Is Ergothioneine Your Next Longevity Supplement?

Ergothioneine, a mushroom-derived antioxidant, has shown the potential to improve lifespan and stave off cognitive decline. Before adding it to your longevity supplement stack, take a look at what science says.

From Reishi to Lion's Mane, mushrooms found their way into the booming anti-aging supplement market. Recently, there has been an increasing interest in ergothioneine (ET), an amino acid commonly found in mushrooms like king oysters and shiitake.

Humans don't synthesize ergothioneine and receive it from the diet. However, Americans consume only about 1 mg of ET daily, mainly due to low mushroom intake.

Human ergothioneine blood levels start decreasing after the age of 60, and such a reduction is associated with more rapid cognitive decline. Meanwhile, high plasma ergothioneine levels have been linked to a lower mortality risk, among other benefits.

Studies indicate that ergothioneine supplementation is safe, but can it prolong human healthspan and even lifespan?

Can ergothioneine extend the human lifespan?

Ergothioneine's longevity benefits are mostly studied in animal models such as worms and rats. While these studies are important for medical research, findings from animals may not always apply to humans.

In a 2025 trial, ergothioneine supplementation extended the lifespan and enhanced mobility in worms, improving stress resistance and reducing age-associated biomarkers.

The same trial included aged rats, which saw enhanced exercise endurance, muscle mass, and blood vessel growth following the ET administration. Higher levels of NAD+, a compound that plays a major role in cellular metabolism and declines with age, were observed in the muscles of mice that received ET.

According to a 2024 study, male mice given daily oral supplementation of ergothioneine showed significantly lower age-related declines in weight and fat mass compared to mice that didn't receive ET. Mice on ergothioneine also experienced slower declines in movement velocities, an important measurement of muscle strength, as well as slower age-related impairments in learning and memory ability.

A study by Swedish researchers that included 3,236 adults associated higher blood plasma levels of ergothioneine with a lower risk of coronary disease, cardiovascular mortality, and death from all causes. There is also data associating low levels of ergothioneine with dementia and Parkinson's disease.

However, researchers Barry Halliwell and Irwin Cheah warn in FEBS Letters that correlation does not imply causation, meaning that studies do not specify the direction of the relationship. They argue that while low ET levels may predispose to disease, disease could also lead to low ET levels.

For example, disease could lead to changes in the diet, causing less ET to be consumed. Another possible explanation is changes in gut microbiota, which may influence ergothioneine uptake and accumulation in the body.

Some studies have suggested that ergothioneine may protect against inflammation and, due to its antioxidant properties, against free radicals, which are cell-damaging molecules, as per the 2022 review. Ergothioneine may also work as a cytoprotectant, guarding cells against harmful substances and protecting against apoptosis, a type of cell death.

ET may protect against cognitive decline

While more research is needed to understand whether ergothioneine supplementation can extend human lifespans, it is likely to help slow down or prevent cognitive decline.

A recent double-blinded, randomized, and placebo-controlled study published in the Journal of Alzheimer's Disease included 19 individuals 60 years or older with mild cognitive impairment (MCI). People with MCI may have trouble with memory and thinking but are still able to do most everyday activities independently.

The participants took either 25 mg of ergothioneine or a placebo three times a week for one year. Compared with the placebo group, individuals on ergothioneine showed improvements in Enhanced Rey Auditory Verbal Learning Test performance, assessing working and long-term memory and learning abilities.

They also showed stabilized levels of neurofilament light chain (NfL). The increased levels of protein NfL are thought to be a biomarker of neuronal damage in neurodegenerative disease.

Ergothioneine intake did not alter clinical safety markers such as blood counts and kidney and liver function, indicating its safety for human consumption.

A study published in 2019 looked at the data of 600 Chinese seniors over the age of 60 living in Singapore. It found that those who consume more than two standard portions of mushrooms (about 150 grams) weekly may be 50% less likely to have MCI. The study authors said they believe that it may be down to ergothioneine.

Some could benefit from ET supplements

Robert Beelman, Ph.D., a professor emeritus of food science at Penn State, takes ergothioneine himself in addition to eating mushrooms.

Beelman tells Wellnesspulse, "I believe there is sufficient evidence to recommend taking an ergothioneine supplement, especially for individuals who do not consume a lot of mushrooms and might be prone to chronic neurological diseases."

Dr. Irwin Cheah, a senior research fellow at the National University of Singapore, says there is associative evidence that low blood levels in human subjects correlate with a wide range of neurodegenerative and other age-related diseases.

However, correlation does not necessarily indicate that low ergothioneine levels cause disease, and the number of studies in humans with supplementation is very limited at present.

Further clinical studies are urgently needed to establish the preventative and therapeutic capabilities of ergothioneine prior to recommending this as a supplement for the promotion of healthy longevity.

Cheah

He says ET supplementation would benefit individuals with low blood levels of ergothioneine the most. However, ergothioneine levels are not routinely measured in health screens, and there are no official guidelines for what blood levels are considered an ergothioneine deficiency as yet.

Is it safe to use ergothioneine supplements?

Human studies measured up to 25 mg of ergothioneine doses, and no side effects were observed.

The Food and Drug Administration (FDA) granted ergothioneine a Generally Recognized as Safe designation, which means a product has been adequately shown to be safe under the conditions of its intended use.

Xiaoying Tian, a postgraduate researcher at the University of Leeds, says ergothioneine should be safe to take within the recommendations of the European Food Safety Authority (EFSA) and the FDA.

According to the EFSA, no adverse effects were observed at the consumption of 800 mg/kg body weight per day. The agency concluded that ergothioneine supplements are likely safe up to a daily dose of 30 mg for adults and 20 mg for children above the age of 3.

Speaking of risks, Tian points to a 2022 study suggesting that human fecal bacteria can metabolize ergothioneine to trimethylamine N-oxide, which may play a role in developing several conditions. However, this only occurred in one sample out of 25.

Some plant foods can be excellent sources of ergothioneine, with the highest ET levels found in king oysters, maitakes, oysters, shiitakes, and porcini mushrooms.

Liver, black beans, red beans, and oat bran also contain ergothioneine.

Does ergothioneine have other benefits?

Ergothioneine supplementation may benefit the skin. A 2024 study included 77 women, on average 48 years old, who took either 25 mg of ergothioneine or a placebo daily for 12 weeks.

At the end of the trial, the ergothioneine group had better wrinkle and texture scores than the placebo group. Plasma ET concentrations were higher in the supplementation group and were associated with higher skin moisture content and lower transepidermal water loss on the arm.

Noteworthy, the study was funded by the company that sells mushrooms used in the trial, and three researchers were employed by the company at the time of the trial.

In a 2022 trial, 92 adults aged 40 to 75 years with reported high anxiety and sleep complaints were randomized into taking 20 mg of ergothioneine or placebo daily for four weeks. A survey revealed that ergothioneine significantly alleviated sleeping difficulties.

The verdict

Ergothioneine supplements appear to be safe, although more clinical trials are needed to determine if they offer longevity benefits in humans. Nevertheless, older individuals with mild cognitive decline are likely to benefit from ET supplementation or adding more ergothioneine-rich foods to their diets.

Always consult a medical professional when trying new supplements to your daily routine.