Lions Mane for Alzheimers & Dimentia

For those who just want the good news this first introduction paragraph is for you. The long and short of it is, in researching Lions manes effects(Hericium erinaceus) on Alzheimer’s disease(AD) – Lions Mane(LM) basically counters everything that causes AD. AD is a complex issue having multiple causes, from trauma to the head, alcohol induced AD, age related neurodegeneration but for the most parts 3 things happen.

Amyloid Beta(AB) plaque builds up on synapses and this leads to increase oxidative damage, inflammation, neurotoxicity, reduction in activity in certain signalling pathways and decrease in syntheses of insulin degradation enzymes(IDE), brain derived neurotrophic factors(BDNF) and never growth factor(NGF), decrease in reactive oxygen regulators and increase in stress derived cell apoptosis(cell death).

Now what LM does is it increase the amount of NGF, BDNF and antioxidant molecules in the brain to reduce oxidative damage/stress, increase anti-inflammatory compounds be activating certain pathways, proteins and enzymes, increase in IDE and prolongs cell life. Now trust me when I say BDNF and NGF are not light words, they carry sooo many different beneficial activities – when LM is increasing both of these it is regulating inflammation, oxidative stress, increasing neurogenesis, neuroplasticity, nerve-regeneration, regulation of maintenance, development, function, and survival of neuronal cells and protects cells against apoptosis(just by the way almost all of this is happening in the hippocampal and cerebral regions of the brain and you should definitely look up why that is important). Now for the normal individual all of these are also very important in why LM increases cognitive function like memory, focus and ability to learn. LM also decreases lipid per oxidation meaning it decreases brain ageing and cognitive decline. So whether you are an athlete, parent, student, an individual suffering from AD or neurodegenerative diseases or an avg Joe, LM can help all of you!

The Nitty Gritty

SO in this blog post I’m going to be summarizing the findings that where presented in this paper – which focused on Lions manes memory enhancement and neuroprotective properties with specific focus on Alzheimer’s and Dementia. The entire study looked at multiple preclinical trials and clinical trials. As well as papers on how Alzheimer’s disease(AD) works.

So scary fact, Alzheimer’s disease(AD) constitutes 70% of all neurodegenerative disease cases and estimated that by 2050 more than 130mil people will develop AD. So I believe as a person who has family members who have AD that finding a natural preventative or cure is vital not only to the human race as the older generation needs there wits about them to pass on knowledge and wisdom but also in keeping a family whole, going to visit a family member and have them not even know who you are is a scary reality that to many face.

The beauty of Lions Mane(LM) is that it doesn’t just effect the brain but the body as well, and it doesn’t just do a single thing in either of those regions. LM has been shown to have the following positive effects:
Immune modulator
Anti cancer/oxidant/inflammatory
increase neurogenesis
increase in synaptic plasticity
reduced apoptosis
decrease amyloid beta plaque(ABP)
inhibition of acetylcholinesterase
blood sugar balance
and more
(some of these terms I will explain other please feel free to chatgpt or google them)

What Cause Alzheimer’s Disease

So one term you might’ve heard before is ‘Plaque’ or ABP, the most famous mycologist, spoke about this on the most famous podcast the JRE. firstly what is Plaque and why is it connected to AD. Now, think of ABP as tiny pieces of garbage that pile up on some of the streets(neural pathways) of the city(your brain). These garbage piles are not supposed to be there, and they can make it hard for the brain’s messages to travel smoothly. Just like how garbage can block roads and make it difficult for cars to pass through, amyloid beta plaque(ABP) can block the signals that help your brain work properly. This can sometimes cause problems with memory and thinking.

So in the brain ABP inhibits signalling between transmitters and receptors, making the processing of information slow and depending on the severity of the condition may make certain receptor never receive signals from other parts of the brain. ABP and an other Alzheimers biomarker Neurofibrillary tangles(NFTs) play a big role in interrupting communication and cell death and causing other effects that cause Alzheimers.

(sort side track on what NFTs are)
Think of neurons as factories that make and transport important materials in the brain. In a healthy neuron, there’s a structure called the cytoskeleton, which acts like a scaffold, helping the neuron maintain its shape and facilitating the movement of molecules within the cell. However, in conditions like Alzheimer’s disease, a protein called tau, which is normally involved in stabilising the cytoskeleton, becomes abnormal. This abnormal tau protein starts to clump together inside the neuron, forming tangled structures known as neurofibrillary tangles. These tangles disrupt the normal functioning of the neuron, impairing its ability to communicate with other neurons and ultimately leading to cell death.

Another 2 major players in AD is inflammation in the brain as well as Oxidative damage caused by reactive oxygen species(ROS). Both of these are basically the cause of ABP and NFTs but from what I understand can also cause NFTs and ABP.

Now ROS isn’t always bad even though they are made out to be the bad guys but in smalll amount they assist in cell signalling, immune response and metabolism but in larger amount or where the shouldn’t be they damage and rupture cells, this can often damage important molecules like DNA, proteins, and lipids, which are like the building blocks of your body. This damage can lead to inflammation, ageing, and even diseases like cancer, heart disease, and neurodegenerative disorders.

Inflammation is also often seen as the bad guy but is vital for immune response and assists in repair of damaged parts of the body by increasing blood flow and signalling for other compounds to get to the inflamed area but when inflammatory compounds are in too high concentration they to can cause many problems, in the brain when inflammatory compounds are in to high a concentration they can cause neurotoxicity.

ABP, NFTs & ROS all lead to the over stimulation of glial cells(which are normally heroes in the brain) and end up causing over production of inflammatory compounds, cytokines and lead to neurotoxicity and neuronal cell death.

So that is basically how Alzheimers works, Increase in ABP, NFTs & ROS as well as high concentrations of inflammatory compounds leading to cell death, inhibition of signalling between neurons(basically a lack of communication between points in the brain) decrease in correct glial cell activation, decrease in neurogenesis, decrease in production of BDNF, NGF preventing the brain from healing or fixing itself and then this all snow balls which we see as people losing motor functions and memory.

now enough of the scary sh*t and onto why Lions mane Dual extracts are not only good for AD patients but everyone.

Lions Mane The Hero

(all of the below information refers to dual extracted LM)

So LM extracts have been shown to promote neuronal growth(which is important to you because it enhances learning and memory, fosters adaptation and flexibility, aids in recovery from injury, promotes mood and emotional well-being, and contributes to overall brain health) via reduction in endoplasmic reticulum(ER) stress induced cell atrophy – basically ER helps with protein synthesis, lipid metabolism, detoxification and calcium storage helping with cell health and function in the brain and body, and stress induced cell atrophy of the ER is caused by increase in inflammatory and oxidative damage/stress which then will lead to over accumulation of lipids and toxins as well as reducing the metabolism of lipids into steroids and phospholipids, decrease hormone synthesis and correct transportation of certain proteins.

LM extract also increased the expression of neurotrophic factors (NGF & BDNF etc.) in astrocytes in the hippocampus, decreasing neurodegenerative induced cell atrophy suggesting hippocampus neurogenesis (Astrocytes provide structural support to neurons and help maintain the integrity of the blood-brain barrier, help regulate the concentration of neurotransmitters which are essential for neuronal communication, are involved in recycling neurotransmitters, store glycogen and can metabolize it to provide energy to neurons when needed, can modulate synaptic activity, play a role in protecting neurons from damage caused by oxidative stress, inflammation, and other harmful factors and play a role in synaptic plasticity).

Preclinical Studies

1. LM extract resulted in the reduction & inhibition of plaque build up and decreased astrocytes & plaque activated microglia, reduced insoluble ABP & Amyloid precursor protein, an increase in NGF in the cerebral & hippocampus regions indicating again neurogenesis in both these regions. 100days of supplementation the increase in neurogenesis was found to be correlated with recovering behavioural and memory deficits.(NO, this doesn’t mean that you have to take LM extracts for 100days before getting benefits, the study is simply saying that after 100days they were able to successfully correlate the increase in neurogenesis to recovering behavioural and memory deficits.)
2. In one study mice were injected with aluminium chloride (AlCl3). The brains of the mice demonstrated reduced acetylcholinesterase(AChE) and Acetyltransferase (ChAT) levels, resulting in learning and memory deficits. LM extracts depicted dose-dependent increased concentrations of AChE and ChAT in the hypothalamus and blood serum, which correlated with enhanced learning and memory in the behavioural tests, suggesting that the neuroprotective effects of LM extract is mediated through the cholinergic signalling pathway.
3. In a rat model of AD induced by AlCl3, which exhibited AlCl3 accumulation in the hippocampus. Treatment with LM extract ameliorated the AlCl3 accumulation, improved behavioural deficits, and enhanced hippocampal neurogenesis, leading to reduced levels of tau phosphorylation, APP(Amyloid precursor protein) over-expression, and Aβ accumulation. Furthermore, the LM treatment was found to mitigate oxidative stress through suppressing NLRP3 inflammasome activation. These results indicate that LM extract also has anti-oxidative and anti-inflammatory activity in the brain.
4. In a different study they researched the effect LM extract had on brain ageing, learning and memory. LM extract delayed cognitive degeneration due to ageing & decreased the amount of reactive oxygen species(ROS)/ prevented the over accumulation of ROS, resulting in less oxidative stress/oxidative damage in the brain.
   

Summary – LM extract has been shown to reduce the build up of plaque(on of the causes of neurodegenerative diseases) and increase NGF in the cerebral and hippocampal regions which resulted in neurogenesis and was correlated to the recovery of behavioural and memory deficits. LM extract increased AChE & ChAT in subjects that had a decreased amount of AChE and ChAT which correlated in enhanced learning and memory, suggesting that the neuroprotective effects of LM extract is mediated through the cholinergic signalling pathway. LM extract also showed that in subjects that had heavy metal induced Alzheimers, the LM extract ameliorated the heavy metals which in term also improved behavioural deficits, and enhanced hippocampal neurogenesis and indicated that LM extract also has anti-oxidative and anti-inflammatory activity in the brain. LM extract was also found to have delayed cognitive degeneration due to ageing & decreased the amount of reactive oxygen species(ROS)/prevented the over accumulation of ROS, resulting in less oxidative stress/oxidative damage in the brain

Clinical Studies

1. Participants were administered daily for 49 weeks with 350 mg mycelia-based capsules of erinacine A. The treatment group depicted a notable improvement in the activity of daily living (ADL), cognitive ability, and mini-mental state scores. Moreover, Treatment Group improved contrast sensitivity in the ophthalmologic examination compared to the placebo group. Although mycelia-based capsules of erinacine A was largely found to be safe and effective, four participants dropped out of the study due to adverse reactions, including nausea, abdominal pain, and skin rash. (Contrast sensitivity scoring indicates how well or poor an individual can perceive subtle differences in contrast levels. Contrast sensitivity is crucial for tasks such as reading, driving at night, recognising faces, and navigating in low-light conditions.)
2. Double-blind, parallel group study investigated the effects of oral administration of four 250 mg capsules containing 96% LM three times daily for 16 weeks in Japanese women and men with mild cognitive impairment. The treatment group demonstrated significant improvement in cognitive functioning scores compared to the placebo group with no apparent side effects. Although there was a positive correlation between the treatment and improved cognitive function, this only lasted during the drug administration period and cognitive function scores decreased thereafter, which suggests the need for long-term LM use for the management of AD.
3. Most recent study was a double-blind, parallel group clinical trial examining the effects of the consumption of 4 LM supplements containing 0.8 g of powdered fruiting bodies daily for 12 weeks. Cognitive abilities were assessed by the Mini-Mental State Examination (MMSE), standard verbal paired-associate learning, and Benton visual retention tests. The LM treatment was found to prevent short-term memory decline and improve cognitive function in the MMSE, indicating the beneficial effects on neural network regeneration and its overall safety(Mini-Mental State Examination is a brief and widely used tool for assessing cognitive function in clinical settings, helping healthcare professionals screen for cognitive impairment and monitor changes in cognitive status over time).
   

Summary – Erinacine A extracted from LM mycelium showed a notable improvement in the Treatment group in the activity of daily living, cognitive ability, and mini-mental state scores and improved contrast sensitivity in the ophthalmologic examination compared to the placebo group but the isolated mycelia-based isolated compound erinacine A seemed to cause adverse reactions. 1000mg of activated LM(micronised or extracted – didn’t specify)
Consentrated and isolated erinacine A extracted from LM mycelium was the only treatment that caused adverse reaction in some while still improving the activity of daily living (ADL), cognitive ability, mini-mental state scores and contrast sensitivity. In a different study double blind, parallel group study, 1000mg of activated/extracted LM(they didn’t specify) had no side effects and still improved cognitive function. In the most recent double-blind, parallel group clinical trial, the treatment group consumed 4 LM supplements containing 0.8 g of powdered fruiting bodies daily, the LM treatment was found to prevent short-term memory decline and improve cognitive function in the MMSE, indicating the beneficial effects on neural network regeneration and its overall safety

My take aways

First things first – you must always get a dual extracted extract wether it is a tincture like ours or powders, if you want the benefits make sure it is dual extracted meaning both alcohol and water were used to extract the beneficial compounds from the mushroom. Second – as some may know I personally don’t believe mycelium is the way to go with mushroom extracts unless it is complimentary to a normal fruiting body(the actual mushroom not its roots) extract and is a solid state fermentation not mycelium on grain. However in the study they did look at other studies that used erinacine enriched mycelial extracts or isolated compounds using mycelium and these enriched extracts did show benefit but the only time any side effects were observed, was in the clinical studies using mycliated grain as the base for extracting and isolating compounds – Non of the studies used normal mycelia extracts, only specifically enriched or used to isolate a compound and that compound was used – anyway that is a discussion for another blog post.

The Dual extract is very important though, in some parts the benefits that are mentioned in this blog post that were found in these studies were from alcohol extracts and some from water extracts, the combination of these two is important to getting the full spectrum of benefits. I say this knowing full well that the study did state that micronised or activated, extracted LM powder(they didn’t specify) can/does still give the user benefit but it will take longer.

The studies show promise for LM being used to treat a myriad of different neurodegenerative diseases and for even the average individual to reduce brain ageing, modulate inflammation & oxidative damage/stress and increase an individuals ability to learn and focus. For Alzheimers specific patients this is an incredible discovery, showing how a natural medicine could potentially be the best treatment for a disease such as Alzheimers, effecting and treating multiple different mechanisms of action.

P.S The next blog post will talk about the mechanisms of action of how LM works in our brain, this blog is just getting a little long so stay tuned