Lion's Mane: A Key to Fighting Alzheimer's and Cognitive Decline?

Lion's Mane: A Key to Fighting Alzheimer's and Cognitive Decline?

Every 65 seconds another American develops Alzheimer’s. [1]

Current estimates indicate that 5.8 million Americans currently suffer from Alzheimer’s dementia, and over the next 30 years that number is projected to be around 14 million.

Beyond that, Alzheimer's disease also happens to be the sixth-leading cause of death in the United States.

But, despite spending $2.3 billion on Alzheimer’s research in 2019, the hope for a cure remains elusive as the few medications that have been developed only provide partial, temporary relief during the diseases early stages. [2][3]

To date, all tested pharmaceuticals have proven ineffective for combating cognitive decline or the physical decline of the body that accompanies the disease’s progression. [3]

In light of these pharmaceutical failures, researchers and practitioners have begun seeking alternative options derived from natural sources to help stop the progression of the disease or prevent it altogether.

One of the more notable sources in recent years is lion’s mane.

Today, we’ll discuss what is lion’s mane, the potential benefits associated with its use, and how it may help pave the way to halting the progression of (or outright preventing) cognitive decline.

But first, let’s brush up on the basics of Alzheimer’s Disease -- what it is, what are the symptoms, and what causes it to develop.

What is Alzheimer’s Disease?

Alzheimer’s disease is a progressive, irreversible neurodegenerative disorder hallmarked by an accumulation of toxic proteins in the brain resulting in cognitive impairment. It is the most common cause of dementia among older adults. [4]

The disease is named for Dr. Alois Alzheimer who first documented abnormalities in the brain tissue of a woman who had died from a mysterious mental illness. Symptoms exhibited by the women included aberrant behavior, language difficulties, and memory loss.

During the post mortem, Dr. Alzheimer noticed strange clumps and tangled bunches of fibers in the woman’s brain tissue. Today, these “clumps” and “fibers” are referred to as 𝛃-amyloid plaques and tau tangles, respectively.

Doctors have yet to determine why certain individuals develop Alzheimer’s.

For individuals who develop early-onset Alzheimer’s (ages 30-mid 60s), researchers believe it is due to a genetic mutation -- likely involving a gene called apolipoprotein E-4 (APOE-4) as research has found a link between the gene and an earlier age of disease onset. However, just because you have the APOE4 variant of the gene does not mean you will definitely develop Alzheimer’s disease. Furthermore, individuals with no APOE4 gene can also develop the disease.

Development of late-onset Alzheimer’s stems from an intricate series of changes in the brain that occur over decades due to a combination of environmental, genetic, and lifestyle factors. The extent of how much each of these factors contributes to the development of the disease varies considerably from one individual to another.

Despite not knowing the root cause of why an individual develops Alzheimer’s, researchers have noted that changes in the brain can begin 10+ years before symptoms manifest themselves.

Common symptoms associated with early-to-moderate Alzheimer’s Disease include:

  • Memory problems
  • Trouble finding words
  • Vision/spatial issues
  • Impaired reasoning or judgment

As the disease progresses, language control, reasoning, memory loss, and overall cognitive function continues to worsen as 𝛃-amyloid plaques and tau tangles continue to proliferate throughout the brain, inducing further shrinkage of brain tissue.

What makes these proteins so dangerous and damaging to neurological tissue is that they interfere with the communication between two of the “big time” brain cells -- neurons and glial cells.

Neurons are brain cells that communicate information and play a key role in cognitive function (memory, learning, thinking, reasoning, etc.).

Glial cells serve several roles in the brain, two of the most important of which are supporting and protecting neurons as well as the connections between them.

With the primer on Alzheimer’s complete, let’s now turn our attention to lion’s mane and how it may help with dementia prevention...

What is Lion’s Mane?

Also known as Hericium erinaceus (Latin for hedgehog), Lion’s Mane is a culinary and medicinal mushroom used for centuries in Asia. Over the past several decades, the mighty mushroom has been the subject of intense research as it was found to offer neuroprotective and neurogenerative effects. [5,6,7,8,9,10]

These effects are likely due to the neuro-friendly compounds naturally occurring in Lion’s Mane called hericenones and erinacines, located in the fruiting body and mycelium of the mushroom.

When discussing mushrooms, we tend to focus on the parts we eat, which if you’re thinking of a traditional white button mushroom is the “cap” and “stalk.” These edible parts are known as the “fruiting bodies”, and they represent the culmination of the hard efforts of the mycelium.

The mycelium can be thought of as the intricate root network of a mushroom. It’s thin and wispy, similar to a spider web.

One of the unique characteristics of lion’s mane is that it doesn’t have the traditional “cap and stalk” look seen with button or portobello mushrooms. Instead, the fruiting body lion’s mane contains long, flowing, white tendrils which sort of look like a lion’s mane.

Generally speaking, the fruiting bodies are more highly concentrated in bio-active goodies like hericenones and beta-glucans than the mycelium is. However, with regards to lion’s mane, its mycelium is particularly rich in erinacines. [11]

More on Erinacines

Erinacines are a group of 15 cyathin diterpenoids noted to possess a variety of pharmacological activities, including:

  • Enhancing nerve growth factor (NGF) release
  • Reducing β-amyloid deposition
  • Increasing expression of insulin-degrading enzyme
  • Mediating neuropathic pain

Erinacines

FIG. 4. Chemical structures of erinacines A–I isolated from mycelium of H. erinaceus. [12]

The two big effects that we’re interested in concerning cognitive decline and Alzheimer’s are increasing nerve growth factor and decreasing β-amyloid deposits in the brain.

For those unaware, nerve growth factor (NGF) is a neuropeptide (brain protein) that maintains neurons, the cells responsible for assisting your brain process and transmit information. Basically, nerve growth factor helps keep your neurons strong and healthy.

Erinacines have also been noted to enhance central cholinergic system function in Alzheimer’s-induced mice, as evidenced by increased acetylcholine (the “learning neurotransmitter”) and choline acetyltransferase (the enzyme that creates acetylcholine) concentrations in the hypothalamus.

Now, let’s look at the other high-profile bioactive goodies found in lion’s mane -- hericenones.

More on Hericenones

Hericenones are aromatic compounds found predominantly in the fruiting body of lion’s mane. [17] Similar to erinacines, hericenones have been shown to be capable of stimulating nerve growth factor synthesis and promoting neurite outgrowth in nerve cells.

Additionally, hericenone D has been observed to exert a similar degree of bioactivity as epinephrine (adrenaline), which also happens a powerful stimulator of nerve growth factor. [18]

Perhaps most noteworthy is that while both erinacines and hericenones are capable of inducing NGF activity in neurons, some reason indicates that a greater effect (larger boost in NGF activity) can result from the combination of both compounds rather than just using one of them.

Lion’s Mane and Combating Cognitive Decline

The vast majority of research into the neurotrophic and neuroprotective effects of lion’s mane comes from isolated cell studies and animal models.

However, a small double-blinded clinical trial was conducted several years ago using 50-80 year old Japanese adults. [14]

Participants in the study were diagnosed with mild cognitive impairment and given a total of three grams (divided into three 1-gram doses) of Lion’s Mane extract or placebo every day for 16 weeks. The group receiving the mushroom supplement saw significant increases in scores on the cognitive function.

However, 4 weeks after the trial concluded (and the participants stopped taking the extract), researchers documented significant decreases in their cognitive function scores. [14] In other words, in this trial, supplementing with Lion’s Mane led to improved cognitive function (so long as you keep using it daily), indicating it may prevent a decline in cognitive function.

Additional animal models also demonstrate that Lion’s Mane may improve both memory and cognitive function in individuals with neurodegenerative diseases, such as Alzheimer’s. [15,16]

Added Neuroprotection

As we’ve mentioned a couple of times, Lion’s Mane extract not only help increase nerve growth factor activity in the brain, it can also help protect the brain from toxic protein build up.

To highlight the neuroprotective effects of Lion’s Mane, let’s discuss a study using mice who were injected with the neurotoxic peptide β-amyloid. Following injection, the mice were placed into a standard "Y" maze, designed to test their memory.

During the trial, mice were either fed with a normal diet or one containing a lion's mane supplement.

As you would expect, the mice not receiving Lion’s Mane, lost their ability to memorize the maze. However, the mice receiving the supplement for 23 days performed significantly better in the Y-maze test. [19]

In fact, the mice even regained their “curiosity” ability as evidenced by the time they spent exploring new objects they encountered compared to older ones they were familiar with.

Based on these findings, researchers concluded that Lion’s Mane could prevent the cognitive deficits induced by the administration of β-amyloid. [19]

Other mouse studies have found that Lion’s Mane prevents the loss of spatial short-term memory as well as visual recognition memory -- both of which decline as Alzheimer’s progresses. [16]

Now, it’s worth mentioning that while no studies have directly investigated the effects of lion’s mane supplements on humans suffering from Alzheimer’s, the current body of evidence does indicate it can boost cognitive functioning, which should “goose” researchers into pursuing Lion’s Mane as a natural alternative treatment to combating Alzheimer’s.

May Support Nerve Regeneration, Too!

In addition to its neurotrophic and anti-dementia properties, other research suggests that Lion’s Mane may help regenerate nerves, too. In fact, one Japanese study noted that Lion’s Mane was the only medicinal mushroom species to enhance NGF synthesis. [12]

Moreover, Lion’s Mane extract has also been shown to decrease recovery time between 23–41% when given to animals with nervous system injuries. [20]

In that study, rats with gluteal nerve damage regained the ability to walk after taking a Lion’s Mane extract!

Additional Benefits of Lion’s Mane

The focus of this article has been on the potential for Lion’s Mane to help stave off cognitive decline and spark the growth of new neurons in the brain. But, there’s far more to Lion’s Mane than just its neurological benefits.

The mighty mushroom has been found to exhibit a number of other alluring effects, including:

  • Lowers blood sugar (via inhibition of alpha-glucosidase -- an enzyme that breaks down carbs in the small intestine)
  • Antibacterial effects
  • Decreased inflammation and oxidative stress
  • Enhanced immune system function
  • Induced cancer cell death [21]
  • Decreased HIV activity
  • Improved circulation (via a decrease in blood clotting)
  • Gut and liver protectant
  • Increased collagen content and bone density

Is Lion’s Mane Safe?

No human studies have thoroughly investigated any potential side effects of lion’s mane mushroom or its extract.

However, rat studies using doses as high as 2.3 grams per pound of bodyweight have found no adverse effects. Based on this, Lion’s Mane appears to be very safe.

Lion’s Mane Dosing

The majority of research on Lion’s Mane uses test tubes and animals; however, the single human study investigating the effects of Lion’s Mane on cognitive functions used an extract that was 96% purity and provided 3 grams per day.

When sourcing your own Lion’s Mane supplement, you’ll often encounter more potent forms of mushroom, displayed as 10:1 or 4:1 extracts, which means 10 pounds of mushrooms concentrated to 1 pound of extract.

You may also come across Lion’s Mane extracts standardized to 30% or 50% polysaccharides. The reason the polysaccharide content is worth paying attention to is that hericenones and erinacines are metabolites of polysaccharides.

Takeaway

While it can be difficult to extrapolate the findings of in vitro studies to what may actually take place in a human brain infested β-amyloid and tau tangles, the current body of evidence is strong enough (in this writer’s humble opinion) to warrant serious investigation by Alzheimer’s researchers.

To date, all pharmaceuticals have failed (some in spectacular fashion). Why not invest some time (and funding) into a natural option that may just be the breakthrough needed to turn the tide in the battle against cognitive decline.

References

1) "Facts and Figures." Alzheimer's Disease and Dementia, www.alz.org/alzheimers-dementia/facts-figures.

2) Fiscal Year 2020 Alzheimer’s Research Fun | Alzheimer's Association (2019).

3) "The Disease – Cure Alzheimer's Fund." Cure Alzheimer's Fund, 26 Sept. 2017, curealz.org/the-disease/.

4) "Alzheimer's Disease Fact Sheet." National Institute on Aging, www.nia.nih.gov/health/alzheimers-disease-fact-sheet.

5) Kawagishi H., Ando M., Sakamoto H., et al. Hericenones C, D and E, stimulators of nerve growth factor (NGF)-synthesis, from the mushroom Hericium erinaceum. Tetrahedron Letters. 1991;32(35):4561–4564. doi: 10.1016/0040-4039(91)80039-9.

6) Kawagishi H., Ando M., Shinba K., et al. Chromans, hericenones F, G and H from the mushroom Hericium erinaceum. Phytochemistry. 1992;32(1):175–178. doi: 10.1016/0031-9422(92)80127-Z.

7) Kawagishi H., Shimada A., Shirai R., et al. Erinacines A, B and C, strong stimulators of nerve growth factor (NGF)-synthesis, from the mycelia of Hericium erinaceum. Tetrahedron Letters. 1994;35(10):1569–1572. doi: 10.1016/S0040-4039(00)76760-8.

8) Kawagishi H., Shimada A., Hosokawa S., et al. Erinacines E, F, and G, stimulators of nerve growth factor (NGF)-synthesis, from the mycelia of Hericium erinaceum. Tetrahedron Letters. 1996;37(41):7399–7402. doi: 10.1016/0040-4039(96)01687-5.

9) Kawagishi H., Simada A., Shizuki K., et al. Erinacine D, a stimulator of NGF-synthesis, from the mycelia of Hericium erinaceum. Heterocyclic Communications. 1996;2(1) doi: 10.1515/HC.1996.2.1.51.

10) Lee E. W., Shizuki K., Hosokawa S., et al. Two novel diterpenoids, erinacines H and I from the mycelia of Hericium erinaceum. Bioscience, Biotechnology, and Biochemistry. 2000;64(11):2402–2405. doi: 10.1271/bbb.64.2402.

11) Li IC, Lee LY, Tzeng TT, et al. Neurohealth Properties of Hericium erinaceus Mycelia Enriched with Erinacines. Behav Neurol. 2018;2018:5802634. Published 2018 May 21. doi:10.1155/2018/5802634

12) Phan, C., David, P., & Sabaratnam, V. (2017). Edible and Medicinal Mushrooms: Emerging Brain Food for the Mitigation of Neurodegenerative Diseases, 20(1), 1–10. https://doi.org/10.1089/jmf.2016.3740

13) Lai P.L., Naidu M., Sabaratnam V., Wong K.H., David R.P., Kuppusamy U.R., Abdullah N., Malek S.N. “Neurotrophic properties of the Lion’s mane medicinal mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia.” International Journal of Medicinal Mushrooms. 2013;15(6):539-54.

14) Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T. 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.

15) Zhang J, An S, Hu W, et al. The Neuroprotective Properties of Hericium erinaceus in Glutamate-Damaged Differentiated PC12 Cells and an Alzheimer’s Disease Mouse Model. Prokai-Tatrai K, ed. International Journal of Molecular Sciences. 2016;17(11):1810. doi:10.3390/ijms17111810.

16) Brandalise F, Cesaroni V, Gregori A, et al. Dietary Supplementation of Hericium erinaceus Increases Mossy Fiber-CA3 Hippocampal Neurotransmission and Recognition Memory in Wild-Type Mice. Evidence-based Complementary and Alternative Medicine : eCAM. 2017;2017:3864340. doi:10.1155/2017/3864340.

17) Bing-Ji Ma, Jin-Wen Shen, Hai-You Yu, Yuan Ruan, Ting-Ting Wu & Xu Zhao (2010) Hericenones and erinacines: stimulators of nerve growth factor (NGF) biosynthesis in Hericium erinaceus, Mycology, 1:2, 92-98, DOI: 10.1080/21501201003735556

18) Int J Mol Sci. 2017;18:1659. Chemical constituents from Hericium erinaceus promote neuronal survival and potentiate neurite outgrowth via the TrkA/Erk1/2 pathway. Zhang C-C, Cao C-Y, Kubo M, et al.

19) Koichiro, M., Yutaro, O., Takahiro, M., Satoshi, I., & Norimichi, N. (2011). Effects of Hericium erinaceus on amyloid β ( 25-35 ) peptide-induced learning and memory deficits in mice, 32(1), 67–72.

20) Wong KH, Naidu M, David P, et al. Peripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by Aqueous Extract of Medicinal Mushroom Hericium erinaceus (Bull.: Fr) Pers. (Aphyllophoromycetideae) [published correction appears in Evid Based Complement Alternat Med. 2018 Dec 16;2018:9820769]. Evid Based Complement Alternat Med. 2011;2011:580752. doi:10.1093/ecam/neq062

21) Kim, S. P., Kang, M. Y., Choi, Y. H., Kim, J. H., Nam, S. H., & Friedman, M. (2011). Mechanism of Hericium erinaceus (Yamabushitake) mushroom-induced apoptosis of U937 human monocytic leukemia cells. Food & Function, 2(6), 348–356. https://doi.org/10.1039/c1fo10030k

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Comments

Crescent - August 7, 2019

Great article about Lion’s Mane; I have always liked the cognitive effects of Lion’s Mane. The evidence provided in your article I believe medical researchers should look more into all types mushrooms that could alleviate the symptoms or be potential cure for diseases and cancers. This almost makes me wonder if Lion’s Mane could help reduce the symptoms of Multiple Sclerosis since it attacks the Myelin Sheaths around the nerves.

Andrea Faulkner - August 7, 2019

What’s the best lions Mayne to get and do you have to avoid caffeine?

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