Ergothioneine
The Magic of Longevity Mushrooms: Ergothioneine’s Remarkable Impact on Lifespan and Cognitive Enhancement (2024)
Japanese scientists show that treating male mice with ergothioneine, a compound found in Lion's Mane in high concentrations, significantly extends the median and average lifespan by 16% and 21%, respectively.
Supplementing male mice with ergothioneine (ERGO) increases the median and average lifespan by 16% and 21%, respectively.
ERGO supplementation enhances learning and memory.
Ergothioneine from mushrooms extends mouse lifespan (video)
Ergothioneine, an amino acid abundant in mushrooms, increased lifespan in male mice when supplemented at 4-5 mg/kg/day starting at 7 weeks old.
Median lifespan increased by 16%, average by 21%, and maximum (when 90% died) by 29% with ergothioneine treatment. However, control lifespan was shorter than historical norms, possibly due to the low ergothioneine chow they received.
Ergothioneine also extended lifespan in a dose-dependent manner in C. elegans worms and reduced worm frailty.
In aging mice, ergothioneine attenuated body weight and fat mass loss, with minor impact on lean mass and total water. Treated mice also showed improved total movement time, distance, average velocity and max running speed.
Oxidative stress and inflammation markers like liver TBARS, plasma CXCL9 and p16 were significantly lower in old ergothioneine-treated mice, while longevity protein SIRT6 was higher.
Plasma creatinine, BUN, uremic toxin ADMA, and kynurenine/tryptophan ratio all remained lower in treated mice, suggesting preserved kidney function and lower kynurenine pathway activity. The neurotoxin quinolinic acid was also reduced.
In memory tests, ergothioneine mice showed enhanced performance at both young and old age. Neurogenesis markers were elevated and microglia skewed towards an anti-inflammatory profile with treatment.
The broad benefits of ergothioneine across lifespan, healthspan and multiple organ systems make mushrooms an attractive dietary component and ergothioneine a promising intervention for aging.
Ergothioneine: New Supplement discovered to Improve Mitochondrial Function (video)
A pre-published study on BioRxiv investigates the relationship between exercise, mitochondrial function, and the amino acid ergothioneine (Ergo). The study reveals a novel mechanism by which exercise enhances mitochondrial function and explores the potential of Ergo supplementation to improve mitochondrial function independently of exercise.
Key Points:
Exercise and Mitochondrial Metabolites: The research examined the differences in metabolites between mitochondria involved in exercise and those that are not. The amino acid Ergo was identified as having significantly increased concentrations in exercised muscle.
Ergo and Mitochondrial Function: The study found a direct relationship between Ergo and increased mitochondrial function. Adding Ergo to muscle cells in a dish led to a rise in oxygen consumption, a key indicator of mitochondrial function.
Mechanism of Action: The study identified the enzyme 3-mercaptopyruvate sulfurtransferase (MPST) as a crucial player in Ergo's effect on mitochondria. Inhibiting MPST negated the positive impact of Ergo on mitochondrial function, suggesting that Ergo works through MPST to enhance mitochondrial activity.
Ergo Supplementation and Physical Performance: Supplementing mice with Ergo in their diet resulted in a nearly 30% improvement in exercise performance compared to a control group. This effect was absent in mice deficient in the MPST enzyme, further confirming the role of MPST in Ergo's mechanism of action.
Ergo, Exercise, and Humans: The study found that exercise increases blood Ergo levels in humans, similar to the findings in mice. This suggests that the relationship between Ergo, exercise, and mitochondrial function may also apply to humans.
Conclusions:
The study concludes that Ergo plays a crucial role in improving mitochondrial function through an MPST-dependent pathway. Exercise increases Ergo levels in mitochondria, and supplementing with Ergo can enhance exercise performance in mice. While further research is needed to confirm these findings in humans, the study suggests that Ergo may be a promising target for supplementation to improve mitochondrial health and physical function.
Ergothioneine: A 'Longevity Vitamin' With Potential Benefits For Age-Related Outcomes? (video)
Ergothioneine (EGT) is a sulfur-containing antioxidant that has been referred to as the “longevity vitamin.” Mammals cannot synthesize EGT, so it must be obtained through the diet.
Key Points
EGT levels decline with age.
Lower levels of EGT are associated with an increased incidence of mild cognitive impairment (MCI), frailty, atherosclerosis, and mortality from cardiovascular disease and all causes.
Mushrooms are a rich dietary source of EGT.
Mushroom intake correlates with blood levels of EGT.
Gut bacteria, specifically Lactobacillus reuteri, produce EGT.
Higher levels of Lactobacillus reuteri in fecal matter correlate with higher fecal levels of EGT.
Lactobacillus reuteri releases EGT in cell culture experiments.
Kefir consumption increases levels of Lactobacillus reuteri.
Hypotheses
The video discusses two main hypotheses:
Dietary insufficiency of EGT: Individuals with MCI may have lower levels of EGT due to not consuming enough EGT-rich foods, such as mushrooms.
Age-related decline in Lactobacillus reuteri: Lower levels of EGT may be due to an age-related decline in the gut bacteria Lactobacillus reuteri, which produces EGT.
Numerical Results
In one study, cognitively normal subjects had higher levels of EGT compared to those with MCI.
In another study, non-frail individuals had higher levels of EGT compared to frail individuals.
A study on coronary artery disease, cardiovascular disease mortality, and all-cause mortality showed that the median and confidence interval for the hazard ratio were below one for all three outcomes. This indicates an association between higher EGT levels and a reduced risk of these conditions.
Oats and kidney beans contain approximately 2 milligrams of EGT per kilogram of dry weight.
Oat bran contains approximately double the amount of EGT found in oats and kidney beans.
Chicken liver contains ten times more EGT than oat bran.
Tempeh contains 201 milligrams of EGT per kilogram of dry weight.
White button mushrooms and great oyster mushrooms contain 630 milligrams and 1.3 grams of EGT per kilogram of dry weight, respectively.
In a study of 15 mushroom species, seven had over 300 milligrams of EGT per kilogram of dry weight.
Garlic and Mexican asparagus also contain decent amounts of EGT.
White asparagus contains significantly less EGT than Mexican asparagus.
In one study, individuals who reported eating more mushrooms had significantly higher blood levels of EGT.
In a cell culture experiment, Lactobacillus reuteri had approximately three-fold higher levels of EGT inside of them than E. coli.
In the same experiment, four out of six strains of Lactobacillus reuteri released decent amounts of EGT into the cell media, with two strains releasing four to five-fold more EGT compared to the negative control.
Conclusion
The video concludes that increasing EGT levels through diet or supplementation with Lactobacillus reuteri may be important for reducing the risk of age-related outcomes such as cognitive impairment, frailty, atherosclerosis, and mortality. However, it is important to note that randomized controlled trials (RCTs) are needed to test this hypothesis.
Ergothioneine Extends Lifespan In Worms, Flies, And Mice: What About In People? (video)
Ergothioneine Extends Lifespan in flies (video)
A Novel "Longevity Vitamin"?? Science Studies, Human Trials & Dosage Of Ergothioneine (video)
Ergothioneine is an amino acid with antioxidant and anti-inflammatory properties. It is not produced by the human body and must be obtained through diet or supplements. Ergothioneine has been classified as a "longevity vitamin" due to its potential benefits in combating aging and age-related conditions.
Key points about ergothioneine:
It is not an essential vitamin, meaning its absence does not directly cause a specific disease. However, insufficient intake may hinder the body's optimal functioning over time.
Ergothioneine is a powerful antioxidant and anti-inflammatory agent.
It is not synthesized by the human body and must be obtained through dietary sources or supplements.
The human body has a unique transporter for ergothioneine, allowing it to enter cells and combat oxidative stress.
This transporter is expressed in various cell types throughout the body, suggesting ergothioneine's potential to act multi-functionally across different organs.
Ergothioneine is highly bioavailable due to the widespread expression of its transporter.
Research has focused on ergothioneine's potential benefits for cognitive health, as the transporter is found in the brain and it can cross the blood-brain barrier.
Studies have shown lower ergothioneine levels in individuals with mild cognitive impairment and Parkinson's disease compared to cognitively normal individuals.
Mushrooms are the top food sources of ergothioneine, with oyster mushrooms being particularly rich.
Other sources include porcini, shiitake, portobello, button mushrooms, tempeh, and garlic.
Three servings of mushroom sources and tempeh can provide 1 to 7 milligrams of ergothioneine.
Mushroom consumption has been associated with a reduced risk of developing mild cognitive impairment.
Studies suggest a correlation between low ergothioneine consumption and higher mortality rates from neurological conditions and lower life expectancy.
The recommended use levels for ergothioneine are 5 milligrams per serving in food fortification and 5 to 10 milligrams per serving in dietary supplements, up to 30 milligrams daily.
Blue California is sponsoring two ongoing clinical trials on ergothioneine.
The first trial investigates the effects of ergothioneine supplementation on cognitive performance, mood, stress, and sleep in healthy individuals aged 55 to 79.
The second trial is a pilot study examining the impact of ergothioneine and taxifolin on immune function and antioxidant status in healthy individuals aged 50 to 65.
Numerical results:
Americans consume an estimated 1 milligram of ergothioneine per day, while Italians consume almost 5 milligrams.
Two servings of mushrooms per week can reduce the odds of mild cognitive impairment by 60%.
The use levels for ergothioneine are 5 milligrams per serving in food fortification and 5 to 10 milligrams per serving in dietary supplements, up to 30 milligrams daily.
In the second clinical trial, participants are taking 80 milligrams of ergothioneine per day, equivalent to consuming about 5 ounces of porcini mushrooms daily.
Overall, ergothioneine shows promise as a longevity vitamin with potential benefits for cognitive health, immune function, and overall well-being. Ongoing research and clinical trials are expected to shed further light on its efficacy and optimal use.
Ergothioneine: A Stress Vitamin with Antiaging, Vascular, and Neuroprotective Roles? (2022)
ET merits classification as a vitamin, specifically a "stress vitamin", based on several features:
Mammals cannot synthesize ET and must obtain it from dietary sources.
ET is taken up by cells via a specific transporter (ETT/SLC22A4) in a sodium- and pH-dependent manner, similar to other vitamins.
Depletion of ET is associated with deleterious consequences and increased susceptibility to oxidative stress.
ET levels are concentrated in tissues frequently exposed to oxidative stress, approaching millimolar concentrations in some.
ET has potent antioxidant and cytoprotective properties:
It is a stable antioxidant that does not auto-oxidize at physiological pH like other antioxidants.
ET can scavenge and neutralize a wide range of reactive oxygen and nitrogen species, including hydroxyl radicals, peroxynitrite, hypochlorous acid, and singlet oxygen.
It chelates divalent metal cations like Cu2+ to counteract metal-mediated oxidative damage.
ET absorbs UV light and prevents UV-induced DNA damage.
Knockdown of the ET transporter leads to increased oxidative damage to proteins, lipids and DNA.
ET has anti-inflammatory effects:
Expression of the ET transporter increases in response to pro-inflammatory cytokines TNF-α and IL-1β.
Mice lacking the ET transporter have increased susceptibility to inflammation after ischemia-reperfusion injury.
ET inhibits NF-κB activation and release of pro-inflammatory interleukin-8 by H2O2 and TNF-α.
ET has important roles in the nervous system:
The brain, especially the cerebellum, contains high levels of ET and its transporter.
ET protects neurons against oxidative stress and excitotoxicity induced by NMDA and cisplatin.
It ameliorates cognitive deficits and neurotoxicity caused by amyloid-β in Alzheimer's disease models.
ET promotes neuronal differentiation via mTOR/S6K1 and neurotrophin signaling pathways.
Levels of ET are depleted in Parkinson's disease, vascular dementia and mild cognitive impairment, suggesting a neuroprotective role.
Mushroom consumption, a dietary source of ET, is inversely correlated with mild cognitive impairment in humans.
ET may have anti-aging effects:
Blood levels of ET decrease significantly with age, especially after 60 years. This is associated with cognitive decline.
ET delays endothelial cell senescence caused by high glucose via sirtuins SIRT1/SIRT6.
It protects dermal fibroblasts against UV-induced skin aging by scavenging ROS and activating Nrf2 antioxidant pathways.
ET levels in the eye lens decrease with age and cataract formation.
ET provides cardiovascular protection:
It reduces endothelial oxidative stress and improves vascular function.
ET causes relaxation of aortic rings via endothelial nitric oxide signaling.
It protects against impaired vasodilation caused by superoxide.
ET inhibits monocyte adhesion to endothelial cells, an early step in cardiovascular disease.
The biology of ergothioneine, an antioxidant nutraceutical (2020)
Ergothioneine (ERG) is an unusual amino acid derived from histidine that has potent antioxidant activities. It is synthesized by certain fungi, especially mushrooms, and some bacteria, but not by plants and animals. However, ERG is acquired by plants from the soil and by animals from their diet, suggesting it may be an important micronutrient or even have vitamin-like properties.
ERG accumulates in tissues prone to oxidative stress, such as erythrocytes, and studies suggest that consuming mushrooms or ERG supplements may offer protection against oxidative stress in various systems. ERG demonstrates strong cytoprotective effects, and its levels are often reduced in chronic inflammatory diseases. Regulatory agencies have deemed ERG safe for consumption, and it holds potential as a nutraceutical and antioxidant.
Mushrooms are the main dietary source of ERG for humans. Different mushroom species vary in their ERG content, with some like oyster mushrooms and shiitake containing up to 4 mg/g dry weight. Even common button mushrooms provide 0.4 mg/g dry weight on average. Regular consumption of mushrooms has been associated with various health benefits, which may be partly attributable to their high ERG levels.
As an antioxidant, ERG can scavenge reactive oxygen species like hydroxyl radicals, singlet oxygen, peroxynitrite and hypochlorite. It prevents oxidative damage to proteins, lipids and DNA. These effects have been demonstrated in many cell culture and animal models. ERG may therefore help protect against chronic oxidative stress, which is implicated in various inflammatory diseases.
Some key findings related to ERG's physiological roles and health effects include:
SLC22A4 knockout mice have severely reduced ERG levels and are more sensitive to oxidative stress. Polymorphisms in the human SLC22A4 gene are associated with increased risk of ischemic stroke, rheumatoid arthritis, Crohn's disease and diabetes complications.
ERG supplementation in human subjects (5-25 mg/day) reduced biomarkers of oxidative stress and inflammation without any adverse effects. ERG is considered safe by regulatory agencies.
In a 3236-subject Swedish study, ERG was the metabolite most strongly associated with a healthy dietary pattern and reduced risk of coronary disease, cardiovascular mortality and overall mortality.
Mushroom consumption is correlated with better cognitive function in observational studies. For example, consuming >2 servings of mushrooms per week was associated with a 50% reduced risk of mild cognitive impairment. This may be related to ERG's antioxidant and anti-inflammatory effects.
ERG accumulates in rat models of fatty liver disease and heart failure, possibly as a protective response. It has shown benefits in animal models of neurological disorders like Parkinson's, Alzheimer's and depression.
As a food additive, ERG can help prevent spoilage due to oxidation. It is used in cosmetics and skin care products for its antioxidant and anti-inflammatory properties.
In summary, ERG is an amino acid with potent antioxidant activities that is obtained from dietary sources, especially mushrooms. It is concentrated in specific tissues by the SLC22A4 transporter, where it likely serves important cytoprotective functions against oxidative stress. ERG shows therapeutic potential for many chronic inflammatory diseases associated with oxidative stress. Regular dietary intake of ERG from mushrooms and other sources may have significant health benefits, though more research in humans is still needed to confirm its efficacy as a nutraceutical.
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