Coffee and nicotine - health habits for our new era? Cholinergic blocking of mAChRs can affect hair growth - is my alopecia a shedding 'booster' side effect?

Investigating this question - and that of nicotine use in 'our special times' (aka chimeric spike injection / CoV era) led to a post so long I made it into a document.

This became a bigger story than my hair, or even Long-Covid hair in general - this is about dementia risk and many standard medications that are likely adding to dementia risk - but it is also a story about the chimeric spike as an anti-cholinergic and dementia and …hair loss risk.

How is our hair and our brain connected? … at the scalp. <pun>

…At the muscarinic Acetylcholine Receptors (mAChRs) and the need for cholinergic function by hair follicles and by brain cells.

A few summary points to get started with -

1. CoV injections and boosters have been associated with sudden hair loss/Alopecia and a Korean study found of autoimmune conditions, SLE/lupus and a skin rash called (hard to spell name) which could be confused with a ‘Monkeypox outbreak’.

   1. Alopecia areata and hair loss have been reported following SARS-CoV2 and following the CoV injections - happening twice for three patients in a case study paper - with an initial injection and then it reoccurred after a second injection. (Rossi, et al., 2021)

   2. A study with 27 patients with new onset Alopecia Areata following CoV injections showed T-cell cytotoxicity was involved. (Wang, et al., 2023)

   3. Long-term risk of autoimmune diseases after mRNA-based SARS-CoV2 vaccination in a Korean, nationwide, population-based cohort study. (Jung, et al., 2024) There was an increased risk for systemic lupus erythematosus (SLE) and Bullous pemphigoid. See Figure 2, Jung, et al., 2024.

   4. “Bullous pemphigoid (a type of pemphigoid) is an autoimmune pruritic [itchy] skin disease that typically occurs in people aged over 60, that may involve the formation of blisters (bullae) in the space between the epidermal and dermal skin layers.” Wikipedia.

2. The mRNA injections do ‘shed’ - spread by passive exposure to exosomes from a recently injected person (2 weeks to 2 months seems to be peak risk of shedding exosomes), or a person who ended up with a gene change and permanent spike production.

   1. ‘Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer–BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines’. (Bansal, et al., 2021)

   2. ‘Circulating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients’, (Ogata, et al., 2021)

   3. My document on the topic of Exosomes and ‘shedding’: (docs.google.com)

3. I have had passive exposure illness and relapses often enough that I started avoiding public places and wearing a KN95 mask in medical settings. The better masks seemed to help, but keeping the visit under an hour still mattered. But… it has been so long that I stopped wearing them and wasn’t when I got an Xray of my broken toe and was waiting for hours in the ER or a patient room. The sudden hair loss started shortly after that rather than immediately after the trauma of breaking the toe.

4. Alopecia can have varied causal factors and autoimmune onset can be more likely during a trauma or infection - when the immune cells are more active and there is also more waste to clean up, then mistakes are more likely to be made. I did have a variety of risk factors and wasn’t using my best diet practices at the time. I started my Cheerful Juice again after the hair loss as the nutrients in it were all fairly key for hair health and I had run out of my mix at the time.

   1. (Cheerful juice Recipe post)

   2. See this post when I first started losing my hair: (Substack)

      1. An older post has a lengthy list of things that may help hair growth, fennel seeds or oil is highlighted. (transcendingsquare.com)

      2. Lavender oil has been soothing. The autoimmune inflammation/attack actually hurt or was itchy. Lavender oil was soothing. This article is a repost from GreenMedInfo: (Substack)

   3. Most recent post on my lost hair . . . and eyebrows and eyelashes too. :-(

Cheerful Juice - good stuff - worth producing for sale.

Hair today, gone tomorrow: Alopecia areata

Good news, I don't have VAIDS (but I also don't have eyebrows and eyelashes).

The Best Buddies: Coffee & Nicotine, ;-)

More recently I was feeling so tired all of the time that I started coffee and nicotine lozenges again. They turn out to potentially have synergistic benefits against potential/alleged/theoretical chimeric spike anticholinergic effects. (Kopańska, et al., 2022) . . . and hair growth may be affected by anti-cholinergic medications or toxins.

“The aim of this study is to review the latest research from the years 2020/2021 regarding disorders in the cholinergic system caused by the SARS-CoV-2 virus. As a result of the research, it was found that the presence of the COVID-19 virus disrupts the activity of the cholinergic system, for example, causing the development of myasthenia gravis or a change in acetylcholine activity. The SARS-CoV-2 spike protein has a sequence similar to neurotoxins, capable of binding nicotinic acetylcholine receptors (nAChR). This may be proof that SARS-CoV-2 can bind nAChR.” (Kopańska, et al., 2022)

Caffeine and nicotine used in synergy with each other and other antiviral drugs is recommended. The chemicals also help protect the ACE2 receptor from chimeric spike entry. Reducing cytokine production is a therapeutic goal and a combined use of non-invasive vagal stimulation therapy is also a recommendation by Kopańska, et al., 2022.

“Nicotine and caffeine have similar structures to antiviral drugs, capable of binding angiotensin-converting enzyme 2 (ACE 2) epitopes that are recognized by SARS-CoV-2, with the potential to inhibit the formation of the ACE 2/SARS-CoV-2 complex. The blocking is enhanced when nicotine and caffeine are used together with antiviral drugs. This is proof that nAChR agonists can be used along with antiviral drugs in COVID-19 therapy. As a result, it is possible to develop COVID-19 therapies that use these compounds to reduce cytokine production.

»> Another promising therapy is non-invasive stimulation of the vagus nerve, which soothes the body’s cytokine storm.” (Kopańska, et al., 2022)

Nicotine as a potential therapeutic for cholinergic dysfunction in post-Covid-19 is discussed by Lietzke, 2023 in the opinion article:

• ‘Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration? (Lietzke, 2023)

Coffee? …has Anti-Alzheimer’s effects, may be due to inhibition of acetylcholinesterase, the enzyme that breaks down acetylcholine.

“Caffeine is an alkaloid with a stimulant effect in the body. It can interfere in transmissions based on acetylcholine, epinephrine, norepinephrine, serotonin, dopamine and glutamate. Clinical studies indicate that it can be involved in the slowing of Alzheimer disease pathology and some other effects. The effects are not well understood.” (Pohanka and Dobes, 2013)

mAChRs & nicotine, Mechanism of Action -

There are muscarinic (mAchRs) and nicotinic (nAChRs) Acetylcholine Receptors (AChRs).

Nicotine is a direct agonist of nAChRs but the muscarinic type are more sensitive to muscarine. Acetylcholine is an agonist of both types. Taking nicotine does seem to spare or support the function of mAChRs. Methacholine chloride is an agonist of mAChRs. Various psychiatric medications include agonist or antagonist activity at mAChRs - olanzapine is an antagonist, clozapine an agonist but also is a dopamine receptor antagonist. (mAChR/medchemexpress) Many medications have known anti-cholinergic effects which with long-term use, may lead to dementia or other neurologic conditions.

Whether chimeric spike is a toxin that has cholinergic inhibiting effects is a separate question than the known issue of medications with those side effects.

Hair follicles and hair coloration need the mAChRs to function. (Hasse, et al., 2007; Yuen, et al., 2024)) Snake venom toxin can inhibit the function of specific subtypes or may inhibit both groups. (Miyoshi and Tu, 1999) The chimeric spike protein contains a sequence that is similar to snake venom toxin. (Kopańska, et al., 2022; Lietzke, 2023)

Cat Cafe Photo by Hannah Wei on Unsplash

Inhibiting acetylcholinesterase (with coffee perhaps?) could help hair growth then… or promoting mAChR function. Bethanechol was used as an agonist of mAChRs in an animal-based study and hair length was increased in the experimental group. (Yuen, et al., 2024)

Abstract: “The role of cholinergic system in hair biology is poorly understood. In M4 muscarinic receptor (mAChR) knockout mice, the hair follicles have a prolonged telogen phase and failed to produce hair shafts. Here, we reported that hair growth was regulated by cholinergic system via mAChRs. Dermal papilla cells expressed different cholinergic biomarkers. Inhibiting AChE or stimulating mAChR in dermal papilla cells, culture vibrissae and skin epidermis promoted the hair growth. In cultured papilla cells treated with bethanechol, an agonist of mAChR, an activation of Wnt/β-catenin signalling was illustrated by various indicative biomarkers, including phosphorylation of GSK-3β and mRNA expression of various molecules for Wnt/β-catenin signalling. Activation of Wnt/β-catenin signalling was mediated by PI3K/AKT and ERK signalling upon the stimulation of bethanechol. In addition, an increase in hair shaft elongation was observed in mouse vibrissae upon the treatment of bethanechol, suggesting the cholinergic role in hair growth.” (Yuen, et al., 2024)

Anti-cholinergic medications or toxins lead to reduced parasympathetic function - which includes digestive functions, and thinking, and finding our way around.

Non-invasive vagal therapy can include deep breathing exercises, Qi gong or yoga, or admiring nature images - or growing house plants and admiring them.

Anti-cholinergic medications or toxins lead to side effects of impaired Parasympathetic response - that is our calmer, think and relax and digest the meal, mode of action. The Sympathetic response is the get up and run, Fear/flight/fright response. It also has some acetylcholine signaling but norepinephrine and other chemicals are main players. (Scott and Fryer, 2012)

“Subtle and not-so-subtle toxicity: Students often learn the adverse effects of anticholinergics from a mnemonic, e.g.: “Blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a bone, the bowel and bladder lose their tone, and the heart runs alone.” This refers to pupillary dilation and impaired lens accommodation, delusions, hallucinations or delirium, flushing, hyperthermia - [overly hot], dry mucosae and skin, gastrointestinal and bladder paralysis, and tachycardia - [racing heartrate without having run anywhere].⁷ Shorter mnemonics fail to capture the broad range of anticholinergic toxicity shown in Table 3.” (ti.ubc.ca/2018/09/10/113-anticholinergic-antimuscarinic-drugs/)

The mAchRs help with smooth muscle contraction and mucus secretion via parasympathetic signaling, which is needed for digestion. (Scott and Fryer, 2012)

“It is worth noting that parasympathetic nerves also signal through nicotinic acetylcholine receptors [nAChRs] and also release nonacetylcholine (noncholinergic) neurotransmitters such as vasoactive intestinal peptide (VIP) and nitric oxide (NO). Although VIP and NO contribute to vasodilation and mucus secretion in some organs, acetylcholine and muscarinic receptors [mAChRs] typically provide dominant control of smooth muscle contraction and secretion caused by parasympathetic signaling.” (Scott and Fryer, 2012)

The mAChRs are also part of our active thinking skills - seen particularly in our ability to find our way around - navigational skills. (Svoboda, et al., 2017) Does impairment of mAChRs sound like Alzheimer’s dementia? Yes, yes it does.

“Muscarinic acetylcholine receptors (mAChRs) have been found to regulate many diverse functions, ranging from motivation and feeding to spatial navigation, an important and widely studied type of cognitive behavior. Systemic administration of non-selective antagonists of mAChRs, such as scopolamine or atropine, have been found to have adverse effects on a vast majority of place navigation tasks.” (Svoboda, et al., 2017)

»»> How well do you know your anticholinergic drugs?

Dementia may be related to prior use of medications that have anticholinergic side effects. An opinion/letter to the editor by a concerned doctor about prescribing habits and risks that patients rarely are informed of:

10 Sep 2018 [113] How well do you know your anticholinergic (antimuscarinic) drugs?

“Table 1: Anticholinergics in the Top 100 (BC Data, 2016)

• Antidepressants: amitriptyline*, bupropion, citalopram, escitalopram, fluoxetine, mirtazapine, paroxetine, sertraline, venlafaxine

• Antipsychotics: aripiprazole, clozapine, olanzapine, quetiapine, risperidone

• Drugs for insomnia: trazodone, zopiclone

• Drugs for pain: amitriptyline*, cyclobenzaprine

Long term use linked to Dementia: A recent narrative review examined the connection between long-term use of AC drugs and the risk of dementia and identified 4 observational studies of elderly people in France, Germany, and the U.S.⁸ Based on signals from 3 of these 4 studies, the review authors conclude that AC drugs may increase the risk of dementia. They also note signals that people who stop using anticholinergics are at lower risk of dementia than those who continue, and that patients who take higher doses of more potent AC drugs are at greater risk of dementia. The 4 observational studies were not randomized controlled trials and thus cannot prove that anticholinergic drugs cause dementia.

Other long-term effects such as increased dental caries are unquestioned.³” (ti.ubc.ca/2018/09/10/113-anticholinergic-antimuscarinic-drugs/)

Cholinergic function helps us think and learn and helps us perform our daily lives:

“The cholinergic system has been shown to play an important role in processes such as circadian rhythmicity (2), addiction (3), motivation, pain, and reward (1), as well as cognitive flexibility (4), perceptual memory (5), spatial learning (6), and many more.” (Svoboda, et al., 2017)

Improving vagal tone - increasing nerve activity between the gut and brain - can increase parasympathetic response.

Risk: Early childhood trauma can leave impairments in Parasympathetic response and vagal tone, long into adulthood. Practicing mindfulness or meditative practices of some type for a couple months can help retrain the body to use calmer pathways when responding to thoughts or external events.

Vagal nerve stimulation can improve relaxation and promote Parasympathetic calming of the body.

Vagal nerve stimulation with non-invasive methods includes exercise like gardening or yoga - moderate pace and something you enjoy and will continue.

• The Vagus Nerve and 10 All-Natural Ways to Increase Vagal Tone, (healingpoints-acu.com).

Viewing nature can reduce stress response by promoting parasympathetic activity.

Viewing nature, or images of green spaces can help recover after stress by promoting activity of the Parasympathetic Nervous System (PNS). . . Which means that my house plants are good for my parasympathetic activity - as long as they aren’t stressing me out from viewing it as a chore or it becoming a chore.

“Simultaneously recorded electrocardiogram and impedance cardiogram signal was used to derive respiratory sinus arrhythmia (RSA) and pre-ejection period (PEP), indicators of respectively parasympathetic and sympathetic activity. The findings provide support for greater recovery after viewing green scenes, as marked by a stronger increase in RSA as a marker of parasympathetic activity. There were no indications for greater recovery after viewing green scenes in PEP as a marker of sympathetic activity, and there were also no indications of greater buffering effects of green space in neither RSA nor PEP. Overall, our findings are consistent with a predominant role of the parasympathetic nervous system in restorative effects of viewing green space.” (van den Berg, et al., 2015)

A small pomegranate among its green shrub. It has some growing to do yet. Photo by Maedeh Alinejad on Unsplash

Pomegranate peel or leaf extract also soothes cytokine storm and how it might help hair follicles and hair growth (Bhinge, et al., 2021) is discussed in more detail in the document: mAChRs & Nicotine, (sync.com/pdf). See the document for more about kinases and pomegranate and maybe the missing citation is somewhere:

“All drugs having anticholinergic action should be avoided if possible in patients troubled with constipation or urinary retention. [*smooth muscle function is needed for bladder and bowel control]

Also, they should be avoided in patients with Alzheimer disease and other dementias. The pathogenesis of dementia is poorly defined but includes defective cholinergic transmission. Drugs currently approved for managing this disorder resemble physostigmine in action and act to elevate CNS levels of acetylcholine. Obviously, anticholinergic drugs can not only worsen mentation in these patients but counter the beneficial effect of their medication.”  (Ref ?)

• Environmental toxins and neurologic risk: (Aggarwal, et al., 2022)

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health care guidance.

Reference List

Other references are in the document (sync.com/pdf)

mAChR, medchemexpress.com, https://www.medchemexpress.com/Targets/mAChR.html

(Bansal, et al., 2021) Sandhya Bansal, Sudhir Perincheri, Timothy Fleming, et al., Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer–BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines. J Immunol November 15, 2021, 207 (10) 2405-2410; DOI: https://doi.org/10.4049/jimmunol.2100637 https://www.jimmunol.org/content/207/10/2405

(Ogata, et al., 2021) Ogata AF, Cheng CA, Desjardins M, Senussi Y, Sherman AC, Powell M, et al., Circulating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients. Clin Infect Dis. 2022 Mar 1;74(4):715-718. doi: 10.1093/cid/ciab465. PMID: 34015087; PMCID: PMC8241425.

(Pohanka and Dobes, 2013) Pohanka M, Dobes P. Caffeine inhibits acetylcholinesterase, but not butyrylcholinesterase. Int J Mol Sci. 2013 May 8;14(5):9873-82. doi: 10.3390/ijms14059873. PMID: 23698772; PMCID: PMC3676818. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676818/