Ergothioneine clinical trial shows improved cognitive function

Blue California says potential ‘longevity vitamin’ demonstrated positive impact on cognitive function, memory and sleep.

Longevity ingredients company Blue California has announced the completion of a human clinical trial of its “ErgoActive” ergothioneine ingredient.

The company sponsored a double-blinded placebo-controlled study, which it claims has demonstrated the “positive impact” of ergothioneine on cognitive function, memory and sleep in healthy elderly subjects with subjective memory complaints. The trial involved daily supplementation for four months.

The results of study, conducted at a clinical research facility in Australia, have yet to be published, but Blue California tells us it has submitted an abstract to a major nutrition conference, scheduled for early July 2024, and intends to publish as soon as it can.

Longevity.Technology: Ergothioneine, an amino acid that is found mainly in mushrooms, has been shown to protect against oxidative damage and cell death [1], and its ability to cross the blood-brain barrier means could prove useful in treating neurodegenerative disorders where oxidative stress plays a key role in disease progression [2]. Ergothioneine’s antioxidant effects and anti-senescence, anti-inflammatory and anti-neurodegenerative properties have led to its being dubbed a ‘longevity vitamin’ [3].

However, ergothioneine cannot be synthesized by animals or plants, so it must be obtained from the diet. As well as mushrooms, plants that take ergothioneine up the soil (where it has been synthesized by bacteria), such as beans, nuts, oats are good sources, as well as meat and milk from animals that eat those plants, and, of course, supplements are also a way of onboarding this longevity vitamin.

Research suggests that inadequate ergothioneine levels may be linked to a wide range of health conditions, including cardiovascular disease, frailty, age-related cognitive decline, and neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Mushroom consumption and dietary ergothioneine intake have previously shown associations with reduced cognitive decline and potential lifespan extension.

Blue California claims that the unique molecular structure of ergothioneine provides stable and enduring antioxidant protection, making it a potentially useful ingredient for formulations combating oxidative stress.

Ergothioneine supports cognitive function // Blue California

Dr Linda May-Zhang, VP of Science and Innovation at Blue California told Longevity.Technology that findings from this trial indicate that ErgoActive ergothioneine supplementation supports aspects of cognitive function, helps prevent subjective memory decline, and enhances the ability to get sleep in a population of healthy older adults with subjective memory complaints over a four-month period.

“ErgoActive showed high bioavailability, resulting in significant and sustained elevations of plasma ergothioneine levels,” she explained. “In addition, ErgoActive intervention reduced liver enzymes ALT and AST, which provides additional evidence for supporting safety.”

May-Zhang says that the results of this short-term study provide multifaceted implications for ErgoActive supplementation to support healthy aging, and that Blue California is currently sponsoring another clinical trial examining the effect of ErgoActive supplementation on aspects of immune function, changes in the gut microbiome, metabolomics and markers of oxidative stress.

Dr Linda May-Zhang is VP of Science and Innovation at Blue California

Given ergothioneine’s neuroprotective and blood-brain barrier crossing abilities, might it play a role in Alzheimer’s therapy? Previous studies have established a potential connection of low plasma ergothioneine levels and an increased risk for mild cognitive impairment or neurodegenerative diseases, including Alzheimer’s disease, says May-Zhang.

“Ergothioneine has great potential to support cognitive functions across various cognitive conditions, which is promising given its status as generally recognized as safe for certain doses and uses, and its availability on the market as a dietary supplement,” she explained.

“The need for future clinical trials is evident, aiming to explore the further benefit of ergothioneine in populations with mild cognitive impairment or neurodegenerative diseases. However, it is important to note that ergothioneine, while beneficial, is currently used as a dietary supplement, not a medicinal drug,” she said, adding that individuals diagnosed with neurodegenerative disorders should consult their healthcare providers before incorporating ergothioneine or any other supplement into their health regimen.

There has been much focus, recently, on the gut-brain axis, with the connection between the gut microbiome and cognitive decline highlighting the complex communication between the gastrointestinal tract and the brain, impacting cognitive health.

“The composition of the gut microbiome can affect the production of neuroactive compounds including neurotransmitters and short-chain fatty acids, which play roles in brain function,” May-Zhang explains. “Imbalance in the gut microbiota can lead to increased systemic inflammation and intestinal permeability, potentially causing neuroinflammation and contributing to cognitive decline. Additionally, the gut microbiome influences stress responses, affecting brain function.”

She explained that ergothioneine has recently been identified as a potential metabolite produced by the gut microbiota, specifically by Lactobacillus reuteri, although this finding has not yet been replicated by other research groups.

“Ergothioneine as a microbial metabolite was thought play a role in the microbiota-gut-brain axis, possibly preventing stress-induced sleep disturbances,” May-Zhang explains. “Emerging research suggests that gut microbes may regulate or utilize ergothioneine, suggesting they may regulate ergothioneine levels in the gut or use it for their own benefit.” May-Zhang references a nascent area of investigation that is looking at whether the gut microbiota influences tissue levels of ergothioneine, and which suggests a possible link between ergothioneine and the gut-brain axis in mediating cognitive function and broader health outcomes.

“Given the promising outcomes of preclinical studies and our recent human trial, we anticipate that ongoing and future clinical research will uncover more benefits of ergothioneine to human health,” she said, adding that the company welcomes partnerships for forthcoming clinical trials, as Blue California is aiming to expand its understanding and applications of ergothioneine’s health benefits.

[1] https://pubmed.ncbi.nlm.nih.gov/10566875/
[2] https://pubmed.ncbi.nlm.nih.gov/28300670/
[3] https://www.pnas.org/doi/10.1073/pnas.1809045115

Photos/graphic courtesy of Blue California