L-Ergothioneine Powder has been approved as a food ingredient by the United States, Europe, Canada, Japan and other countries/regions. It is also a popular raw material in the field of cosmetics. In 2016, EGT passed the safety assessment of the European Commission as a new food ingredient. EGT is safe for use in regular foods and dietary supplements. As a dietary supplement: 30 mg per day for the general population and 20 mg per day for children over 3 years of age. Not approved for use in pregnant and lactating women.
• Skin protective effects of ergothioneine
Ultraviolet rays from sunlight increase the production of reactive oxygen species in skin tissue. UVA and UVB may induce skin problems caused by reactive oxygen species.
• UVA
Solar ultraviolet rays are mainly composed of UVA (>90%) and UVB (<10%). So our skin is exposed to UVA every day. UVA can penetrate deep into the dermis. Therefore, UVA will continuously induce reactive oxygen species to damage human skin, such as roughness, wrinkles, pigmentation and skin malignant tumors. The degradation of collagen is the direct cause of wrinkles. Ergothioneine can inhibit UVA-induced reactive oxygen species production in human skin fibroblasts. Its efficacy is higher than that of coenzyme Q10. Ergothioneine has many advantages in terms of antioxidant capacity compared to other candidate ingredients.
Ergothioneine is associated with reduced degradation of type I procollagen and upregulation of Nrf2 expression due to activation of matrix metalloproteinase (MMP)-1. This is also a manifestation of ergothioneine inhibiting UVA-induced reactive oxygen species production in human skin fibroblasts. Some scholars believe that ergothioneine can repair DNA in cells exposed to ultraviolet rays.
Guanjie's research shows that after using zebrafish to irradiate ultraviolet light and establish a zebrafish photoaging model, when ergothioneine was at concentrations of 1000 and 2000 μg/mL, the zebrafish type I collagen content was 2.54±0.126 and 2.87±0.130ng/ mgprot. Compared with the model control group (1.66±0.074ng/mgprot), they were significantly increased (p = <0.01 and <0.001 respectively). This shows that ergothioneine has anti-photoaging effects at both 1000 and 2000 μg/mL concentrations.
• UVB
UVB irradiation induces keratinocytes to produce reactive oxygen species, apoptosis and inflammation. Ergothioneine can inhibit UVB-induced skin inflammation and subsequent DNA halogenation in mice. Ergothioneine pretreatment in keratinocytes can significantly inhibit UVB-induced fibroblast senescence.
• The therapeutic potential of EGT
Figure 1 Diseases caused by ROS induction
The production of excess ROS affects lipids, cellular proteins, DNA and RNA to varying degrees. Involves aging and various diseases, including neurodegenerative diseases, cardiovascular diseases, endocrine diseases, liver diseases, kidney diseases, digestive diseases and respiratory diseases.
Figure 2 Therapeutic potential of EGT and diseases associated with reduced EGT levels
Recently, there have been an increasing number of reports on the therapeutic effects of L-Ergothioneine Powder supplementation on different diseases and failures caused by ROS. At the same time, there are also reports that the levels of ergothioneine in many bodies have decreased, leading to related diseases. Therefore, scholars are paying more and more attention to the therapeutic potential of ergothioneine in attenuating tissue damage induced by oxidative stress.
• Senescence
The level of ergothioneine in the body is one of the hallmarks of aging, and its decrease is closely related to cognitive sensitivity. Ergothioneine is also thought to be a metabolite associated with maintaining or improving step speed.
Telomere shortening has been implicated in aging and age-related diseases. Ergothioneine can increase telomerase activity under conditions of oxidative stress. It has anti-aging effects by reducing the shortening rate of telomeres and maintaining their length. Therefore, ergothioneine plays a potential role in healthy aging.
In a research report by TPV, after establishing a zebrafish aging model, the zebrafish telomerase activities were 14.1±0.495 and 17.6±1.05IU/gprot when ergothioneine was at concentrations of 500 and 1000 μg/mL, respectively. Compared with the model control group (11.3±0.295 IU/gprot), they were significantly increased (p = <0.05 and <0.01 respectively). It shows that ergothioneine has anti-aging effects at both 500 and 1000 μg/mL concentrations.
Neurodegenerative diseases
• Dementia
Levels of ergothioneine in the blood of people with dementia were significantly lower when compared to both healthy older adults and healthy younger adults. Reductions in ergothioneine may be linked to increases in reactive oxygen species in the brains of people with dementia. Likewise, ergothioneine levels were lower in blood samples from people over the age of 60 with mild cognitive impairment (MCI) than in age-matched healthy subjects. And people with mild cognitive impairment may develop dementia. These results suggest that ergothioneine reduction may be a risk factor for neurodegeneration.
• Alzheimer's disease (AD)
Alzheimer's disease is the most common cause of dementia. It is characterized by the deposition of amyloid-beta (Aβ) peptide in amyloid plaques. After intracerebroventricular injection of Aβ peptide in mice, oral administration of ergothioneine in advance can inhibit the accumulation of Aβ peptide in the hippocampus and maintain the activity of superoxide dismutase SOD in the brain. The results showed that mice given ergothioneine in advance showed resistance to Aβ peptide-induced loss of learning and memory abilities.
• Depression
Ergothioneine can enter the brain through the blood-brain barrier, promote neuronal differentiation, and reduce depression symptoms. In addition, ergothioneine can prevent depressive behaviors caused by social defeat stress (SDS), such as social avoidance and depression-like sleep abnormalities (especially rapid eye movement sleep).
• Encephalitis
Microglia play an important role in maintaining brain homeostasis. Their pathological overactivation is associated with the development of different neurodegenerative diseases due to encephalitis. L-Ergothioneine Powder supplementation can significantly inhibit lipopolysaccharide-induced reactive oxygen species production, cell hypertrophy, and IL-1β upregulation in mouse microglia. Ergothioneine has the potential to prevent severe inflammation in the brain.
• Insomnia
In Huarui Bio's research report, a zebrafish insomnia model was established, and a behavioral analyzer was used to detect the amount of zebrafish's awakening activity and the total awakening time. The results showed that when ergothioneine was at a concentration of 20.0mg/mL, the arousal activity of zebrafish (433±70.1mm) was significantly reduced compared with the model group (800±107mm) (p<0.05). The total awakening time of zebrafish (11.0±1.72s) was significantly reduced compared with the model group (19.6±2.42s) (p<0.05). This shows that ergothioneine has the effect of improving sleep at a concentration of 20.0mg/mL.
• Cardiovascular Disease (CVD)
Cardiovascular disease is a common complication of diabetes mellitus (DM). Ergothioneine is the metabolite most closely associated with a healthy diet. and was associated with a lower risk of overall mortality, cardiovascular disease mortality, and coronary artery disease. The risk of cardiovascular disease and death can be reduced with ergothioneine. In rats with type 2 diabetes, the following indicators are upregulated: mean arterial pressure; levels of cardiac creatinine kinase, which reflects cardiac damage; and cardiac inflammation. In contrast, the expression of cardiac antioxidant enzymes was downregulated. Oral administration of ergothioneine attenuated these pathological features, suggesting that ergothioneine may protect the heart from diabetes-related cardiac damage.
Liver damage/disease
• Ischemia-reperfusion (IR) liver injury
IR injury occurs in blood flow occlusion and reperfusion because reactive oxygen species are produced after blood reperfusion. Indicators used to assess liver damage in rats induced by IR include aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) (these indicators will be upregulated when the liver is damaged). Ergothioneine can inhibit these indicators, indicating that ergothioneine can protect the liver from IR liver damage.
• Non-alcoholic fatty liver disease (NAFLD)
Elevated ergothioneine can be observed in the liver of a guinea pig model of non-alcoholic fatty liver disease (NAFLD). The accumulation of ergothioneine in the damaged liver can inhibit further oxidative damage in NAFLD and delay tissue damage.
• Liver Fibrosis
The accumulation of ergothioneine in satellite cells, a type of glial cell, has a protective effect against liver fibrosis.
Kidney damage/disease
• Chronic kidney disease (CKD)
Studies have found that patients with chronic kidney disease have reduced blood levels of ergothioneine. But recovered after kidney transplantation.
• Renal fibrosis
The renal fibrosis mouse model has obvious pathological characteristics, including increased reactive oxygen species production, enhanced macrophage infiltration, and collagen deposition. Deletion of the octn1 gene worsens these characteristics. The ergothioneine/OCTN1 signaling axis may play an anti-fibrotic role in renal fibrosis.
Respiratory diseases
• Alveolar epithelial cell damage
Type 2 alveolar epithelial cell death and epithelial-to-mesenchymal transition (EMT) lead to the development of pulmonary fibrosis. Ergothioneine inhibits TGF-β-induced epithelial-mesenchymal transition and cigarette smoke-induced cell death in human lung epithelial cells. So taking ergothioneine may be a way to prevent pulmonary fibrosis.
• Acute respiratory distress syndrome (ARDS)
Oxidative stress and proinflammatory cytokines induce the expression of IL-8, a potent neutrophil attractant/activator that plays an important role in the development of acute lung injury. Ergothioneine can inhibit the induction of IL-8 in epithelial cells and be used to rescue patients with acute respiratory distress syndrome.
• Metabolic syndrome
In pre-diabetes (type 2), after confirming that participants met criteria for metabolic syndrome, they consumed 100 grams of white button mushrooms (containing approximately 3.2 mg of L-Ergothioneine Powder daily for 16 weeks and found: Serum oxidative stress-inducing factor decreased; increased antioxidant markers; and increased adiponectin, an anti-inflammatory hormone.
• Preeclampsia
Preeclampsia is a multifactorial hypertensive pregnancy disorder. Ergothioneine maintains mitochondrial function by increasing antioxidant levels and suppressing the inflammatory response associated with preeclampsia. Pregnant women at risk of preeclampsia are therefore encouraged to use ergothioneine.
• Anemia
Ergothioneine levels are significantly reduced in patients with sickle cell anemia (SCA). Likewise, there is a strong correlation between ergothioneine and other markers of red blood cell metabolism. Therefore, ergothioneine supplementation may be an antioxidant treatment alternative to existing treatments.
• Viral infection
Ergothioneine inhibits transcriptional activators in human immunodeficiency virus type 1 (HIV-1). It may therefore be beneficial for patients infected with chronic immunodeficiency diseases. Studies have shown that ergothioneine can inhibit hepatitis C virus genome replication and reduce its blood load. Taken together with these findings, the protective capacity of ergothioneine against various reactive oxygen species-mediated/inflammation-related diseases prompts us to consider the possibility that ergothioneine may reduce the severity and mortality of COVID-19.
• Crohn's disease
Crohn's disease is an inflammatory bowel disease. It is defined as a chronic, relapsing, inflammatory disease of the gastrointestinal tract. Plasma concentrations of ergothioneine were found to be significantly lower in patients with Crohn's disease than in healthy subjects. This reveals that ergothioneine may be involved in the regulatory process of inflammation. Meanwhile, a nonsynonymous single nucleotide polymorphism in the SLC22A4 (OCTN1) gene associated with the L503F variant of OCTN1 has been associated with Crohn's disease in Caucasian populations40. Therefore, these findings suggest that the ergothioneine/OCTN1 axis may be involved in the pathogenesis of Crohn's disease. But further research is needed on whether ergothioneine supplementation is beneficial for Crohn's disease.
What Are Other Potential Applications?
Ergothioneine is a powerful natural antioxidant that is very safe for humans. Stable even in high temperatures or acidic environments. Therefore, ergothioneine has wide applicability in cosmetics, pharmaceuticals, supplements, and food additives. In fact, it can be used as a food additive to prevent discoloration and quality changes caused by oxidation of products. Consider the harmful effects of synthetic additives such as sulfites on human health.
The FDA requires sulfites to be declared on the label when the concentration in food is ≥10 ppm. Therefore, ergothioneine, as a natural antioxidant compound, is expected to become a substitute for sulfites. Ergothioneine has a synergistic effect on certain active ingredients, which allows it to be extended to the application scenarios of these active ingredients in the future.
• Vitamin C
Asmus KD et al. found that in the presence of vitamin C, the oxidized form of ergothione is repaired by rapid reduction to produce ascorbic acid free radicals. Synergistic interaction between EGT and ascorbic acid. Interactions similar to those between vitamin E and ascorbic acid may contribute to important biological redox protection.
• Collagen
The synergistic effect of ergothioneine on collagen is mainly to promote the production of collagen. Hseu YC et al tested the effect of ergothioneine concentration on type I procollagen levels. The results showed that ergothioneine dose-dependently increased the expression of type I procollagen, thereby protecting human skin fibroblasts (HSF) from UVA radiation-induced collagen degradation.
• Glutathione
HseuYC et al. found that 0.5 μM ergothioneine significantly increased glutathione production in HSF cells compared with control cells. This indicates that ergothioneine is a potent antioxidant inducer that can cope with oxidative stress caused by UVA irradiation.
Shaanxi Guanjie Biotechnology Co., Ltd. uses bioengineering to produce L-Ergothioneine Powder greenly and efficiently. Continuously optimizing strains and purification processes, it has become a leading company in the global ergothioneine industry. Welcome to request samples and information:info@gybiotech.com
