Autoimmune Mysthenia gravis and choline transport across nerve synapses; my current structured water hot beverage recipe.
Pomegranate peel might help as a acetylcholinesterase inhibitor. Adequate choline and cholesterol may also be helpful. Also likely helpful, not getting CoV injections or infections.
Draft from Sept. 20 - someone mentioned their concern that I may have Mysthenia gravis (MG). They had belatedly been diagnosed with and therefore aware of it and that it often isn’t diagnosed early but should be because treatment can help, sooner better than later. It is a rare autoimmune disease that causes a droopy eye - and upon learning more, general weakness and fatigue may be present throughout the body, not just in the droopy eye muscles.
A post by DoorlessCarp, ~ re use of 18F-FDG PET/CT scans for the purpose of diagnosing turbocancers that are occurring after CoV jabs. His lengthy article included a case study example with mysthenia gravis, so I figured I should spend the time looking into what the condition is. Procrastination is avoiding reality, or it can be.
I had noticed quite a few years ago that one cheek felt droopy, my smile feels droopy on that side. I asked my family doctor about it and she didn’t notice anything wrong with a cranial nerve screening she did. That was pre-CoV but it does seem more noticeable now. In learning more about MG, it may be congenital due to errors in choline transport - which suggests lack of choline due to genetics might be an additional risk factor. Statin drug use seems to be a risk factor and CoV infections or injections may be a risk too.
Huperzine and other phytonutrient acetylcholinesterase inhibitors might be helpful, and those include gallic acid and ellagic acid which are in pomegranate products.
Acetylcholinesterase inhibitors and cholinergic modulation in Myasthenia Gravis and neuroinflammation
Abstract
The cholinergic network affects various cellular functions including neurotransmission, and immune reactions. In Myasthenia Gravis (MG), diagnosis and symptomatic therapy are based on cholinergic modulation by acetylcholinesterase inhibitors (AChEI). In Alzheimer's disease (AD) a neurodegenerative disorder associated with inflammatory pathology, cholinergic systems cell loss occurs early. Treatments with special AChEI enhance cholinergic transmission and may act as anti-inflammatory agent via immunocompetent cells expressing alpha-7 acetylcholine receptor (AChR). In Multiple Sclerosis (MS) an inflammatory T-cell-mediated disease, demyelination and neurodegeneration follow neuroinflammation. MS treatment includes anti-inflammatory and immunomodulatory drugs. AChEI can induce cholinergic up-regulation with subsequent effect on neuroinflammation via alpha-7-AChR expressing cells. These effects are additional to the cognitive benefit induced by AChEI.” (Brenner, et al., 2008)
Phytonutrient AChEIs include huperzine. (Murray, et al., 2013)
“Huperzine A (5), an alkaloid found in Huperzia spp., is an AChEi commercialized as a dietary supplement for memory support and it is used to treat [Alzheimer’s disease] AD symptoms in China. This alkaloid has been thoroughly studied with promising results yielded particularly from the evaluation of cognitive performance of animals as well as from studies on its efficacy, tolerance and safety.” […]
“Several reviews on the newly discovered AChEi obtained from plants, fungus and marine organisms have also been published over the last years [7-10]. The majority of these AChEi belong to the alkaloid group, including indole, isoquinoline, quinolizidine, piperidine and steroidal alkaloids. On the other hand, several non-alkaloidal and potent AChEi have been obtained from natural sources, including terpenoids, flavonoids and other phenolic compounds.” (Murray, et al., 2013)
Helpful.
And for the slamdunk and win:
“In several studies published during the period covered in the present review various phenolic compounds with different structural characteristics were reported as AChEi. Some of them are structurally simple such as gallic acid (188, IC50 = 5.85 µM) and ellagic acid (189, IC50 = 45.63 µM)” (Murray, et al., 2013)
This post is now being filed under pomegranate. It really is the royal fruit. Why procrastinate when there is pomegranate to eat?
One type of MG involves autoimmune antibodies against the Ig-like domain in Muscle specific kinase which interferes with nerve signaling. IgG4 Muscle specific kinase (MuSK) antibodies interfere with nerve signaling leaving weakness in the muscle in Mysthenia gravis (MG). (Huijbers, et al., 2013)
“Here we demonstrate that human IgG4 MuSK antibodies bind to the first Ig-like domain in MuSK and prevent low-density lipoprotein receptor-related protein 4 (Lrp4) from binding MuSK, thereby inhibiting Agrin-stimulated MuSK phosphorylation. We show that inhibiting the association between Lrp4 and MuSK seems to be the major mechanism by which the MuSK IgG4 antibodies disrupt MuSK signaling and cause MG, because these antibodies neither modulate MuSK surface expression nor have a direct effect on MuSK dimerization.” (Huijbers, et al., 2013)
Thirty to fifty percent of mysthenia gravis patients have the IgG4 MuSK type and it may not respond as well to acetylcholinesterase inhibitors. The differences between it from standard AChR-MG may be enough to suggest that it is a different disease. (Borges and Richman, 2020)
“MuSK-MG differs from AChR-MG, in exhibiting more focal muscle involvement, including neck, shoulder, facial and bulbar-innervated muscles, as well as wasting of the involved muscles. MuSK-MG is highly associated with the HLA DR14-DQ5 haplotype and occurs predominantly in females with onset in the fourth decade of life. Some of the standard treatments of AChR-MG have been found to have limited effectiveness in MuSK-MG, including thymectomy and cholinesterase inhibitors. Therefore, current treatment involves immunosuppression, primarily by corticosteroids. In addition, patients respond especially well to B cell depletion agents, e.g., rituximab, with long-term remissions.” (Borges and Richman, 2020)
It is the nicotinic acetylcholine receptor being discussed, they just refer to it as AChR instead of nAChR. I wonder if this is why I liked nicotine so much. My gut didn’t like it though.
“Most MG patients have circulating antibodies (Abs) to the NMJ postsynaptic neurotransmitter receptor, nicotinic acetylcholine receptor (AChR), AChR-MG (3, 4). The pathogenic role of these Abs has been demonstrated by induction of MG in experimental animals by both passive transfer of MG serum Abs (5) or anti-AChR monoclonal Abs (mAbs) (6–8) and by active immunization with purified AChR (9). For both AChR-MG and its experimental models, the Abs induce a destructive inflammatory attack on the AChR-containing postsynaptic membrane (10–13). In generalized MG, AChR Abs are present in 90 percent of patients. The remaining cases were initially designated as seronegative MG.” (Borges and Richman, 2020)
Congenital types of mysthenia gravis exist
There are other types of MG including congenital reasons. Excerpt from the Abstract mentions a couple SNPs but others are included in the paper.
“Congenital myasthenic syndromes (CMS) are genetic disorders characterised by impaired neuromuscular transmission. This review provides an overview on CMS and highlights recent advances in the field, including novel CMS causative genes and improved therapeutic strategies. CMS due to mutations in SLC5A7 and SLC18A3, impairing the synthesis and recycling of acetylcholine, have recently been described.” (Rodríguez Cruz, et al., 2018)
I have had odd vision since childhood. Maybe my issue is a congenital type. Hyperhomocysteinemia/uria can cause vision or eye conditions and that is a genetic risk that I had classic symptoms of as a child. (Kawasaki, et al., 1999)
I do have two SNPs in my SLC23A1 an SLC2AS…but I don’t know if those are related. SLC23A1 790 G>AGG and SLC2A2 Thr 110 IleC>TCC. Both have “No Impact” per the screening company’s individualized report.
The SLC23A1 and SLC23A2… gene is the Vitamin C Transporter gene. (Duell, et al., 2013)
“The SLC2A2 gene codes the sugar transporter-receptor hGLUT2.” (Michau, et al., 2013)
So, not directly related except they are all solute carriers -SLC-
Genecards: SLC5A7 Gene - Solute Carrier Family 5 Member 7
“This gene encodes a sodium ion- and chloride ion-dependent high-affinity transporter that mediates choline uptake for acetylcholine synthesis in cholinergic neurons. The protein transports choline from the extracellular space into presynaptic terminals for synthesis into acetylcholine. Increased choline uptake results from increased density of this protein in synaptosomal plasma membranes in response to depolarization of cholinergic terminals. Dysfunction of cholinergic signaling has been implicated in various disorders including depression, attention-deficit disorder, and schizophrenia.”
I do seem to have genetic differences in my choline metabolism and/or methylation cycles. Genotype - the genes you have - but epigenetic control affects whether they are turned on or off and of our set of two genes, only one generally is active. So a single gene that is different may not be activated by the body and the good gene is the one that is used. Phenotype - the outcome of your mix of genes plus life factors that may change the potential. Whether I have low choline from gene differences, or no choline carrier protein due to other gene differences, the symptoms that occur from lack of choline might be a similar phenotype. The bigger difference would be that taking extra choline is easier than making up for no choline carrier proteins.
Recent changes include more consistent use of my B supplements and I am adding phosphatidylcholine to my structured water hot beverage (Tibetan yak butter tea equivalent).
Structured water hot vanilla Chaga drink - a little like hot chocolate or a creamy coffee
Recipe ~ 2 1/2 cups hot water, a half or 1 teaspoon of MCT oil and a squirt/teaspoon of the phosphatidylcholine (gooey), about a half teaspoon of vanilla extract, half teaspoon of Chaga powder*. And I do typically add some THC and CBD drops too. Blend at high speed for 30 seconds. It gets frothy and looks like cappuccino.
*Chaga powder purchased from PureBulk was lower oxalate than some that I bought some from nuts.com. It was so high oxalate I can’t use it. I can’t seem to tolerate coffee very well anymore so I gave up trying. Chaga is a bark like medicinal fungus that dissolves nicely in water as powder and seems coffee like.
Cholesterol is involved somehow - Statin use can be a causal factor of Mysthenia gravis.
Statin use has been found to be a cause of new onset mysthenia gravis and also a cause of worsening of milder cases. (search results for one paper show a variety of results on the topic) That might suggest that my eating a cholesterol free vegan diet added risk.
Random browsing - not looking good here - but this is different - IgG4-related disease is when too much IgG4 is being made. (Haldar, et al., 2016) IgG4-related disease is an immune mediated connective tissue disorder that can affect many areas of the body. SARS CoV 2 infection and injections may increase IgG4 and may exacerbate pre-existing IgG4-related disease. (Kobak, 2022)
“IgG4-related disease (IgG4-RD) is a chronic, immune-mediated disorder that often manifests with multiorgan involvement and tumor-like masses most often affecting the pancreas, bile ducts, lacrimal glands, orbital tissues, salivary glands, lungs, kidneys, retroperitoneal tissues, aorta, meninges, and thyroid gland.” (MerckManuals.com)
IgG4 is a CoV topic - excess are being made and it adds to autoimmune risk - related posts:
Elevated IgG4 ~> VAIDS/ a preprint; Flavonoids -> let nature do the microbiology. Short story - the wrong type of antibodies are being made in greater amounts than the type that would fight infection. Instead, the spike is tolerated, ignored, by immune cells. (Substack) March 29, 2023
IgG4 antibodies - the autoimmune kind we don't want, are elevated by increasing # of CoV jabs. Passive exposure is likely similar. My comment regarding a post by Arkmedic, with resources for self-care. We need to be treating more, the sooner the better, and stick with it. Autoimmune disease is not fun. (Substack) Dec. 27, 2022
A post by Igor Chudov, Immune Tolerance: IgG4 Class Switch Starts with Even Two Doses of mRNA Vaccines. This is bad news - and a very interesting new study, Jan. 12, 2023, (Substack)
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
(Borges and Richman, 2020) Borges, L.S., Richman, D.P., Muscle-Specific Kinase Myasthenia Gravis, Frontiers in Immunology, 11, 2020, DOI=10.3389/fimmu.2020.00707, ISSN=1664-3224 https://www.frontiersin.org/articles/10.3389/fimmu.2020.00707
(Brenner, et al., 2008) Brenner T, Nizri E, Irony-Tur-Sinai M, Hamra-Amitay Y, Wirguin I. Acetylcholinesterase inhibitors and cholinergic modulation in Myasthenia Gravis and neuroinflammation. J Neuroimmunol. 2008 Sep 15;201-202:121-7. doi: 10.1016/j.jneuroim.2008.05.022. Epub 2008 Aug 5. PMID: 18684515. https://pubmed.ncbi.nlm.nih.gov/18684515/ paywall
(Haldar, et al., 2016) Haldar D, Cockwell P, Richter AG, Roberts KJ, Hirschfield GM. An overview of the diagnosis and management of immunoglobulin G4-related disease. CMAJ. 2016 Sep 20;188(13):953-961. doi: 10.1503/cmaj.151402. Epub 2016 Jun 20. PMID: 27325130; PMCID: PMC5026513. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026513/
(Huijbers, et al., 2013) Huijbers M.G., Zhang, W., Klooster, R., Jan J. Verschuuren, J.J., et al., MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and Lrp4, PNAS, 110(51);20783-20788, December 2, 2013, https://doi.org/10.1073/pnas.1313944110 https://www.pnas.org/doi/abs/10.1073/pnas.1313944110
(Kawasaki, et al., 1999) Kawasaki, A., Purvin, V.A., Burgett, R.A., Hyperhomocysteinaemia in young patients with non-arteritic anterior ischaemic optic neuropathy, British Journal of Ophthalmology 1999;83:1287-1290. https://bjo.bmj.com/content/83/11/1287
(Murray, et al., 2013) Murray AP, Faraoni MB, Castro MJ, Alza NP, Cavallaro V. Natural AChE Inhibitors from Plants and their Contribution to Alzheimer's Disease Therapy. Curr Neuropharmacol. 2013 Jul;11(4):388-413. doi: 10.2174/1570159X11311040004. PMID: 24381530; PMCID: PMC3744903. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744903/
(Rodríguez Cruz, et al., 2018) Rodríguez Cruz PM, Palace J, Beeson D. The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes. International Journal of Molecular Sciences. 2018; 19(6):1677. https://doi.org/10.3390/ijms19061677 https://www.mdpi.com/1422-0067/19/6/1677
(Yamanaka, et al., 2016) Yamanaka, R., Tabata, S., Shindo, Y. et al. Mitochondrial Mg2+ homeostasis decides cellular energy metabolism and vulnerability to stress. Sci Rep 6, 30027 (2016). https://doi.org/10.1038/srep30027 https://www.nature.com/articles/srep30027
Thanks for the cross ref. Very interesting reviews, especially the IgG4 aspect, adds a whole new level to class switching. Would non specific igG4 do this too?
"IgG4 MuSK antibodies bind to the first Ig-like domain in MuSK and prevent low-density lipoprotein receptor-related protein 4 (Lrp4) from binding MuSK, thereby inhibiting Agrin-stimulated MuSK phosphorylation."
My Aunt in your late 70's developed MG three months after she received a DPT vax (she cut her head hence the doctors decided she needed DPT). Three months she was like paralysed . The drugs and IVGL work but would be nice if can be reversed naturally. I found high doses of Manganese helped greatly.