Mushrooms That Improve the Brain, Without the Trip


In today’s high-stress world, many are looking for coffee alternatives and natural ways to boost brain power, remove brain fog and improve focus without caffeine. The secret to achieving these benefits along with improved life expectancy may lie in the consumption of functional mushrooms like Shiitake, Oyster and Lion’s Mane according to researchers. While illegal “magic” mushrooms steal all the press and generate giggles and fear among those who don’t follow Dead & Co., legal “functional mushrooms” such as Lion’s Mane, Cordyceps, Reishi and Chaga also impact the brain in a positive fashion – without the psychedelic side effects and pesky legality issues.


Ergothioneine (ERGO) is a naturally occurring antioxidant that is highly water soluble and found densely accumulated in certain varieties of mushrooms, including Lion’s Mane, Oyster, and Shiitake. When consumed via food or mushroom teas, ERGO is absorbed through the gut and into the brain where it has shown great benefit-potential; including neuronal maturation and even neurogenesis, or the growth of new neurons.


According to research compiled by Dr. Robert Beelman from Penn State University, the Japanese, who are known for their mushroom consumption, particularly Lion’s Mane, Shiitake and Oyster mushrooms, have the highest ERGO rates of the countries measured and Japan is near the top of the world in avoidance of chronic aging diseases and in life expectancy. The Japanese enjoy these mushrooms in foods and in brewed, immune booster teas given the water solubility advantages.


Ancient Chinese medicine and traditional Ayurvedic medicine has known of and passed along the benefits of Lion’s Mane and other functional mushrooms like Cordyceps, Reishi and Chaga for hundreds, if not for thousands of years. In these traditions, Lion’s Mane has been associated with increased memory and focus, likely due to its high ERGO content.


Evidence1 that ERGO is very important to our brains lies in the fact that our bodies have a unique transporter for ERGO known as OCTN1/SLC22A4 (OCTN1). The OCTN1 transporter allows ERGO to be easily absorbed in the GI tract and then quickly directed to the brain. Despite ERGO having a natural tendency to dissolve in water, OCTN1 allows ERGO to cross the plasma membrane of organ cells. Research has been conducted that suggests ERGO is associated with: 2,3

  • Enhanced memory in both mice and humans

  • Antidepressant activity in mice, and

  • Neurogenesis in that newborn neuron markers were measured at significantly increased levels


Getting ERGO into Your Diet

Diets rich in mushrooms and in animals who graze on plants regeneratively grown in soil rich in mushroom mycelium are the primary routes that humans can get ERGO. ERGO is ingested by mammals as part of a daily diet and is then received by the special OCTN1 transporter to be rushed to the brain. This process alone would suggest that ERGO plays a key role in brain function. Further evidence that ERGO is critical for brain function is suggested by low ERGO levels being found in those who:4

  • Are elderly

  • Suffer from mild cognitive impairment (MCI)

  • Have Parkinson’s disease

  • Are frail

  • Have dementia

  • Are suffering neurodegeneration


How ERGO Works

ERGO works in the brain in a variety of ways. Immune cells known as microglia help govern the brain’s immune response and are inhibited by Reactive Oxidative Species (ROS). ERGO is known to suppress the production of ROS and cellular hypertrophy thus directly helping support the immune system in the brain.5


Major components of the blood brain barrier (BBB) that are also highly sensitive to oxidative stress are the brain microvascular endothelial cells (BMEC). Destruction of BMECs by ROS is associated with several neurological diseases and ERGO has been shown to suppress ROS production and protect against cell death.6


As we age, our immune systems often decline and thus are unable to defend against common age related diseases. Evidence suggests that it is possible that ERGO consumption via mushrooms and mushroom teas may help support a positive immune system response against a variety of age-related conditions.


Dementia

There is mounting evidence that ERGO and mushrooms support brain health. ERGO levels have been shown to be low in patients with cognitive related disorders and may indicate neurodegeneration in the elderly.7 White matter hyperintensities and brain atrophy markers are significantly associated with lower ERGO levels.8


A random, double-blind placebo study was recently conducted that showed ERGO consumption through mushrooms statistically enhanced cognitive function in that composite memory, verbal memory, psychomotor speed, reaction time, working memory, complex attention, and sustained attention were all significantly improved by the mushrooms rich in ERGO, possibly via the growth of spines in the hippocampus.9


Parkinson’s Disease (PD)

Many studies have suggested a relationship between ROS-induced mitochondrial dysfunction and the onset of PD. ERGO levels among those with PD are historically lower than those of healthy people.10


Given that ERGO suppresses the production of ROS, there is strong support for ERGO helping provide immune system support against PD; as ERGO may protect neurons against oxidative stress associated with PD.11


Depression

It has long been hypothesized that depression results from a decline in neurogenesis, oxidative stress, and a disruption of neural plasticity.12 ERGO activates special protein complexes (mTORC1 and TrkB) that are targets in the treatment of depression to promote neuronal maturation, a critical component of neurogenesis.13


Conclusion

In conclusion, our bodies were built with their own special ERGO transporters (OCTN1) in order to quickly and efficiently deliver ERGO to our brains from our guts. Patients with cognition-related and neurodegenerative disorders show consistent deficiencies in ERGO; whereas ERGO can help regulate neurogenesis, neuronal differentiation, and microglial activation while protecting against neurotoxicity. Further, ERGO containing foods and beverages have been shown to enhance cognitive function.


While further studies are necessary to clarify and quantify the specific benefits, a diet rich in ERGO will help maintain human health while guarding against chronic aging disease and improving life expectancy. Packed with Life online tea store’s immune booster tea features the ERGO rich mushroom, Lion’s Mane along with Cordyceps (Energy), Reishi (Stress), and Chaga (Longevity).


Why is mushroom tea a good way to get ERGO into our bodies? Our bodies are made up of over 65% water and ERGO is a highly water soluble nutrient, so brewing a mushroom tea is a very effective way to extract the ERGO nutrients from the mushrooms so that they can be fully absorbed into your system; most efficiently reaching the OCTN1 receptors.


As an online tea supplier focused on providing healthy hydration and the best immune booster tea, Packed with Life seeks to educate the public on the benefits of all mushrooms in order to positively impact life itself.


References:

1https://www.realmushrooms.com/ergothioneine-supplement-guide - Lion’s Mane ERGO level; Sugiura T, Kato S, Shimizu T, Wakayama T, Nakamichi N, Kubo Y, et al. Functional expression of carnitine/organic cation transporter OCTN1/SLC22A4 in mouse small intestine and liver. Drug Metab Dispos. 2010; 38: 1665– 72; Nakamichi N, Taguchi T, Hosotani H, Wakayama T, Shimizu T, Sugiura T, et al. Functional expression of carnitine/organic cation transporter OCTN1 in mouse brain neurons: possible involvement in neuronal differentiation. Neurochem Int. 2012; 61: 1121– 32; Kato Y, Kubo Y, Iwata D, Kato S, Sudo T, Sugiura T, et al. Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1. Pharm Res. 2010; 27: 832– 40; Tang R, Cheah I, Yew T, Halliwell B. Distribution and accumulation of dietary ergothioneine and its metabolites in mouse tissues. Sci Rep. 2018; 8: 1601.

2Watanabe N, Matsumoto S, Suzuki M, Fukaya T, Kato Y, Hashiya N. Effect of ergothioneine on the cognitive function improvement in healthy volunteers and mild cognitive impairment subjects–A randomized, double-blind, parallel-group comparison study. Jpn Pharmacol Ther. 2020; 48: 685– 97; Nakamichi N, Nakao S, Nishiyama M, Takeda Y, Ishimoto T, Masuo Y, et al. Oral administration of the food derived hydrophilic antioxidant ergothioneine enhances object recognition memory in mice. Curr Mol Pharmacol. 2020; 13: 1– 15.

3Nakamichi N, Nakayama K, Ishimoto T, Masuo Y, Wakayama T, Sekiguchi H, et al. Food-derived hydrophilic antioxidant ergothioneine is distributed to the brain and exerts antidepressant effect in mice. Brain Behav. 2016; 6:e00477.

4​​Cheah I, Feng L, Tang R, Lim K, Halliwell B. Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration? Biochem Biophys Res Commun. 2016; 478: 162– 7; Teruya T, Chen Y, Kondoh H, Fukuji Y, Yanagida M. Whole-blood metabolomics of dementia patients reveal classes of disease-linked metabolites. Proc Natl Acad Sci USA. 2021; 118:e2022857118; Hatano T, Saiki S, Okuzumi A, Mohney RP, Hattori N. Identification of novel biomarkers for Parkinson’s disease by metabolomic technologies. J Neurol Neurosurg Psychiatry. 2016; 87: 295– 301; Kameda M, Teruya T, Yanagida M, Kondoh H. Frailty markers comprise blood metabolites involved in antioxidation, cognition, and mobility. Proc Natl Acad Sci USA. 2020; 117: 9483– 9; Wu L-Y, Cheah IK, Chong JR, Chai YL, Tan JY, Hilal S, et al. Low plasma ergothioneine levels are associated with neurodegeneration and cerebrovascular disease in dementia. Free Radic Biol Med. 2021; 177: 201– 11.

5Ishimoto T, Nakamichi N, Nishijima H, Masuo Y, Kato Y. Carnitine/organic cation transporter OCTN1 negatively regulates activation in murine cultured microglial cells. Neurochem Res. 2018; 43: 116– 28.

6Grammas P, Martinez J, Miller B. Cerebral microvascular endothelium and the pathogenesis of neurodegenerative diseases. Expert Rev Mol Med. 2011; 13:e19.

7Cheah I, Feng L, Tang R, Lim K, Halliwell B. Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration? Biochem Biophys Res Commun. 2016; 478: 162– 7; Teruya T, Chen Y, Kondoh H, Fukuji Y, Yanagida M. Whole-blood metabolomics of dementia patients reveal classes of disease-linked metabolites. Proc Natl Acad Sci USA. 2021; 118:e2022857118; Kameda M, Teruya T, Yanagida M, Kondoh H. Frailty markers comprise blood metabolites involved in antioxidation, cognition, and mobility. Proc Natl Acad Sci USA. 2020; 117: 9483– 9.

8Wu L-Y, Cheah IK, Chong JR, Chai YL, Tan JY, Hilal S, et al. Low plasma ergothioneine levels are associated with neurodegeneration and cerebrovascular disease in dementia. Free Radic Biol Med. 2021; 177: 201– 11.

9Watanabe N, Matsumoto S, Suzuki M, Fukaya T, Kato Y, Hashiya N. Effect of ergothioneine on the cognitive function improvement in healthy volunteers and mild cognitive impairment subjects–A randomized, double-blind, parallel-group comparison study. Jpn Pharmacol Ther. 2020; 48: 685– 97.

10Hatano T, Saiki S, Okuzumi A, Mohney RP, Hattori N. Identification of novel biomarkers for Parkinson’s disease by metabolomic technologies. J Neurol Neurosurg Psychiatry. 2016; 87: 295– 301.

11Song 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: 3492– 9.

12Boku S, Nakagawa S, Toda H, Hishimoto A. Neural basis of major depressive disorder: beyond monoamine hypothesis. Psychiatry Clin Neurosci. 2018; 72: 3– 12; 44Eren I, Naziroğlu M, Demirdaş A. Protective effects of lamotrigine, aripiprazole and escitalopram on depression-induced oxidative stress in rat brain. Neurochem Res. 2007; 32: 1188– 95; 45Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008; 11: 851– 76; 46Snyder J, Soumier A, Brewer M, Pickel J, Cameron H. Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature. 2011; 476: 458– 62; 47Cobb J, Simpson J, Mahajan G, Overholser J, Jurjus G, Dieter L, et al. Hippocampal volume and total cell numbers in major depressive disorder. J Psychiatr Res. 2013; 47: 299– 306.

13Ishimoto T, Nakamichi N, Hosotani H, Masuo Y, Sugiura T, Kato Y. Organic cation transporter-mediated ergothioneine uptake in mouse neural progenitor cells suppresses proliferation and promotes differentiation into neurons. PLoS One. 2014; 9:e89434; Nakamichi N, Nakao S, Nishiyama M, Takeda Y, Ishimoto T, Masuo Y, et al. Oral administration of the food derived hydrophilic antioxidant ergothioneine enhances object recognition memory in mice. Curr Mol Pharmacol. 2020; 13: 1– 15; Ishimoto T, Masuo Y, Kato Y, Nakamichi N. Ergothioneine-induced neuronal differentiation is mediated through activation of S6K1 and neurotrophin 4/5-TrkB signaling in murine neural stem cells. Cell Signal. 2019; 53: 269– 80; Ignácio ZM, Réus GZ, Arent CO, Abelaira HM, Pitcher MR, Quevedo J. New perspectives on the involvement of mTOR in depression as well as in the action of antidepressant drugs. Br J Clin Pharmacol. 2016; 82: 1280– 90.

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https://febs.onlinelibrary.wiley.com/toc/18733468/2022/596/10

https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14271

https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14271



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