Prevention of Early Alzheimer’s Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study

Summary & key facts

In a small, early clinical trial, people with mild Alzheimer’s disease took three capsules a day made from Hericium erinaceus mycelia (a mushroom) that contained a compound called erinacine A, for 49 weeks. The study was double-blind, so neither participants nor researchers knew who got the real capsules or a placebo. Compared with the placebo group, the people who took the erinacine A capsules showed better scores on several thinking and daily-function tests, had better contrast vision, showed different patterns on brain scans, and did not show some of the blood-marker declines seen in the placebo group. Four people stopped the trial because of stomach upset, nausea, or a skin rash. This was a pilot study, so the results are promising but not final and need confirmation in larger studies.

Key facts:

• The trial lasted 49 weeks after a 3-week no-drug screening period and was double-blind and randomized, meaning people were randomly assigned to get either the mushroom extract capsules or matching placebo pills and neither side knew who got which.
• Participants took three capsules a day; each capsule weighed 350 mg and contained erinacine A at a concentration of about 5 mg per gram.
• People on erinacine A showed better scores on the Mini-Mental State Examination, a common short test of thinking, while the placebo group had a drop in a different cognitive test called the Cognitive Abilities Screening Instrument.
• There was a significant difference between groups on a test of daily living skills (Instrumental Activities of Daily Living), with the erinacine A group doing better than the placebo group.
• The erinacine A group had better contrast sensitivity, meaning they could distinguish shades and edges better than the placebo group after 49 weeks.
• Blood markers that fell in the placebo group over the study — including calcium, albumin, apolipoprotein E4, hemoglobin, and brain-derived neurotrophic factor — did not fall in the erinacine A group; the placebo group also showed increases in alpha1-antichymotrypsin and amyloid-beta 1-40 that the erinacine A group did not.
• Brain imaging showed that one measure of water movement in a language-related brain pathway (the arcuate fasciculus) increased in the placebo group but not in the erinacine A group, while another measure decreased in the erinacine A group in a memory-related tract (the parahippocampal cingulum); these changes suggest different effects on brain tissue over time.
• Four people left the study because of side effects (abdominal discomfort, nausea, or skin rash); apart from those, no other adverse events were reported in the trial.
• The authors conclude that erinacine A–enriched Hericium erinaceus mycelia appeared safe and showed potential cognitive and brain-related benefits in mild Alzheimer’s, but they describe this as preliminary and imply larger studies are needed to confirm the findings.

Abstract

OBJECTIVE: mycelia (EAHE) capsules (350 mg/capsule; containing 5 mg/g erinacine A active ingredient) per day for the treatment of patients with mild Alzheimer's Disease (AD). METHODS: This study comprised a 3-week no-drug screening period, followed by a 49-week double-blind treatment period with 2-parallel groups in which eligible patients were randomized to either three 5 mg/g EAHE mycelia capsules per day or identical appearing placebo capsules. Cognitive assessments, ophthalmic examinations, biomarker collection, and neuroimaging were followed throughout the study period. RESULTS: After 49 weeks of EAHE intervention, a significant decrease in Cognitive Abilities Screening Instrument score was noted in the placebo group, a significant improvement in Mini-Mental State Examination score was observed in the EAHE group and a significant Instrumental Activities of Daily Living score difference were found between the two groups. In addition, EAHE group achieved a significantly better contrast sensitivity when compared to the placebo group. Moreover, only the placebo group observed significantly lowered biomarkers such as calcium, albumin, apolipoprotein E4, hemoglobin, and brain-derived neurotrophic factor and significantly elevated alpha1-antichymotrypsin and amyloid-beta peptide 1-40 over the study period. Using diffusion tensor imaging, the mean apparent diffusion coefficient (ADC) values from the arcuate fasciculus region in the dominant hemisphere significantly increased in the placebo group while no significant difference was found in the EAHE group in comparison to their baselines. Moreover, ADC values from the parahippocampal cingulum region in the dominant hemisphere significantly decreased in the EAHE group whereas no significant difference was found in the placebo group when compared to their baselines. Lastly, except for four subjects who dropped out of the study due to abdominal discomfort, nausea, and skin rash, no other adverse events were reported. CONCLUSION: Three 350 mg/g EAHE capsules intervention for 49 weeks demonstrated higher CASI, MMSE, and IADL scores and achieved a better contrast sensitivity in patients with mild AD when compared to the placebo group, suggesting that EAHE is safe, well-tolerated, and may be important in achieving neurocognitive benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04065061.

Topics

Antioxidants, Aging, Portulaca oleracea Fungal Biology and Applications Medicinal Plants and Neuroprotection

Categories

Health Sciences Medicine Pharmacology

Tags

Alternative medicine Gastroenterology Internal medicine Medicine Pathology Placebo

Substances

Other