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Lion's Mane on Cognition Impairment

According to the 2023 Alzheimer’s Disease Facts and Figures report, more than 6 million Americans are living with Alzheimer’s [15]. Even younger populations are affected, with 5 to 6% of cases comprising of early onset before 65 years old. [8] The lifetime risk of Alzheimer’s at age 45 is 1 in 5 for women and 1 in 10 for men. This rises to 1 in 9 people aged 65 and older [15]. Though this disease can affect many, the promise of a cure is currently slim. 244 compounds have been tested from 2002-2012 in 413 Alzheimer’s clinical trials; only 1 has been approved [1]. Even that one cannot stop the progression of Alzheimer’s. Since a cure is far from being realized, a shift is occurring away from finding a treatment, and instead focusing on prevention [11]. Lion’s Mane has been of interest due to its natural origins and wide range of benefits.

What is Lion's Mane?

Lion’s Mane, scientific name Hericium erinaceus, is a natural mushroom identified by its long spines. Considered a “medicinal mushroom,” lion's mane is an established candidate to promote brain health [3]. The mushroom has been known to have nootropic effects and can be added to dietary formulas and has been used in supplements, like Focase. Hericenones and erinacines are two active ingredients in Lion’s Mane that are proven to modulate the biosynthesis of nerve growth factor (NGF) in nerve cells in vitro [5]. There are also studies demonstrating potent antioxidant benefits [4, 13, 14]. Due to its natural origins and potential health benefits, Lion's mane is being evaluated for the possibility of a less intrusive strategy against cognitive issues.

Lion’s Mane Significantly Increased Cognitive Function in Older Adults with Mild Cognitive Impairment [9]

Mori et al. conducted a double-blind, parallel-group, placebo-controlled study with 50–80-year-old Japanese men & women who were diagnosed with mild cognitive impairment. This study evaluated the efficacy of Lion’s Mane on cognitive impairment. The participants were divided into 2 groups of 15, with half taking a placebo, and the other taking four 250 mg tablets three times a day for 16 weeks. The results: Even at week 8, the group showed significantly increased scores on the cognitive function scale compared to the placebo, with the significant increase also occurring at weeks 12 and 16. But, after 4 weeks of not taking Lion’s Mane, the scores significantly decreased. There were no adverse effects of taking Lion’s Mane.

Lion’s Mane Showed Significant Benefit of Decreasing Cognitive Decline in Participants with Mild Alzheimer's Disease [7]

Li et al. evaluated the efficacy and safety of Lion’s Mane mycelia on patients with mild Alzheimer’s disease. The double-blind placebo-controlled study started with a 3-week non-drug period, then 49 weeks with the participants taking three 350 mg capsules with 5 mg of erinacine A per gram every day or an identical placebo. After 49 weeks:

  • The placebo group’s Cognitive Abilities Screening Instrument score decreased significantly while the Lion’s Mane group’s Mini-Mental State Examination score increased significantly.
  • The placebo group also had a significant decrease in brain-derived neurotrophic factor and significantly increased amyloid-beta peptide 1-40.
  • The average apparent diffusion coefficient (ADC) values from the arcuate fasciculus (ARC) region in the dominant hemisphere significantly increased in the placebo group, while there was no significant difference in the Lion’s Mane group when comparing their baseline. This indicates that there was more disorganization of the neural structure in the placebo group.
  • The ADC values from the parahippocampal cingulum (PHC) region in the dominant hemisphere of the Lion’s Mane group decreased significantly, while there was no significant difference when comparing the baseline of the placebo group. This implies a more well-organized neural structure in the Lion’s Mane-treated group.
  • The Lion’s Mane group showed higher scores in the CASI (Cognitive Abilities Screening Instrument), MMSE (Mini-Mental State Examination), and IADL (Instrumental Activities of Daily Living) evaluations when compared to the placebo group. 
  • Only 7 participants left the study. 3 were unsatisfied with the efficacy (1 was from the placebo group) and 4 were due to the presence of side effects (1 was from the placebo group) like nausea, abdominal discomfort, or skin rash. The side effects could not be ruled to be from the lion’s mane since it is common for participants at the sample age to have other medications prescribed to them for other treatments.

Their Conclusion:

  • “Based on the results of this pilot, randomized, double-blinded, controlled study, subjects with mild AD showed a significant benefit in reducing cognitive decline and improving contrast sensitivity after oral administration of three 5 mg/g EAHE mycelia capsules per day for 49 weeks when compared with placebo.”
  • The researchers state that the reduction in cognitive decline may be associated with the improved biomarkers that resulted, such as calcium, albumin, Hb, Hcy, SOD, BDNF, APOE4, and α-ACT. The benefits may also be associated with the reduced structural deterioration in the ARC and PHC regions after treatment with Lion’s Mane.
Lion’s Mane Improves Cognitive Function in Healthy Adults:

Lion’s Mane has shown promise for Alzheimer’s, but its benefits have extended past that to healthy participants as well. Saitsu et al evaluated the improvement of cognitive functions of Lion’s Mane fruiting body in 39 participants after 12 weeks in a randomized double-blind placebo-controlled parallel-group comparative study in 2019 [12]. The participants took either a placebo or four 800 mg of the fruiting body of Lion’s Mane.

After seeing the results, the study discusses the possible mechanisms responsible for the benefits. Hericenones in lions mane have been noted to activate the synthesis of NGF in the astrocytes in the late 1990s [5]. NGF has been looked at to be a possible treatment for Parkinson's disease by direct injection into the brain but this is very invasive and has it's risks.

Lions Mane as a Convenient, Safe Common Supplement for Brain Health

These findings shed light on Lion’s Mane's remarkable potential as a natural, convenient, and non-invasive strategy to support brain health against cognitive decline. With its roots in traditional medicine and backed by rigorous scientific inquiry, Lion’s Mane represents a beacon of hope in the quest for effective interventions against neurodegenerative diseases and improving brain health.

References

1. Cummings, Jeffrey L et al. “Alzheimer's disease drug-development pipeline: few candidates, frequent failures.” Alzheimer's research & therapy vol. 6,4 37. 3 Jul. 2014, doi:10.1186/alzrt269

2. Docherty, Sarah et al. “The Acute and Chronic Effects of Lion's Mane Mushroom Supplementation on Cognitive Function, Stress and Mood in Young Adults: A Double-Blind, Parallel Groups, Pilot Study.” Nutrients vol. 15,22 4842. 20 Nov. 2023, doi:10.3390/nu15224842

3. Gargano, Maria Letizia et al. “The Role of Medicinal Mushrooms in Brain Cancer Therapies: Review.” International journal of medicinal mushrooms vol. 23,5 (2021): 13-20. doi:10.1615/IntJMedMushrooms.2021038277

4. Han, Zi-Hua et al. “Evaluation of in vivo antioxidant activity of Hericium erinaceus polysaccharides.” International journal of biological macromolecules vol. 52 (2013): 66-71. doi:10.1016/j.ijbiomac.2012.09.009

5. Kawagishi, H et al. “Erinacines A, B and C, strong stimulators of nerve growth factor (NGF)-synthesis, from the mycelia of Hericium erinaceum.” Tetrahedron Letters. (1994)

6. Li, I-Chen et al. “Acute and developmental toxicity assessment of erincine A-enriched Hericium erinaceus mycelia in Sprague-Dawley rats.” Drug and chemical toxicology vol. 41,4 (2018): 459-464. doi:10.1080/01480545.2017.1381110 https://pubmed.ncbi.nlm.nih.gov/29359595/

7. Li, I-Chen et al. “Prevention of Early Alzheimer's Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study.” Frontiers in aging neuroscience vol. 12 155. 3 Jun. 2020, doi:10.3389/fnagi.2020.00155 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283924/

8. Mendez, Mario F. “Early-onset Alzheimer Disease and Its Variants.” Continuum (Minneapolis, Minn.) vol. 25,1 (2019): 34-51. doi:10.1212/CON.0000000000000687

9. Mori, Koichiro et al. “Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial.” Phytotherapy research : PTR vol. 23,3 (2009): 367-72. doi:10.1002/ptr.2634 (use the abstract only since full not available anymore)

10. Nagano, Mayumi et al. “Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake.” Biomedical research (Tokyo, Japan) vol. 31,4 (2010): 231-7. doi:10.2220/biomedres.31.231

11. Robinson, Louise et al. “Dementia: timely diagnosis and early intervention.” BMJ (Clinical research ed.) vol. 350 h3029. 16 Jun. 2015, doi:10.1136/bmj.h3029

12. Saitsu, Yuusuke et al. “Improvement of cognitive functions by oral intake of Hericium erinaceus.” Biomedical research (Tokyo, Japan) vol. 40,4 (2019): 125-131. doi:10.2220/biomedres.40.125 https://www.jstage.jst.go.jp/article/biomedres/40/4/40_125/_pdf/-char/en

13. Wong, Jing-Yang et al. “Gastroprotective Effects of Lion's Mane Mushroom Hericium erinaceus (Bull.:Fr.) Pers. (Aphyllophoromycetideae) Extract against Ethanol-Induced Ulcer in Rats.” Evidence-based complementary and alternative medicine : eCAM vol. 2013 (2013): 492976. doi:10.1155/2013/492976

14. Zhang, Zuofa et al. “Antioxidant and hepatoprotective potential of endo-polysaccharides from Hericium erinaceus grown on tofu whey.” International journal of biological macromolecules vol. 51,5 (2012): 1140-6. doi:10.1016/j.ijbiomac.2012.09.002

15. “2023 Alzheimer's disease facts and figures.” Alzheimer's & dementia : the journal of the Alzheimer's Association vol. 19,4 (2023): 1598-1695. doi:10.1002/alz.13016