There is a wealth of growing evidence indicating that the Lion’s Mane mushroom (Hericium erinaceus) is not the only ‘smart mushroom’ that can protect and regenerate nerves within the brain and body.
Reishi mushroom (Ganoderma lucidum) has been a revered medicine since antiquity and is well known for the beneficial influence it can have on the mind and emotions, and new research is shining an irrefutable light on its ability to safeguard, heal and restore the structure and function of nerve cells within the central and peripheral nervous systems. In fact, with its millennia-long history of use, Reishi is now emerging as one of the premier medicinals in support of cognitive function, memory and the natural remediation of nerve deterioration and cognitive decline.
This article will summarise two recent studies from 2020 in order to understand exactly how Reishi works to protect neurological integrity. Both studies are primarily concerned with increased learning capacity, enhanced memory and problem solving skills, and the regeneration of damaged neurons due to stress of various kinds.
One study focuses on the triterpenes in Reishi and the therapeutic potential they hold in the treatment of advanced Alzheimer’s disease, while the second study utilises hot water extractions of the mushroom fruiting body (rich in beta-glucans & polyphenols) and how this can ameliorate and reverse the damaging effects of oxygen deprivation to the brain and body. The results of these combined studies are nothing short of illuminating. Before we can fully appreciate how meaningful these discoveries are though, we must frame them within their proper context…
I CAN’T REMEMBER…
Neuro-degenerative conditions today have become an all-pervasive affliction. Human ingenuity has enabled us to develop and mass produce technology which, ironically, has led to a steady cognitive decline in the collective culture of humanity that consume this technology. This techno-centric dependency – especially the dopaminergic reward/punishment mechanism of current social media algorithms, the excessive and unyielding onslaught of information from countless angles, plus the ‘convenience’ of predictive text and having your spelling automatically corrected – is causing fundamental areas of the brain to atrophy.
The addictive nature of screen-time and the rapidly obsolete content therein is itself a catalyst for sympathetic nervous system activation. It causes us to remain in an ongoing, moderate fight-or-flight state, which also interferes with the innate healing and repair mechanisms of regular, quality sleep.
What is now manifesting across all nationalities, ages and genders is a dramatic increase in emotional disorders, mental illness, burnout from unnatural and unprecedented stress levels, various forms of addiction, and a sharp increase in neurodegenerative conditions such as memory loss, learning difficulties and early onset dementia.
Diagnosis rates for the various forms of dementia in the United States actually increased by more than 200% in people aged between 30 and 64 over a four year period between 2013 and 2017. Considering that the American population didn’t triple within those four years, this statistic should act as a harbinger for where this current trajectory is headed.
The field of nootropics has been rapidly expanding throughout the last couple of decades. Nootropics themselves are simply pharmaceutical drugs, herbs or supplements that can improve cognition, memory and learning, as well as promote creativity and problem solving skills.
As with all emerging spheres of medical study, the realm of nootropics is rife with misinformation and emotionally manipulative marketing, yet it also contains many natural substances that have been well known for hundreds or even thousands of years with an arsenal of scientific literature to support their efficacy. The kingdom of mushrooms offers some of the most therapeutically potent, time tested and scientifically validated players in this field.
One such example are psychoactive mushrooms like the different species of psilocybin fungi, which are capable of improving the structural integrity and functional plasticity of neurons within the frontal cortex. This is an area of the brain that is primarily concerned with problem solving, decision making and regulating personality expression. Psilocybin amongst other things, can stimulate the growth of new neurites (axons or dendrites) from the body of nerve cells in the frontal cortex, which increases synapse function and correspondingly, the complexity of neural transmission.
This is one of many reasons that psilocybin fungi are now the subject of numerous studies researching the antidepressant and trauma resolving properties they contain. Certain benefits are attainable at a very low, regular dose, while other, more dramatic results are only achievable at a much higher and less frequent dose, which of course brings with it a strong psychoactive experience. While this holds the potential to be a profound and utterly transformative experience, it isn’t for everybody.
Lion’s Mane mushroom (Hericium erinaceus) is another species that has been thrust into the limelight in recent years due to incredible new discoveries on its ability to stimulate neurogenesis within the body. Unlike psilocybin mushrooms this species is not psychoactive at all, and is generally recognised as very safe for all people.
Lion’s Mane contains two main groups of terpene-bound polyphenols (hericenones and erinacines) that can stimulate mast cells within the central and peripheral nervous systems to release Nerve-Growth-Factor (NGF) – an endogenous neurotrophin that repairs neurons and myelin. NGF promotes the healing and regeneration of injuries and physical trauma, but is also secreted in areas of the brain such as the temporal lobe, or more specifically the hippocampus, where emotions and information are processed and memories are formed.
This is an area of the brain that is integral to learning, which is why Lion’s Mane is routinely used by students and high performing individuals, and has been the focus of research investigating its therapeutic potential in the treatment of neurodegenerative conditions like Alzheimer’s disease and other forms of dementia. It is widely used as a cognitive performance enhancer that amongst other things can regulate the presence and function of grey matter within certain areas of the brain.
Lion’s Mane has been a staple of traditional Chinese medicine for millennia where it has been historically prescribed for strengthening digestion in the stomach, for addressing Qi deficiency, in the treatment of certain types of cancer and also as a nutritive substance that nourishes the five primary organs (heart, liver, lungs, spleen & kidneys).
This means that Lion’s Mane has always been, amongst other things, used to promote overall vitality and wellbeing. This would invariably support a greater sense of emotional fortitude and a more stable mental state, and Lion’s Mane was often recommended for those who were abjectly depressed or had become psychologically withered from stress.
However, the closely related effects of this mushroom on the regeneration of neurological tissue were not discovered until very recent history. Even endogenous NGF wasn’t discovered until the 1950’s, when two professors (Rita Levi-Montalcini & Stanley Cohen) at Washington University first isolated it, but their discovery didn’t gain broader recognition until three decades later in 1986, when it was awarded the Nobel Prize in Medicine & Physiology.
The neurologically active compounds in Lion’s Mane however were not discovered until 1990, where Kawagishi et al isolated the first ever hericenones from the fruiting body. Later that same decade an assortment of different researchers began isolating more hericenones and newly discovered erinacines from the fungal mycelium. New hericenones and erinacines have been found as recently as 2008 by Ma & Ueda et al.
But where does Reishi mushroom fit into this? The title of this article is referring specifically to Reishi after all, so why are we digressing so much into other species such as Psilocybin and Lion’s Mane? The answer is simple – aside from the family of psilocybin fungi and especially Lion’s Mane, there aren’t any other medicinal mushrooms that directly influence the nervous system to regenerate in this way, or so we thought.
Lion’s Mane is an important preface here, because like Reishi it too is not psychoactive, it has a very long history of traditional use and boasts a broad catalogue of scientifically verified medical applications. Now it appears that they both share similar yet unique abilities to preserve and repair neurological function. Fascinatingly, like genuine hidden treasures of nature, these species are now revealing more of their embedded potency to us, at a time in the complex lineage of humanity when we are in the greatest need.
REISHI – The Herb of Spiritual Potency
The Mandarin name for Reishi mushroom is ‘Lingzhi’, which translates as the ‘Herb of Spiritual Potency’ or the ‘Mushroom of Immortality’. Another of Reishi’s traditional common names is ‘The Great Protector’, and for very good reason. It is a long revered adaptogen that strengthens the immune system, regulates high blood pressure, blood sugar and is an effective natural medicine in the treatment of diabetes, is a tonic to the liver and kidneys and is renowned as a ‘Shen tonic’ – a substance that calms the mind/emotions and generates a peaceful state of equanimity that can catalyse spiritual potential.
A great deal of the scientific literature has focused on Reishi’s effect on modulating immune function and its role in treating numerous types of cancer, and throughout many decades of study, a lot of the ancient wisdom surrounding this medicine has been systematically corroborated through modern scientific enquiry.
However, more studies are now being conducted in regards to the neuro-protective benefits of Reishi. Traditional Chinese medicine has stated for millennia that it can exhibit a stabilising influence on the emotions and support a healthy mental state, but it was never understood until now that this mushroom was capable of directly repairing and protecting the integrity of the central and peripheral nervous systems.
Up until now this was an exciting niche that was reserved exclusively for species like Lion’s Mane, which is why the recent discoveries with Reishi are so ground-breaking, because we are now starting to comprehend that Lion’s Mane is not an island in this regard – there are immensely well studied, potent fungal medicines with an incredibly long history of use that do offer similar benefits.
Reishi mushroom contains hundreds of important bioactive compounds that exhibit therapeutic potential. Broadly speaking there are about 200 polysaccharide compounds that are found in the fruiting body of this fungus, numerous polyphenols and approximately 140 triterpenes.
The mushroom itself is very tough like wood, and is therefore inedible, yet a strong medicine can be made from extracting the therapeutic compounds into a solvent. These constituents are generally soluble in either hot water or ethanol, and so we must look at both types of extracts in order to paint a complete picture of how the entire organism might help to protect and regenerate the nervous system.
ETHANOLIC EXTRACTION – Triterpenes
When comparing the nerve regenerating benefits of both Lion’s Mane and Reishi, it is very interesting to point out that the compounds primarily responsible in Lion’s Mane were all newly discovered constituents, whereas the compounds in Reishi that favourably influence the nervous system are (so far) all substances that we have been studying for a long time already.
One recent study by Nanhui Yu and Yongpan Huang et al, was a combination of various in viv (isolated cells) and in vitro (animal clinical trials) experiments that were published at the end of January 2020. The experiments were concerned with the way in which Reishi inhibits the development of Alzheimer’s disease. Research in this area is a large part of what has proven Lion’s Mane to be such a legitimate medicine for the brain and central nervous system, so this is a perfect way to begin testing the same capacity in Reishi.
This particular series of tests primarily observed the triterpenes in Reishi – the lipid-based, antioxidant compounds that act as precursors to steroid hormones. There are many different triterpenes in Reishi such as ganoderic acids, lucidenic acids and various sterols, and they are all alcohol/ethanol soluble.
Many enlightening conclusions were reached through the various testing methods applied. Firstly, cognitive impairment of test subjects was observed – these were all rodents, some of which were suffering with advanced Alzheimer’s disease. Compared to the healthy rodents, the afflicted subjects expressed severely impaired cognitive function, decreased learning and memory, spatial awareness orientation and recognition.
In a dose-dependent manner, the Alzheimer’s subjects who were prescribed Reishi triterpenes had an almost completely restored cognitive capacity – they were functioning almost as well as the mentally healthy subjects and were even out-competing other affected subjects that were prescribed Donepezil, a commonly prescribed pharmaceutical drug for dementia.
Next the direct effects of Reishi triterpenes on the hippocampus tissue of test subjects was observed. In cases of Alzheimer’s disease, nerve cells typically become inflamed and lose their structural integrity, which leads to increased necrosis of the cells. However, administration of Reishi to the affected subjects showed very clearly that neuronal cell structure was actually very regular, and there was no visible necrosis to nerve cells at all.
Within the hippocampus of subjects with Alzheimer’s disease there was a major decrease in healthy nerve cells and a dramatic increase in neurofibrillary tangles (NFT) – an abnormal accumulation of proteins within the nerve cells that is an obvious biomarker for this condition. Conversely, the group treated with Reishi triterpenes showed a significant increase in healthy nerve cells and a major reduction in NFT’s. Again, the Reishi group presented better results than the group treated with the drug Donepezil.
Next, oxidative damage and apoptosis (cell death) were measured across the various test groups by observing the Rho Kinase Signalling Pathways (ROCK pathways). These are enzyme-signalling pathways that are largely responsible for the shape and movement of various cells in the body – in this instance, the structure and function of nerve cells in the hippocampus. Hyperactivity of the ROCK pathways and an increase in their related proteins invariably results in oxidative stress and is common to various types of cancer and of course, Alzheimer’s disease.
By observing the ROCK pathways, the Alzheimer’s disease group expressed a much higher number of inflammatory proteins and enzymes, which dramatically increased the volume of nerve cells undergoing the destructive process of apoptosis. Also, opposing antioxidant proteins and enzymes had significantly declined in the Alzheimer’s group, leading to elevated oxidative damage to the hippocampus.
However, the Alzheimer’s group that were treated with Reishi expressed completely opposing results. Firstly, the number of cells undergoing apoptosis prominently decreased, oxidative proteins and enzymes were pacified and their antioxidant counterparts notably increased, inhibiting oxidative damage and apoptosis. Therefore it was determined that Reishi triterpenes are able to regulate the ROCK signalling pathways and inhibit the destruction of healthy neurons, while salvaging and repairing impaired neurons and restoring their healthy function.
To really put this theory to the test however, a more extreme scenario was created adding a pharmaceutical ROCK pathway inhibitor into the process for comparison. Again, in a dose-dependent manner, the Reishi triterpenes out-performed the pharmaceutical drug in almost every instance, providing more successful inhibition of the ROCK pathways, reducing related inflammatory proteins, enzymes and elevating the antioxidant equivalents.
The in vitro findings of this particular series of experiments echoed the same conclusive results. A neuro-toxic amino acid (Aβ25-35) that acts as a common biomarker for Alzheimer’s disease was introduced to the cell model. Naturally it obstructed cell function and growth, and inhibited the activity of antioxidant enzymes like Superoxide Dismutase (SOD) while magnifying the activity of other pro-inflammatory compounds.
This of course led to an increase in cellular apoptosis. Yet, as you might expect at this point, the introduction of Reishi triterpenes had the opposite effect – cell integrity improved, SOD levels increased and related pro-inflammatory substances like malondialdehyde and lactate dehydrogenase were substantially reduced. This created a protective environment for the hippocampal neurons and restrained them from undergoing the terminal process of apoptosis.
As with all other tests in this collective experiment, the Reishi group performed the highest, second only to the healthy control group. Every one of these tests implemented a dosage scale – sometimes it was the highest dose that delivered the strongest results, while in other experiments it was a lower/medium dosage which was optimal. The maximum dosage exhibited no toxicity even when administered for an extended duration, highlighting that these compounds are indeed very safe in a very broad range of doses and circumstances.
HOT WATER EXTRACTION – Beta-Glucans & Polyphenols
A recent study published in June 2020 that was conducted in India by Purva Sharma and Rajkumar Tulsawani, reveals that Reishi does in fact offer similar benefits to both Lion’s Mane and also the Cordyceps mushroom. This detailed research, like the previous study, also utilised in vitro and in vivo methods and the results are eye opening to say the least.
The study was investigating a condition called ‘hypobaric hypoxia’. This is essentially high altitude sickness, where the body is deprived of sufficient oxygen. The respiratory system can no longer transfer enough oxygen to the bloodstream, causing the muscles to stop responding and the integrity of the central nervous system to deteriorate. This causes severe cognitive impairment, lack of spatial awareness, memory loss and a dramatic reduction in problem solving skills. In many cases, the damage to the body and brain can have a permanent, lasting effect.
While altitude sickness is not something that most of us have to deal with, a decrease in oxygenation within the body is a very real issue that so many of us are exposed to. For example, lack of movement/exercise, too much of a sedentary lifestyle, bad posture, irresponsible food choices and lifestyle habits like smoking and excessive alcohol consumption – all of these can increase blood pressure and lower cellular oxygenation.
Stress, overload of information, multitasking, environmental pollution – all of this restricts our breathing and reduces the amount of oxygen we are delivering to the cells of the body. Nowadays, the average adult actually over-breathes and takes between 12 to 18 shallow breaths per minute. This causes only one third of the lung capacity to be used. Our modern lifestyles have caused us to reproduce a mild form of altitude sickness which is ongoing, even at sea level. This is an enormous problem the world over.
This series of experiments only used hot water extracts of this mushroom, which would be rich in an assortment of unique polysaccharides/beta-glucans and polyphenols, but comparatively very low in the aforementioned triterpene compounds from the previous study.
So what exactly did this research discover? Well firstly, in cases of hypobaric hypoxia, something that becomes severely impaired is the function of the hippocampus – an area of the brain that, as we have seen, also becomes impaired and degenerates in cases of Alzheimer’s disease and other forms of dementia. Hypobaric hypoxia causes severe dysfunction within the limbic system – a mechanism within the brain that deals with emotion and memory. The hippocampus is central component to the healthy functioning of the limbic system.
In this study, subjects suffering from hypobaric hypoxia were experiencing cerebral edema, impairments in learning, memory and decision making amongst others. Oxidative stress caused significant neuronal damage within the hippocampus which led to increased inflammation, blood brain barrier dysfunction and eventually neuronal apoptosis.
Various testing methods were then applied to explore the therapeutic potential of the Reishi extract. Initial observations confirmed that supplementing with the extract created a substantial antioxidant reaction within the affected tissue and promoted neurological homeostasis. Severely affected subjects experienced constant and repetitive amnesia, yet when treated with the Reishi extract they showed a remarkable increase in memory recall.
Hypobaric hypoxia caused fear and stress-related neurotransmitters such as epinephrine and norepinephrine to become highly elevated in the hippocampus and blood plasma, while serotonin (associated with parasympathetic healing and repair) was reduced. It was also observed that glutamate buildup was occurring in the hippocampus, causing neurons to rapidly die. Introduction of the Reishi extract to the affected group exhibited an adaptogenic affect, reducing the adrenalinergic neurotransmitters, increasing serotonin and also inhibiting the dangerous accumulation of glutamate in the hippocampus.
Cerebral edema (fluid accumulation in the brain) was also a frequent result of hyperbaric hypoxia due to disruption of the blood-brain barrier. Again, in the presence of the Reishi extract, there was an exceptional decrease in fluid retention as well as a remarkable reduction in damage to the surrounding neurons.
Hypobaric hypoxia obviously caused an acute oxygen deficit, but this consequently caused severe respiratory and metabolic acidosis due to gas, electrolyte and metabolite imbalances in the blood, all of which increased physical and mental exhaustion. However, the Reishi extract adjusted the pH of the blood to within a normal range, balance between blood gases was restored and the disorder of electrolytes and serum metabolites was ameliorated.
The extreme fatigue associated with hypobaric hypoxia was also observed by a significant decrease in serum levels of the important antioxidant glutathione. Enzymes directly responsible for the production of ATP (cellular energy) within the hippocampus were also greatly repressed, yet once a suitable dosage of Reishi extract was administered to the affected group, glutathione levels in the blood normalised and ATP production within the hippocampus sufficiently resumed.
Cases of hypobaric hypoxia also showed elevated activity of protein coding genes such as the HIF 1a gene – a master regulator of cellular and systemic homeostasis in the event of oxygen deprivation to the brain and body. Long after healthy oxygen levels had resumed post-trauma, the HIF 1a gene was still highly active and causing inflammation within the brain when compared to healthy subjects that had not experienced hypobaric hypoxia, where the gene expression was inactive.
The affected group also showed decreased expression of the Brain-Derived-Neurotrophic-Factor (BDNF) gene which is responsible for the plasticity and survival of neurons as well as modulating a number of important neurotransmitters.
BDNF is essential for learning and memory, so the inhibition of this gene is a very influential factor in the damaging effects of hyperbaric hypoxia. After treating the affected group with the Reishi extract, the BDNF gene activity was restored and expression of the HIF 1a gene was inhibited, and the resulting levels of pro-inflammatory cytokines (immune signalling molecules) were correspondingly reduced. A much greater degree of genetic and neurological homeostasis was achieved and the post-trauma recovery was exponentially more successful than the affected group that did not receive the Reishi extract treatment.
The results of this research, although preliminary, are nothing short of astonishing and demand extensive human clinical trials in order to further ascertain the dosage necessary for treating a range of neurodegenerative conditions that, as we have already seen, are becoming frighteningly commonplace in today’s society.
What is fascinating here is the obvious comparison between the nerve regenerating properties of Lion’s Mane and Reishi – Lion’s Mane possesses compounds that are able to stimulate NGF production within the body, yet Reishi doesn’t stimulate NGF at all but achieves similar results by operating across a diverse spectrum of physiological pathways.
By acting as a homeostatic regulator of neuro-endocrine, cardiovascular and immune systems as well as modulating gene expression, Reishi extracts are able to inhibit deterioration and ultimately the destruction of nerve cells as well as repairing and recovering the structural integrity and function of neurons. This increases synaptic transmission and the corresponding cognitive abilities that accompany a high functioning brain and central nervous system. In many cases, a high yet safe dose was able to out-perform leading pharmaceutical drugs.
In the two studies referenced in this article, the temporal lobe surfaces as a predominant region of the brain that is positively influenced by Reishi. The temporal lobe is responsible for processing sensory input and translating it into a derived meanings that form important memories and enable us to learn, understand language and navigate emotional states.
The impact Reishi makes on the temporal lobe is adaptogenic, with notable effects on the hippocampus – a complex structure within the temporal lobe that is central to learning and memory – especially the navigation of time and space – yet is susceptible to damage through disease, injury and stress. Reishi mushroom, with its long and storied past as a diverse and superior medicine, is only now revealing these properties to us and claiming its position as one of the greatest neuro-protective, cognitive-enhancement substances we have available.
However, we must also reflect on the fact that these two studies collectively incorporated hot water and ethanolic extracts of this mushroom, shining an important spotlight on the need for dual-extraction if we intend to harness the full potential of this remarkable medicine. As the industry of commercial mushroom extracts expands, the number of poor quality products grows with it. This requires diligence because the provenance and production methods are absolutely crucial to the effectiveness of the end product.
Currently the majority of products are neither grown nor extracted correctly and the health benefits will be correspondingly underwhelming. Organically grown fruiting bodies on hardwood logs in a controlled environment, then dual-extracted separately in a multi-step process that captures everything of medicinal value – this takes longer and is more costly to produce, but it is the only method for creating a medicine that is capable of reflecting these recent discoveries as well as the long appreciated benefits outlined by traditional medical systems.