Blue California Publishes Peer-Reviewed Human Clinical Trial

Rancho Santa Margarita, CA (June 30, 2025) - Blue California announces the publication of its landmark clinical trial evaluating ErgoActive^® ergothioneine in the peer-reviewed journal Nutraceuticals. This randomized, double-blind, placebo-controlled study is the first dose-ranging clinical trial of ergothioneine to assess its impact on cognitive function, sleep quality, and physiological biomarkers in healthy older adults.

ErgoActive^® is Blue California’s high-purity, nature-identical L-ergothioneine, produced via sustainable precision fermentation with FDA-notified GRAS (GRN #734). A naturally occurring amino acid antioxidant found in mushrooms and other foods, ergothioneine is gaining global attention as a “longevity vitamin” due to its potential role in neuroprotection, mitochondrial function and healthy aging.

Clinical Trial Highlights Cognitive and Physiological Benefits

A total of 147 adults aged 55–79 with subjective memory complaints (but no dementia) were randomized to receive 10 mg or 25 mg/day of ErgoActive^® or placebo for 16 weeks. Assessments included the CNS Vital Signs cognitive domains, subjective memory, sleep quality, plasma ergothioneine, leukocyte telomere length, and safety.

Key Findings¹:

• Plasma ergothioneine increased ~3–6-fold (10 mg) and ~6–16-fold (25 mg) by weeks 4 and 16, confirming excellent bioavailability
• Subjective prospective memory and sleep initiation improved dose-dependently, with positive trends with 10 mg and significant effects at 25 mg (p < 0.05)
• Reaction time improved in 10 mg and 25 mg treatment groups that varied with time (p < 0.05)
• Early within-group increase in composite memory at week 4 in the 25 mg group
• A within-group increase in telomere length at 10 mg was observed in female participants
• Safe and well-tolerated, with significant reductions in plasma ALT and AST (p < 0.05), suggesting improved liver function

Despite high baseline cognitive scores (neurocognitive index median = 105) and baseline ergothioneine levels above the theoretical threshold proposed to delineate ‘healthy’ from ‘unhealthy’², meaningful improvements were observed in both subjective and physiological outcomes, highlighting the potential for ergothioneine to benefit even high-functioning older adults and supporting the generalizability of these findings.

“This publication reflects years of investment in building the scientific foundation for ergothioneine,” said Dr. Linda May-Zhang, VP of Science & Innovation at Blue California and co-author of the study. “We focused on healthy individuals with subjective memory complaints, a group often considered at higher risk for cognitive decline, yet still within the window for early intervention. 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.”

Driving Consumer Relevance

Interest in healthy aging has never been higher. According to market reports, the global brain health supplements market is projected to reach $23.4 billion by 2030³, while sleep solutions are experiencing rapid growth due to rising awareness of their role in longevity and mental performance. Consumers over 50 are particularly motivated to address memory concerns, sleep difficulties, and age-related decline.

ErgoActive^® meets this demand by offering clinically substantiated benefits spanning cognitive and sleep health, well-aligned with the evolving healthspan and wellness market, which increasingly prioritizes clinically backed ingredients.

Previous clinical studies have suggested benefits of ergothioneine for learning performance and neuronal injury biomarkers in older adults with mild cognitive impairment⁴, as well as sleep quality improvements in healthy adults at doses of 8–20 mg/day^5,6. This new study strengthens and extends the evidence base by demonstrating that daily ergothioneine supplementation leads to dose-dependent improvements in subjective memory and sleep in healthy older adults.

A Broader Commitment to Healthy Aging Research

This study was conducted as part of Blue California’s broader ErgoActive^® Research Program for Healthy Aging and Longevity, a long-term initiative supporting both company-sponsored and investigator-led research through academic partnerships, clinical trials, preclinical research, and material grants. The program reflects Blue California’s commitment to advancing ergothioneine science through transparent, rigorous, and collaborative research.

“This trial was conducted at Australia’s national science agency, CSIRO, and represents a successful example of cross-continental collaboration to advance ergothioneine science,” continued Dr. May-Zhang. “We are especially grateful to work with high-caliber investigators like Dr. Ian Zajac and Dr. Naomi Kakoschke, and our independent biostatistician Dr. Barbara Kuhn-Sherlock, whose expertise and contributions were instrumental to this study.

About ErgoActive^®

ErgoActive^® is Blue California’s branded, high-purity L-ergothioneine ingredient, produced via sustainable precision fermentation. With excellent water solubility and a neutral taste profile, ErgoActive^® is highly versatile, compatible with tablets, capsules, soft gels, gummies, functional foods, and beverages.

Read the full study here: https://www.mdpi.com/1661-3821/5/3/15

Learn more about ErgoActive^®:  https://bluecal-ingredients.com/ergothioneine/

References:
1. Zajac IT, Kakoschke N, Kuhn-Sherlock B, May-Zhang LS. The Effect of Ergothioneine Supplementation on Cognitive Function, Memory, and Sleep in Older Adults with Subjective Memory Complaints: A Randomized Placebo-Controlled Trial. Nutraceuticals. 2025; 5(3):15. 

2. Halliwell B, Cheah I.  Are age-related neurodegenerative diseases caused by a lack of the diet-derived compound ergothioneine?  Free Radical Biology and Medicine. 2024; 217: 60-67. 

3. Grand View Research. Brain Health Supplements Market Size, Share & Trends Analysis Report By Product (Natural Molecules, Vitamins & Minerals), By Application (Memory Enhancement, Attention & Focus), By Region, And Segment Forecasts, 2023 – 2030. Report ID: GVR-2-68038-866-4

3. Yau YF, Cheah IK, Mahendran R, et al. Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study. Journal of Alzheimer’s Disease. 2024;102(3):841-854. 

4. Katsube M, Watanabe H, Suzuki K, et al. Food-derived antioxidant ergothioneine improves sleep difficulties in humans. Journal of Functional Foods. 2022; 95: 105165. 

5. Okumura H, Araragi Y, Nishioka K, et al. Estimation and Validation of an Effective Ergothioneine Dose for Improved Sleep Quality Using Physiologically Based Pharmacokinetic Model. Food Science & Nutrition. 2025; 13(6): e70382.