Ergothioneine: A “Longevity Vitamin” from Mushrooms

What is Ergothioneine

Ergothioneine (ERGO) is one of the most exciting nutrients in modern longevity research. It is a sulfur-containing amino acid that humans cannot make, meaning it must come from the diet. Although ergothioneine is found in small amounts in some foods, mushrooms are by far the richest dietary source. And here is what is super interesting about ERGO: the human body has a dedicated transport system to absorb and utilizing ERGO.¹

Whenever nature creates a dedicated transport system for a dietary compound, it deserves attention. And here are top 5 things you absolutely must know about ERGO:

• It is a leading longevity compound found almost exclusively in mushrooms.
• The body has a dedicated transporter for ERGO for its absorption and utilization, indicating a unique biological importance.
• ERGO is concentrated in certain tissues at higher levels to provide strong protection against oxidative stress, including the brain, eyes, liver, kidneys, bone marrow, red blood cells, and immune cells.
• Higher blood ERGO levels are associated with healthier aging, better cognitive function, and lower mortality risk.
• ERGO is available as as dietary supplement, but eating mushrooms is the most economical and beneficial way to obtain ERGO. 

·   Why Scientists Are Calling Ergothioneine a Longevity Vitamin

ERGO was discovered in 1909, but I first learned about it back in 2018, when a famous biochemist, Dr. Bruce Ames, referred to it as a  'longevity vitamin.' Ames used this term to describe dietary compounds that may not cause an obvious short-term deficiency disease when intake is low, but may still be required for optimal long-term health. Ergothioneine fits this concept perfectly.^2-5

While there is no recognized ergothioneine deficiency disease in the same way there is scurvy for vitamin C or rickets for vitamin D, research has shown chronically low ergothioneine intake reduces the body's ability to protect tissues from age-related oxidative and inflammatory stress.^2-5

The hypothesis that ERGO is an essential nutrient for human is compelling because the body actively transports, retains, and concentrates ergothioneine in vulnerable tissues. When the body creates a dedicated transporter for a dietary compound, it usually means that compound matters. And since we can’t make ERGO in our body, we must rely on dietary intake to meet this physiological need. That is the very definition of an essential vitamin.

Ergothioneine Is Not Just Another Antioxidant

ERGO is special. The transport feature alone separates ERGO from many dietary antioxidants. Many antioxidants show impressive effects in test tubes but are poorly absorbed, rapidly metabolized, or fail to reach meaningful concentrations in the tissues where they are needed most.

ERGO is different because the body actively takes it up. It is not merely floating around randomly after a meal; it is selectively accumulated throughout the body, especially into highly metabolically active tissue like the brain and liver.^7,8

The special ERGO transporter is known as the organic cation transporter novel 1 (OCTN1). It is produced by the SLC22A4 gene to promote the absorption of ERGO from the gut into the bloodstream and from the blood into individual cells. OCTN1 also helps concentrate ERGO into cells where oxidative stress can be high such as the brain, white and red blood cells, liver, eyes, and kidneys. It also raises mitochondrial ERGO content. Nature wants us to use this gift for health!

ERGO belongs to a class of sulfur-containing compounds known as thiols, a group that also includes important cellular protectants such as glutathione and coenzyme Q10. What distinguishes ERGO from many other thiols is its small molecular size and its ability to be distributed widely throughout the body. ERGO shares some common features with glutathione, but ERGO is a single, unique amino acid, while glutathione contains three amino acids bound together.

Through its specialized transport system, ERGO is taken up by cells and accumulates not only in the cellular fluid but also within mitochondria, the structures responsible for energy production. This broad cellular distribution allows ergothioneine to help support antioxidant defenses throughout the body and within each individual cell.

Human studies have demonstrated that ingesting or supplementing with ERGO increases circulating blood levels and enhances overall thiol status, suggesting a potential role in supporting cellular resilience and protection against oxidative stress.^7-9

Ergothioneine, Mitochondria, and Cellular Resilience

Mitochondrial function is central to healthy aging. Mitochondria generate cellular energy, regulate redox balance, influence inflammatory signaling, and help determine whether cells remain resilient under stress. Mitochondrial dysfunction is recognized as one of the hallmarks of aging.

Ergothioneine may support mitochondrial resilience because it is concentrated in tissues with high energy demands and oxidative exposure. Laboratory studies suggest that ergothioneine helps protect cells and mitochondrial against oxidative stress, metal-induced damage, and inflammatory insults.

The Mushroom-Longevity Connection: Human Data

Mushrooms have been part of traditional diets for centuries, especially in Asian and European cultures. The longevity of a population (e.g., a “Blue Zone”) may be related to dietary mushroom (ergothioneine) intake. In other words, people appear to live longer in areas where mushroom ingestion is highest. The folklore of many mushrooms, particularly in traditional medicines, is as a longevity promoter.

Modern research is now beginning to verify the longevity promotion effect of mushrooms. For example, in an analysis of nationally representative of U.S. adults from NHANES III, mushroom intake was associated with a lower risk of all-cause mortality compared with no mushroom intake after adjustment for demographic, lifestyle, and dietary factors. The investigators also reported a dose-response relationship, suggesting that greater mushroom intake was linked to lower risk.

The biological plausibility of this association is strong because mushrooms are rich in ergothioneine, but they are also rich in glutathione, fibers, beta-glucans, and other compounds involved in longevity promotion, antioxidant actions, and immune regulation.^10,11 In fact, the mushroom-longevity link is likely the result of multiple mushroom constituents working together. That is exactly why dietary intake should be emphasized over supplementation as the primary strategy.

Ergothioneine and Brain Health

The brain is one of the most metabolically active organs in the body. It consumes large amounts of oxygen, contains abundant polyunsaturated fatty acids, and is vulnerable to oxidative stress. These features make brain tissue an important target for nutritional strategies that support antioxidant defenses and mitochondrial function like ERGO.

There is emerging data on the role of low ERGO levels being linked to both cognitive and functional (physical) decline in older adults. These studies suggest that ergothioneine status may be a meaningful marker of brain health and resilience as well as longevity.^12-15 I would not be surprised to see blood tests to determine ERGO status becoming as popular as vitamin D3 blood tests.

Ergothioneine and Cardiovascular Health

Cardiovascular aging involves oxidative stress, inflammatory signaling, endothelial dysfunction, and metabolic changes. Ergothioneine has attracted interest because it may help support antioxidant defenses in vascular tissues and may be associated with better metabolic health.

Preclinical studies, a major detailed metabolic study, and a population-based study indicate ERGO exerts several mechanisms associated with a reduced mortality and decreased risk of cardiovascular disease that would justify the human evidence.^16,17

Mushrooms and the Immune System

Immune aging is characterized by a gradual decline in immune precision combined with increased inflammatory tone. This combination is sometimes called immunosenescence and inflammaging. Mushrooms are particularly relevant because they contain beta-glucans, compounds that interact with immune cells and help support normal immune function. ERGO may complement these mushroom compounds by supporting cellular antioxidant defenses in immune cells. ¹⁸  

Eat Mushrooms: The Food-First Ergothioneine Boosting Strategy

Mushrooms are the key dietary source of ERGO as they represent about 95% of the total dietary intake. Other foods with modest levels of ERGO include oat bran, black or red beans, and organ meats (e.g., liver and kidney). So, dietary intake of mushrooms is the most practical and biologically logical way to increase ERGO intake. Mushrooms provide ERGO in a natural food matrix along with many other compounds that support health. This is why a food-first strategy is so important. An ERGO supplement can provide ERGO, but it cannot fully replicate the complexity of mushrooms.

A recent chemical analysis of common mushrooms detected thousands of  bioactive compounds and metabolites. The better-known compounds include not only ergothioneine, but also beta-glucans that support immune function, prebiotic fibers that nourish the microbiome, glutathione that supports antioxidant defenses, B vitamins involved in energy metabolism, selenium for antioxidant function, and potassium for cardiovascular health. And more compounds are continuing to be discovered.¹⁹

The ERGO content of mushrooms varies by species and growing conditions.^20,21 The table below estimates ergothioneine intake from both a 3.5 and 8-ounce serving of fresh mushrooms. The 8-oz serving is generous serving, but it provides a practical way to effective boost ERGO intake through diet.

Cooking, Storage, and Preparation

From a dietary standpoint, increasing mushroom intake is simple. I have found that simply sautéing an 8-ounce package of fresh mushrooms in olive oil to create a side dish is the easiest and best way to boost mushroom intake. Of course you can also mushrooms to soups, salads, stir-fries, pasta sauces, grain bowls, tacos, and vegetable dishes.

I also recommend consuming a variety of mushrooms rather than relying on one type. King oyster, oyster, maitake, shiitake, lion's mane, portobello, cremini, and white button mushrooms can all contribute to your intake.

Mushrooms are generally best cooked. Cooking improves texture, flavor, and digestibility. Sauteeing, roasting, grilling, or simmering mushrooms in soups are all excellent options.

ERGO is relatively stable compared and does not break down with cooking. with many antioxidants, but levels can still vary with storage and preparation. Fresh mushrooms should be stored in breathable packaging in the refrigerator and used within a few days for best quality. Avoid soaking mushrooms in water for long periods, as this can affect texture and potentially reduce water-soluble compounds. Wipe or briefly rinse them and cook promptly.

Pair mushrooms with other longevity foods. Olive oil, garlic, onions, herbs, cruciferous vegetables, legumes, and whole grains all complement mushrooms well and create meals that support metabolic health, gut health, and healthy aging.

Suggested Ways to Add More Mushrooms to Your Diet

• Sauté in olive oil add herbs and garlic for additional benefits.
• Add shiitake or oyster mushrooms to vegetable stir-fries.
• Use chopped mushrooms in taco meat, chili, or pasta sauce to reduce meat content while preserving flavor.
• Roast maitake, portabello, or king oyster mushrooms with olive oil, garlic, and herbs.
  
• Add cremini or portobello mushrooms to omelets, frittatas, and breakfast scrambles.
• Use lion's mane as a seafood-like or meat-like substitute in sauteed dishes.
  
• Add mixed mushrooms to soups, stews, and grain bowls.
• Keep dried shiitake mushrooms available for broths and sauces.

Recommended ERGO Intake: Dietary Intake Versus Supplementation

There is no official recommended dietary allowance for ergothioneine, but my estimation is that a target intake is 5-10 mg daily. That target is easily hit with a practical goal to consume an 8-oz serving of mushrooms 3 to 5 servings per week, using a variety of mushrooms. For individuals who enjoy mushrooms, daily intake is easily able to provide meaningful ERGO intake.

However, unlike many cultures, most people in the United States do not consume mushrooms daily. For example, the estimated intake level of ERGO in the United States is 1.1 mg/day compared to up to 4.6 mg/day in Italy. If someone does not see themselves increasing their mushroom intake for whatever reason, ERGO supplementation makes sense. However, for most people, my first recommendation is to get ERGO from your diet. Mushroom consumption provides context, synergy, and additional nutrients. And it generally is a more economical approach as well.

Who May Especially Benefit from ERGO?

Most adults can benefit from boosting ERGO intake by eating more mushrooms as part of a healthy diet. However, several groups may be especially interested in increasing ERGO intake: adults over 40 focused on healthy aging, individuals interested in cognitive health, people seeking metabolic support, those with low vegetable intake, and anyone following a longevity-oriented diet.

Mushrooms are also attractive for people reducing meat intake because they provide savory flavor and satisfying texture. Replacing a portion of red or processed meat with mushrooms may improve the overall quality of the diet. The NHANES III mortality analysis found that substituting one serving per day of mushrooms for one serving of red or processed meat was associated with a lower risk of all-cause mortality. This finding supports a simple dietary message: mushrooms can make the diet healthier not only by what they add, but also by what they replace.

CLOSING COMMENTS

Among all emerging longevity nutrients, ergothioneine may be one of the most overlooked. What makes it so compelling is not just that it acts as an antioxidant, but that the body has developed a dedicated transport system to capture and concentrate it. To me, that is a powerful clue. Nature usually does not create a specific transport system for a compound unless that compound serves an important purpose.

Now, I am a huge proponent of supplementation, but in this case, I do not believe it is necessary to take an ERGO supplement. Instead, I think the message should be eat more mushrooms. Mushrooms provide ergothioneine in its natural food matrix along with beta-glucans, glutathione, minerals, fibers, and many other protective compounds. This is exactly how nutritional science should be applied: identify the key compound, understand the mechanism, and then return to the food source whenever possible.

That said, there are also numerous examples where taking a supplement provides an advantage over trying to get the same level of a phytochemical or nutrient from a food source alone. But for ERGO, focus on the food source. After all, mushrooms are magical.  

References:

1. Gründemann D, Harlfinger S, Golz S, et al. Discovery of the ergothioneine transporter. Proc Natl Acad Sci U S A. 2005;102(14):5256-5261.

2. Ames BN. Prolonging healthy aging: longevity vitamins and proteins. Proc Natl Acad Sci U S A. 2018;115(43):10836-10844.

3. Beelman RB, Kalaras MD, Phillips AT, Richie JP Jr. Is ergothioneine a 'longevity vitamin' limited in the American diet? J Nutr Sci. 2020;9:e52.

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5. Syahputra RA, Ahmed A, Asriadi, et al. Ergothioneine as a functional nutraceutical: Mechanisms, bioavailability, and therapeutic implications. J Nutr Biochem. 2025 Nov;145:110006.

7. Weigand-Heller AJ, Kris-Etherton PM, Beelman RB. The bioavailability of ergothioneine from mushrooms (Agaricus bisporus) and the acute effects on antioxidant capacity and biomarkers of inflammation. Prev Med. 2012 May;54 Suppl:S75-8.

8. Cheah IK, Tang RMY, Yew TSZ, et al Administration of pure ergothioneine to healthy human subjects: uptake, metabolism, and effects on biomarkers of oxidative damage and inflammation. Antioxid Redox Signal. 2017;26(5):193-206.

9. Turck D, Bresson J-L, Burlingame B, Dean T, et al. Safety of synthetic l-ergothioneine (Ergoneine®) as a novel food pursuant to Regulation (EC) No 258/97. EFSA J. 2016;14(11):e04629.

10. Ba DM, Ssentongo P, Beelman RB, et al. Association of mushroom consumption with all-cause and cause-specific mortality among American adults: prospective cohort study findings from NHANES III. Nutr J. 2021;20(1):38.

11. Ba DM, Gao X, Al-Shaar L, et al. Prospective study of dietary mushroom intake and risk of mortality: results from continuous NHANES 2003-2014 and a meta-analysis. Nutr J. 2021;20(1):80.

12. Feng L, Cheah IK, Ng MMX, et al. The association between mushroom consumption and mild cognitive impairment: a community-based cross-sectional study in Singapore. J Alzheimers Dis. 2019;68(1):197-203.

13. Wu LY, Cheah IK, Tang RMY, et al. Low plasma ergothioneine predicts cognitive and functional decline in an elderly cohort attending memory clinics. Antioxidants (Basel). 2022;11(9):1717.

14. Cheah IK, Tang RMY, Yew TSZ, Lim KHC, Halliwell B. Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline. Biochem Biophys Res Commun. 2016;478(1):162-167.

15. May-Zhang LS, Auyeung TW, et al. Ergothioneine for cognitive health, longevity and healthy ageing: where are we now? Proc Nutr Soc. 2025;84:1-13.

16. Lam-Sidun D, Peters KM, Borradaile NM. Mushroom-Derived Medicine? Preclinical Studies Suggest Potential Benefits of Ergothioneine for Cardiometabolic Health. Int J Mol Sci. 2021 Mar 23;22(6):3246.

17. Smith E, Ottosson F, Hellstrand S, et al. Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease. Heart. 2020;106(9):691-697.

18. Valverde ME, Hernández-Pérez T, Paredes-López O. Edible mushrooms: improving human health and promoting quality life. Int J Microbiol. 2015;2015:376387.

19. Uffelman CN, Doenges KA, Armstrong M, et al. Metabolomics profiling of white button, crimini, portabella, lion's mane, maitake, oyster, and shiitake mushrooms using untargeted metabolomics and targeted amino acid analysis. Foods. 2023;12(15):2871.

20. Dubost NJ, Beelman RB, Peterson D, Royse DJ. Identification and quantification of ergothioneine in cultivated mushrooms by liquid chromatography-mass spectroscopy. Int J Med Mushrooms. 2006;8(3):215-222.

21. Kalaras MD, Richie JP Jr, Calcagnotto A, Beelman RB. Mushrooms: a rich source of the antioxidants ergothioneine and glutathione. Food Chem. 2017;233:429-433.