Analysis of 19 studies, including cellular, animal and human clinical and observational studies published over the past 10 years, indicated that ergothioneine (ET) plays a role in neurotransmission and neuroprotection, thereby offering cognitive improvements.
The compound’s antioxidative, anti-inflammatory and antisenescence properties were linked to its potential to slow age-related neurodegenerative disorders, according to scientists from Universiti Malaya in Kuala Lumpur.
Writing in Inflammopharmacology, the researchers said ergothioneine’s potential is “undeniable” but noted that some key knowledge gaps remain, notably around the “optimal doses of ET for cognitive enhancement and neuroprotection… [and] the need to investigate the bioavailability of ET across different formulations, such as pure ET and dietary sources.”
Previous studies have noted the ongoing challenge of effectively delivering ergothioneine to the brain.
“Hence, strategies to enhance bioavailability and overcome the blood–brain barrier are critical for translating these promising discoveries into clinical success,” they noted.
Ergothioneine
A sulfur-containing amino acid, ergothioneine functions as an antioxidant. Mushrooms are one of its primary sources in nature.
The science of L-ergothioneine has been developing over the last 20 years. A 2005 paper by Gründemann et al. published in PNAS reported the existence of a specific transporter for ergothioneine, where cells accumulate the amino acid and “avidly retain it”.
“In the human body, the ability to absorb, distribute, and retain [ergothioneine] depends entirely on this specific transporter,” wrote Gründemann in a later review published in Preventive Medicine. “Its existence implies a beneficial role for [ergothioneine] and its blockade or inactivation in animal models may be essential to at last understand the function of [ergothioneine].”
A 2010 paper by Solomon Snyder, MD, Professor of Neuroscience at Johns Hopkins University School of Medicine, describes the amino acid as a possible vitamin: “Evidence that [ergothioneine] is a physiologic antioxidant raises the question of its ‘status’ in biology. Despite its high concentration and ubiquitous presence, all mammalian ET derives from dietary sources. The existence of [ergothioneine transporter] establishes [ergothioneine] as an important normal body constituent. In this sense, [ergothioneine] probably fits the definition of a vitamin.
“Classic criteria require that depletion of a putative vitamin elicit pathological consequences. No pathological syndrome of [ergothioneine] deficiency has been reported. However, lack of such reports may simply reflect the relative dearth of [ergothioneine] research as well as the difficulty of depleting [ergothioneine].”
Commercialization of the ingredient was hampered for many years by the cost, but recent advances in precision fermentation have led to the launch of cost-effective ergothioneine by companies like Blue California and NNB Nutrition.
Commenting on the new review, Shawn Wells, CSO of NNB Nutrition, which markets ergothioneine under the brand name Mitoprime, told NutraIngredients: “Ergothioneine is emerging as a powerhouse micronutrient for cognitive health, showing impressive neuroprotective, anti-inflammatory and antioxidant capabilities. This review underscores its potential to slow cognitive decline by reducing oxidative stress, promoting neuronal growth, enhancing neurotransmission and facilitating the clearance of toxic proteins such as amyloid-beta.
“As ergothioneine levels naturally decline with age and correlate with neurodegenerative conditions, incorporating ET-rich foods or supplements could significantly support cognitive longevity and brain health.”
Hallmarks of Aging
There are 12 hallmarks of aging, outlined in a 2023 review by Professor Carlos López-Otín, and dietary ingredients can potentially act on one or more of these processes. From a nutritional perspective, the main processes that have received attention are mitochondrial dysfunction, telomere shortening, chronic inflammation and cellular senescence.
Source: Inflammopharmacology, 2025. doi: 10.1007/s10787-025-01746-6. “The role of Ergothioneine in cognition and age-related neurodegenerative disease: a systematic review”. Authors: N.H. Takhor and C.W. Phan.