Hearing protection is a game of balance; Ototoxicity, TRP channels, Salicylate, Histamine and Retinoid Toxicity
Also, bitter taste receptors, Nrf2, NF-kB and mitochondrial function. What is easy? What is hard? The known can be easy and the unknown can be hard until it becomes known, via experience or reading.
Highlights: Working on the hearing-loss topic in a document led to a lengthy list of nutrient deficiencies or excess that may be causal factors in tinnitus or hearing loss. That list looked so much like my list of nutrients involved in schizophrenia and Alzheimer’s dementia risk, and the list of mitochondrial support nutrients depleted by psychiatric medications, that I looked up ‘comorbidity of hearing loss and schizophrenia’. YES, there is a much greater incidence of tinnitus or hearing loss in patients with schizophrenia than in the standard population. And there is also a strong link between mitochondrial dysfunction or disease and hearing loss…
Hmmmm.
That means that protecting our mitochondrial function will likely also help protect our brain and our hearing. So, a long story short, if you work on protecting your hearing and preventing tinnitus, you will likely also be working on preventing schizophrenia and dementia and supporting your mitochondrial function. Mitochondrial support might help hair growth too or prevent premature balding or alopecia. Premature balding seems to be a related risk to later cognitive loss. Related concern: Retinoid toxicity can be a causal factor for alopecia - hair loss, and for tinnitus or hearing loss. Salicylate sensitivity or excess intake also has similar risks to hair cells within hearing and the hair on our head. *Hair cells in the ears are not “hair”.
Hair cells are surrounded by a jelly like fluid which transmits sound waves from the tympanic membrane into the snail like spiral of the cochlea - how far the sound wave travels will vary with the frequency - low or high pitch? And that signaling will inform the brain about the sound. A musician might recognize a note was played or sung wrong while an uneducated ear might not ‘hear’ a difference, although both people heard the same thing. Practice with Suzuki style recordings can train the ear to recognize pitch changes with more accuracy. (It helped me at least.)
Imagine the little yellow hair cells in the image below, as tiny buildings that a strong hurricane wind can topple over an break. Loud explosive sound or wind might be a similar force within the watery inner ear, but more like a tsunami wave flowing by. Fluid that is too thin and watery wouldn’t be protective enough, and dehydration might leave the hair cells without enough of a cushion against motion.
Messages from the brain travel through the efferent synapse and might cue a listener to pay attention for that frequency - listen for the melody. TRP channels and bitter taste receptors may play a role in fine-tuning our listening or learning auditory patterns. When a sound wave or motion tips over the cluster of hair cell ‘hairs’, then an afferent nerve signal is sent to the brain - a sound of that frequency was ‘heard’.
Cells that DO MORE activity, tend to have more mitochondria present than cells that are less functionally busy.
Think about sound - it is a constant throb from our heartbeat and the quiet flow of our breath. It is also the rattling of silverware on plates across the whole restaurant… We can pay less attention to background noise, due to our reticular activating system in the brainstem (RAS), but someone wearing hearing aids may not have that luxury anymore. Someone with elevated hormone D and calcium may not either. Sound hypersensitivity or a hyperactive startle reflex can be auditory health concerns too. Lack of endocannabinoids seems to be involved in the hyperactive startle reflex - over-reacting to a sudden sound, even if you expect the sound. Excess calcium might be a factor in hypersensitivity to sound - the rattling silverware.
…yes, there is a connection between hypercalcemia and hypersensitivity to sound but Brave AI says it isn’t understood why… hyperparathyroidism may be a factor. The current treatment approach (omg) for sound hypersensitivity is to expose the person to more sound, to try to increase tolerance. Sound perception doesn’t really work that way though. With a strong odor or a strong taste, the sensory cells will stop firing after a while and the person becomes “nose blind” to the background odor. Someone new entering the room may be knocked off their feet by the strong odor while the person sitting there all day no longer notices it.
As we learn later in this deep dive (it starts out easy but picks up pace), pain signaling associated with sound perception doesn’t fade, it doesn’t become “nose blind”. Hearing perception becomes damaged is what happens with ongoing exposure to sound. Picture every sound wave, every beat of the music, as hitting on a the shoreline of a beach - those waves are capable of smoothing the beach rocks into shiny pebbles.
The beach rocks in our inner ears are like clusters of skyscrapers, or cellphone towers, which can wave somewhat along with the wave action of the surrounding fluid. This takes place within the hair cell containing organs of the inner ear that perceive sound, - the cochlea, and within the utricle and sacculus of the vestibular system which perceive the motion of our head.
What damages hair cells in the cochlea may or may not also be damaging to the hair cells in the vestibular organs, and vice versa. Things that lead to mitochondrial dysfunction would likely harm function in both areas. As we get further into this post, it becomes clear that things that damage hearing, “ototoxins,” are likely also “mitotoxins” - damaging to mitochondria. And known mitotoxins likely also have ototoxic effects. Later in the post I introduce a new concept “bitotoxins” - substances that damage bitter taste receptors - which also may have negative effects on auditory processing - how well we can listen or pay attention.
Ear anatomy, inner ear, (med.uth.edu).
How does hearing work? Video: (x.com/CuriousX247).
How does loud volume in digital earbuds harm the inner ear hair cells? Video: (x.com/EMT_More).
Messages from the brain travel through the efferent synapse and might cue a listener to pay attention for that frequency - listen for the melody. TRP channels and bitter taste receptors may play a role in fine-tuning our listening or learning auditory patterns. When a sound wave or motion tips over the cluster of hair cell ‘hairs’, then an afferent nerve signal is sent to the brain - a sound of that frequency was ‘heard’.
Hearing protection would help - block out the tsunami and give the inner ear a break from crashing sound waves, or from the motion changes of high-speed gymnastics or amusement park rides.
Headphones, earmuffs, and other sound protecting devices protect us against inflammation in general and that helps protect our mitochondria, our brain, and our ears and hearing too. Strenuous work, or emotional upset, or sleeplessness, might increase inflammation and lead to short-term sensitivity to noise and irritability. Chronic noise or high-speed motion might lead to an ongoing hypersensitivity to noise or motion - TRP channels become expressed in greater number when there is ongoing inflammatory signaling - more on that is included later in the post. A quiet timeout might be just what your ears and your brain need.
Overview of Risks to Our Hearing
Before going deeper into TRPA1 channels and their link to NMDA receptors or to hearing, here is a summary of the main factors affecting tinnitus or hearing risk. They would have additive risks, one might not lead to hearing damage, while a combination of all three might add up to tinnitus or hearing loss.
Triple whammy on hearing and motion sensation:
Ototoxins - medications or other substances particularly damaging to the inner ear or hearing/nerve signaling. Ototoxic antibiotic kanamycin may be in Pfizer CoV injections and the Sars-CoV2 chimeric spike seems to have ototoxic effects. *Listed in a follow-up post Ototoxicity Part 2.
Loud noise or strong vibrations (and any other stressors in life).
Nutrient deficiencies or imbalance. Magnesium, zinc, water, potassium, folate, cysteine, glycine, taurine, thiamine, niacin, all of the B vitamins, CoQ10, alpha lipoic acid, vitamin C, iodine, selenium, N-acetyl carnitine, N-acetyl-glucosamine, … all of the mitochondrial support nutrients. Lack of vitamin A would be a risk, but an excess of activated retinoids is also a risk. Individuals need to figure out if their body is over-activating vitamin A and carotenoids into the active hormone forms of Retinoic Acid. Those help us fight infections, but will cause harm if the body thinks we are in constant need of infection fighting. Retinoid Toxicity can feel like you have a bad flu all of the time.
Life can be viewed as a scale, a balancing act between good and bad, between excess and moderation. Does the Inflammatory signaling of daily life outweigh the Anti-inflammatory signaling and our detox capabilities? Or are you keeping up with detox of daily oxidative waste?
Life is a balancing act. Will you let inflammation weigh you down?
If the negatives of life outweigh the positives, then it will add up to ill health and reduced quality of life. We need the positive self-care strategies to keep up with, or out-weigh the negatives in order to not be accumulating damage. An excess of oxidative stress can accumulate if there is not enough nutrients to detox it. And we need water and movement and a good night’s sleep to help move toxins on through the body to be excreted in sweat or urine. Our brain flow increases during sleep and that is when neuroinflammation from a busy day is cleared out.
Grow the positives, shrink the negatives. Add up to better health.
Hearing can be damaged with a combination of physical damage from sound or a blow to the head, or an infection with internal pressure on the ear, and nutrient deficiency leading to poor detoxification of inflammatory waste chemicals, and exposure to toxins from the environment or medications which are particularly damaging to hearing. Medications and other substances known to be particularly harmful to the inner ear or hearing are called ototoxins.
12 Medications That May Cause Tinnitus (Ringing in the Ears), 2024, goodrx.com.
Noise and Vibration Protection - headphones, noise canceling devices, and also fabric choices in our surroundings can help muffle noise.
Noise or Strong Vibrations: Physically, loud audio noise is also adding to the risk of hearing damage or loss. Damage is accruing over the lifespan as we cannot regrow the motion sensing inner ear Hair Cells, although treatments have been developed that may help. (Ku, et al., 2014; news.mit.edu) Caspases as an enzyme therapy may prevent the loss of regenerative function.
Ear protecting headphones should be worn for lawn mowing, vacuuming, and other loud activities like target shooting or watching action movies ;-). Personal Protective Equipment should be provided for employees when noise is present. Various types of headphones or sound canceling ear plugs are available. (cdc.gov/niosh/noise/prevent/ppe)
Earbud devices should be used with caution as volume may be loud enough to be damaging.
Action movies or public events with the speaker system set too loud may be causing us damage that we aren’t realizing. If it seems uncomfortably loud, discretely pull out a set of sound dampening ear plugs and protect your hearing and health – or leave.
Traffic sounds or strong vibrations of a thumping fan can add to the body’s load of inflammatory chemicals. It will need to be cleaned up, detoxed with use of glutathione or other antioxidants. Ear plugs may protect hearing while the entire body is experiencing increased inflammation. …Leave. Don’t rent that loud apartment. It will be bad for your long-term overall health.
What if you can’t leave? The fabric that we choose for our clothing can help protect against EMF and maybe sound vibrations, or fabric type can make things worse. Choose linen, wool, or unbleached organic cotton fabric for your clothing… (halaihealingplace.com/high-vibrations) Synthetic fabrics attract positively charged ions which are inflammatory and natural fabrics like linen repel the positively charged ions and attract negatively charged ions. Polyester can leave us feeling itchy and hot compared to wearing cotton or linen. Leather, rayon, and silk are somewhere in the middle, see the list below.
“In 2003 Dr. Heidi Yellen conducted a study on the frequencies of fabrics. While demonstrating that a healthy person carries a signature frequency of 100 units of energy, measured in megaHertZ (mHz); an average person carries a frequency of 70-90 mHz and a diseased person generally measures 15 mHz. In her comprehensive study of textiles, Dr. Yellen showed that wearing a material resonating at less than 100 mHz compromises well-being and anything above 100 mHz enhances well-being.” (halaihealingplace.com/high-vibrations)
Tested Fabric Frequency Vibration Values:
5000 mHz - Linen and Wool *Individualize! If you are allergic to wool, then it would add to inflammation for you to wear it rather than reducing inflammation.
100 - 110 mHz - Organic unbleached cotton
40 mHz - Organic bleached cotton
30 mHz - Leather
15 mHz - Bamboo, Rayon, Tencel and Viscose
10 mHz - Silk or Conventional bleached cotton (grown with pesticides)
0 mHz - Synthetics (acrylic, polyester, spandex, nylon, waterproof fabrics and others mostly derived from petroleum). (halaihealingplace.com/high-vibrations)
Acoustically fabrics are rated as either (1) sound transmitting – no interference – if you can blow through the silk or chiffon scarf, then so can sound waves; or (2) sound absorbing, or (3) sound blocking/repelling.
Wool felt is sound absorbing, so it might make a hearing protective winter hat or earmuffs. Window curtains or door hangings can be chosen which muffle noise. Having more folds or pleats to the fabric will increase the sound muffling effects. A pleated linen or wool skirt might help protect the wearer from the inflammatory effect of loud vibrating sounds and reduce EMF exposure. A thick cotton work shirt or jacket will protect a worker against wind or sound vibrations. A traffic policeman’s uniform should be made from protective linen or organic cotton rather than inflammatory synthetic fabrics. (weekendbuilds.com/best-acoustic-fabrics)
With a long history of skin rashes, I have spent my lifetime avoiding all polyester clothing… cotton for me! Maybe I should invest in some nice linen clothing and give it a try. I did have a pleated wool skirt phase during high school. Pleated plaid – it is a puzzle for seamstresses to solve. I don’t like noisy or itchy clothing. Corduroy pants are just too noisy for me, even if it is cotton.
‘Linen and Health – Do you know the health benefits of wearing linen?’, (so-linen.com) Linen may help protect from EMF exposure somewhat. It repels positively charged ions and attracts negatively charged ones which are health promoting instead of an inflammatory health risk.
Ototoxicity - substances known to be a risk to hearing.
Ototoxicity refers to substances that cause damage to the inner ear leading to hearing loss or vestibular balance and sensory changes. A list of known ototoxins is included toward the end of this post. The antibiotic neomycin is an example and thiazide diuretics and salicylate or NSAID pain relievers.
12 Medications That May Cause Tinnitus (Ringing in the Ears), 2024, goodrx.com.
Ototoxicity, (ScienceDirect).
Known Ototoxins are listed in Ototoxicity Part 2, (Substack).
Retinoid medications or Retinoid toxicity may also have ototoxic effects, mentioned earlier and discussed more later. The chimeric spike of SARS-CoV-2 may act as an ototoxin and may also be increasing risk of Retinoid toxicity, based on research with the Epstein Barr Virus and epithelial cells. SARS-CoV2 colonizes endothelial cells instead of epithelial cells. But both cell types are promoted by activated Retinoic Acid and a gene change in a liver enzyme may be triggered by the viral infection - theoretically, this is on the edge of EBV or vaccine injury research. Anything that damages the liver might increase release of an excess of activated retinoids into the rest of the body. An excess of active retinoids over time can cause liver, heart, and brain damage and may be a risk factor in dementia risk along with an excess of histamine and glutamates adding to hippocampus excitotoxicity. That is discussed a little more later in the post. (*Post way too long for email.)
Loud noise is still loud noise, and a hearing risk, but why do some people tolerate it better than others?
The answer, I think, is on the cutting edge of science, at the edge of Nobel Prize winning science. The 2021 Nobel Prize for Physiology was awarded to David Julius and Ardem Patapoutian for their work on the TRPV1 ion channel which responds to capsaicin from hot peppers. They also worked with TRPM8 and other TRP channels. (nobelprize.org) TRPA1 channels are involved in hearing and function in many other ways throughout the body.
// Aside - has anyone been awarded the Nobel Prize for work on extraoral functions of bitter taste receptors? The answer appears to be “No”. G-protein coupled channels have in 2012 (Lefkowitz and Kobilka), and odor sensing receptors won in 2004 (Axel and Buck). Bitter taste receptors are a type of G-protein coupled channel and so are cannabinoid receptors and the niacin/butyrate GP109 receptor. //
Pertinent question: What do mitochondria and our inner ear have in common?
Answer: A susceptibility to oxidative stress and an excess of inflammatory TNF-alpha versus a lack of anti-inflammatory Nrf2 and a lack of our endogenous, internally made antioxidant, glutathione.
TNF-alpha can cause an increase in the expression of TRPA1 ion channels, so there are more of them present in a person experiencing chronic stress. (Fast forward to a self-care solution - magnesium, niacin, butyrate and pomegranate peel or other polyphenol or other Nrf2 promoting foods would be protective. Cysteine, glycine, taurine an N-acetyl carnitine amino acid supplements may help, and Mitochondrial support methyl folate, B12, thiamin, and other Bs, omega 3 fatty acids, zinc, iodine, selenium, vitamin C, alpha lipoic acid and CoQ10.)
Yes, hearing and mitochondrial function are related:
“Hearing impairment is common in patients with mitochondrial disorders, affecting over half of all cases at some time in the course of the disease.” (Scarpelli, et al,, 2012)
This doesn’t necessarily mean that protecting your mitochondria directly affects your inner ears. I think it means that both the inner ears and mitochondria need the same support against oxidative stress and proper hydration – magnesium and antioxidants being critical for both.
Polyphenols and omega 3 fatty acids promote Nrf2 which has a protective effect on hearing and mitochondria by reducing oxidative stress. (Brave AI Summary, lots of research results) Pomegranate, ginseng, saffron, gingko biloba – all may help hearing and possibly in part by promoting Nrf2 which promotes production of glutathione. Taking the amino acids cysteine and glycine can help provide the glutathione precursors we would need to make the endogenous, internally made antioxidant.
Promoting Nrf2 also is inhibiting TNFalpha which is important because inflammatory TNFa promotes more expression of TRPA1 channels (Liu, et al., 2020; Talavera, et al., 2020)) which can lead to more symptoms, as more TRP channels are available to be opened to flood the cell with activity stimulating calcium.
TRP channels are like an on/off switch for cells or for nerve signaling.
TRPA1 channels can send pain signals, or other functions may occur after calcium flows through the open channel across the cell membrane into the cell where it will cause activity to occur. An excess of calcium entry can cause a cell to become overly active even to the point of cell death - this is called excitotoxicity. Dietary glutamate seasonings or aspartame artificial sweeteners can be an external factor in excess brain excitotoxicity and NMDA receptor signaling. An excess of NMDA receptor activity tends to be seen with schizophrenia and hearing loss, and there may be a progression towards cognitive decline and Alzheimer’s dementia.
Magnesium helps prevent over-activation of TRP channels and the risk of excitotoxicity from excessive NMDA receptor activation.
Abnormal NMDA receptor activity may contribute to hearing loss and tinnitus, ...and add to hippocampus damage and later risk of Alzheimer’s dementia.
Noise exposure can cause excitotoxic trauma to the cochlea, leading to NMDA receptor-mediated damage and hearing loss. Lithium chloride, an NMDA receptor antagonist, has been shown to regenerate cochlear synapses damaged by noise-induced excitotoxic trauma.
NMDA receptors are expressed in the inner ear, particularly in the spiral ganglion cells and cochlear hair cells. NMDA receptor expression increased with age in “spiral ganglion neurons (SGN) of the CBA/CaJ mouse cochlea”, while GABA and nicotinic Acetylcholine receptor (nAChR) expression decreased in an animal-based study on “age-related hearing loss – presbycusis”. (Tang, et al., 2014) Nicotine use may improve some aspects of auditory processing in healthy young adults, differentiating sounds in difficult listening settings - fine detail, (Pham, et al., 2019), but smoking is linked to hearing loss and tinnitus, (Brave AI summary), and mitochondrial dysfunction. (Brave AI different summary)
NMDA receptors may be involved in autoimmune inner ear disease, which can cause hearing loss and vestibular symptoms. The immune response may target NMDA receptors in the inner ear, leading to damage and hearing impairment. A case report describes a patient with anti-NMDA receptor encephalitis associated with atrial fibrillation and bilateral sensorineural hearing loss. The patient’s hearing loss improved with immunosuppressive therapy, suggesting an autoimmune mechanism. (Taraschenko, et al., 2014) A similar case study involved an ovarian teratoma preceding autoimmune encephalitis, mania, and bilateral hearing loss. Immunosuppressive treatment and surgical removal of the teratoma helped hearing and improved physical and mental symptoms. (Cheng, et al., 2021)
It is worth noting that NMDA receptor over-activation can be exciting and fun and may be diagnosed as some form of mania or Bipolar disorder and prescribed psychiatric medications, instead of being treated as a physical or dietary issue. Psych medications tend to deplete nutrients and worsen mitochondrial dysfunction and symptoms of mental illness. Histamine excess can also be causal in mania and may be related to NMDA activity and can result from Retinoid toxicity. MCAS has been a problem seen in patients with ‘LongCovid’ following an infection or Covid injection and that would lead to histamine excess too. Histamine is normally a modulatory, brakes, within the brain. An excess means the car’s brakes are broken… Whee! …Mania, or severe paranoia may result. Suicide can be a result of histamine or Retinoid excess even it seems there are no apparent problems in the person’s life. The excess of histamine or Retinoic acid IS the problem.
Talk therapy or psychiatric drugs (other than anti-histamine types) will not help the underlying problem within the person’s brain. If you or a loved one is using an anti-histamine such as Diphenhydramine (Benadryl), Hydroxyzine (Vistaril), Cyproheptadine (Periactin), or Mepyramine (Pyribenzamine), for a psychiatric diagnosis, and it seems to help, then please consider trying a low histamine diet and see if that helps even more. Histamine normally modulates, so an excess is the cause of the anxiety or mania. Removing anything that is triggering mast cells will stop the histamine excess and normalize mental function. Flickering lights triggers mast cells, maybe at an action movie, or strobe lights at a concert, or night driving with oncoming headlights flickering - a migraine the next day suggests histamine excess occurred. Genetically some people don’t have enzyme function to deactivate it. Others may be low in folate needed to deactivate it. See jenniferdepew.com, page MCAS/Histamine, for more on flickering lights and mast cells.
How does this relate to hearing loss or tinnitus? Anything, of any type, that increases oxidative stress, is increasing risk to our hearing. Over-active mast cells increase inflammation with the release of cytokines and the histamine and are telling the immune system to start fighting! something… like tomatoes in the diet or fermented foods. If the person doesn’t know the mast cells are at war with tomatoes and fermented foods, then histamine excess can be a daily problem and extreme anxiety may be a daily problem… for years. The person may think they are “just an anxious person” when really they are a person suffering from a body at war with tomato sauce (also a source of glutamates, and adding to NMDA receptor over-activity and damage to the hippocampus… and Alzheimer’s dementia risk).
The reason things may seem hard, can be because they aren’t easy.
<You can throw your rotten tomatoes here: (___) >
*I did learn about this stuff the hard way. Many years of migraines later… you are learning it the easier way, reading about it.
Research suggests that NMDA receptor blockade may prevent or treat noise-induced tinnitus and hearing loss. NMDA receptor antagonist AM-101 helped treat synaptopathic tinnitus. (Bing, et al., 2015) A study by Chen, et al., 2001 showed that NMDA receptor antagonist (+)-MK-801, can protect against permanent noise-induced hearing loss, but not its potentiation by ototoxic carbon monoxide. Carbon monoxide exposure damaged hearing in some way other than via NMDA receptor activity. (Chen, et al., 2001) (NMDA Brave AI summary)
“Outer hair cell (OHC) loss was not protected by (+)-MK-801 administration. The data suggest that NMDA receptor stimulation may play a role in [Noise-Induced Hearing Loss] NIHL resulting from fairly mild noise exposure. The data do not support a role for NMDA receptor stimulation in the potentiation of NIHL that results from simultaneous exposure to CO and noise.” (Chen, et al., 2001)
Noise or salicylate induced cochlear tinnitus do seem to be related to NMDA receptor activation. (Bing, et al., 2015) Salicylate excess from aspirin or NSAID painkillers, or from dietary sensitivity, can have ototoxic effects on hearing. Being overly acidic or lacking in glycine can increase risk of salicylate accumulation and gene differences in methylation limiting folate can be a factor. Salicylate excess is frequently misdiagnosed as it can appear to be asthma, leg lymphedema, digestive upset, and ADHD like scattered thinking … and tinnitus.
The chances are very good that you would have four or five diagnoses, four or five sets of symptom management medications and four or five specialists, before you were told about salicylate excess or the fairly simple solution - stop use of salicylates. Also, correct an overly acidic physiology (too much phosphorus, animal or simple sugar and starch rich diet, acidic beverages, dehydration, methylation cycle dysfunction). And have adequate glycine intake from protein rich foods or a glycine supplement. Some people might prefer betaine, trimethylglycine, others the dimethylglycine.
Avoiding salicylates is not easy though. Simple to write and simple to do are two different things. Aspirin and NSAID pain-relievers, minty toothpaste, topical pain-relieving ointments, mint lozenges, and a bunch of spices… and dried fruit or mushrooms are rich in salicylates. It is far easier to supplement with Dimethylglycine and reduce over-acidity than it is to restrict dietary salicylates. *DMG supplementation of about 3-5 grams three times a day may be safe and helpful. DMG can help promote sleep when taken before bedtime - cooling the body which is a stage of preparation prior to falling asleep. Betaine, TMG, tends to be in methylation support capsule products in mg amounts. **Salicylate excess also inhibits the methylation cycle function which would add to mitochondrial dysfunction and overall health degeneration.
“For both salicylate- and noise-induced tinnitus, aberrant N-methyl-d-aspartate (NMDA) receptor activation and related auditory nerve excitation have been suggested as origin of cochlear tinnitus.” (Bing, et al., 2015)
NMDA receptors are involved with how we listen, what we pay attention to, maybe, rather than actually responding to sound waves tipping over the hair cells. The hair cells’ motion, the physical waving of the stereocilia of the hair cells, leads to potassium channels opening at their base, and an inflow of calcium leads to an auditory nerve signal firing in a connected/nearby nerve synapse - a sound was heard. (McPherson, 2018) The NMDA receptors associated with a hair cell’s synapses may affect what we think about the sound, or if we are going to start listening harder. NMDA receptors can send outgoing messages from the inner ear or receive messages from the brain stem and affect the hearing process. Acetylcholine can be a signaling chemical in auditory processing too at nicotinic acetylcholine receptors, (nAChRs).
The waving movement design of hair cells in the inner ear also detects movement in the water surrounding fish and helps the fish to escape from predators or to find a mate. (McPherson, 2018)
We are a fish out of water and we need to carry our ocean internally.
Adequate hydration and magnesium and potassium are essential for our inner ear hair cells to have a supporting cushion of cellular fluid. Dehydration can lead to tinnitus, or tinnitus can be a symptom indicating a need to evaluate for dehydration or fluid imbalance - puffy swelling in the legs or body suggest that fluid is not staying where it is needed and is instead collecting in extracellular spaces leaving tissues like joint capsules or maybe the inner ear, high and dry. (Brave AI summary) Edema can be a symptom of salicylate or NSAID excess and that can include an excess of COX 2 inhibiting phytonutrient antioxidants - an excess of pomegranate peel.
Things don’t seem easy, when they aren’t easy. Facts…
TRPA1 channels in the inner ear cochlea do not seem to be involved in hearing directly. (Ramkumar, et al., 2022)
TRPA1 channels are expressed in greater numbers on the support cells of the inner ear than on the hair cells, although they or other TRP channels are interconnected with the motion sensitive pore of the hair cells which is faster acting. Calcium flow is in milliseconds for the hair cell transducer pore and seconds for TRP channels. (Ramkumar, et al., 2022; García-Añoveros and Duggan, 2007)
What do TRPA1 channels do for us within the inner ear?
They do their main job - signal pain! (Nagata, et al., 2005; Vélez-Ortega, et al., 2023)
We hear the loud noise first - in milliseconds (mechanical transduction by the pore of the hair cell cluster) and feel the pain from it a second later (associated TRPA1 or other TRP channels).
If a noise seems painfully loud… then it is! Sometimes things are easy. If something is repetitively annoying, then that too is a pattern that you don’t want repeating in your mind and waving through your inner ear hair cells. If you are the caretaker for a historic building, do you want to host loud bands or have jackhammers going in the parking lot all day? The vibrations would be wearing on the building’s structure - and give everyone inside a headache.
Grounding in nature restores our vibrations to the lower natural setting — sitting outdoors, or leaning against a tree, helps us absorb more healing negatively charged ions and get in synch with the far slower frequency of the planet’s vibration than modern life gives us.
TRPA1 channels may play a role in auditory processing and plasticity along with the NMDA receptors. (Vélez-Ortega, et al., 2023)
Plasticity refers to learning and forgetting within the brain. What we pay attention to more can become a patterned pathway, while what we don’t use regularly becomes forgotten information or a changed habit. That is called brain or nerve plasticity - we can learn the melody of a new song and forget an old one that we no longer listen to or never sing anymore.
Noise sensitivity following loud noise involves regulation by the TRPA1 channels.
The oxidative stress chemicals left after some sort of trauma or cellular workload are activators of the TRPA1 channels. Any stimulation will be adding to the oxidative signaling and that is also signaling to make even greater concentrations of TRP channels. There’s a problem here, something painful, we need to pay even closer attention to the issue!
*References for this background info on TRP channels and pain signaling is in my pomegranate for nociceptive pain paper which has an extensive section on TRP channels and also gets into bitter taste receptors and leptin receptors within the Tables of supporting information. ‘Pomegranate Products for the Pain of Histamine Excess.’ copyright 2024, Jennifer Depew, RD, (Pom pdf in my sync file)
Several Substack posts have the leptin & bitter taste receptors sections; Leptin Resistance Protocol - (Substack); and the GLP-1 story & bitter taste receptors also is in a few, (Substack).
Having healthy white blood cells ready to clean up bits of cellular debris would be protective of hearing. Sound waves within the ear are creating oxidative stress waste. Having an impaired or already overloaded amount of cellular mess would increase risk of inner ear cells being damaged or dying from the toxic signaling. The mess is too big, and clean-up can’t keep up — taking extra nutrients is handing the janitorial crew more supplies. Getting a good night’s sleep helps give the janitors the whole night shift to work. While a thorough stretching work-out during the day helps move toxic debris out through sweat or moves lymphatic flow to be cleaned and excreted in urine eventually.
Dysfunctional senescence is another route for cells during chronic degeneration, but senescence isn’t necessarily part of healthy aging. We should be removing aged cells and some polyphenols may help promote that.
*Senescence during fetal growth stages is a normal part of inner ear development, but that is not related here. It shows us that nature doesn’t make mistakes, stuff might just be happening at the wrong time. Cancer is likely from cells that no longer have normal controls in place, so anything might happen, an excess of activity. Phytonutrients are the way plants handle whatever the weather throws at them without having to consult a doctor. MicroRNA is the nature magic, also a side story for now.
“TRPA1 channels are activated by endogenous products of oxidative stress and extracellular ATP. Since both these stimuli are present in vivo after acoustic trauma, TRPA1 activation after noise may affect cochlear sensitivity through supporting cell contractions. Consistently, TRPA1 deficiency results in larger but less prolonged noise-induced temporary shift of hearing thresholds, accompanied by permanent changes of latency of the auditory brainstem responses. We conclude that TRPA1 contributes to the regulation of cochlear sensitivity after acoustic trauma.” (Vélez-Ortega, et al., 2023)
The value in pain… is in directing us to change our habits, and to stop the cause of the pain.
Inflammation in general includes both pain-signaling by TRP channels, and an increase in expression of TRP channels at the location of the pain or throughout the body. Nature is helping us by making us more sensitive to pain, so we will pay more attention to it …and locate the cause of the pain, change our habits and stop the cause of the pain. As long as the pain continues, the increase in TRP channel expression and increasing sensitivity will continue to escalate.
When will you get off that merry-go-round?
Taking pain-relieving medications may be masking the pain, but the cause is likely still present and an ongoing increase in number of TRP channels is likely to still be happening. Pain relievers may also be adding ototoxic damage to a sensitive situation.
“TRPV1 expression in the cochlea is under control of oxidative stress (produced primarily by NOX3 NADPH oxidase) as well as STAT1 and STAT3 transcription factors, which differentially modulate inflammatory and apoptotic signals in the cochlea. Inhibition of oxidative stress or inflammation reduces the expression of TRPV1 channels and protects against cochlear damage and hearing loss.” (Ramkumar, et al., 2022)
Studying TRP channels is not easy because their activation or inhibition seems to be modulated by unknown factors (*bitter taste receptors maybe, my guess). Both capsaicin from hot peppers and the cancer drug cisplatin can activate TRPV1 channels. Cisplatin is ototoxic and ‘knocking’ out the TRPV1 channels (in a genetic knockout mouse model), helps protect against hearing loss during cisplatin treatment, but activating the channels with capsaicin was protective of hearing loss from cisplatin exposure.
“TRPV1 channels are activated by both capsaicin and cisplatin, which produce differential effects on the inner ear. How these differential actions are produced is yet to be determined. It is clear that TRPV1 is an essential component of cisplatin ototoxicity as knockdown of these channels protects against hearing loss. In contrast, activation of TRPV1 by capsaicin protected against subsequent hearing loss induced by cisplatin.” […]
“TRPV1 has been shown to mediate the entry of aminoglycosides [*an antibiotic which is an ototoxin] into the hair cells.” […]
“To date, several types of TRP channels have been identified in the cochlea. These channels are divided into seven subfamilies based on sequence homology and include TRPV (vanilloid), TRPA (ankyrin), TRPN1, TRPM (melastatin), TRPC (classical), TRPP (polycystin), and TRPML (mucolipin).” (Ramkumar, et al., 2022)
Are phytonutrients magic? or magically attuned to decrease inflammatory signaling?
Coincidentally, or causally, capsaicin can activate bitter taste receptors in people with certain variants of the bitter taste receptors TAS2R38 and TAS2R3, -4, -5. (Nolden, et al., 2016)
There are 25 known types of bitter taste receptors in humans. Other species can have even more, more fine-tuning of their taste sensitivity.
“Extraoral” bitter taste receptors are found in many organs of the body where they do medically functional things, in addition to signaling a bitter taste on the tongue. The general theory is that we taste bitter substances to avoid bitter toxins, but dose makes the medicine or the poison. I think bitter tastes are nature’s medicine cabinet for us and by making some of them tasty, spicy or pleasant, we can taste our way to a correct dose of something fairly specific needed for our current state of health or illness - based on past taste and health experiences that are remembered, or an experienced grandma or herbalist.
Satiety and having eaten enough is also somewhat regulated by bitter tastes passing through our digestive tract. Ghrelin and GLP-1 hormone are affected by bitter taste receptors. Bitter taste receptors seem to work in coordination with leptin receptors as well as other types of TRP or calcium channels. Bitter taste receptors on a cell membrane are like a doorbell buzzer, it can be activated from the outside, and something else happens inside. TRP or calcium channels are pores through the membrane which can be open or closed and preferentially let only a few types of chemicals through. (Lu, et al., 2017) I digress. Hearing is the topic.
…Hearing is still the topic — research has shown that bitter taste receptors, TAS2Rs, are present in the inner ears of various species, including humans, mice, and rats. They are expressed in the cochlear and vestibular systems, which are responsible for hearing and balance, respectively. The exact functions of TAS2Rs in the inner ears are still being learned but may include:
Detection of toxins: One possibility is that TAS2Rs in the inner ears detect toxins or harmful substances in the endolymph, the fluid that fills the inner ear structures. This could help protect the inner ear from damage and signal for immune cells.
TAS2Rs can respond to bacterial infection by sensing proteins commonly produced by bacteria. TAS2R38 could signal presence of Quorum sensing molecules (QSMs) derived from Gram-negative bacteria, (acyl-homoserine lactones (AHLs), quinolones and their metabolites) or “quorum detection molecules (different from AHLs) released by Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus [33], Staphylococcus epidermidis [34], or Bacillus cereus [35].” (Tuzim and Korolczuk, 2021)
The rs1376251 allele of TAS2R50 was most commonly found in a study on chronic ear infection from samples of middle ear fluid from the sick compared to the control group. (Kaufman, et al., 2021)
Regulation of ion balance: TAS2Rs may play a role in maintaining ion balance in the inner ear, which is crucial for proper functioning of the auditory and vestibular systems. (Tuzim and Korolczuk, 2021)
Modulation of auditory processing: Some studies suggest that TAS2Rs in the cochlea may modulate auditory processing, potentially influencing sound perception or hearing thresholds.” (Brave AI summary)
“Emerging evidence also supports the hypothesis that in addition to innate immunity, TAS2Rs function as a novel arm of the adaptive immune response. Some human resting or activated lymphocytes have been found to express multiple TAS2R isoforms and respond to multiple types of bitter agonists.” (Tuzim and Korolczuk, 2021)
Bitter taste receptors do function in coordination with TRP channels, in the graphic abstract example shown below. TRPM5 is blue-green in this example and is a fairly common partner of bitter taste receptors (olive-green in the graphic) which are found in extraoral/non-tongue tissue throughout the body doing a variety of important functions for us.
The short story shown above, is a bitter tasting phytonutrient or bacterial chemical or some agonist causes activation of a bitter taste receptor on a cell membrane. That causes action within the cell, which leads to a calcium increase in the cell, which activates the TRPM5 ion channel in the membrane from within. The TRPM5 channel opens and allows entry of sodium into the cell which activates a calcium homeostasis modulator channel, CALHM1 or 3, which releases ATP from inside the cell into the exterior. Within extracellular fluid ATP acts as a signaling chemical instead of being used for energy. It can cause activation of other TRP channels or attract immune cells that are nearby.
Within the lungs bitter taste receptors can help thin mucus and increase movement of it up and out through more opened airway passages - eating citrus peel can do that for asthma or lung congestion! Citrus peel might make a histamine excess problem worse, but is EXTREMELY effective at relieving stubborn congestion. Eat some more every 4-6 hours or as symptoms persist. Dosing by taste seems to work, it seems to taste more bitter as the congestion symptoms become milder. **Based on my personal experience during 2020 covid19-like illness, untested, self-recovery.
Respiratory congestion and infections may include ear congestion and a risk for hearing. “Ear Congestion” - overview and self-care tips, (verywellhealth.com).
Genes that may be a cause of deafness if dysfunctional.
By using Survivorship Bias logic on the genes that may be associated with deafness if a dysfunctional allele occurs in a baby, we can get a feel for what the body might find critically important for the survival of our hearing function.
A research team, Hickox, et al., 2017, screened samples of Hair cell and other inner ear tissue samples for all proteins found in the samples. Thousands were identified, some proteins were new to the location, others were already known as hair cell proteins. The research team then compared what they found with genes known to cause deafness, and looked closer at proteins found in the Hair Cell samples, thinking the hair cells would be more critical to hearing than other parts of the inner ear.
I think they are onto something in Table 4 - candidate genes for deafness - they MAY be causal of deafness. More research is needed to confirm or refute. I may be wrong in my interpretation of their lengthy paper and its exhaustive data. (I went to bed while writing this section, good morning, I’m back at it).
The last gene in “Table 4. Candidate deafness genes identified uniquely in the GFP+ [hair cell] HC sample” is “Casz1 Q9CWL2 Castor zinc finger 1”. (Hickox, et al., 2017) Zinc finger protein is a gene transcription factor which I mentioned as being necessary for our ability to make bitter taste receptors…. that suggests that bitter taste receptors do have some critical role in hearing that prevents deafness. Or it suggests that the zinc finger protein is simply critical during the fetal development of our ability to hear. Casz1 is needed for normal fetal development of the heart. (Liu, et al., 2014)
»»» Critical take-home-point number 1 - we need zinc to be able to hear well and women/pregnant people really need adequate zinc during pregnancy in order to grow a baby well.
»»» Take-home-point #2 - our inner ear needs to be able to inhibit inflammatory TNFalpha and NF-kB.
»»» Take-home-point #3 - Mitochondrial function seems essential for hair cell function.
Inflammation inhibitor proteins:
Interesting tie-in between hippocampal brain health and our inner ear hair cells. A protein that is involved in brain cell survival within the hippocampus was found in inner ear hair cell tissue - Nfatc4 Q8K120 Nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 4, (Hickox, et al., 2017). Anti-inflammatory Nrf2 is also a Nuclear factor gene and protein. Nuclear factor proteins are also involved in gene transcription.
“Nuclear factor of activated T cells (NFATc4) is required for BDNF-dependent survival of adult-born neurons and spatial memory formation in the hippocampus” (Wikidata)
Otud7b B2RUR8 OTU domain containing 7B, (Hickox, et al., 2017) — Not having this protein would be like not having Nrf2’s anti-inflammatory help to keep NFkB inhibited. This protein negatively regulates, keeps in check, the inflammatory NF-kappa-B pathway. (uniprot.org)
Asb3 A8Y5I6 Ankyrin repeat and SOCS box-containing 3, (Table 4, Hickox, et al., 2017)
Not super helpful Alphabet Soup: “While the ankyrin repeats of ASB3 interact with the C-terminal 37 amino acids of TNF-R2, the SOCS box of ASB3 is responsible for recruiting the E3 ubiquitin ligase adaptors Elongins-B/C, leading to TNF-R2 ubiquitination on multiple lysine residues within its C-terminal region.” … The Asb3 protein isn’t part of TRPA1 ion channels ankyrin repeat domains, but it does seem involved in deactivation (ubiquitination) of the inflammatory TNF-alpha pathway. (Chung, et al., 2005)
Mitochondrial function proteins
The number of mitochondria in a cell type varies with the amount of work that cell type performs. Cells that do more active work may have several hundreds of mitochondria within them while other cell types have less than a hundred. Mitochondria transform energy from sugars, fats or occasionally amino acids, into usable energy held within molecules of magnesium-ATP. …Magnesium is VERY important for protecting our hearing and for mitochondrial function.
Seven mitochondrial proteins that were found in an inner ear hair cell sample, which potentially may be a risk for deafness if a dysfunctional allele occurred, (Genes from Table 4, Hickox, et al., 2017):
Mrpl9(1) Q99N94 Mitochondrial ribosomal protein L9
Mrps11(1) Q3U8Y1 Mitochondrial ribosomal protein S11
Mpc1 D3Z786 Mitochondrial pyruvate carrier 1
Tars2 Q3TP97 Threonyl-tRNA synthetase 2, mitochondrial (putative)
This is also a mitochondrial protein, important in the electron transport chain: Uqcc2 D3Z4D6 Ubiquinol-cytochrome c reductase complex assembly factor 2 (Brave AI Summary)
And this is also an electron transport chain protein, Sdhc D3Z1A8 Succinate dehydrogenase complex, subunit C, integral membrane protein (Brave AI summary)
A mitochondrial inner membrane protein: Ppox P51175 Protoporphyrinogen oxidase, “This protein is a flavoprotein associated with the outer surface of the inner mitochondrial membrane.[7]” (en.wikipedia.org/wiki/Protoporphyrinogen_oxidase)
A good question: ‘Why study inner ear hair cell mitochondria?’ (Lesus, et al., 2019) Their answer in part - mitochondrial deafness is common with aminoglycoside damage. And mitochondria have different subtypes and a large-size subtype of mitochondria seem to have an important role in hair cells of the cochlea and vestibular system.
“Both cochlear and vestibular hair cells have specialized subsets of mitochondria in the apical portion of the hair cell. In cochlear outer hair cells, these large subcuticular mitochondria (see Fig. 5-14 in [16]) surround the apically-located Hensen bodies [39]”. (Lesus, et al., 2019)
Without getting into the microscopic detail, the larger take home point seems to be that anything that is ‘mito-toxic’ is likely also ototoxic. Unlike “Bitotoxin” (*damaging to bitter taste receptors, a word I just made up in this post), Mitotoxin is a word - substances that are damaging to mitochondria. (Wikipedia) A lot of medications have been found to be mitotoxic. The drug approval process hadn’t required, or known about, mitochondrial risks from drugs and so testing for mitochondrial damage hadn’t/hasn’t been a requirement. But it should be added. And drugs that were ‘grandfathered’ in, didn’t require any additional safety testing… and they should be tested for safety.
This last protein I’m going to mention (there were more on Table 4 but they seemed less related) may be part of the mechanical transduction nerve signal that is sent from a hair cell in response to the physical shift caused by a sound wave or head motion. (The associated TRPA1 channel is activated by an associated electrical polarity change related to the physical movement of the hair cell ‘hairs’.)
Plekho1(2) F6XQM2 Pleckstrin homology domain containing, family O member 1, (Hickox, et al., 2017) — This protein might have a role in the mechanical transduction of motion into a nerve signal in hair cells - The PH domain is often associated with proteins involved in mechanotransduction, such as harmonin, in hair cells." (Brave AI guessing) The proteins were from inner ear tissue samples - so the hair cell origin is known.
Bitter taste receptors are in our brain in our hippocampus - and in our inner ears - are they a link between the risk of hearing loss being associated with later cognitive decline?
“Over the past decades, researchers have detected numerous functional TAS2Rs and their downstream effector proteins, such as α-gustducine, PLCβ2, IP3R3, and TRPM5, in animal and human central nervous systems (CNSs), with the highest recorded expression on neuronal populations of the brain stem, hypothalamus, cerebral cortex, cerebellum, nucleus accumbens, hippocampus, and cuboidal epithelial cells of the choroid plexus (CP) located in the ventricular system (Tables 1, 2, 3) [120, 189,190,191,192,193]. Although several exogenous bitter ligands that can cross the blood–brain barrier (BBB), such as food-derived di- and tripeptides [190, 194] or Q [189], have been identified so far, whether these molecules physiologically achieve sufficiently high concentration in the CNS, which is necessary for the activation of brain TAS2Rs, is not known. The importance of these receptors should not be neglected, as some of their bitter agonists show neuroactive [195], neuroprotective [196], or anti-glioma properties [197]. However, the function of the above structures in the nervous system has not yet been determined.” (Tuzim and Korolczuk, 2021)
Medications given to patients diagnosed with schizophrenia seem to be bitter taste receptor toxic — Bitotoxic?
Smoking of whatever sort, may also harm bitter taste receptors, as smokers frequently lose their sense of taste. (Tuzim and Korolczuk, 2021) Aside-mentioned earlier/ Adequate zinc is critical as the gene transcription for us to make bitter taste receptors requires zinc.
“Analysis of autopsied human brain tissue has shown altered expression of TAS2R mRNA at least in the frontal cortex and substantia nigra of patients with Parkinson's disease, in the frontal and entorhinal cortex of patients with Alzheimer's disease and progressive supranuclear palsy, and in the frontal cortex and cerebellum of patients with Creutzfeldt-Jakob disease [200, 201,202,]. Furthermore, post-mortem studies of brain samples from the dorsolateral prefrontal cortex of patients with chronic schizophrenia revealed down-regulation of hTAS2R4, -5, -13, and -50 mRNA compared to those in control subjects with no history of psychiatric episodes. The expression level of all TAS2Rs was found to correlate inversely with the daily chlorpromazine dose. None of them, however, was associated with the duration of the diseases or the severity of negative symptoms. This suggests that these receptors are possibly involved in the mechanism of action or side effects of antipsychotics [202].” (Tuzim and Korolczuk, 2021)
Additional details about extraoral bitter taste receptors.
GABA is an amino acid which we can make and it acts as a calming, inhibiting neurotransmitter within the brain… and was mentioned earlier as having some roles within the inner ear. Here we learn that GABA may be involved in regulation of extraoral bitter taste receptors.
GABA, worth noting - “Low molecular weight compounds are also known as bitterness-masking compounds. Indeed, some umami substances, irrespective of their structure (peptide and non-peptide), can induce receptor-mediated inhibition of bitter ligand binding to human bitter taste receptors [273]. This was further confirmed by Pydi et al., who identified γ-aminobutyric acid (GABA) and Nα,Nα-bis(carboxymethyl)-l-lysine as the first endogenous antagonist and inverse agonist of TAS2R4 [274]. GABA is not only the principal inhibitory neurotransmitter in the adult brain, but is also found outside the CNS, such as is in the airway epithelium, stomach, lungs, kidney, blood cells, pancreas, and testis [275]. This indicates that GABA might play a key role in regulating the function of TAS2R4 in some of these tissues or organs. The antagonist activity of GABA on the remaining 24 TAS2Rs remains to be analysed.” (Tuzim and Korolczuk, 2021)
Medications that are modified for taste may have lost their medical potency. And gene alleles that affect bitter taste may also interfere with function of a pharmaceutical based on a bitter tasting chemical and its actions on bitter taste receptors in the body.
Conclusion: “Undeniably, the discovery of extra-oral TAS2Rs has revolutionised the field of pharmacology, toxicology, and nutrigenomics. On one hand, these proteins may be responsible for several side effects associated with the use of various drugs, 30% of which affect GPCRs and most of which possess bitter taste [37, 280]. On the other hand, it is worth debating whether the debiterattion of bitter medications, especially those designed for children, reduces their therapeutic effectiveness. The taste of substances has not been considered in the context of their effects on TAS2Rs. Hence, this aspect should be considered prior to the widespread practice of improving the taste values of food products.” (Tuzim and Korolczuk, 2021)
Reason number 1,678,999 that pomegranate and pomegranate peel are super cool - and green and black tea too, and goji berries, persimmons, and sumac powder. Catechins including EGCG, theaflavones and isoflavones including genistein are known agonists of the TAS2R39 bitter taste receptors which may regulate enterohormones affecting food intake. While EGCG is specific to the TAS2R39 type other catechins activate other bitter taste receptors too. TAS2R39 responds to inflammatory cytokines and TGF-beta. (Jalševac , et al., 2022) That catechins and other polyphenols activate a receptor geared to respond to inflammation suggests they may be anti-inflammatory by blocking that.
“The importance of TAS2Rs in the respiratory system came out of a study that inspected nasal mucosa in patients suffering from allergies. Both healthy individuals and allergic rhinitis patients were included in the study, which showed that bitter taste receptors, including TAS2R39, are ubiquitously present in nasal tissue and that their expression is increased in allergic patients. Further experiments revealed that TAS2R39 expression in this type of tissue increases when stimulated by certain cytokines, namely IL-3, IL-5, IL-10 and TGF-β. Whereas interleukins induced the expression of several bitter taste receptors, TGF-β up-regulated only TAS2R39 (14).” (Jalševac , et al., 2022)
[Xanthohumol (XN) from hops is too, bile acids, and Quorum sensing molecules (QSMs) derived from Gram-negative bacteria which might include acyl-homoserine lactones, quinolones and their metabolites. Catechins prefer to bind to TAS2R39.]
How does pomegranate peel extract seem to help every part of the body? Bitter taste receptors may be the secret. Clearly it would be helpful for the body to be able to sense if there was a bacterial inner ear infection.
“Emerging evidence also supports the hypothesis that in addition to innate immunity, TAS2Rs function as a novel arm of the adaptive immune response. Some human resting or activated lymphocytes have been found to express multiple TAS2R isoforms and respond to multiple types of bitter agonists.” (Tuzim and Korolczuk, 2021)
TRPA1 channels elevated in Alzheimer’s dementia
TRPA1 channels have a role in the hippocampus and Alzheimer’s risk too. (Lee, et al., 2016)
“TRPA1 − Ca2+ − PP2B signaling may play a crucial role in regulating astrocyte-derived inflammation and pathogenesis of AD (Alzheimer’s disease).” (Lee, et al., 2016) *protein phosphatase 2B (PP2B)
TRPA1 in Cochlea Channels - Brave AI
TRPA1 channels are expressed in non-sensory supporting cells of the cochlea, specifically in Hensen’s cells and other supporting cells. These channels are activated by endogenous products of oxidative stress and extracellular ATP, which are present in vivo after acoustic trauma.
Research has shown that TRPA1 activation in Hensen’s cells leads to prolonged Ca2+ responses, which propagate across the organ of Corti and cause long-lasting contractions of pillar and Deiters’ cells. This supports the hypothesis that TRPA1 channels contribute to the regulation of cochlear sensitivity after acoustic trauma.
Studies have demonstrated that:
TRPA1 channels are expressed in Hensen’s cells and other supporting cells of the mouse cochlea (Vélez-Ortega, et al., 2023).
TRPA1 activation in Hensen’s cells causes prolonged Ca2+ responses, which propagate across the organ of Corti and lead to long-lasting contractions of pillar and Deiters’ cells (Vélez-Ortega, et al., 2023).
TRPA1 deficiency results in larger but less prolonged noise-induced temporary shifts in hearing thresholds, accompanied by permanent changes in latency of auditory brainstem responses (Vélez-Ortega, et al., 2023).
Additionally, TRPC channels have been detected in the human cochlea, specifically in the organ of Corti, stria vascularis, and spiral lamina. - Again, how sound is processed seems the role of TRP channels within Hair cells, as gene knockouts of different types of TRPC channels can affect hearing, but the basic mechanical transduction of a soundwave still signals in their absence. (Englisch, et al., 2023).
An understatement: “All in all, hearing remains a complex function.” (Englisch, et al., 2023)
Implications
The presence and activation of TRPA1 channels in supporting cells of the cochlea suggest a role in regulating cochlear sensitivity after acoustic trauma. This may involve changes in the mechanical properties of the cochlear hair cells or supporting cells, leading to altered sound processing and potentially contributing to hearing loss or tinnitus.
Future studies will be necessary to fully elucidate the functional significance of TRPA1 channels in the cochlea and their potential involvement in hearing disorders.
References for that Brave AI summary:
(Englisch, et al., 2023; García-Añoveros and Duggan, 2007; Ramkumar, et al., 2022; Vélez-Ortega, et al., 2023)
There is more… a lot more on TRPA1 channels and hearing and lifestyle or dietary factors that may be involved in tinnitus or risk of hearing damage.
However, we have firmly established in this post that mitochondrial health and hearing function are closely linked. Protecting one is likely also protecting the other. However, extremely loud noise or an explosive force is going to risk damaging the delicate hair cells.
In checking a variety of nutrients individually, Brave AI got a laugh out of me for this:
B vitamin Para-aminobenzoic acid (PABA)? Brave AI is funny sometimes, it can find no specific research suggesting that PABA protects hearing, however Apple iPods are putting out a new protective sound feature but AI isn’t sure if they used PABA in the new Apple Ipod devices. PABA does protect against sunburn, but AI suggests that I should use headphones or sound canceling earmuffs if I really want ear protection. That’s sensible, thanks AI. (Brave AI summary) (Apple Ipods – sound protection built in, and another one that monitors the person’s breathing during sleep for signs of sleep apnea, which is a gradual dementia risk too.)
B vitamin, PABA, may have pain-relieving potential due to inhibition of TRPA1 and TRPV4 ion channels. (Bang, et al., 2012) There is no RDA for PABA (also called vitamin B10). Supplements of 100-500 mg/day is likely safe. PABA is water-soluble but high dose use of 12 grams or more per day may have toxic effects.
Odd, FDA removed the GRAS status of PABA for use in sunscreens in 2019. How is a water-soluble B vitamin going to harm us topically? (healthline.com)
Brave AI is correct - headphones provide better hearing protection than applying sunscreen, whether the sunscreen has PABA or zinc oxide. Getting out of noon-day sun and into the shade would likely be helpful to hearing by reducing the body-load of oxidative stress chemicals. Inflammation is inflammatory, no matter what its source.
Nutrients in more detail and known ototoxins are listed in Ototoxicity - Part 2, (deNutrients.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.
References are in a document of growing length, stay tuned.