“This publication reflects years of investment in building the scientific foundation for ergothioneine,” said Dr. Linda May-Zhang, vice president of science & innovation at Blue California and co-author on the study. “These findings offer clinical evidence that ergothioneine supports neurocognitive and physiological resilience in aging humans and provide a strong foundation for future studies in populations with lower ergothioneine status or greater risk for age-related decline.”
Blue California, the first to produce L-ergothioneine via fermentation, launched its ErgoActive ingredient in 2015 as an alternative to chemical synthesis and mushroom extraction and received FDA Generally Recognized as Safe (GRAS) status in 2019.
Ergothioniene and the aging brain
Discovered in 1909 in the ergot fungus by French chemist Charles Tanret, ergothioneine is a sulfur-based amino acid found at its highest levels in mushrooms and fermented foods. Exclusively biosynthesized by fungi and mycobacteria, it is captured by plants through their roots and only available to humans through diet.
In 2005, Dirk Gründemann and his colleagues at the University of Cologne found that humans have a powerful and highly specific transporter for the uptake of ergothioneine—sparking a scientific stir around its potential as an essential micronutrient. A subsequent study by prominent biochemist Dr. Bruce Ames proposed the concept of ‘longevity vitamin’ and ergothioneine as one of several nutrients that may contribute to long-term health and reduced risk of age-related diseases.
In the realm of cognitive function, previous clinical studies have suggested the antioxidant benefits of ergothioneine for learning performance and neuronal injury biomarkers in older adults with mild cognitive impairment, as well as sleep quality improvements in healthy adults at doses of 8 to 20 mg/day.
This latest clinical trial, published in the journal Nutraceuticals, was conducted at Australia’s national science agency, CSIRO, as part of Blue California’s ErgoActive Research Program for Healthy Aging and Longevity. Launched in mid-2025 to formalize the company’s ongoing research investments and collaborations, it builds on in vitro research showing that ErgoActive inhibits shortening of telomeres (the caps on chromosomes) typically associated with oxidative stress and a biomarker of aging. Blue California has filed patents on these findings and on the therapeutic uses of ergothioneine for chronic conditions associated with heart disease, diabetes, cancer and viral illness including COVID-19.
Study details
The randomized, double-blind, placebo-controlled trial recruited 147 adults between the ages of 55 and 79 with subjective memory complaints, a group Dr. May-Zhang says is often considered at higher risk for cognitive decline, yet still within the window for early intervention.
Participants consumed either 10 mg/day of ErgoActive, 25 mg/day of ErgoActive or a placebo for 16 weeks and were evaluated for changes in composite memory (CNS Vital Signs) and other cognitive domains, subjective memory and sleep quality and blood biomarkers.
Supplementation with both doses of ergothioneine increased plasma levels over 16 weeks. Although not sustained, the 25 mg dose led to short-term memory improvement. Reaction time improved in both groups, in a time-dependent manner, but other domains showed null, variable or limited effects.
“The most significant finding was that participants taking ErgoActive showed a dose-dependent improvement in subjective prospective memory, while the placebo group declined,” Dr. May-Zhang said. “Prospective memory, the ability to remember to carry out planned actions like taking medication or following through on a task, is highly relevant to daily life. Although subjective measures are sometimes overlooked, they can be more sensitive to early cognitive changes than objective tests.”
The study also observed a dose-dependent improvement in participants’ subjective ability to fall asleep. Dr. May-Zhang noted this was particularly interesting as ergothioneine is not known to induce drowsiness. These findings align with two other interventional studies that reported benefits of ergothioneine on sleep quality.
While the trial did not directly measure mechanisms of action, preclinical research suggests several pathways by which ergothioneine supports brain health.
“Ergothioneine helps reduce oxidative stress and inflammation, supports mitochondrial health, promotes neurogenesis and even seems to regulate glutamate, an excitatory brain chemical,” Dr. May-Zhang said. “Together, these effects provide a strong rationale for the cognitive and sleep benefits observed.”
Expanding ergothioneine research and market
Blue California intends to pursue larger and longer studies to confirm these preliminary cognitive and sleep-related findings, particularly in populations with lower baseline ergothioneine levels or greater risk of decline.
Other research objectives include exploring broader aspects of healthy aging and how ergothioneine may benefit systems beyond the brain, such as immune function, metabolic health and physical performance.
Beyond company-initiated studies on cognitive health with CSIRO and another on immune function with the University of Southampton, Blue California collaborates with independent investigators at institutions including Columbia University, Stanford, Harvard and Australian Catholic University.
“Many of these projects remain early stage and confidential, but together they form the backbone of the ErgoActive Research Program, spanning cognition, sleep, immune function, mitochondrial health, physical performance and other domains relevant to healthy aging,” Dr. May-Zhang said. “Altogether, this trial is part of a broader mission to expand the evidence to support ergothioneine as a ‘longevity vitamin’ and a foundational nutrient for healthy aging.”
While Blue California notes that commercialization is still early stage due to the previous lack of clinical substantiation, it says that adoption is accelerating in a global ergothioneine market projected to grow from $40 million in 2023 to over $600 million by 2032. Several recent high profile product launches formulated with ErgoActive include Life Extension’s Mega L-Ergothioneine, Dr. Gundry’s Mighty Cell functional gummies and Longevity.Technology’s Fueling Longevity Today.
Source: Nutraceuticals. "Ergothioneine Supplementation on Cognitive Function, Memory, and Sleep in Older Adults with Subjective Memory Complaints: A Randomized Placebo-Controlled Trial." doi: 10.3390/nutraceuticals5030015. Authors:
