Lion’s Mane to Combat Cognitive Decline

NGF acts on a specific group of neurons in the brain, called cholinergic neurons, that utilize the chemical messenger, or neurotransmitter, acetylcholine. They play a key role in the neuropathology of Alzheimer’s disease (AD).

Mori and colleagues investigated the impact of LM on laboratory mice with beta-amyloid-generated learning and memory impairment.² The mice were injected with beta amyloid in their ventricles, the fluid-filled spaces of their brains. They were given food containing LM over 23 days. A maze test and a novel object recognition test evaluated their memory. Investigators found that LM protected mice from developing learning and memory deficits brought on by exposure to beta amyloid.

Tsai-Teng and colleagues examined the effects of LM extracts on brain pathology and repair in a transgenic mouse model of Alzheimer’s disease.³ The extracts, given by mouth over 30 days, reduced the concentration of beta amyloid plaques, specifically acting on the more loosely constructed periphery of the plaque and on soluble amyloid, which dissolves in water. LM also increased levels of insulin-degrading enzyme,^c which not only breaks down insulin but also degrades amyloid.

Microglia and reactive astrocytes^d were reduced in number, both in the brain surface layers, called the cortex, and the hippocampus, the deep brain structure necessary for memory formation. Furthermore, LM extracts increased levels of NGF and stimulated brain cell proliferation, known as neurogenesis, in the hippocampus. Nesting skills (building a nest by shredding material), which become impaired due to the neuropathologic changes that occur in the brains of AD transgenic mice, were restored by intake of LM extracts.

A study by Ratto and colleagues explored the effects of LM extracts not only on age-induced cognitive decline in an elderly mouse model but also its impact on concurrent motor regression.⁴ Both cognitive and motor deterioration occur during aging simultaneously and are a part of the process called geriatric frailty. Investigators found that elderly mice given LM mushroom extract for two months showed significant improvement in recognition memory (but not locomotor performance) compared to elderly control mice, thus showing resistance to age-related cognitive decline. At the cellular level, there was increased neurogenesis both in the hippocampus and the cerebellum, a part of the brain devoted to balance and coordinated movements.

A clinical study evaluating the impact of LM on cognitive performance in patients diagnosed with mild cognitive impairment was published in 2009, with positive results.⁵ The substance was given as a concentrate powder tablet at a dosage of 250 mg and administered three times per day. Investigators enrolled 30 Japanese subjects between the ages of 50 and 80 who were randomly assigned to receive either LM tablets or placebo for 16 weeks. The cognitive test used to measure intellectual function was the Revised Hasegawa Dementia Scale (HDS-R). LM significantly improved HDS-R scores at weeks 8, 12, and 16, compared to placebo. Four weeks after stopping LM, scores significantly declined. No adverse effects from LM were detected using laboratory testing.

In June 2020, Li and colleagues published a study investigating the efficacy of LM in improving cognitive performance in mild Alzheimer’s disease.⁶ Investigators enrolled 49 subjects with probable Alzheimer’s and randomly assigned them to receive either three 350-mg capsules of LM extract daily or placebo. A total of 41 subjects completed the study, which was conducted over 49 weeks after a three-week screening period. Several cognitive assessment tests were used including the Cognitive Abilities Screening Instrument (CASI), the Mini-Mental State Examination (MMSE), and the Instrumental Activities of Daily Living (IADL). Investigators also looked at serum biomarkers and MRI brain sequences to assess structural integrity on a cellular- and circuit-wide level. They also tested vision, including both acuity and contrast sensitivity.

In the placebo group, cognitive performance analysis showed a significant decrease in CASI scores over time compared to baseline. In the LM group, after 49 weeks, MMSE scores significantly increased, as did IADL scores.

An earlier study in 2019 by Saitsu and colleagues also revealed improvement in MMSE scores following LM administration for 12 weeks to 16 healthy participants over age 50 compared to 15 subjects on placebo.⁷

Biomarker results suggest possible neuroprotection. Brain-derived neurotrophic factor, which is required for brain cell maintenance, growth, and repair and comes from the same family of proteins as NGF, decreased significantly over time only in the placebo group. On the other hand, homocysteine (a marker of inflammation negatively correlated with cognitive performance) significantly decreased only in the LM group.

Similarly, brain imaging data pointed to greater structural integrity in circuits important to memory and language processing in the LM group. A consistent trend toward improved contrast sensitivity on vision testing was detected in the LM group but not in the control group.

Overall, there is a small but growing body of evidence that LM might have cognitive protective properties. One can purchase a bottle of 60 500-mg capsules of Host Defense Lion’s Mane at Sprouts for $29. Host Defense Lion’s Mane powder (100 g) costs $28. The liquid extract (1 fl oz) sells on Amazon for $15.

a. NGF is one member of a family of neurotrophic factors that promote growth, maintenance, and proliferation of neurons (the defining cells of the nervous system).

b. Axons are the cable-like extensions from neurons that convey electrical signals that are converted to chemical signals at the bulbous tip of the axon, while dendrites are receiving projections that receive the chemical messages sent from neighboring neurons.

c. Insulin is the protein messenger that tells cells to take up glucose (the building block of sugar).

d. Microglia are immune cells unique to the central nervous system that induce inflammation in reaction to amyloid plaque build-up. Astrocytes are helper cells in the central nervous system that also increase when neurons are destroyed.

1. Spelman K, Sutherland E, Bagade A. Neurological activity of lion’s mane (Hericium erinaceus). J Restor Med. 2017;6(1):19-26. doi: 10.14200/jrm.2017.6.0108.

2. Mori K, et al. Effects of Hericium erinaceus on amyloid β (25-35) peptide-induced learning and memory deficits in mice. Biomedical Research. 2011;32(1):67-72. doi: 10.2220/biomedres.32.67.

3. Tsai-Teng T, et al. Erinacine A-enriched Hericium erinaceus mycelium ameliorates Alzheimer’s disease-related pathologies in APPswe/PS1dE9 transgenic mice. J Biomed Sci. 2016;23(1):49. doi: 10.1186/s12929-016-0266-z.

4. Ratto D, et al. Hericium erinaceus improves recognition memory and induces hippocampal and cerebellar neurogenesis in frail mice during aging. Nutrients. 2019;11(4):715. doi: 10.3390/nu11040715.

5. Mori K, et al. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: A double‐blind placebo‐controlled clinical trial. Phytother Res. 2009;23(3):367-372. doi: 10.1002/ptr.2634.

6. Li I, et al. Prevention of early Alzheimer’s disease by erinacine A-enriched Hericium erinaceus mycelia pilot double-blind placebo-controlled study. Front Aging Neurosci. 2020;12:155. doi: 10.3389/fnagi.2020.00155.

7. Saitsu Y, et al. Improvement of cognitive functions by oral intake of Hericium erinaceus. Biomed Res. 2019;40(4):125-131. doi: 10.2220/biomedres.40.125.

8. Lakshmanan H, et al. Haematological, biochemical and histopathological aspects of Hericium erinaceus ingestion in a rodent model: a sub-chronic toxicological assessment.” J Ethnopharmacol. 2016;194:1051-1059. doi: 10.1016/j.jep.2016.10.084.

Dr. Ari Magill is a holistic neurologist and medical consultant based in Scottsdale, AZ. He received medical school training at University of Texas Southwestern in Dallas and residency training at the University of Arizona in Tucson. He is passionate about finding innovative treatments for cognitive impairment, emphasizing lifestyle change and natural supplements.