May 2023
Despite existing data revealing the nootropic effects of H. erinaceus, only a limited number of intervention studies have been conducted so far, while others are currently ongoing [16].
Recently, we studied the preventive effect during physiological aging on cognitive [40] and locomotor frailty [41] of the H. erinaceus primordium characterized by a high content of ERGO and the lack of erinacines and hericenones [42
5. H. erinaceus In Vitro Preclinical Studies and Molecular Mechanism Underlying the Nootropic Effects
In (over 65 years old, the functional deficiency of NGF is related to progressive neurodegeneration and dementia-like diseases. Natural compounds able to induce the NGF biosynthesis are considered potentially effective against cognitive disturbances, e.g., dementia [45]. In this context, the neuroprotective role of H. erinaceus extracts is crucial.
The gut microbiota and the brain communicate with each other through several mechanisms, and this bidirectional communication is named the gut-microbiome–brain axis.
In a pilot clinical study on 13 healthy adults, seven days of H. erinaceus dry powder in submerged culture displayed beneficial health effects on the GM detected as 16S ribosomal RNA. In particular, H. erinaceus upregulated the relative abundance of some short-chain fatty acid (SCFA)-producing bacteria and downregulated some pathobionts (Table 4) [112].
εκκρεμεί από 8. H. Erinaceus Pilot Clinical Trials on Cognitive Functions και μετάFew clinical studies have been conducted on H. erinaceus nootropic effects [125].
A pilot interventional study was conducted on 31 subjects over 50 years old that were healthy, and with normal cognitive functions after H. erinaceus oral administration. The dry powder of H. erinaceus sporophore (0.8 g four times a day, for 12 weeks) was tested in this randomized, double-blind placebo-controlled parallel-group comparative study [74]. Three different tests were used to assess the effects of H. erinaceus on cognitive functions: Mini Mental State Examination (MMSE), standard verbal-paired-associate learning test, and Benton visual retention. The first is an assessment of associative and episodic memory. H. erinaceus oral intake significantly improved cognitive functions and prevented deterioration. The authors concluded that H. erinaceus oral consumption is safe and seems a convenient method for preventing dementia so far. In a college-age cohort (n = 24), the 4-week-long ingestion of 10 g H. erinaceus/day did not elicit any statistically significant changes of either cognition nor metabolic flexibility markers [86].
Mild cognitive impairment (MCI) is typically considered the initial stage between the cognitive decline of normal aging and the more serious decline of dementia [126].
The efficacy of H. erinaceus oral administration for improving cognitive impairment was tested in a double-blind placebo-controlled parallel-group clinical trial of thirty Japanese patients diagnosed with MCI [73]. MCI was tested with the cognitive function scale, based on the Revised Hasegawa Dementia Scale (HDS-R). H. erinaceus was administrated for 16 weeks as four 250 mg tablets containing 96% of sporophore dry powder, three times a day. After 4 weeks of intake, cognitive functions were monitored. Compared with the placebo group, the H. erinaceus group showed significantly increased scores of the cognitive function scale (score value 22–25 vs. 30); meanwhile, after intake termination, the scores decreased significantly. The safety of H. erinaceus intake was tested through laboratory analysis and confirmed by the absence of adverse outcomes. Nonetheless, the bioactive compounds contained within H. erinaceus tablets used for this study have not been extensively addressed [73].
Patients with mild AD (n = 49) were investigated for their cognitive functions in a double-blind placebo-controlled parallel-group study. The oral administration consisted of 15 mg erinacine A per day as dried erinacine-A-enriched H. erinaceus mycelia (EAHE) [127]. Cognitive assessments, ophthalmologic examinations, biomarker collection, neuroimaging, and laboratory test analyses to check for safety were followed throughout. In the EAHE group, after 49 weeks of EAHE intervention, a significant improvement in the MMSE score was observed, and a significant Instrumental Activities of Daily Living score difference was found between the two groups [127].
In relation to blood markers, only the placebo group displayed a significantly lower amount of calcium, albumin, apolipoprotein E4, hemoglobin, and BDNF, and parallelly showed a significant increase in alpha1-antichymotrypsin and amyloid-beta peptide 1–40. Furthermore, in neuroimaging of the dominant hemisphere, the mean apparent diffusion coefficient values obtained from the arcuate fasciculus region was significantly enhanced in the placebo group. Any significant difference was determined in the EAHE group after intervention compared to the baseline level. Moreover, ADC values from the parahippocampal cingulum region were significantly diminished in the EAHE group [127].
9. ConclusionsTo sum up, the mass of scientific data reported leaves no doubt about the nootropic properties of H. erinaceus. It also clearly appears that different nootropic substances are present in both the H. erinaceus mycelium and sporophore. The efforts of our laboratory aimed to obtain standardized extracts by performing chemical analysis and/or through a metabolomics approach on specific bioactive compounds. We suggest that this could be a general practice to follow. In our in-depth thinking, among the bioactive compounds, ERGO is one of the most promising. This research activity is needed to obtain dietary supplements, functional foods, or drugs to promote a healthy brain. Furthermore, the pharmacologically active ingredients, as well as the mode of action, require further in-depth clinical investigation.
Erinacine A contained within the mycelium is one of the key components responsible for the H. erinaceus nootropic effects, as confirmed both in vitro, as well as in preclinical investigations in vivo. Moreover, sporophore extracts were proven to possess nootropic or neuroprotective power, too. In the above-reported pilot clinical studies, sporophore oral consumption was checked as a beneficial food, revealing an improvement of specific cognitive functions. To increase the array of nootropic substances even more, the free radical scavenger and cytoprotective powerful antioxidant ERGO, contained in both the mycelium and sporophore, attenuates oxidative stress and nitrosamine damage in an injured or aging brain.
More intriguingly, we want to underline that following H. erinaceus intervention, on top of the improved pathological phenotype consistently evidenced in clinical trials, the downstream molecular pathway responsible for the phenotypic rescue involves, as evidenced in vitro and in preclinical studies, the NGF and BDNF. However, we highlight the urgent need for additional in-depth clinical studies to clarify the mode of action by which H. erinaceus compounds are able to promote functional neurophysiological recovery in human, and assess the link between H. erinaceus, microbiota, and cognition in more detail.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218917/
- - -- - - - - -
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987239/
https://pubmed.ncbi.nlm.nih.gov/18844328/
https://www.google.com/search?q=hericium+dementia&client=firefox-b-d&sca_esv=559361602&ei=_ALmZLSxEu-Mxc8P1JmNgAo&start=10&sa=N&ved=2ahUKEwi0n7mY6_KAAxVvRvEDHdRMA6AQ8tMDegQIBBAE&biw=1958&bih=882&dpr=0.7
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133811/
https://galeapps.gale.com/apps/auth?userGroupName=googlescholar&da=true&origURL=https%3A%2F%2Fgo.gale.com%2Fps%2Flogout.do%3FuserGroupName%3Dgooglescholar%26page%3Dtrue%26prodId%3DAONE&prodId=AONE
https://www.frontiersin.org/articles/10.3389/fnagi.2020.00155/full
https://www.mycomedica.eu/hericium.html
https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Lions-Mane-Cognitive-Vitality-For-Researchers.pdf
https://www.centerforcognitivehealth.com/lions-mane-a-mushroom-to-remember/
https://www.jstage.jst.go.jp/article/biomedres/40/4/40_125/_article/-char/ja/
https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/hericium-erinaceus
https://access.portico.org/Portico/auView?auId=ark:%2F27927%2Fpjbf78xcsgs
Lion's mane dementia study
https://www.google.com/search?client=firefox-b-d&sca_esv=559361602&q=Lion%27s+mane+dementia+study&sa=X&ved=2ahUKEwi0n7mY6_KAAxVvRvEDHdRMA6AQ1QJ6BAhJEAE
Improvement of cognitive functions by oral intake of Hericium erinaceus
https://www.google.com/search?client=firefox-b-d&sca_esv=559361602&q=Improvement+of+cognitive+functions+by+oral+intake+of+Hericium+erinaceus&sa=X&ved=2ahUKEwi0n7mY6_KAAxVvRvEDHdRMA6AQ1QJ6BAhIEAE
Hericium erinaceus nerve regeneration
https://www.google.com/search?client=firefox-b-d&sca_esv=559361602&q=Hericium+erinaceus+nerve+regeneration&sa=X&ved=2ahUKEwi0n7mY6_KAAxVvRvEDHdRMA6AQ1QJ6BAhGEAE
Lion's mane Parkinson's study
https://www.google.com/search?client=firefox-b-d&sca_esv=559361602&q=Lion%27s+mane+Parkinson%27s+study&sa=X&ved=2ahUKEwi0n7mY6_KAAxVvRvEDHdRMA6AQ1QJ6BAhDEAE
Lion's Mane mild cognitive impairment
https://www.google.com/search?client=firefox-b-d&sca_esv=559361602&q=Lion%27s+Mane+mild+cognitive+impairment&sa=X&ved=2ahUKEwi0n7mY6_KAAxVvRvEDHdRMA6AQ1QJ6BAhHEAE
dementia lion's mane
https://www.google.com/search?client=firefox-b-d&q=dementia+lion%27s+mane
frontotemporal dementia lion's mane
https://www.google.com/search?client=firefox-b-d&q=frontotemporal+dementia+lion%27s+mane
lewy body dementia lion's mane
https://www.google.com/search?client=firefox-b-d&q=lewy+body+dementia+lion%27s+mane
lionesses dementia
https://www.google.com/search?client=firefox-b-d&q=lionesses+dementia
dementia AND (hericium OR lion's mane)
https://pubmed.ncbi.nlm.nih.gov/?term=dementia+AND+%28hericium+OR+lion%27s+mane%29&sort=date&size=200
Despite existing data revealing the nootropic effects of H. erinaceus, only a limited number of intervention studies have been conducted so far, while others are currently ongoing [16].
Recently, we studied the preventive effect during physiological aging on cognitive [40] and locomotor frailty [41] of the H. erinaceus primordium characterized by a high content of ERGO and the lack of erinacines and hericenones [42
5. H. erinaceus In Vitro Preclinical Studies and Molecular Mechanism Underlying the Nootropic Effects
In (over 65 years old, the functional deficiency of NGF is related to progressive neurodegeneration and dementia-like diseases. Natural compounds able to induce the NGF biosynthesis are considered potentially effective against cognitive disturbances, e.g., dementia [45]. In this context, the neuroprotective role of H. erinaceus extracts is crucial.
The gut microbiota and the brain communicate with each other through several mechanisms, and this bidirectional communication is named the gut-microbiome–brain axis.
In a pilot clinical study on 13 healthy adults, seven days of H. erinaceus dry powder in submerged culture displayed beneficial health effects on the GM detected as 16S ribosomal RNA. In particular, H. erinaceus upregulated the relative abundance of some short-chain fatty acid (SCFA)-producing bacteria and downregulated some pathobionts (Table 4) [112].
εκκρεμεί από 8. H. Erinaceus Pilot Clinical Trials on Cognitive Functions και μετάFew clinical studies have been conducted on H. erinaceus nootropic effects [125].
A pilot interventional study was conducted on 31 subjects over 50 years old that were healthy, and with normal cognitive functions after H. erinaceus oral administration. The dry powder of H. erinaceus sporophore (0.8 g four times a day, for 12 weeks) was tested in this randomized, double-blind placebo-controlled parallel-group comparative study [74]. Three different tests were used to assess the effects of H. erinaceus on cognitive functions: Mini Mental State Examination (MMSE), standard verbal-paired-associate learning test, and Benton visual retention. The first is an assessment of associative and episodic memory. H. erinaceus oral intake significantly improved cognitive functions and prevented deterioration. The authors concluded that H. erinaceus oral consumption is safe and seems a convenient method for preventing dementia so far. In a college-age cohort (n = 24), the 4-week-long ingestion of 10 g H. erinaceus/day did not elicit any statistically significant changes of either cognition nor metabolic flexibility markers [86].
Mild cognitive impairment (MCI) is typically considered the initial stage between the cognitive decline of normal aging and the more serious decline of dementia [126].
The efficacy of H. erinaceus oral administration for improving cognitive impairment was tested in a double-blind placebo-controlled parallel-group clinical trial of thirty Japanese patients diagnosed with MCI [73]. MCI was tested with the cognitive function scale, based on the Revised Hasegawa Dementia Scale (HDS-R). H. erinaceus was administrated for 16 weeks as four 250 mg tablets containing 96% of sporophore dry powder, three times a day. After 4 weeks of intake, cognitive functions were monitored. Compared with the placebo group, the H. erinaceus group showed significantly increased scores of the cognitive function scale (score value 22–25 vs. 30); meanwhile, after intake termination, the scores decreased significantly. The safety of H. erinaceus intake was tested through laboratory analysis and confirmed by the absence of adverse outcomes. Nonetheless, the bioactive compounds contained within H. erinaceus tablets used for this study have not been extensively addressed [73].
Patients with mild AD (n = 49) were investigated for their cognitive functions in a double-blind placebo-controlled parallel-group study. The oral administration consisted of 15 mg erinacine A per day as dried erinacine-A-enriched H. erinaceus mycelia (EAHE) [127]. Cognitive assessments, ophthalmologic examinations, biomarker collection, neuroimaging, and laboratory test analyses to check for safety were followed throughout. In the EAHE group, after 49 weeks of EAHE intervention, a significant improvement in the MMSE score was observed, and a significant Instrumental Activities of Daily Living score difference was found between the two groups [127].
In relation to blood markers, only the placebo group displayed a significantly lower amount of calcium, albumin, apolipoprotein E4, hemoglobin, and BDNF, and parallelly showed a significant increase in alpha1-antichymotrypsin and amyloid-beta peptide 1–40. Furthermore, in neuroimaging of the dominant hemisphere, the mean apparent diffusion coefficient values obtained from the arcuate fasciculus region was significantly enhanced in the placebo group. Any significant difference was determined in the EAHE group after intervention compared to the baseline level. Moreover, ADC values from the parahippocampal cingulum region were significantly diminished in the EAHE group [127].
9. ConclusionsTo sum up, the mass of scientific data reported leaves no doubt about the nootropic properties of H. erinaceus. It also clearly appears that different nootropic substances are present in both the H. erinaceus mycelium and sporophore. The efforts of our laboratory aimed to obtain standardized extracts by performing chemical analysis and/or through a metabolomics approach on specific bioactive compounds. We suggest that this could be a general practice to follow. In our in-depth thinking, among the bioactive compounds, ERGO is one of the most promising. This research activity is needed to obtain dietary supplements, functional foods, or drugs to promote a healthy brain. Furthermore, the pharmacologically active ingredients, as well as the mode of action, require further in-depth clinical investigation.
Erinacine A contained within the mycelium is one of the key components responsible for the H. erinaceus nootropic effects, as confirmed both in vitro, as well as in preclinical investigations in vivo. Moreover, sporophore extracts were proven to possess nootropic or neuroprotective power, too. In the above-reported pilot clinical studies, sporophore oral consumption was checked as a beneficial food, revealing an improvement of specific cognitive functions. To increase the array of nootropic substances even more, the free radical scavenger and cytoprotective powerful antioxidant ERGO, contained in both the mycelium and sporophore, attenuates oxidative stress and nitrosamine damage in an injured or aging brain.
More intriguingly, we want to underline that following H. erinaceus intervention, on top of the improved pathological phenotype consistently evidenced in clinical trials, the downstream molecular pathway responsible for the phenotypic rescue involves, as evidenced in vitro and in preclinical studies, the NGF and BDNF. However, we highlight the urgent need for additional in-depth clinical studies to clarify the mode of action by which H. erinaceus compounds are able to promote functional neurophysiological recovery in human, and assess the link between H. erinaceus, microbiota, and cognition in more detail.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218917/
- - -- - - - - -
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987239/
https://pubmed.ncbi.nlm.nih.gov/18844328/
https://www.google.com/search?q=hericium+dementia&client=firefox-b-d&sca_esv=559361602&ei=_ALmZLSxEu-Mxc8P1JmNgAo&start=10&sa=N&ved=2ahUKEwi0n7mY6_KAAxVvRvEDHdRMA6AQ8tMDegQIBBAE&biw=1958&bih=882&dpr=0.7
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133811/
https://galeapps.gale.com/apps/auth?userGroupName=googlescholar&da=true&origURL=https%3A%2F%2Fgo.gale.com%2Fps%2Flogout.do%3FuserGroupName%3Dgooglescholar%26page%3Dtrue%26prodId%3DAONE&prodId=AONE
https://www.frontiersin.org/articles/10.3389/fnagi.2020.00155/full
https://www.mycomedica.eu/hericium.html
https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Lions-Mane-Cognitive-Vitality-For-Researchers.pdf
https://www.centerforcognitivehealth.com/lions-mane-a-mushroom-to-remember/
https://www.jstage.jst.go.jp/article/biomedres/40/4/40_125/_article/-char/ja/
https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/hericium-erinaceus
https://access.portico.org/Portico/auView?auId=ark:%2F27927%2Fpjbf78xcsgs
Lion's mane dementia study
https://www.google.com/search?client=firefox-b-d&sca_esv=559361602&q=Lion%27s+mane+dementia+study&sa=X&ved=2ahUKEwi0n7mY6_KAAxVvRvEDHdRMA6AQ1QJ6BAhJEAE
Improvement of cognitive functions by oral intake of Hericium erinaceus
https://www.google.com/search?client=firefox-b-d&sca_esv=559361602&q=Improvement+of+cognitive+functions+by+oral+intake+of+Hericium+erinaceus&sa=X&ved=2ahUKEwi0n7mY6_KAAxVvRvEDHdRMA6AQ1QJ6BAhIEAE
Hericium erinaceus nerve regeneration
https://www.google.com/search?client=firefox-b-d&sca_esv=559361602&q=Hericium+erinaceus+nerve+regeneration&sa=X&ved=2ahUKEwi0n7mY6_KAAxVvRvEDHdRMA6AQ1QJ6BAhGEAE
Lion's mane Parkinson's study
https://www.google.com/search?client=firefox-b-d&sca_esv=559361602&q=Lion%27s+mane+Parkinson%27s+study&sa=X&ved=2ahUKEwi0n7mY6_KAAxVvRvEDHdRMA6AQ1QJ6BAhDEAE
Lion's Mane mild cognitive impairment
https://www.google.com/search?client=firefox-b-d&sca_esv=559361602&q=Lion%27s+Mane+mild+cognitive+impairment&sa=X&ved=2ahUKEwi0n7mY6_KAAxVvRvEDHdRMA6AQ1QJ6BAhHEAE
dementia lion's mane
https://www.google.com/search?client=firefox-b-d&q=dementia+lion%27s+mane
frontotemporal dementia lion's mane
https://www.google.com/search?client=firefox-b-d&q=frontotemporal+dementia+lion%27s+mane
lewy body dementia lion's mane
https://www.google.com/search?client=firefox-b-d&q=lewy+body+dementia+lion%27s+mane
lionesses dementia
https://www.google.com/search?client=firefox-b-d&q=lionesses+dementia
dementia AND (hericium OR lion's mane)
https://pubmed.ncbi.nlm.nih.gov/?term=dementia+AND+%28hericium+OR+lion%27s+mane%29&sort=date&size=200
