# L-ergothioneine **Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/l-ergothioneine **Data Source:** Hermetica Superfoods Ingredient Encyclopedia **Updated:** 2026-04-05 **Evidence Score:** 2 / 10 **Category:** Compound **Also Known As:** ergothioneine, EGT, ET, (S)-ergothioneine, 2-mercaptohistidine trimethylbetaine, thiourocanic acid betaine, sympectothion ## Overview L-ergothioneine is a naturally occurring thione-form amino acid derivative synthesized exclusively by fungi and certain bacteria, absorbed into human tissues via the OCTN1 transporter. It functions as a highly stable antioxidant by scavenging [reactive oxygen species](/ingredients/condition/antioxidant) and chelating metal ions, protecting cells from oxidative and [inflammatory](/ingredients/condition/inflammation) damage. ## Health Benefits • Acts as a stable antioxidant, protecting against oxidative stress[3]. • Detoxifies [reactive oxygen species](/ingredients/condition/antioxidant) (ROS) and elevates intracellular thiol levels[3]. • Protects the liver and kidneys from oxidative damage[3]. • Reduces expression of MMP1 in UV-irradiated human dermal fibroblasts, potentially providing [anti-aging](/ingredients/condition/longevity) skin effects[3]. • Conserves levels of [glutathione](/ingredients/condition/detox) and α-tocopherol[3]. ## Mechanism of Action L-ergothioneine exists predominantly in its thione tautomeric form, which confers exceptional radical-scavenging stability compared to conventional thiols. It is actively concentrated in tissues via the organic cation transporter OCTN1 (SLC22A4), accumulating in mitochondria, erythrocytes, and the liver where [oxidative stress](/ingredients/condition/antioxidant) is highest. It chelates divalent metal ions such as Cu²⁺ and Fe²⁺, inhibiting Fenton-type reactions, and suppresses the NF-κB pathway to reduce downstream MMP1 expression and [pro-inflammatory cytokine](/ingredients/condition/inflammation) production. ## Clinical Summary Preclinical studies in rodent models demonstrate [hepatoprotective](/ingredients/condition/detox) and nephroprotective effects, with measurable reductions in [lipid peroxidation](/ingredients/condition/antioxidant) markers such as MDA following ergothioneine supplementation. In vitro studies using UV-irradiated human dermal fibroblasts show significant downregulation of MMP1 expression, suggesting anti-photoaging potential. Human epidemiological data correlate low plasma ergothioneine levels with increased risk of [cardiovascular](/ingredients/condition/heart-health) disease and [cognitive](/ingredients/condition/cognitive) decline, though large-scale randomized controlled trials in humans remain limited. Early-phase human pharmacokinetic studies confirm oral bioavailability and tissue accumulation, but clinical efficacy trials with quantified outcomes are still emerging. ## Nutritional Profile L-ergothioneine is a naturally occurring amino acid derivative (thiohistidine betaine) and specialized bioactive compound, not a significant source of macronutrients or conventional micronutrients. Molecular weight: 229.3 g/mol. It contains a unique sulfur-containing imidazole ring structure with a thione tautomeric form that confers exceptional [antioxidant](/ingredients/condition/antioxidant) stability. Found in highest concentrations in mushrooms (e.g., king oyster/Pleurotus eryngii: ~40–50 mg/100g dry weight; shiitake: ~11–13 mg/100g dry weight; white button: ~0.4–2.0 mg/100g dry weight), black beans (~0.1 mg/100g), oat bran (~0.18 mg/100g), and organ meats such as liver and kidney (~0.2–1.5 mg/100g wet weight). As a pure compound used in formulations or supplements, it is typically dosed at 5–30 mg/day. Bioavailability is notably high in humans due to a dedicated transporter protein, OCTN1 (SLC22A4), which actively shuttles ergothioneine into cells and tissues, resulting in preferential accumulation in mitochondria, erythrocytes, liver, kidney, bone marrow, and the lens of the eye. Plasma concentrations in humans typically range from 1–4 µmol/L under normal dietary intake. It is not synthesized endogenously in humans and is therefore considered a '[longevity](/ingredients/condition/longevity) vitamin' candidate. Contains no significant caloric value, fiber, or fat in its isolated form. ## Dosage & Preparation No clinically studied dosage ranges or forms are available for L-ergothioneine. Consult a healthcare provider before starting any new supplement. ## Safety & Drug Interactions L-ergothioneine has a well-established safety profile with no significant adverse effects reported in human studies at supplemental doses typically ranging from 5 to 30 mg per day. No confirmed drug interactions have been documented, though theoretical caution is warranted with medications transported by OCTN1, such as certain cationic drugs including verapamil and quinidine, due to shared transporter competition. Pregnant and breastfeeding individuals lack sufficient clinical trial data to confirm safety, and conservative avoidance or physician consultation is recommended. It is generally recognized as safe at dietary levels obtained through mushroom-rich diets. ## Scientific Research No specific human clinical trials, RCTs, or meta-analyses are available for L-ergothioneine. The research is primarily based on biochemical and in-vitro studies. ## Historical & Cultural Context There is no historical or traditional use mentioned in the research for L-ergothioneine. ## Synergistic Combinations Vitamin C, [Glutathione](/ingredients/condition/detox), Alpha-lipoic acid, CoQ10, Resveratrol ## Frequently Asked Questions ### What foods are highest in L-ergothioneine? Mushrooms are by far the richest dietary source of L-ergothioneine, with king oyster (Pleurotus eryngii) and shiitake mushrooms containing up to 5 mg per 100g fresh weight. Black beans and oat bran contain trace amounts, but fungi remain the primary dietary pathway since humans cannot synthesize ergothioneine endogenously. ### How does L-ergothioneine differ from glutathione as an antioxidant? Unlike glutathione, which exists in a thiol form prone to oxidation, L-ergothioneine exists predominantly as a thione tautomer that is chemically more resistant to auto-oxidation in aqueous environments, giving it a longer functional half-life in tissues. Glutathione is synthesized endogenously in most cells, whereas ergothioneine must be obtained entirely from diet or supplementation and is selectively transported by OCTN1 to high-stress tissues. ### What is the recommended dosage of L-ergothioneine supplements? Clinical and pharmacokinetic studies have typically investigated oral doses between 5 mg and 30 mg per day, with 5–10 mg considered a physiologically relevant supplemental range approximating achievable dietary intake. No official recommended daily intake has been established by regulatory bodies, and optimal therapeutic dosing for specific health outcomes has not yet been confirmed by large-scale RCTs. ### Can L-ergothioneine protect against skin aging? In vitro studies using UV-irradiated human dermal fibroblasts show that L-ergothioneine reduces MMP1 (matrix metalloproteinase-1) expression, the enzyme responsible for collagen degradation and wrinkle formation. Its metal-chelating and ROS-scavenging properties additionally protect dermal cells from UV-induced oxidative damage, making it an ingredient of interest in topical and ingestible anti-aging formulations, though robust human clinical trial data are still limited. ### Is L-ergothioneine deficiency linked to any diseases? Epidemiological studies have associated low plasma L-ergothioneine concentrations with higher risks of cardiovascular disease, mild cognitive impairment, and frailty in aging populations. A 2020 study published in Redox Biology found significantly reduced ergothioneine levels in patients with mild cognitive impairment compared to healthy controls, suggesting a potential neuroprotective role. Researchers hypothesize that OCTN1 gene variants reducing transporter efficiency may contribute to ergothioneine insufficiency and increased disease susceptibility. ### Does L-ergothioneine interact with common medications? L-ergothioneine has a favorable safety profile with minimal reported drug interactions due to its natural occurrence in foods and its role as a supportive antioxidant rather than a direct metabolic modifier. However, those taking anticoagulants or antidiabetic medications should consult a healthcare provider, as ergothioneine may theoretically enhance the effects of these drugs through its antioxidant mechanisms. No major pharmacokinetic interactions with cytochrome P450 enzymes have been documented in clinical literature. ### What is the bioavailability of L-ergothioneine supplements compared to food sources? L-ergothioneine from supplements is generally well-absorbed due to its stability and the presence of specific membrane transporters (organic cation transporter 1) that facilitate cellular uptake. Food sources like mushrooms and beans provide ergothioneine in its natural form, but bioavailability varies depending on food matrix and digestive factors. Supplemental forms typically achieve reliable serum levels, making them a consistent alternative to relying solely on dietary sources. ### Is L-ergothioneine safe for long-term supplementation? L-ergothioneine is considered safe for long-term use, with no established upper intake limit and no serious adverse effects reported in human studies at supplemental doses. Its natural presence in the human diet and endogenous production in certain tissues supports its safety profile across extended supplementation periods. However, pregnant and nursing women should seek professional guidance before beginning supplementation, as long-term safety data in these populations remains limited. --- *Source: Hermetica Superfoods Ingredient Encyclopedia — https://ingredients.hermeticasuperfoods.com* *License: CC BY-NC-SA 4.0 — Attribution required. Commercial use: admin@hermeticasuperfoods.com*