TRP pathways - TRPV for inflammation

[Changexpert]

Recently, I have come across transient receptor potential channel (TRP). The definition from Wikipedia states:

Many of these channels mediate a variety of sensations like the sensations of pain, hotness, warmth or coldness, different kinds of tastes, pressure, and vision.

There are 7 channels total and each channel consists of a few receptors. One channel that caught my eye particularly was TRPV, which is associated with pain, burning, hot, and pungent odor.

Ever since taking mb12 by accident (took it before I even knew about methylation/this forum), my body has been very sensitive to irritants. I would often get body rashes, scalp bumps, and tingling sensation from bed sheets/carpets/dust. Sometimes, my scalp or body would start itching without any known issue. Anti-inflammatory supplements like quercetin and bromelain helped with inflammation, but it was only temporary, and I could not take them for a long-term due to different side effects.

One observation I have made is that whenever I consume spicy or pungent tasting food (vinegar, mustard, wasabi, jalepenos, banana pepper, fermented food), my body and scalp would start tingling instantly. I always connected them with histamine reaction, but never fully understood why. Also, for some reason, this symptom worsened as I was taking more magnesium.

To understand what is going on, it is important to understand the relationship among magnesium, calcium, and vitamin D. I made a post about them here. In a nut shell, too much/frequent magnesium intake decreases serum calcium level. In response to this, parathyroid hormone (PTH) is secreted to initiate osteoclast (break down of bones), pulling bone calcium to the blood. During this process, hydrogen ion is created, which is often referred as "excess acidity." Hydrogen ion activates TRPV1 pathway, which brings a wide range of problems. These problems include apoptosis induction via TGF-B, increased endogenous hair growth inhibitors (interleukin-1beta, transforming growth factor-beta(2)), decreased hair growth promoters (hepatocyte growth factor, insulin-like growth factor-I, stem cell factor), and increased intracellular calcium level (0).

TRPV1 is activated by active ingredients in some foods like garlic (allicin), chili peppers (capsaicin), wasabi (allyl isothiocynate), and vinegar. Too much TRPV1 activation can lead to osteoporosis, joint pains, and heightened sensitivity (1). I noticed that joint pain is frequently brought up in this forum. At the same time, garlic, ACV, and fermented foods are one of most famous superfoods that a lot of people take. All these foods are driving TRPV1 pathway for more pain and inflammation. Continuous TRPV1 activation can result in various cancesr, digestive tract issues, bladder disease, pulmonary inflammation, diabetes, calcification of arteries/veins, and itch (2).

There are several prescription strength medications to antagonize TRPV1 pathway, but they are not readily available. Carotenoids have been successful at mediating TRPV1, but they do not interact with capsaicin (3). The list of carotenoids that works for TRPV1 regulation includes lutein and B-carotene. Lycopene did not work for some reason. Another study lists herbal remedies that agonzie or antagonize TRPV1 pathway.

Even though too much/frequent TRPV1 activation is unwanted, it is important to keep in mind that inflammation is one of our body's main defense mechanism. One rat study noted that too much inhibition of TRPV1 can lead to a systematic inflammation, rather than localized inflammation (4). Summing up, we can note that both overstimulation and understimulation of TRPV1 can lead to a systematic inflammation. Balance never gets old when it comes to health.


TRPV1 agonist/activators (Increases intracellular Ca level):
H+ ions (I think this is one of the main reasons why too much acidity hurts our body)
Capsaicin (chili pepper)
Ginger (derived products, tumeric/curcumin included, lowers inflammation, but increases Ca level)
Ginseng (dose dependent, can act as Capsaicin inhibitor as well)
Cannobinoids
Mustard oil
Pungent tasting food
Spicy food
Heat (above 43 degree celcius - may be why prolonged intense exercise/frequent hot shower is not good)


TRPV1 inhibitors
Thapsigargin
Yohimbie
Carotenoids (B-carotene, lutein)
Resveratrol (not much study on this...)

If you know any other TRPV1 related supplements/ingredients please share them. Thank you.

 

[Hutan]

@Changexpert, you might be interested in this recent paper if you haven't seen it. It's discussed somewhere in PR I think. The paper doesn't cover treatment/ impact of foods. But the study did find that some SNPs on the TRP genes were more common in their CFS patient sample than in their controls. There are of course problems with these studies - if you look at enough SNPs you will always find some with higher frequencies in one sample as compared to a control sample.

Interestingly though, this was a pilot study - the researchers clearly think something may be going wrong with the TRP ion channels in CFS and plan to do more work.

Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients

Sonya M. Marshall-Gradisnik, Peter Smith, Ekua W. Brenu, Bernd Nilius, Sandra B. Ramos and Donald R. Staines

Immunology and Immunogenetics Insights 2015:7 1-6

Abstract
Background: The transient receptor potential (TRP) superfamily in humans comprises 27 cation channels with permeability to monovalent and divalent cations. These channels are widely expressed within humans on cells and tissues and have significant sensory and regulatory roles on most physiological functions. Chronic fatigue syndrome (CFS) is an unexplained disorder with multiple physiological impairments.

Objectives: The purpose of this study was to determine the role of TRPs in CFS.

Methods: The study comprised 115 CFS patients (age = 48.68 ± 1.06 years) and 90 nonfatigued controls (age = 46.48 ± 1.22 years). CFS patients were defined according to the 1994 Center for Disease Prevention and Control criteria for CFS. A total of 240 single nucleotide polymorphisms (SNPs) for 21 mammalian TRP ion channel genes (TRPA1, TRPC1, TRPC2, TRPC3, TRPC4, TRPC6, TRPC7, TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPV1, TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6) were examined via the Agena Biosciences iPLEX Gold assay. Statistical analysis was performed using the PLINK analysis software.

Results: Thirteen SNPs were significantly associated with CFS patients compared with the controls. Nine of these SNPs were associated with TRPM3 (rs12682832; P ≤ 0.003, rs11142508; P < 0.004, rs1160742; P < 0.08, rs4454352; P ≤ 0.013, rs1328153; P ≤ 0.013, rs3763619; P ≤ 0.014, rs7865858; P ≤ 0.021, rs1504401; P ≤ 0041, rs10115622; P ≤ 0.050), while the remainder were associated with TRPA1 (rs2383844; P ≤ 0.040, rs4738202; P ≤ 0.018) and TRPC4 (rs6650469; P ≤ 0.016, rs655207; P ≤ 0.018).

Conclusion: The data from this pilot study suggest an association between TRP ion channels, predominantly TRPM3 and CFS. This and other TRPs identified may contribute to the etiology and pathomechanism of CFS.

 

[ahmo]

@Hutan I have 10 of those snps listed. No telling whether my variants are problematic or not. I don't eat any chili related things, body generally doesn't want ginger either. But lot's of carrots/carotenoids.

 

[Hutan]

@ahmo, the paper is open source (good on the NCNED team). You can download a pdf of the whole paper here and check out what alleles were more common in CFS patients.

http://www.la-press.com/examination...rphisms-snps-in-transient-recep-article-a4824

I have to go right now, don't have time to check, but from memory, discussion on the other thread found some support for the identified SNPs being more common in the ME/CFS population i.e. others here also had the identified SNPS.

 

[mariovitali]

Please see this Thread, regarding TRPV1 and Heat Shock Proteins :


http://forums.phoenixrising.me/inde...e-treatment-for-cfs.37244/page-10#post-616408


This is a table which lists correlations of TRPV with other CFS Topics notice how calcium homeostasis and Inflammatory response are located on the top of the list