Human knockout mouse* field updates (*me) re TRP channels, IBS, and mast cell degranulation.

Sadly, ginger and hot pepper still need to be on my foods to avoid list.

Story time, I will try to keep it brief. Irritable Bowel Syndrome (IBS) is a stress related diarrhea condition that is annoying but shouldn’t cause weight loss or have middle of the night accidents - if that is happening then the condition is more severe and might be called colitis or Inflammatory Bowel Disorder. IBS typically will present as a very sudden need to go to the bathroom after eating or drinking something. “Something?” Anything? Every time? or What foods in particular?

Background - mast cells are involved in IBS: “Abnormalities of mast cell structure or function may play prominent roles in irritable bowel syndrome (IBS) symptom genesis. Mast cells show close apposition to sensory nerves and release bioactive substances in response to varied stimuli including infection, stress, and other neuroendocrine factors. Most studies focus on patients who develop IBS after enteric infection or who report diarrhea-predominant symptoms. Three topics underlying IBS pathogenesis have been emphasized in recent investigations. Visceral hypersensitivity to luminal stimulation is found in most IBS patients and may contribute to abdominal pain. Mast cell dysfunction also may disrupt epithelial barrier function which alters mucosal permeability potentially leading to altered bowel function and pain. Mast cell products including histamine, proteases, prostaglandins, and cytokines may participate in hypersensitivity and permeability defects, especially with diarrhea-predominant IBS.” (Hasler, et al., 2022)

I developed this problem in 2016 when I had several maximal stress events occur within a few months. As a dietitian I had worked with clients with the problem and therefore had read about it somewhat and bought a book written by a Registered Dietitian with the problem. Her collection of tips on which foods were triggers, along with my own odd symptoms helped me to find the biochemical connection between the odd collection of triggering foods or lifestyle factors - TRP channel activation. TRP channels are involved in pain signaling among many, many other roles in the body.

I have been avoiding the TRP channel activating spices and foods ever since then, for the most part. It included some favorites - ginger, hot pepper, curry blends with turmeric, mint, cinnamon, cloves, nutmeg, horseradish, others including coffee, tea, and a large acidic load, like from a glass of lemonade drunk suddenly instead of sipped slowly. Also, TRP channels can be activated physically by the body getting too hot or too cold, or from sudden pressure changes from a change in position on a amusement park ride, or from internal pressure from a gassy food or beverage. *Varied types of TRP channels react to different things - there are many types and many have multiple activating triggers.

~~

Speeding ahead to post CoV era - I learned of histamine excess and Mast Cell Activation Syndrome from the LongCovid community and it helped me immensely. I have since learned that I have gene alleles in both types of enzymes that break down histamine. Buying the enzymes might help but there is expense in that and I haven’t looked at cost or availability yet.

~~

My recent craving for and use of seaweed in my diet was encouraging and led me to try pickled ginger with my Nori rolls. I love it and I seemed to be tolerating it better than I had in 2016 when I stopped using it . . . and I added a bit of hot pepper, and a bit more.

After a month of having the TRP channel activators that I had been avoiding - it did seem to be a problem. But not exactly as I had had in 2016. Food was staying in (no sudden diarrhea) but I was GASSY and that was painful.

Postmenopausal whining - what is up with my abs? Why does my body seem to think I am pregnant and need maternity pants? I got out a tape measure and measured my rapidly changing size waist and hips, when looking at clothing site - hips 38, waist/belly 39 - wait what? I need Tweedledee or Tweedledum’s pants. It seems to be the gassiness and edema. I really need to drink some of my pomegranate and dandelion root tea everyday but sometimes don’t make a new batch. Powdered sumac (zataar seasoning) is an effective diuretic too and I use that when I don’t have tea now. *and use less salt. I seem to be salt sensitive now.

I have gained some weight though and think I was getting a little hypothyroid after too many years of restricting iodine sources due to having hyperthyroidism (~2012/13) from not having used selenium along with iodine.

~~

The point - what was going on? Were the TRP channel activators somehow causing mast cell degranulation too? So that I was getting histamine symptoms even though the TRP channel activators aren’t necessarily histamine foods?

Yes - the communication seems to be two way. Degranulation of mast cells will activate TRP channels and cause pain sensations, and activation of TRP channels can cause degranulation of mast cells.

Okay then, no more trying ginger, coffee, etcetera, to see if I have become less sensitive to it. While, yes, I do seem to be less sensitive to it - the symptoms recently were not as bad as in 2016 - but I did feel inflammation, fatigue and pain from the extreme gassiness. In 2016 and since, the TRP activators tended to cause pain throughout the gut - it literally hurt to drink even a few sips of coffee.

The problem is not the same as a “food allergy” however allergy cells are being activated 🤧 🙃 😪 and therefore - it is still uncomfortable - like hayfever season with seasonal allergies, but without the risk of anaphylaxis, like with a peanut butter or bee sting type of allergy.

TRP channel activation causes Substance P release which can degranulate mast cells. (Traina, 2019; Wen-Wu, et al., 2012)

*Oh, by the way - you are unlikely to be told about TRP channel activators by anyone in a health care setting for the purposes of reducing bowel discomfort - this was my own discovery. Sadly, what I have learned is that most people would rather be in discomfort waiting for help from their doctor than to be willing to listen to a dietitian with personal experience.

I can only help those willing to be helped without a prescription pad and a drug. It does get depressing though and leads me to feeling like why bother trying to share info that is about underlying mechanisim of action when the public only seem to want to hear from white coat doctors who are male. Seriously, not untrue.

I think people need to dig a bit deeper into their personal comfort or discomfort feelings regarding self care. When an authority figure is telling you to self-harm, for your own good or the benefit of others or the planet - then do they have your interests in mind, or they want you to self-harm for their own goals? Nocebo is the negative expectations we are being sold by media - you can’t be healthy without a doctor and a million-dollar medical bill! You just CAN’T! It is your NEED and your RIGHT to have that expensive DOCTOR and THAT super-necessary MILLION-DOLLAR treatment! We should mandate it so taxpayers make sure everyone gets the super necessary ‘safe and effective’ million dollar treatment….. or mRNA injections …. or Vioxx, statin drugs or olanzapine, or many other things proven to be not as advertised.

Advertising nudges us into thinking something is better than it really is, and maybe more critically vital to our lives than it really is. Caution against believing negative expectations about health - it might just be that the ‘healthcare provider’ doesn’t know what they are talking about.

See post: And what do osmomechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids have in common? (substack) and migraine headache should be on this graphic.

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use. While I am a Registered Dietitian this information is not intended to provide individual health care guidance. Please see an individual health care professional for individualized health care guidance.

Reference List

(Traina, 2019) Traina G. Mast Cells in Gut and Brain and Their Potential Role as an Emerging Therapeutic Target for Neural Diseases. Front Cell Neurosci. 2019 Jul 30;13:345. doi: 10.3389/fncel.2019.00345. PMID: 31417365; PMCID: PMC6682652. https://www.frontiersin.org/articles/10.3389/fncel.2019.00345/full

(Hasler, et al., 2022) Hasler, WL, Grabauskas, G, Singh, P, Owyang, C. Mast cell mediation of visceral sensation and permeability in irritable bowel syndrome. Neurogastroenterology & Motility. 2022; 34:e14339. doi:10.1111/nmo.14339 https://onlinelibrary.wiley.com/doi/full/10.1111/nmo.14339

(Wen-Wu, et al., 2012) Wen-Wu Li, Tian-Zhi Guo, De-yong Liang, Yuan Sun, Wade S. Kingery, J. David Clark; Substance P Signaling Controls Mast Cell Activation, Degranulation, and Nociceptive Sensitization in a Rat Fracture Model of Complex Regional Pain Syndrome. Anesthesiology 2012; 116:882–895 doi: https://doi.org/10.1097/ALN.0b013e31824bb303 https://pubs.asahq.org/anesthesiology/article/116/4/882/13128/Substance-P-Signaling-Controls-Mast-Cell.