal supplement for those with autoimmune issues like multiple sclerosis or anyone who wants to support healthy aging. While more research is needed to fully understand the benefits of ergothioneine, this naturally occurring compound has huge potential when it comes to improving overall health and wellness. If you have symptoms related to mood, energy, or mental clarity or simply want to have healthier brain aging, talk to your medical team about the potential benefit of adding ergothioneine to your wellness plan.

The Wahls Protocol® Supplement line carries Egro Plus, a fermentation-based L-Ergothianene supplement

Ergo Plus features the concentrated form of the histone derivative L-ergothioneine produced via a proprietary fermentation-based method. Through its antioxidant and cytoprotectant mechanisms, L-ergothioneine combats oxidative stress throughout the body and provides multiple health benefits.*

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References:

1. Phan CW, David P, Naidu M, Wong KH, Sabaratnam V. Therapeutic potential of culinary-medicinal mushrooms for the management of neurodegenerative diseases: diversity, metabolite, and mechanism. Crit Rev Biotechnol. 2015;35(3):355-368.

2. Bell V, Silva C, Guina J, Fernandes TH. Mushrooms as future generation healthy foods. Front Nutr. 2022;9:1050099.

3. Fijalkowska A, Jedrejko K, Sulkowska-Ziaja K, Ziaja M, Kala K, Muszynska B. Edible Mushrooms as a Potential Component of Dietary Interventions for Major Depressive Disorder. Foods. 2022;11(10).

4. Lazur J, Hnatyk K, Kala K, Sulkowska-Ziaja K, Muszynska B. Discovering the Potential Mechanisms of Medicinal Mushrooms Antidepressant Activity: A Review. Antioxidants (Basel). 2023;12(3).

5. Abitbol A, Mallard B, Tiralongo E, Tiralongo J. Mushroom Natural Products in Neurodegenerative Disease Drug Discovery. Cells. 2022;11(23).

6. Cordaro M, Modafferi S, D’Amico R, et al. Natural Compounds Such as Hericium erinaceus and Coriolus versicolor Modulate Neuroinflammation, Oxidative Stress and Lipoxin A4 Expression in Rotenone-Induced Parkinson’s Disease in Mice. Biomedicines. 2022;10(10).

7. Nakamichi N, Nakayama K, Ishimoto T, et al. Food-derived hydrophilic antioxidant ergothioneine is distributed to the brain and exerts antidepressant effect in mice. Brain Behav. 2016;6(6):e00477.

8. Nakamichi N, Tsuzuku S, Shibagaki F. Ergothioneine and central nervous system diseases. Neurochem Res. 2022;47(9):2513-2521.

9. Ishimoto T, Kato Y. Ergothioneine in the brain. FEBS Lett. 2022;596(10):1290-1298.

10. Fukuchi M, Watanabe K, Mitazaki S, Fukuda M, Matsumoto S. Aminothioneine, a product derived from golden oyster mushrooms (Pleurotus cornucopiae var. citrinopileatus), activates Ca(2+) signal-mediated brain-derived neurotrophic factor expression in cultured cortical neurons. Biochem Biophys Rep. 2021;28:101185.

11. Huang JH, Li Y, Zhang S, et al. Amelioration effect of water extract from Ganoderma resinaceum FQ23 solid-state fermentation fungal substance with high-yield ergothioneine on anxiety-like insomnia mice. Food Funct. 2022;13(24):12925-12937.

12. Wijesinghe P, Whitmore CA, Campbell M, et al. Ergothioneine, a dietary antioxidant improves amyloid beta clearance in the neuroretina of a mouse model of Alzheimer’s disease. Front Neurosci. 2023;17:1107436.

13. Song TY, Chen CL, Liao JW, Ou HC, Tsai MS. Ergothioneine protects against neuronal injury induced by cisplatin both in vitro and in vivo. Food Chem Toxicol. 2010;48(12):3492-3499.

14. Song TY, Lin HC, Chen CL, Wu JH, Liao JW, Hu ML. Ergothioneine and melatonin attenuate oxidative stress and protect against learning and memory deficits in C57BL/6J mice treated with D-galactose. Free Radic Res. 2014;48(9):1049-1060.

15. Wu LY, Kan CN, Cheah IK, et al. Low Plasma Ergothioneine Predicts Cognitive and Functional Decline in an Elderly Cohort Attending Memory Clinics. Antioxidants (Basel). 2022;11(9).

16. Yang NC, Lin HC, Wu JH, et al. Ergothioneine protects against neuronal injury induced by beta-amyloid in mice. Food Chem Toxicol. 2012;50(11):3902-3911.