Ototoxicity Part 4 - Autoimmune disease & Hearing Loss
This got longer than I intended. Plan - I'm going to organize this series into a book format with chapters and more complete diet/self-care info. For now, my eyes are going funky and I need a break.
This series has been very revealing. It deserves some reorganization and recognition by individuals in pain, and by the medical industry who allegedly wants to help improve health. The complete reference list is in a document. I will post that eventually, but need an eye-rest right now - a little tired, squinty, and a few tears. This is disturbing information - the powers that be are still pushing the mRNA injections for CoV and expanding it for other purposes. Our hearing and our brains are at risk.
Pomegranate peel and many other natural solutions can help, however, the chimeric spike is a diabolical bioweapon causing harm in many ways. And it is sad.
“Globally, around 360 million people have ear disorders leading to hearing loss, with children constituting around 32 million of the affected population. According to WHO, these ear diseases cost around 750 billion international dollars worldwide which is quite a burden economically [4]. Of all disorders involving the ear, otitis media (OM) is the most prevalent globally in both high and middle-income countries. Similarly, 60% of the hearing losses are due to preventable causes [5].” (Hamayal, et al., 2024)
Before we move onto autoimmune disease as a causal factor in hearing loss or tinnitus, a few more thoughts about Part 3 and ‘mini-microphones’ or ‘mini-drums’ in our inner ear - the video of a hair cell ‘dancing’ to the sound of “Rock Around the Clock” shows us, in real time, that the hair cell’s pulsing action, on the membrane of the hair cell, does look like drumsticks tapping on a drum more than it looks like ‘hair waving in the wind’. The stereocilia ‘hairs’ are stiff rather than flexibly ‘soft’ like hair on our scalp. Hair can be bristly feeling, especially razor stubble, but you wouldn’t liken it to a drum-stick tapping on a membrane. The stereocilia structures of the inner ear look more like little skyscrapers than razor stubble hair. Types of damage that may occur to hair cells is shown in Figure 1.
More on the prostaglandin prostacyclin’s anti-inflammatory and other beneficial roles in vascular health from Dr. Jack Kruse on X.com
“Prostaglandins are capable of creating their own ATP source for the surrounding cells through cyclooxygenase (COX) isoenzymes pathway. A type of prostaglandin that can do this is prostacyclin (PGI2). This is augmented by PBM and UVA light to release Nitric oxide.
Nitric Oxide (NO), Reactive Oxygen Species (*oxidative stress chemical is the phrase I tend to use for ROS); Molecule of the Year 1992; Signaling Molecule - it can activate various receptor types or TRP channels; Regulator of Microcirculation (=Photovasorelaxation); Blocks CCO (<ATP production).
NO inhibits ATP creation in the mitochondria. So Prostacyclin works with it in a coupled cycle. Prostacyclin is released by vascular endothelium cells is a pathophysiological mediator providing both proliferation and anti-inflammatory functions. It meets the criterion of a targeted circadian biomolecule:
It energizes all the cells it come in contact with
It improves proliferation of cells
It inhibits inflammation in and around cells
It is readily available, local to every cell no matter where the cell(s) maybe located in the human body.” (x.com/DrJackKruse)
Arachidonic acid in cell membrane phospholipids will be converted into Free Arachidonic Acid by the enzyme Phospholipase A2. The Arachidonic Acid may then be converted into COX-1 or COX-2 which aspirin and NSAIDS inhibit. Pomegranate peel and other phytonutrient antioxidants inhibit COX2. Roughly, these are all inflammatory pathways and breast cancer and prostate cancer cells use the HPETE as an energy source, so having less around is better than having more.
Note that in order to make a prostaglandin out of the arachidonic acid from an endogenously produced endocannabinoid, you need to free the endocannabinoid from the cell membrane wall.
“Anandamide can be generated from its membrane phospholipid precursor N-arachidonoyl phosphatidylethanolamine (NAPE) through hydrolysis by a phospholipase D (NAPE-PLD).” (Liu, et al., 2007)
Endocannabinoids are a molecule made from a phospholipid and a lipid. Arachidonic acid is the lipid in the endocannabinoid anandamide or THC is the equivalent form found in medical marijuana. Arachidonoylethanolamide is the ethanolamide of arachidonic acid. Add a phosphorus group, a ‘phosphatidyl’, and the molecule gains an electric charge and polarity, a + end and a - end a little like a battery. (Tsuboi, et al., 2018)
By Mariana Ruiz Villarreal ,LadyofHats - Own work, Public Domain, (commons.wikimedia.org)
Phospholipids will cluster together into a single or double-layer membrane from the electrical attraction and the lipid’s tendency to avoid water. Cell fluid is mostly water while cell membranes are mostly phospholipids and cholesterol and omega 3 fatty acids or other fats. Add in too much polyunsaturated or synthesized trans-fats and a cell membrane may become more fragile or dysfunctional. A lack of cholesterol would leave cell receptors and TRP channels without their preferred cholesterol rich area to locate in within the membrane phospholipid bilayer.
The double layer membrane forms because the lipid end is attracted to the other lipid ends but avoid the water-soluble phosphatidyl end of the endocannabinoid molecule. It becomes like a floating raft, but a water balloon rather than being flat.
Receptors and TRP channels pass through both sides of the lipid bilayer membrane, or some types may be embedded on the outer surface as surface marker proteins.
Too much Arachidonic acid might be released from the cell membrane in response to inflammatory calcium signaling within the cell if there is too much TRP channel activity. That would flood the cell with lots of calcium, which signals the release of endocannabinoids from the cell wall. That can directly add to cell membrane breakdown or fragility if lots of endocannabinoids were released due to lots of inflammatory calcium signaling happening all at once. The cartoon visual - calcium inside of the cell is telling the water balloon to self-destruct one endocannabinoid brick at a time.
Medical marijuana is giving us precursors for prostaglandins and eicosanoids without our breaking down our cell membranes to free endocannabinoids. And while some arachidonic acid release may help from the prostaglandin conversion, an excess of free arachidonic acid signals some types of TRP channels and can increase inflammatory signaling. An excess of free arachidonic acid is associated with a variety of conditions.
Ending the influx of too much calcium is a need. It might be from dietary glutamate stimulating NMDA receptors (NMDA receptors are a type of glutamate receptor), or ongoing pain leading to an increased number of TRP channels and an excess of calcium entry into the cell as the pain continues.
Are phospholipids involved in hearing loss? Yes.
Autoimmune Hearing Loss - autoimmunity & hearing loss is continued after the cannabinoid and Pain/aside, and Ankyrin Binding sections, starting at the Calcium binding section which follows.
Phospholipid autoimmune hearing loss is associated with systemic autoimmune diseases where autoantibodies directed against phospholipids (anti-PLs) are present. These autoantibodies, such as anti-cardiolipin (anti-CL) and anti-beta-2-glycoprotein-1 (anti-beta-2-GP1), are typically found in conditions like systemic lupus erythematosus and antiphospholipid syndrome (APS). These antibodies are linked to thrombotic phenomena and are considered pro-atherogenic.
Research indicates that these autoantibodies might play a role in sudden sensorineural hearing loss (SSHL) by affecting blood flow to the inner ear. The presence of these antibodies can lead to vascular occlusion, which in turn can cause hearing loss. Studies have shown that anti-CL and anti-beta-2-GP1 antibodies occur in 10.5% to 19% of patients with SSHL.
Treatment for phospholipid autoimmune hearing loss often involves immunosuppressive therapy, including corticosteroids like prednisone, intravenous immunoglobulin (IVIG), and other medications such as mycophenolate, azathioprine, and cyclophosphamide. Early and appropriate treatment can potentially reverse the hearing loss, although the condition can sometimes lead to permanent damage if not treated promptly.
Autoimmune antibodies against phospholipids can lead to vascular problems and reduced blood flow to the brain, eyes and ears leading to headaches, vision and hearing problems. The condition is rare. Symptoms of Susac Syndrome may occur in the inner ears, eyes, and/or brain and the condition is frequently misdiagnosed as multiple sclerosis, stroke, encephalitis or other conditions.
“Brain symptoms [of Susac Syndrome, due to reduced blood flow ~ encephalopathy] may include:
Severe headache; Personality Changes; Slurred Speech; Trouble walking.
Problems with thinking, such as short-term memory loss, slow thought processing and reduced ability to solve problems.
That pattern of symptoms reflects the impact of oxidative stress on the brain and ears - hearing loss and cognitive decline are connected at a most basic level, both areas need blood circulation. With reduced blood flow the cells are getting less oxygen and nutrients and less of the cell’s waste and acidity is being removed.
If headaches, vision changes and tinnitus are a combined symptoms pattern, then, circulation and oxidative stress levels likely need to be addressed no matter what other diagnosis is given. An external source of cannabinoids may help supply the body with anti-inflammatory chemicals without having to break down cell membranes to make them.
*Pain can become a ‘habit’ in which case the best treatment might be a mental reset - “Habitual pain is not ‘real’ pain and therefore I don’t need to feel this nerve pain anymore….” strangely, that can be both true, lingering pain pathways remain after a long ago healed injury or remembered trauma, and a mental readjustment can work, even on chronic pain that had lasted a long time. Education about the nerve pathways is the primary ‘treatment’ in that case, plus the medical record showing that there doesn’t seem to be an injury anymore. See: John E. Sarno's book “Healing Back Pain: The Mind-Body Connection,” published in 1991. *lots of used copies are available, (Goodbooks.com)
Phantom limb sensation has to do with endocannabinoid deficiency which is needed for plasticity of the nerve synapses - our ability to learn or forget a nerve pathway. Without endocannabinoids, there isn’t enough signaling to stop maintaining that old pathway, “Forget it, we don’t need it anymore.” Endocannabinoids can make learning a new skill easier too. Phantom limb pain:
Phospholipids are concentrated in the cell membranes, so rich food sources include cucumber seeds, the pulp of orange juice, corn on the cob and the bright yellow germ of the corn kernel. Animal foods with a lot of membranes like eel or sardines or a rich bone broth… or brain tissue and some organ meats, those are from a different source than in that plant-food-oriented list. (Substack)
Nrf2, Notch, CDKs (phosphorylation of proteins) may all have disrupted or overactive function due to the Ankyrin binding sequences in the chimeric spike/S1 subunit.
The presence of ankyrin binding sequences in the chimeric spike protein (Liviero, et al, 2021) helps explain why lack of Nrf2 has been a problem in ‘Covid19’ - Nrf2 also has an ankyrin repeat domain, so chimeric spike may be binding with Nrf2 and disabling its function. Nrf2 promoting foods or supplements have been found helpful for treatment, including the polyphenol quercetin or pomegranate peel.
“Ankyrin repeats are found in many types of proteins besides TRP channels, including several large families of transcription factors (e.g. NFκB and Notch) and regulatory proteins (e.g. cyclin-dependent kinase inhibitors) for example.” (Gaudet, 2008)
Notch protein inhibition is being studied for helping promote regeneration of inner ear hair cells.
Cyclin-dependent kinases (CDKs) are a group of proteins involved in modulating which genes get transcribed into proteins and cell division - controlling growth:
Cyclin-dependent kinases (CDKs) are serine/threonine kinases whose activity depends on a regulatory subunit - a cyclin. Based on the sequence of the kinase domain, CDKs belong to the CMGC group of kinases (named for the initials of some members), along with mitogen-activated protein kinases (MAPKs), glycogen synthase kinase-3 beta (Gsk3β), members of the dual-specificity tyrosine-regulated kinase (DYRK) family and CDK-like kinases [1].” […]
“…the importance of CDKs acting as a major eukaryotic protein kinase family involved in the integration of extracellular and intracellular signals to modulate gene transcription and cell division has been clearly established [3–6].” (Malumbres, et al., 2014)
FOXO3 is a transcription factor that can regulate the expression of CDK inhibitors.
The FOXO3 transcription factor can stimulate the gene transcription of cyclin-dependent kinase inhibitors such as CDKN1A (p21Cip1) and CDKN1B (p27Kip1), which help to control the cell cycle by inhibiting CDK activity. FOXO3 has a protective effect in the inner ear against damage occurring from loud noise exposure.
“A team led by Dr. Patricia White of the University of Rochester previously showed that a protein called Forkhead Box O3 (FOXO3) is expressed in both inner and outer hair cells. FOXO3 is a transcription factor—a type of protein that plays a role in gene regulation. Upon noise exposure, FOXO3 travels into the hair cell nucleus, suggesting it might play a role in the protective response to noise-induced damage. To test this hypothesis, the scientists used mice that had been genetically modified to lack the gene for FOXO3. The study was supported in part by NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD). Results were published on April 21, 2017, in Scientific Reports.”
- ‘Protein involved in hearing loss recovery’, 2017, (nih.gov/news)
Related FOXO3 info and Reason number 1,679,000 Why Pomegranate Peel is the Bee’s Knees — an excerpt from my pomegranate paper’s ‘Table 8. Causal Factors of Pain Hypersensitivity’:
Mitogen-activated protein kinase (MAPK) is inhibited by phytonutrients in pomegranate peel extract (PPE) by the regulation of FOXO3, which would decrease unwanted phosphorylation of proteins, observed in an animal-based study in which PPE reduced ototoxicity caused by amikacin (AMK). (Liu, et al, 2017)
Ototoxicity, damage to Hair cells within the inner ear, is associated with certain medications like amikacin and also seems to be caused by CoV/chimeric spike subunit S1 disrupting ankyrin binding domains of TRP channels in the Hair cells. (Liviero, et al, 2021) Disruption of TRPV-1 channel function by spike protein due to the ankyrin repeat domains may affect a variety of functions in the body including hearing and cause other symptoms resembling Covid19. Liviero, et al, noted the TRPV1 symptoms and suggest trying inhibitors or down-regulators, (Liviero, et al, 2021), however TRP channels have multiple functions and just inhibiting them has not worked for other conditions.
Preventing fusion cleavage with pomegranate peel might be more helpful, then there would be less free S1 subunit floating around ready to bind with ankyrin repeat domains on TRPV-1, TRPA-1, TRPC, or Nrf2, Notch, or CDK kinases. If Notch is being over-activated by S1 chimeric spike, that would add to cancerous cell division as it is considered an oncogene but also can act as a tumor suppressor depending on type of cancer and the stage of progression. Notch signaling and that of Notch1 are critical during fetal development of the inner ear - the complex arrangement of the inner and outer hair cells is affected or controlled by Notch, shown with genetic knockout mice. (Brave AI summary)
According to the Centers for Disease Control and Prevention (CDC), approximately 1.8 per 1,000 infants screened were identified with permanent hearing loss in 2020. (Brave AI summary - It has a few CDC type links, says more current rates are not available.) I wonder what the rate has been since CoV injections started in 2021? VAERS data might be interesting regarding infants and hearing, but this would be more of a prenatal follow-up question. How are the babies of woman who were injected or exposed by exosome shedding?
Post-translational modification of proteins can make them dysfunctional, or more inflammatory, or may add to cancerous out of control cell growth.
What makes post-translational modification (PTM) of proteins more likely, whether by phosphorylation, glycation, or by other changes?
Answer: Oxidative stress levels, mitochondrial dysfunction, high fructose diet, general malnutrition, lack of endocannabinoids, lack of CoQ10. That would be a different paper – or would it? See: Table 10. Nutrients of Concern, *(earlier version, this post). Later version is in the paper, ‘Pomegranate Products for the Pain of Histamine Excess.’ (Pom pdf in my sync file)
If pomegranate isn’t available or not a favorite, then persimmons have similar phytonutrients, the peel and leaves too. Pomegranate leaves or flowers also have catechins and other helpful phytonutrients. The pectin of the inner pith in itself is a health food, like citrus peel pectin. Goji berries (also called Wolf berries), Sumac powder, green or black tea, and red raspberries have a little of the flavan-3-ols, catechins or ellagitannins or hydrolysable tannins are other names. Raspberry leaves make a health supporting tea commonly used during pregnancy but is not a catechin source.
Carrier proteins or binding proteins are transport for active forms of vitamin A and D and electrically active trace minerals.
Catechins and other phytonutrients can help bind minerals and carry the electrically active atoms in a safe way. Iron chelators and zinc ionophores are frequently the same phytonutrient, being able to bind different minerals and be used in medically different ways - or could be a combined treatment for someone with a few problems. The iron chelator helps bind free iron if anemia of chronic inflammation is a problem adding to fatigue. A zinc ionophore can bind zinc and carry it preferentially to a cell that has a lot of iron, which tend to be cancerous or infected, and then the zinc is deposited and it can kill the infected cell. Anti-malarial medication artemisinin is an example of a plant sourced zinc ionophore, and I found it helpful for the fatigue following a covid-like infection in early 2020.
Vitamin D and vitamin A are also carried by a binding protein in their active forms because they do too many important things to be free, or will be inactivated quickly, so the binding protein is like a police car circling the neighborhood, ready if needed to fight an infectious microbe. Vitamin D Binding Protein or GcMAF is the name of the protein transport for activated hormone D, “…Gc protein-derived Macrophage Activating Factor (GcMAF), an endogenous glycosylated vitamin D binding protein responsible for macrophage cell activation”. (Siniscalco, et al., 2014) Jeff Bradstreet is one of the authors of that paper and he got suddenly dead along with other GcMAF researchers - individually, not in a plane load going to a conference like HIV researchers. Jeff Bradstreet had a website blog (web.archive.org/web/20140819190451/http:/drbradstreet.org/?s=gcmaf):
“I am very proud of our recent work published in the highly regarded Journal of Inflammation. http://www.jneuroinflammation.com/content/11/1/78 By clicking on the hyperlink you browser should take you straight to the article which is available for no cost at the journal’s website. Once you are there click on the pdf button (the yellow arrow shows you where to click once you get to the article on the web). Before you jump to article page let me explain in easier language why this article is so important. It is the first article any of us as authors have written that was accepted without any critique or changes, which means the reviewers thought very highly of it. While that is important, it is only part of the significance of our findings. It has always bothered me that minor changes on the gut bacteria and yeast (microbiome) could result in wild and crazy changes in a child’s behaviors. While that observation is common among those of us treating the biology of autism, it was actually very difficult to understand mechanistically at the level of the child’s biology, at least until now.
We believe we have uncovered the nexus (intersection) of the observations regarding Vitamin D deficiency, GcMAF observed improvements in behavior, see: http://www.la-press.com/initial-observations-of-elevated-alpha-n-acetylgalactosaminidase-activ-article-a3450 , immune dysregulation, brain inflammatory changes (mostly in microglial regulation), and the microbiome. Briefly, the endocannabinoid system is part of the cell systems that regulate the immune system and the brain. In particular, it seems the CB2R (cannabinoid 2 receptor) reads the background environment of the individual (diet, microbiome, etc) and sets the tone of the immune defenses. Last year we published the first observations of CB2 dysfunction in autism (J Autism Dev Disord. 2013 Nov;43(11):2686-95. doi: 10.1007/s10803-013-1824-9.). With this follow on work it seems likely that the endocannabinoid system is at the center of the complex biomedical disruptions underpinning the autism epidemic we are observing. Now for your homework. Go the Journal of Neuroinflammation website and get the entire article. After you read it you can ask you questions. (use the link provided in the first paragraph).” ** More current link: semanticscholar.org, (Bradstreet, et al., 2012)
An excerpt from that paper:
“Autism spectrum disorders (ASD) are developmental disorders affecting 1:88 children, and which appear to be associated with a variety of complex immune dysregulations including autoimmunity. The enzyme, alpha-N-acetylgalactosaminidase (Nagalase) deglycosylates serum Gc protein (vitamin D3 – binding protein) rendering it incapable of activating macrophage defenses. Increased Nagalase activity has been associated with a variety of malignancies, immune disorders and viral infections. Macrophage activating factor (GcMAF) has been repeatedly published as an intervention to lower serum Nagalase activity for a variety of cancer and HIV patients. GcMAF is a naturally occurring protein with well-established safety and therapeutic benefit(s) supported by numerous human studies. Methods: Initially, parents of 40 individuals with ASD sought testing for Nagalase serum activity as part of an evaluation of immune dysregulation.” […]
“In this first report of Nagalase activity in patients with autism, it appears that most individuals have substantially higher levels than the expected healthy ranges. Although Nagalase is a nonspecific marker of immune dysregulation, its observed levels in autism may have both etiological and therapeutic significance. Importantly, this is also the first report of reduction of Nagalase activity in an autism population with GcMAF injections.” (Bradstreet, et al., 2012; pdf copy in my sync file)
Giving injections of GcMAF helped reduce elevated Nagalase enzyme levels in patients with autism. It was slightly more than double that of normal levels.
“The average pre-treatment Nagalase activity of the autism group was 1.93 nmol/min/mg of substrate. This was well above the laboratory reported normal range of <0.95 nmol/min/mg. For the ASD group the average level at the time of second testing was 1.03 nmol/min/mg, reflecting an average reduction of 0.90 nmol/min/mg (P < 0.0001).” (Bradstreet, et al., 2012; pdf copy in my sync file)
To bring this closer to homes without autism, Nagalase enzyme is on the surface of the influenza virus and reduces GcMAF levels in patients with an influenza infection and cancer cells may make excess of the enzyme.
The majority of search research on excessive levels of Nagalase enzyme are about cancer. Tumor cells may produce too much of it and lead to reduced levels of Vitamin D Binding protein and therefore too little activated hormone D in circulation to fight cancer or comorbid infections. A flu virus strain has been observed to have Nagalase on its surface though and influenza patients had reduced amounts of Vitamin D Binding Protein/GcMAF/MAF. (Yamamoto and Urade, 2005)
“Serum vitamin D3-binding protein (Gc protein) is the precursor for the principal macrophage activating factor (MAF). The precursor activity of serum Gc protein was reduced in all influenza virus-infected patients. These patient sera contained α-N-acetylgalactosaminidase (Nagalase) that deglycosylates Gc protein. Deglycosylated Gc protein cannot be converted to MAF, thus it loses the MAF precursor activity, leading to immunosuppression.” — ‘Pathogenic significance of α-N-acetylgalactosaminidase activity found in the hemagglutinin of influenza virus’, (Yamamoto and Urade, 2005)
There is a strong association between low levels of 25-D (inactive vitamin D) and hearing loss, particularly in the elderly. Bilateral, both ears, and SSNHL. (Brave AI Summary) Vitamin D is needed for immune function, but it and vitamin K2 are critically important in calcium/magnesium metabolism. Interestingly, Brave AI can find no research on the role of vitamin K or K2 on hearing loss. A search on PubMed found a case report of ten patients who had SSNHL occur during vitamin K inhibiting oral anticoagulant therapy. Three of the cases did not improve. (Mierzwa, et al., 2004)
“It was not possible to demonstrate a relationship between the SSNHL and oral anticoagulation. Vascular compromise cannot be excluded as a cause for sudden hearing loss in patients undergoing oral anticoagulant therapy. It is possible that oral anticoagulants influence the viscosity of the plasma leading to interference with the microcirculation in the inner ear. Further research into this area is currently being conducted.” (Mierzwa, et al., 2004)
Presenting as odd - my search ‘vitamin K inner ear’ - Search Results - PubMed. I got lucky with one full Abstract in English. Despite Mierzwa, et al’s encouraging suggestion that research is underway, that was one of only six results. The others - no Abstract available, and old and foreign… in Japanese, 1969, (/4884757/), German, 1963, /13927594/; Italian, 1959, /13808171/; Italian, 1957, [Relations between cochleovestibular lesions and liver changes caused by streptomycin and therapeutic possibilities of liver protective substances]/13509982/; English, but 1925, Ménière's syndrome; observations on vitamin deficiency as the causative factor; the cochlear disturbance, *this surfaces for ‘vitamin K’ so that may have been a keyword /15393403/. Survivor bias logic - anything newer than 1970 and in English has been removed from the database…. just a guess…. and anticoagulant therapy is probably not good for hearing health….
“The role of vitamin D in Meniere's disease is unclear as no cause has been identified for the increase in endolymphatic fluid.” (Hamayal, et al., 2024)
Additionally, rats raised with extra vitamin K2, “(30 mg/kg, once daily 5 days per week)”, throughout their ‘adult’ timespan, from age 3 months, for the next 17 months and compared to the control group being raised on standard lab animal diet. There was a clear improvement in age or inflammation related biomarkers and healthier hippocampus and cerebral cortex tissue. See: ‘Vitamin K2 (Menaquinone-7) Reverses Age-Related Structural and Cognitive Deterioration in Naturally Aging Rats.’ (Elkattawy, et al., 2022)
“Vit. K2 improved functional performance, reduced social anxiety, depressive-like behavior, and enhanced memory performance with concomitant preservation of hippocampal and cerebral cortex tyrosine hydroxylase expression. Biochemically, Vit. K2 administration restored oxidative-anti-oxidative homeostasis in the brain. Vit. K2 modulated inflammatory signaling, as evidenced by suppression in the brain of NLRP3, caspase-1, Il-1β, TNFα, IL-6, and CD68 expression. Concomitantly, histopathological examination revealed consistent hippocampal and cerebral cortex improvement. Thus, it can be inferred that Vit K2 can slow down age-related changes in the brain associated with modulation of NLRP3/caspase-1/Nrf-2 signaling.” (Elkattawy, et al., 2022)
Woot, there it is… A 30 mg/kg dose for a lab rat would be about 15 mg as a lab rat may weigh around a half a kilogram. The human equivalent dose for a 70 kg person (~ 150 pounds) would be ~ 700 mg or a safety range from 200 mg - 1100 mg per day. The experimental dose was given 5 times a week ongoing from 3 months, which is teen/early adulthood in a rat’s lifespan, through 2 years old which is towards the end of a rat’s lifespan, which is typically 2-4 years.
The equivalent dose would be ~ 15 mg times kilograms body weight would be 1050 mg (1.05 grams) per day, five times a week, for a 70 kg person.
What can humans buy for a vitamin K2 dose?
Life Extension offers a ‘high dose’ Mega Vitamin K2 product with 45 mg of K2 (45000 mcg). $23.40/30 capsules (lifeextension.com) I have used this product, but it has a gelatin capsule which I am suspicious might be a glyphosate source.
Practically every other vitamin K2 product that I have looked at available for sale is in micrograms, a thousandth smaller amount. 100 mcg product, $20.96/365 capsules, (bulksupplements.com) Seems like a good deal? A full year’s supply? 365 x 100 mcg = 36500 mcg = 36.5 mg → There is less vitamin K2 in the entire bottle than in one capsule of the Life Extension product. The bottle of Life Extension Mega Vitamin K2 contains 1350 mg of vitamin K2 or 1.35 grams.
Bulk Supplements does sell vitamin K2 as a powder - that would be the way to get a one gram dose. (bulksupplements.com)
I had already noticed this dosing discrepancy between doses used in animal-based studies on soft tissue calcification and those available for humans to purchase. Awesome results were being achieved with vitamin K2! But then I checked dosing and supplements available… seriously odd. Practically all available vitamin K2 supplements are in micrograms while the animal research used milligrams and the human dose equivalent, weight-based, might have been one gram per day.
To get one gram per day with the Life Extension product (45 mg), I would need to take 22 gelatin capsules per day. To get one gram/day with the Bulk Supplement product (100 mcg = 0.0001 gram), I would need to take 10 of them to get one milligram… and there is 1000 mg in a gram, so I would need to take 10 x 1000 to get one gram… I would need to take 10,000 capsules/day to get the one-gram equivalent dose to the animal-study that had showed such great results at slowing hippocampal damage during aging.
Math matters!
Vitamin D, CYP enzymes and Glyphosate
The liver is the main site of vitamin A activation and transport, making retinol-binding protein (RBP) and it carries activated vitamin A in the circulating blood.
Glyphosate may be interfering with vitamin D metabolism and other areas of physiology - any reactions involving CYP enzymes. If supplementing, the vitamin D3 form may bypass some of the inhibitory effects of glyphosate. A D2 form is what is used for food fortification and in many standard supplements. Gelatin capsules on a supplement may also be a source of more glyphosate as it may be incorporated into an animal’s proteins and gelatin and collagen contain a lot of the similar amino acid glycine. Protein assembly can swap in a bulkier glyphosate in place of the glycine, but then the resulting protein might not fold properly, or a receptor site might be dysfunctional because of the larger glyphosate in the way.
Calcium binding proteins have a critical role in the inner ear for controlling levels of calcium supply as there is an ongoing influx and outflow of calcium.
Calcium binding proteins and parvalbumin - critical within the inner ear to control calcium levels and electrical conductivity.
Calcium flow in and out of hair cells is key in the mechanical transduction of motion into a nerve signal. Calcium binding proteins help control the calcium.
“Many types of hair cells are intensely labeled by fluorescent antibodies against one or more of the diffusible calcium-binding proteins calbindin-D28k, calretinin, parvalbumin-α, and parvalbumin-β (also known as oncomodulin or PV-3).” - Audition, M.A. Rutherford, W.M. Roberts, in The Senses: A Comprehensive Reference, 2008, 3.22.3 Hair Cells, Viewable at ScienceDirect.
“Well, isn’t that interesting.” - The Church Lady, SNL
Animals without albumin had worse otoxicity from the diuretic furosemide (Lasix) frequently prescribed to patients with hypertension. The animals bred to not have albumin in their serum had a large and rapid negative response in the endocochlear potential (EP) when exposed to furosemide in comparison to the control animals. (Rybak, et al., 1993)
Furosemide commonly may cause Hyponatremia, Hypokalemia, Hypomagnesemia, and/or Hypocalcemia (acute deficiency of all the electrolytes = dehydration) and severe Dizziness is also a potential side effect. Tell your doctor right away if you experience hearing changes. Other symptoms are listed:(drugs.com/sfx/furosemide-side-effects). Dizziness will occur with severe dehydration, but in the case of an ototoxin, hair cells of the vestibular system may have been effected and a doctor should be consulted if it continues after hydration was restored.
Pure Maple Syrup can be used to make a rehydration beverage or sports hydration beverage, research tested for athletes rather than dehydrated patients. Mix 1/4 cup of Pure Maple Syrup with one liter/quart of water. *The original maple tree version, not flavored pancake syrup brands.
Manganese content is so excellent that an overdose might be reached with generous daily use of 1/2 cup or more, so limit intake to 1/4-1/2 cup per day for an adult and adjust for children based on size. Manganese supports methylation cycle function and glutathione production.
Rehydrating efficacy of maple water after exercise-induced dehydration
A maple syrup extract Inhibits the Beta Amyloid and Tau Oligomerization of Alzheimer’s disease, March 2015. maplescience.org/research.
*NEW CLINICAL STUDY* Substituting Refined Sugars With Maple Syrup Decreases Key Cardiometabolic Risk Factors in Individuals With Mild Metabolic Alterations: A Randomized, Double-Blind, Controlled Crossover Trial, Aug. 2024. — five percent of the total diet calories were substituted with Pure Maple Syrup and it improved glucose metabolism, cardiac/Metabolic syndrome labs decreasing systolic blood pressure and androgenic fat mass in subjects who were obese. they served as their own control group with a period of time spent on their same diet but with five percent of the calories exchanged for an artificially flavored sugar syrup. maplescience.org/research.
Example - five percent of a 15oo calorie diet would be 75 calories. Pure maple syrup has 110 calories per ounce ~ two tablespoons (info on the bottle). In the study, then, four teaspoons (~ 73 calories) would be exchanged for 75 calories of bread or some other food.
The 1/4 cup of maple syrup in a liter of water for sports hydration would be 220 calories then and might be exchanged for 3 ounces of bread at 75 calories per ounce, (fatsecret.com/calories-nutrition/generic/bread) or a 12-ounce soda has 140-150 calories or a 20-ounce has 210-240 calories. High fructose corn sweeteners may add to risk of non-alcoholic fatty liver disease which has increased in rate, severity and at a much earlier age of onset than in the past. It has negative effects on the gut microbiome too. (Wang, et al., 2022)
Herbal Suntea could be used as the base liquid for more flavor and more polyphenols and is structured water which is more like cellular fluid and is better for health.
“As an exploratory outcome, we further observed that substituting refined sugars with maple syrup promoted selective taxonomic changes in the gut microbiota such as a significant reduction in the abundance of Klebsiella species and decreased microbial functions associated with bacterial-induced cytokine response, when compared with substitution with sucrose syrup.”
— Substituting Refined Sugars With Maple Syrup Decreases Key Cardiometabolic Risk Factors in Individuals With Mild Metabolic Alterations: A Randomized, Double-Blind, Controlled Crossover Trial, Aug. 2024, maplescience.org/research.
and lots more research on the health benefits of phytonutrients and other aspects found in Pure Maple Syrup - maplescience.org/research.
Klebsiella species are normal microbiome species in the gut but in the lungs K. pneumoniae is a cause of pneumonia and meningitis is a further risk from it. Colonization in the gut is associated with the same strain found in the respiratory infections, so it is safer for respiratory risks to not have Klebsiella species in large numbers in the gut microbiome. (Chang, et al, 2021)
Multi-drug resistant strains of Klebsiella have become a problem in hospitals and some strains may produce an enterotoxin which could sicken someone as a gut microbe (1) and some strains have developed resistance to disinfects such as chlorhexidine. (2) Klebsiella species have a protective capsule which helps them resist phagocytosis, engulfment by white blood cells, (3), and makes them more difficult to kill with disinfectants or remove from surfaces. They can form a biofilm cluster.
“Increased resistance of Klebsiella to disinfectants was noted recently, for example, against chlorhexidine, an antiseptic used in hospitals to decontaminate floors and surfaces (Naparstek et al., 2012).” (2)
Pure Maple syrup is a functional food helpful for reducing inflammation. Refined sugar and artificial sweeteners promote gut dysbiosis while Pure Maple Syrup is more beneficial for the gut microbiome and may improve efficacy of antibiotics by significant amounts - less medication was needed for the same antibiotic outcome when a maple syrup extract was given at the same time. It seemed to increase permeability of the bacterial membrane so more of the antibiotics was absorbed, killing more of the bacterial infection.
The 9 Health Benefits of Pure Maple Syrup, (mainemapleproducers.com). *There are probably more than nine.
Syrup is syrup…. Pure Maple Syrup is simply a more nutritious and even antimicrobial source of sugars. Don’t treat it as a ‘free food’ - work it into the diet balance as a carbohydrate swap, for other sweeteners or a little less bread or potatoes for example and add in the liter of maple syrup water throughout the day.
Before moving on from drug resistant Klebsiella strains, you get one guess as to what another phytonutrient rich functional food is that has been found HIGHLY EFFECTIVE against Klebsiella in the gut microbiome …. if you guessed pomegranate peel extract, you are correct. (Brave AI summary)
When all your standard answers stop working, then looking in new directions is needed, or in ancient directions. Pomegranate fruit are revered in the Bible and in other ancient texts. If something has been working well for over 2000 years, why quit using it? Low profit margin…. when illness is profitable, then health will not be for sale, only illness management will be available. Go sit with your back against a tree for 20 minutes and pay me $100…. and your health will improve and my bank account will improve. Fair? Buy this standard antibiotic for $100 and your drug-resistant gut dysbiosis will continue to be a problem but you had a fancy appointment in a fancy office. Eat some pomegranate pith along with the seeds, and dry or freeze some to use during off season and your gut dysbiosis will reset for the price of one pomegranate. Fair?
If you guessed Tea Tree or Cinnamon Essential Oils, then you are also correct. Both have been found effective against the biofilm properties of Klebsiella and other Gram-negative species. Cinnamon oil may have been superior to Tea Tree oil, or a combination was effective - for topical cleaning or for treatment use. Testing other essential oils is a recommendation for further research. (Farazdaq and Sharba, 2022) Essential oils used in combination is a well-tested preventative against Plague in the Middle Ages. Thieves’ would use it to steal from the homes with sick people. See the post ‘Lavender & other essential oils to protect against plague or flu.’ (jenniferdepew.com)
The problem with the modern approach to cleaning or antibiotic treatment is a goal of complete sterility. Nature isn’t ‘sterile’ and it is the beneficial species which help keep negative species in check. Plant phytonutrients tend to kill negative species and allow the beneficial ones to remain. Using essential oils for cleaning is ‘sterilizing’ the negative species, while allowing a beneficial microbiome community to remain.
Autoimmune Disease and Sudden Sensorineural Hearing Loss (SSNHL or SSHL)
Autoimmune disease is associated with sudden hearing loss conditions - sudden being symptoms may begin and progressively worsen into deafness within three months.
Classification and hearing evolution of patients with sudden sensorineural hearing loss. (Penido, et al., 2013)
Food allergies can lead to congestion and that may lead to hearing problems - or an autoimmune molecular mimicry problem occurred and the inner ear parvalbumin became a target….? Albumin antibodies are not typically screened for in autoimmune disease, I have seen it mentioned only in a few research papers.
“Another common allergen that can have a negative impact on the ears is food items such as nuts, eggs, dairy products, and gluten. Food intolerance may have some adverse effects such as infections in the ear as well as itchiness and tinnitus. It has been noted that children are often more susceptible to losing their hearing due to specific food allergies.” (entcenter.md/blog/hearing-loss-due-to-allergies)
Molecular mimicry is more likely to occur in a person who is low in vitamin D which is needed for promoting ‘Tolerance’ T regulatory immune cells which helps us to be less reactive against our own body proteins or a growing fetus.
Gluten, dairy or soy lectins can increase risk of a leaky gut membrane and dietary proteins reaching the blood stream. White blood cells can set up antibodies against the food protein that start attacking similar body proteins. Gluten tends to set up a reaction against thyroid tissue as they are chemically similar in shape. Hypothyroidism is associated with hearing loss and autoimmune hypothyroidism can be related to gluten sensitivity.
Egg white albumin mimicry may cause skin rashes or attack hair follicles in the scalp or hair cells in the ears …it seems. Brave AI gave a summary for which I can’t find the supporting data or matching references. I re-asked with an open-ended question and that led to a list of proteins that have been identified in autoimmune hearing loss - matching what I saw in papers on the topic. (Penido, et al., 2013; Tripathi and Deshmukh, 2022) It includes a few inner ear proteins and antiphospholipid antibodies, but albumin or parvalbumin is not mentioned. Autoimmune albumin antibodies is not a standard lab test or special order that I have found. I have seen it in a few research papers but not in the search results for sudden hearing loss that I read. Phospholipid autoimmune antibodies may be related to the phospholipid content of the CoV mRNA Lipid nanoparticles.
Possibility… egg white allergy/autoimmune disease and hearing loss? Maybe try cutting out albumin sources (there’s lots) and see if symptoms improve, within a few weeks of changing or six months. Strictly cutting out gluten for six months will make the antibodies against it fade away. The memory B cells will still be ready to make more antibodies so avoiding gluten is still important but symptoms should be improved. Avoiding eggs would be the first step, other animal products have albumin containing plasma too, and there is a plant version of albumin in nuts which can be a co-allergy with egg white. Seeds can be a source of plant albumin, hemp kernels, and ginger. Wheat also has some plant albumin.
It turns out that nuts and seeds and whole grains and beans, are just little plant eggs. Which came first, the chicken, the egg, or a tree nut? Nature loves a good protein design and repeats it. The tree nut phyto-albumin probably existed before chicken eggs did. This is a molecular mimicry autoimmune reaction and any further antigens leaking through a bad gut will continue to trigger more autoimmune antibody production.
If this is a problem for you then STOP EATING EGG WHITE, AND MOST ANIMAL PRODUCTS, INCLUDING FISH, ALSO NUTS AND SEEDS. I am serious, I have had autoimmune egg white and then nut symptoms. Removing the food improves the symptoms but might not reverse the condition - hearing damage or hair loss/alopecia.
Brave AI acting puzzled:
*I can’t find any supporting references that specify albumin autoimmune antibodies, however, food allergies in childhood to eggs or nuts has been seen as a fairly common problem by an Ear, Nose, Throat specialist.
Autoimmune albumin antibodies have been implicated in hearing loss, particularly in cases of sudden sensorineural hearing loss (SSNHL) and autoimmune inner ear disease (AIED). Albumin is a protein component of blood plasma, and its presence in the inner ear is unusual. However, studies have demonstrated that autoimmune responses against albumin can occur in the inner ear, leading to damage and hearing loss.
Several studies have reported the presence of antialbumin antibodies in patients with AIED and SSNHL. For example, a study published in the Journal of Otolaryngology found that 12 out of 60 patients with SSNHL had elevated levels of antialbumin antibodies. Another study published in the European Archives of Oto-Rhino-Laryngology reported that 6 out of 8 patients with AIED showed positive antialbumin antibody titers.
The exact mechanisms by which autoimmune albumin antibodies contribute to hearing loss are not fully understood. However, it is thought that these antibodies may bind to albumin in the inner ear, triggering an inflammatory response and leading to damage to the cochlea and other auditory structures.
Treatment for autoimmune albumin antibody-mediated hearing loss typically involves immunosuppressive therapy, such as corticosteroids or other medications that reduce immune system activity. In some cases, intratympanic therapy, which involves injecting medications directly into the middle ear, may also be effective.
In summary, autoimmune albumin antibodies have been linked to hearing loss, particularly in cases of SSNHL and AIED. Further research is needed to fully understand the mechanisms underlying this phenomenon and to develop effective treatments.
Key points:
Autoimmune albumin antibodies have been detected in patients with sudden sensorineural hearing loss (SSNHL) and autoimmune inner ear disease (AIED).
The presence of these antibodies may contribute to hearing loss through an inflammatory response in the inner ear.
Immunosuppressive therapy, including corticosteroids and other medications, may be effective in treating autoimmune albumin antibody-mediated hearing loss.
Intratympanic therapy may also be beneficial in some cases.
Fitzgerald, M. V., Mark, E. J., & Harris, J. P. (2014). Autoimmune inner ear disease. Autoimmune Diseases, 2014, 1-12.
Harris, J. P., Cruz, O. L., & Zanoni, A. (2013). Sudden sensorineural hearing loss: A review of the literature. Otolaryngology - Head and Neck Surgery, 149(3), 341-348.
*Titles similar to real titles but the authors and journals didn’t match.
Interesting - “COVID-19 is a global pandemic caused by the novel coronavirus SARS-CoV-2, and Italy was the first European country to experience a large-scale outbreak. With this, every aspect of healthcare, the economy, and society has been deeply affected in Italy, so much so that fundamental changes are expected in the post-COVID-19 era. One aspect is that access to emergency care in Otolaryngology (ORL) patients has already changed in the month following the onset of the COVID-19 outbreak, and, seemingly, many non-COVID illnesses have been disappearing.” […] “Although some illnesses, such as rhinitis, sinusitis, uvular edema, and tinnitus, do not usually require immediate attention, it is more difficult to explain the large reduction, ranging from 80.2% to 88.9%, of other diagnoses, such as vertigo, epistaxis, sudden hearing loss, otitis media, and peritonsillar abscesses, which often merit urgent ORL consultations. The reduction of some diagnoses may be the consequence of national lockdown orders. For example, the 84.6% reduction in the number of nasal bone fractures may be related to the near-absence of motor vehicle accidents reported during this time. In contrast, it is more difficult to explain the reduction of other acute diseases such as sudden hearing loss, whose frequency decreased 83.3%, especially when compared to non-disease conditions, such as cerumen impaction, whose reduction in presentation, interestingly, was slightly more modest at 73.7%.” https://typeset.io/journals/european-archives-of-oto-rhino-laryngology-32ydzlb0/2020
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fantastic article Jennifer, just brilliant and extremely important... I may need to contact you for further discussion, email or anywhere to contact pls.. thank you
fantastic article Jennifer, just brilliant and extremely important... I may need to contact you for further discussion, email or anywhere to contact pls.. thank you
Mind-boggling information and research. Thank you so much.