Ergothioneine

Several observational studies suggest a connection between ergothioneine levels and cognition, but no clinical trials have been conducted testing the ability of ergothioneine supplementation to impact cognitive health. Our search identified:

• 1 randomized clinical trial in healthy adults looking at effects on sleep
• 4 observational studies on the relationship between ergothioneine levels and cognition
• 1 observational study on the relationship between mushroom intake and cognition
• Numerous preclinical studies on possible mechanisms of action

Mushroom consumption can be considered a rough proxy for ergothioneine intake. In a study of 2,840 participants aged 60 or older assessing the relationship between mushroom consumption and cognition, participants with the highest mushroom intake showed better performance on various cognitive tests relative to those with the lowest intake [1]. In a study including 470 adults over age 50, performance on several cognitive domains, including executive function and memory was better in participants with higher plasma levels of ergothioneine [2]. While these studies suggest a connection between ergothioneine levels and brain health, it has not yet been shown in clinical studies whether supplementation can prevent or slow cognitive decline. One clinical trial in 92 healthy adults aged 40 to 75 years old found that ergothioneine supplementation improved sleep quality [3], which could potentially impact brain health.

For Dementia Patients

Blood levels of ergothioneine have been shown to be low in patients with mild cognitive impairment and dementia [2; 4; 5]. Dementia patients with the lowest ergothioneine levels tend to show faster rates of decline and brain volume loss [6]. However, these observational studies do not tell us the direction of the relationship. Ergothioneine could be lower because of brain cell loss. There is no evidence to date indicating whether ergothioneine supplementation can moderate these declines.

Ergothioneine has been granted generally recognized as safe (GRAS) status by the FDA [7]. No adverse effects were reported following short-term ergothioneine supplementation in small clinical trials assessing safety and sleep, with 45 and 92 participants, respectively [3; 8]. Large scale clinical trials or studies assessing the long-term effects of ergothioneine supplementation have not yet been conducted. Ergothioneine may interact with some medications, including the anticonvulsants gabapentin and pregabalin [9].

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

Ergothioneine is available as oral supplements. Manufacturer recommended doses range from 5 to 20 mg per day. Doses up to 25 mg have been safely used in clinical studies, but there is no clinical evidence to indicate whether these doses improve health outcomes. The European Commission concluded that ergothioneine supplements are likely safe up to 30 mg/day for adults and 20 mg/day for children [10]. Ergothioneine can also be obtained through the diet. Mushrooms contain the highest levels of ergothioneine, especially, king oyster, maitake, oyster, shiitake, and porcini mushrooms [11; 12]. Other foods rich in ergothioneine include liver, black beans, red beans, and oat bran [12].

Information on dosing, safety, and drug interactions for ergothioneine from WebMD

Full scientific report (PDF) on Cognitive Vitality Reports

1. Ba DM, Gao X, Al-Shaar L et al. (2022) Mushroom intake and cognitive performance among US older adults: the National Health and Nutrition Examination Survey, 2011-2014. The British journal of nutrition 128, 1-8.
2. Wu LY, Kan CN, Cheah IK et al. (2022) Low Plasma Ergothioneine Predicts Cognitive and Functional Decline in an Elderly Cohort Attending Memory Clinics. Antioxidants (Basel, Switzerland) 11.
3. Katsube M, Watanabe H, Suzuki K et al. (2022) Food-derived antioxidant ergothioneine improves sleep difficulties in humans. Journal of Functional Foods 95, 105165.
4. Cheah IK, Feng L, Tang RMY et al. (2016) Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration? Biochemical and Biophysical Research Communications 478, 162-167.
5. Teruya T, Chen YJ, Kondoh H et al. (2021) Whole-blood metabolomics of dementia patients reveal classes of disease-linked metabolites. Proc Natl Acad Sci U S A 118.
6. Wu LY, Cheah IK, Chong JR et al. (2021) Low plasma ergothioneine levels are associated with neurodegeneration and cerebrovascular disease in dementia. Free radical biology & medicine 177, 201-211.
7. (2011) GRAS Notice.
8. Cheah IK, Tang RM, Yew TS et al. (2017) Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation. Antioxid Redox Signal 26, 193-206.
9. Gründemann D, Hartmann L, Flögel S (2022) The ergothioneine transporter (ETT): substrates and locations, an inventory. FEBS letters 596, 1252-1269 .
10. Turck D, Bresson J-L, Burlingame B et al. (2016) Safety of synthetic l-ergothioneine (Ergoneine®) as a novel food pursuant to Regulation (EC) No 258/97. EFSA Journal 14, e04629.
11. Feeney MJ, Dwyer J, Hasler-Lewis CM et al. (2014) Mushrooms and Health Summit proceedings. The Journal of nutrition 144, 1128s-1136s.
12. Ey J, Schömig E, Taubert D (2007) Dietary Sources and Antioxidant Effects of Ergothioneine. Journal of Agricultural and Food Chemistry 55, 6466-6474.