Li I.C., Chang H.H., Lin C.H., Chen W.P., Lu T.H., Lee L.Y., Chen Y.W., Chen Y.P., Chen C.C., Lin D.P.C. Prevention of Early Alzheimer's Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study. Frontiers in Aging Neuroscience. 2020;12:155.
Rationale
Erinacine A is a diterpenoid from H. erinaceus mycelium that crosses the blood–brain barrier and stimulates NGF/BDNF cascades. Rodent AD models showed reduced amyloid pathology and improved spatial memory. Before this work there were no long-term clinical data on erinacine A-standardized H. erinaceus mycelium in early AD patients.
Methods
A pilot randomized double-blind placebo-controlled single-center study (Taiwan). Included 49 outpatients aged 50–85 with mild AD (MMSE 15–25) on stable standard anti-dementia therapy. Participants were randomized to EAHE (3 × 350 mg mycelium capsules containing 5 mg/g erinacine A; ≈1.05 g/day mycelium, ≈5.25 mg/day erinacine A) or placebo for 49 weeks. Primary outcomes: cognition (MMSE), functional independence (Instrumental Activities of Daily Living, IADL), inflammation and oxidative-stress biomarkers. Cerebral atrophy by MRI was assessed in a subgroup.
Results
Of 49 randomized patients, 41 completed the protocol (21 EAHE, 20 placebo). In the EAHE group mean MMSE significantly rose from a baseline 15.0 to 18.5 (p = 0.035) while placebo barely changed. IADL improved significantly more in EAHE than placebo (p = 0.042). MRI showed less cerebral atrophy in the EAHE subgroup than placebo. Pro-inflammatory markers and malondialdehyde fell in the EAHE group. The safety profile did not differ from placebo.
Conclusions
49 weeks of erinacine A-standardized H. erinaceus mycelium in patients with mild AD was associated with improved cognitive and functional measures and slowed cerebral atrophy versus placebo. The results support the hypothesis that erinacine A provides the mycelium's neuroprotective action in humans and justify larger phase II studies.
Identifiers & funding
- DOI: 10.3389/fnagi.2020.00155.
- PMID: 32581767.
- PMCID: PMC7283924.
- Registration: ClinicalTrials.gov NCT04065061.
- Corresponding author: Chin-Chu Chen, Grape King Bio Ltd., Taiwan.
Worth noting
The study was funded by an industrial sponsor (Grape King Bio) — noted in the card; caution applies. The sample (49 randomized) is small for clinically meaningful AD outcomes; treat results as preliminary. The main contribution: demonstrating that standardized mycelium with a fixed erinacine A content produces a detectable clinical effect over 49 weeks, and that MRI atrophy can serve as an objective biomarker. Compared with other H. erinaceus RCTs in cognitive impairment (Mori 2009 in MCI — 16 weeks, Saitsu 2019 — 12 weeks), the 49-week design is a necessity for AD, where natural progression is slow.