Aminothionein
Anti-Aging Cos&Beauty

“Longevity vitamin” Ergothioneine: “Guardian” of memory and skin, “darling” of synthetic biology

The Japanese corporation L Corporation recently obtained a patent for Aminothionein®, a component derived from the Golden Oyster mushroom, used to improve age-related sustained attention decline. The company conducted repeated studies on Aminothionein® extracted from the Golden Oyster mushroom and has obtained patents such as “Food Additives and Food Antioxidants,” “Antidepressant Medications,” and “Diagnosis and Treatment of Crohn’s Disease Using Aminothionein®.”

Although Aminothionein may sound relatively unfamiliar, it is a high-potential ingredient in the skincare industry and a popular raw material in synthetic biology. Market Watch data indicates that the market size of Aminothionein® is expected to reach $171.9 million by 2028, with a compound annual growth rate of 36.2% during the forecast period from 2022 to 2028. In recent years, Aminothionein’s visibility has been increasing, and some researchers suggest classifying it as a “Stress Vitamin.” Bruce Ames, Professor Emeritus of Biochemistry and Molecular Biology at the University of California, Berkeley, refers to it as a “Longevity Vitamin” based on its characteristics.

Structural formulas of two tautomers of ergothioneine
Structural formulas of two tautomers of ergothioneine

The antioxidant effects of Aminothionein are primarily manifested through several mechanisms

1) it can prevent the formation of free radicals such as OH, directly scavenging reactive oxygen species (ROS) like hypochlorous acid and peroxynitrite;

2) it effectively chelates various divalent metal cations;

3) it can interact with other endogenous antioxidant defense systems, such as activating intracellular antioxidant pathways involving MAPKs and regulating the levels of peroxidases and antioxidant enzymes;

4) it inhibits the oxidation of various hemoglobins.

In comparison to other antioxidants, Aminothionein has the following characteristics

1) it is an adaptive antioxidant that preferentially accumulates in cells and tissues exposed to oxidative stress and damage. The organic cation transporter OCTN1 (now known as SLC22A4, a transporter protein with 551 amino acids and three glycosylation sites) in the human body can transport Aminothionein to the desired sites;

2) there is a regenerative cycle for Aminothionein in the human body. Binding with glutathione allows it to be regenerated, enabling it to circulate and react with singlet oxygen for a more comprehensive and prolonged antioxidant effect;

3) Aminothionein is excreted slowly in the body, allowing it to be highly retained in the tissues and red blood cells of humans and other animals, maximizing its effectiveness;

4) Aminothionein primarily exists in the form of a thione, providing ideal thermal stability and pH stability.

Guardian of Memory and Skin

Guardian of Memory

Oxidative stress is a major contributor to neurodegenerative diseases. For instance, oxidative stress caused by the deposition of beta-amyloid (Aβ) plays a crucial role in the pathogenesis of Alzheimer’s disease. Studies indicate that Aminothionein serves as a protector of brain health and cognitive function, able to penetrate the blood-brain barrier and exert its effects in the brain.

The potential mechanisms of Aminothionein in neurodegenerative diseases are diverse

1) Aminothionein can directly inhibit the accumulation of bacteria and Aβ in the hippocampal region and lipid peroxidation in neuronal cells;

2) it can influence other antioxidants, such as maintaining the GSH/GSSG ratio and superoxide dismutase activity, and restoring acetylcholinesterase activity in the brain;

3) it can prevent the formation of peroxynitrite, protecting or reducing neurons from Aβ-induced apoptosis and cisplatin-induced neuronal damage in a dose-dependent manner;

4) it can directly reduce ROS levels, inhibit the transcription pathway of NF-κB, and prevent the production of pro-inflammatory cytokines, thereby suppressing neuroinflammation in the brain;

5) it can protect neurons from cytotoxicity induced by high glucose.

Starting in 2020, the Japanese market introduced functional foods with Aminothionein, emphasizing their role in improving memory function in the elderly. Aminothionein supplements, such as those introduced by Gaisei Pharmaceutical Co., Ltd., have been specifically designed for addressing memory decline in middle-aged and elderly individuals.

Guardian of the Skin

Due to its unique antioxidant capabilities, Aminothionein has emerged as a high-potential anti-aging ingredient in the skincare industry.

Aminothionein’s skincare benefits primarily focus on anti-aging, and its mechanisms of action include the following five points:

1) Anti-photoaging, mainly combating ultraviolet (UV) radiation by inhibiting UV-induced peroxidation reactions, inflammation factors/β-Gel, and MMPs expression;

2) Antioxidant effects, preventing oxidative damage, repairing DNA damage, inhibiting apoptosis, and increasing cellular vitality;

3) Anti-glycation, reducing the formation of advanced glycation end products (AGEs);

4) Prevention of mitochondrial membrane potential and tDNA damage;

5) Prevention of telomere damage, activating telomerase activity, and reducing telomere shortening.

Additionally, Aminothionein has some role in eye protection, improving cardiovascular health, and aiding in muscle repair.

When Aminothionein Meets Synthetic Biology

Due to its rarity, Aminothionein is exceptionally expensive. In 2014, the cost of one kilogram was close to one million dollars. Even with advancements in technology, the price remains high. According to industry insiders, Barnet, a U.S. raw material company, uses a chemical synthesis route for Aminothionein, and due to cost considerations, its market price, when converted to pure powder, is approximately 7,000 yuan/g, which is 20 times that of gold.

Aminothionein can be obtained through three methods: mushroom extraction, chemical synthesis, and synthetic biology. Mushroom extraction is abandoned due to low content and high costs. The chemical synthesis method is prone to chiral isomer impurities and solvent residues, and it is costly with potential environmental impacts. Currently, Aminothionein is mainly produced through synthetic biology fermentation.

Enterprises, universities, and research institutions are actively researching how to efficiently produce Aminothionein through synthetic biology, aiming to increase purity, yield, and reduce costs. The use of natural edible fungi or engineered bacteria for the fermentation production of Aminothionein from food-grade raw materials meets safety requirements for food applications. Research in Japan indicates that using engineered microorganisms for fermentation could potentially reduce the production cost of Aminothionein by 99%.

Blue California was the first company to produce L-Aminothionein through fermentation, launching the ErgoActive ingredient in 2015 as an alternative to chemically synthesized and mushroom-extracted Aminothionein.

In response to investor inquiries last year, Huaxi Biology stated that the company uses different host cells and technological routes to produce Aminothionein with varying purities. A breakthrough in fermentation yield has been achieved through synthetic biology, going from several hundred milligrams per liter to several grams per liter. The Bioyouth™-EGT Pure ultra-pure Aminothionein, with a purity exceeding 99%, is reportedly produced through co-fermentation of the mycelium of Hericium erinaceus and Tricholoma matsutake.

Aminothionein

The Global Compliance Journey of Aminothionein

In July 2017, the European Union (EU) approved L-Aminothionein as a new food ingredient (2017/1281), allowing its application in dietary supplements at a daily dosage of 30 mg for the general population and 20 mg for children aged 3 and above. However, it cannot be used in pregnant or lactating women. In October of the same year, the European Food Safety Authority (EFSA) endorsed the “Scientific Opinion on the Safety of L-Aminothionein.”

In 2018, (EU) 2018/462 expanded the use of L-Aminothionein to include not only dietary supplements but also common foods such as beverages and cereal bars.

In August 2019, Aminothionein received Generally Recognized as Safe (GRAS) certification from the United States Food and Drug Administration (FDA), allowing its application in common foods.

In summary, as synthetic biology advances rapidly, the cost of Aminothionein is expected to decrease continuously. When Aminothionein becomes more affordable and regulatory restrictions are lifted, it may become a popular ingredient in both cosmetic and food formulations, similar to hyaluronic acid.

Reference

Borodina I, Kenny LC, McCarthy CM, Paramasivan K, Pretorius E, Roberts TJ, van der Hoek SA, Kell DB. The biology of ergothioneine, an antioxidant nutraceutical. Nutr Res Rev. 2020 Dec;33(2):190-217. doi: 10.1017/S0954422419000301. Epub 2020 Feb 13. PMID: 32051057; PMCID: PMC7653990.

Fu Tong-Tong, Shen Liang. Ergothioneine as a Natural Antioxidant Against Oxidative Stress-Related Diseases. Frontiers in Pharmacology. VOLUME=13.2022. Link DOI=10.3389/fphar.2022.850813. ISSN 1663-9812.

SIYOMICRO-ERGO? Application of Ergothioneine in the Anti-Aging Field – Zhongke Xinyang.

Rise of Domestic Raw Materials! This Pharmaceutical-Grade Raw Material Company Has Lowered the Price of Ergothioneine! – Tianqin Beauty Planning.

“Noble” Ingredients: For Product Efficacy or Telling More Pleasing Stories? | Ingredient Feature 48 – Jumei Beauty.

Ergothioneine, Moving Towards Affordability? – Beauty Net.

Ergothioneine: A Stress Vitamin with Antiaging, Vascular, and Neuroprotective Roles? Bindu D. Paul. Antioxidants & Redox Signaling 2022 36:16-18, 1306-1317.

Liu Qi, Mao Yufeng, Liao Xiaoping, Luo Jiahao, Ma Hongwu, Jiang Wenxia. New Progress in the Study of Ergothioneine Biosynthesis. Chinese Journal of Biotechnology, 2022, 38(4): 1408-1420. DOI: 10.13345/j.cjb.210797.

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