Understanding the side effects of Lion's Mane Mushroom supplement: Gathering anecdotal experiences

Interestingly a 2023 study by Martínez‐Mármol et al. [1] showed that compounds isolated from Lion's mane (Hericium erinaceus) were effective at increasing axonal growth and neurite branching. Simultaneously in the popular media[2], there seems to be a growing interest around mushrooms supplements including Turkey Tail, Chaga, Reishi, and Lion's Mane. However, after searching briefly - there seems to be numerous accounts of severe and long-lasting side effects that occur in a subset of individuals when taking oral supplementation with Lion's Mane Mushroom specifically. These unofficial reports seem to be documented primarily on the subreddit r/LionsManeRecovery (or subreddit wiki) and Youtube (Dr. Tyler Pazner & Ryan Russo, Ryan Russo). I was shocked to read the severity of some of these accounts both in symptoms and durations - this post is an attempt to gather some of these anecdotal experiences and generate discussion around the relevant research that exists as well as understand the validity/relevance of these anecdotes.

Below is a list of side effects extracted from 25 anecdotes gathered from the subreddit r/LionsManeRecovery.

Anecdotal side-effects:

Increased anxiety, panic attacks, and lasting mood changes
- [Anec. 1; Anec. 2; Anec. 5; Anec. 7; Anec. 9; Anec. 10; Anec. 13; Anec. 14; Anec. 15; Anec.16; Anec. 17; Anec. 18; Anec. 19; Anec. 20; Anec. 21; Anec. 23]
Insomnia (Chronic)
- [Anec. 3; Anec. 4; Anec. 5; Anec. 7; Anec. 8; Anec. 9; Anec. 10; Anec. 11; Anec. 12; Anec.16; Anec. 17; Anec. 19; Anec. 23; Anec. 25]
Mental fog, dissociation, or confusion
- [Anec. 5; Anec. 7; Anec. 9; Anec. 15; Anec. 19; Anec. 20; Anec. 21; Anec. 25]
Chest pain and accelerated heartbeat (at rest and during light activity)
- [Anec. 1; Anec. 4; [Anec. 10; Anec. 19; Anec. 23]
Nerve sensations (burning nerve pain, muscle pain/twitchiness, "internal vibrations")
- [Anec. 1; Anec. 10; Anec. 11; Anec. 17; Anec. 24]
Headache
- [Anec. 5; Anec 6; Anec. 8; Anec. 9]
Altered temperature regulation
- [Anec. 7; Anec. 9; Anec. 17]
Flu-like symptoms (sore throat, fever, “sick feeling”, muscle/joint aches)
- [Anec. 9; Anec. 14; Anec. 22]

Other information:

Symptom duration (upper bounds):

2.5 years; 1.5 years;

Dosing ranges observed:

0.5 - 5 grams per day

Distributors/Brands:

Om (powder), Dr. Emil's Nutrition (capsule), Crack Relouded (powder), Fungies (gummies), Gaia, Everyday Dose (Fruiting bodies), Toniiq, Gorilla Mind, Nutravita (capsule), Nature's Answer (capsule),

Age ranges observed:

21- 40 years (likely biased on the lower end since these anecdotes are from Reddit)

Questions:

I will be incentivizing each of these questions with ~$10 bounties paid in ResearchCoin for sufficient answers.

Have there been any research conducted in humans regarding dosing or oral supplementation of Lion's Mane mushroom?
Are there any ongoing human trials of Lion's Mane mushroom?
Are these side effects observed in other supplements or nootropics?
(Answered) What are the active compounds present in the Lion's Mane mushroom?
1. Ergosterol:
  1. [Scite.ai Summary of Ergosterol]: “Ergosterol is a major sterol in fungal membranes and is critical for defining membrane fluidity and regulating cellular processes [3]. Ergosterol synthesis has been well defined in model yeast, but little is known about sterol organization in the context of fungal pathogenesis [3]. Ergosterol is also an important constituent of the fungal cell membrane and is essential for fungal growth and development, as well as adaptation to stress in fungi [6]. Ergosterol is used as a measure of fungal biomass and can be used to quantify exposure to fungi [5]. Ergosterol is produced by living fungal biomass and is a potential biomarker in pathogenic medically important fungal isolates [7]. Azoles inhibit ergosterol biosynthesis, and ergosterol is required for vacuolar H+-ATPase function, which is essential for fungal virulence [4]. Ergosterol is also a precursor for steroid drugs [6].”
2. Hericenone C
3. Hericene A
  1. ..
4. Cerevisterol
  1. …
5. 3β,5α,9α-trihydroxy-ergosta-7,22-dien-6-one
  1. …
Are any of the active compounds of Lion's Mane altered by preparation method?
Are any of the active compounds found in other supplements?
What is known in published literature about the effects of each of the active compounds?

References:

Martinez-Marmol et al. 2023; Hericerin derivatives activates a pan-neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory. Journal of Neurochemistry; https://onlinelibrary.wiley.com/doi/10.1111/jnc.15767
Hannah Flynn. “Improving memory: Lion's mane mushrooms may double neuron growth”. 2023. MedicalNewsToday. Link.
Choy et al. 2023. "Ergosterol distribution controls surface structure formation and fungal pathogenicity. BioRxiv." https://www.biorxiv.org/content/10.1101/2023.02.17.528979v1
Zhang et al. 2010. “Requirement for Ergosterol in V-ATPase Function Underlies Antifungal Activity of Azole Drugs”. PLOS Pathogens. https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000939
Sordillo et al. 2009. “Development of a new isotopically labeled internal standard for ergosterol measurement by GC/MS”. Journal of Environmental Monitoring. https://pubs.rsc.org/en/content/articlelanding/2009/EM/b901824g
Hu et al. 2017. “Recent Advances in Ergosterol Biosynthesis and Regulation Mechanisms in Saccharomyces cerevisiae”. Indian Journal of Microbiology. https://link.springer.com/article/10.1007/s12088-017-0657-1
Lafi et al. 2018. “Determination of Ergosterol as a Potential Biomarker in Pathogenic Medically Important Fungal Isolates”. Jurnal Sains Kesihatan Malaysia. https://scite.ai/reports/determination-of-ergosterol-as-a-A3YZ4bO

Note: This is intended to be a living document that will be updated with feedback or review from the community. Please comment any additions, corrections, changes, or suggestions. If you have additional questions for me to add, I will also incentivize those with $10 bounties if they are sufficiently rigorous.

Disclaimer:

I do not have relevant expertise in this and thus can only offer questions to spur discussion around what is known in the published literature about the Lion's Mane mushroom supplementation and how it relates to the numerous anecdotal experiences on the internet. I understand the incredible variability and general lack of rigor present with anecdotal experiences, so this is an attempt to increase rigor and expand discussion while keeping focus around the published literature.

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Understanding the side effects of Lion's Mane Mushroom supplement: Gathering anecdotal experiences