Ergothioneine

Human intervention studies

• In a National University of Singapore study of healthy volunteers given pure ergothioneine (Cheah 2017), it was avidly absorbed and retained, and markers of oxidative damage and inflammation (allantoin, 8-hydroxy-2'-deoxyguanosine, 8-iso-prostaglandin F2alpha, protein carbonyls and C-reactive protein) trended down, but most changes were not significant (PMID: 27488221).
• In a randomized crossover trial at Penn State in 10 healthy men (Weigand-Heller 2012), mushroom meals delivered ergothioneine into red blood cells and showed a trend toward a smaller rise in blood triglycerides after the meal, while total antioxidant capacity (ORAC) fell (PMID: 22230474).
• Yau 2024, a randomized double-blind placebo-controlled pilot at the National University of Singapore, tested 25 mg three times a week for one year in 19 adults aged 60 or older with mild cognitive impairment. The registered primary outcomes were ergothioneine uptake, safety, oxidative damage and inflammation (ClinicalTrials.gov NCT03641404). Safety markers did not change; as secondary outcomes, scores for learning on the Rey Auditory Verbal Learning Test improved and plasma neurofilament light, a marker of nerve cell damage, stayed stable while it rose significantly with placebo (PMID: 39544014).
• The Okumura 2025 paper, from Japan, was company-funded. In an 8-week study of 28 people given 5 or 10 mg a day, blood levels were used to build a pharmacokinetic model. In a randomized double-blind placebo-controlled trial of 100 adults given 8 mg a day or placebo for 16 weeks, the primary measure, MRI-based brain healthcare quotients, did not differ between groups, while two factors of a sleep questionnaire (feeling refreshed and sleep length) improved more with ergothioneine. The research was funded by the company where five of the eight authors worked (PMID: 40475978).
• In 10 healthy men at the National University of Singapore (Toh 2014), a shiitake mushroom diet raised plasma ergothioneine for more than 48 hours and modestly increased the kidney clearance of a single dose of gabapentin, from 76.9 to 91.1 mL/min, without changing total exposure (PMID: 24168107).

Observational studies

• The Malmo Diet and Cancer study at Lund University followed 3,236 adults without cardiovascular disease or diabetes for a median of 21.4 years. Ergothioneine was the plasma metabolite most strongly linked to a health-conscious eating pattern; each 1 standard deviation higher level was associated with lower risk of coronary disease (hazard ratio 0.85), cardiovascular death (0.79) and death from any cause (0.86) (PMID: 31672783).
• In 470 older adults from Singapore memory clinics followed for up to 5 years, lower plasma ergothioneine was associated with poorer cognition at baseline and, in people without dementia, with faster decline in function, memory, executive function, attention, visuomotor speed and language; the association was largely explained by cerebrovascular disease and brain atrophy (PMID: 36139790).
• A frailty study of 19 older patients by Kyoto University and the Okinawa Institute of Science and Technology found ergothioneine among the blood metabolites lower in frail than in non-frail patients (PMID: 32295884).
• In the Hunter Community Study of 439 adults aged 55 to 85 in Australia, serum ergothioneine was lower at older ages (partial correlation -0.15) (PMID: 24392160).

Animal lifespan studies

• In a 2024 Kanazawa University mouse study, male C57BL/6J mice given ergothioneine in drinking water from 7 weeks of age (36 per group) lived longer than controls (log-rank p<0.001); median survival was 704 against 605 days (16 percent longer), and age-related losses in body weight, fat mass and movement speed at 88 weeks were smaller (PMID: 38446314). Only male mice were tested, and the authors declared no competing interests (PMID: 38446314).
• In a 2025 study of worms and aged rats, ergothioneine extended worm lifespan and mobility, and in aged rats it improved exercise endurance and muscle mass and raised muscle NAD+ (PMID: 39842434).
• In a 2022 fruit fly study at South China Agricultural University, ergothioneine extended fly lifespan across genetic backgrounds and both sexes, an effect that depended on gut microbes; one author was from a biotechnology company (PMID: 34877949).
• Deleting a putative ergothioneine transporter in a 2013 worm knockout study shortened worm lifespan, but ergothioneine uptake was not impaired and extra ergothioneine did not rescue the worms, so the authors concluded that ergothioneine transport did not explain the effect (PMID: 24074059).

The 'longevity vitamin' proposal

• Paul and Snyder at Johns Hopkins suggested in 2010 that ergothioneine may represent a new vitamin, because it comes only from the diet and its depletion harmed cells (PMID: 19911007).
• In 2018 Bruce Ames, at Children's Hospital Oakland Research Institute, proposed a class of 'longevity vitamins', nutrients needed for proteins that protect against long-term damage, and reviewed the case for ergothioneine as one of 10 putative longevity vitamins, alongside pyrroloquinoline quinone, queuine and several carotenoids (PMID: 30322941).
• In follow-up proposals, the Penn State group asked whether ergothioneine is a 'longevity vitamin' limited in the American diet (PMID: 33244403), and the Singapore group proposed that low body ergothioneine raises the risk of neurodegenerative and possibly other age-related diseases (PMID: 38492784).
• The proposal has limits. Classical vitamins were identified through deficiency diseases, and because ergothioneine is present in most foods, the harm caused by lacking it has been difficult to assess (PMID: 32051057, PMID: 34619979). A 2026 review listed its metabolism, mechanisms and the factors that control body levels as questions needing more research (PMID: 42632425). No trial testing whether ergothioneine intake changes lifespan or rates of age-related disease in people was found.

Registered trials without results

A Stanford University trial is testing ergothioneine against placebo for 12 weeks in 28 people with kidney failure, with red blood cell ergothioneine as the primary outcome (ClinicalTrials.gov NCT06487546), and a National University of Singapore trial plans to give golden oyster mushroom powder, a source of ergothioneine, to 600 adults for 24 months with a cognitive test as the primary outcome (ClinicalTrials.gov NCT07775833). Both were listed as recruiting on 27 October 2026.

Animal toxicology

In the safety assessment reviewed by the European Food Safety Authority, a 90-day rodent toxicity study (OECD Test Guideline 408) set a no-observed-adverse-effect level of 800 mg per kg of body weight a day for synthetic L-ergothioneine, and a screening study found no effects on reproduction or development (PMID: 32625352).

Gaps

No human trial data in pregnancy or breastfeeding were found; the European conclusion for those groups rests on animal toxicology and intake estimates (PMID: 32625352). Drug interaction data are limited to one study with gabapentin (PMID: 24168107).