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[theory] TRPM Channels in CFS Mechanism

Discussion in 'General ME/CFS Discussion' started by Deltrus, Jun 20, 2016.

  1. Deltrus

    Deltrus Senior Member

    I'm just a person with no qualifications so don't take this theory too seriously, it is mostly speculation.

    Studies have shown that TRP channels may be related to CFS:


    Certain TRP SNP mutations are associated with CFS. Usually mutations hamper effectiveness.

    Secondly TRPM3 surface expression was significantly reduced on certain immune cells. They did not test to see if TRPM3 is poorly expressed in many different cells, only immune cells. They also didn't check levels of other cations such as magnesium, zinc etc.

    Relevant info from the web on TRP channels:


    • TRPM6 and 7 are hampered by extremely low ATP, while TRPM3 is barely working from DNA mutations and low gene expression. This leads to low levels of intracellular cations such as magnesium, zinc, copper, calcium, manganese.
    • Any ATP that is produced is not bio-available because it is not bound to magnesium.
    • TRPM6/7 never activate because of low ATP
    • Methylation cycle stops working because of low intracellular zinc, copper, and magnesium. (essential cofactors for methylation)
    • Neurotransmitter production is impaired through poor methylation. Neurotransmitter release is impaired because calcium is needed to release neurotransmitters from vesicles.
    • Viruses proliferate because of impaired DNA repair and low glutathione. Those processes are dependent on methylation.
    • The initial trigger of CFS would be ATP depletion, due to repetitive stress, bad viral infections, etc.
    • This wouldn't show up like normal zinc, magnesium etc deficiency because only certain cells are dependent on TRPM channels for cation transport, and even then they probably have a few backup mechanisms, so the deficiency is there but not as severe as it could be. It is also possible that the ATP depletion is only in certain muscles/nerves.
    • Most people do not get CFS because TRPM3 doesn't require ATP to function, and so even if there is low ATP, there can still be high Zinc/Magnesium etc.
    • In the second study listed near the top of this post, it shows that there was a significant reduction in intracellular calcium levels due to low amounts of TRPM3. Through this, we can infer that the dysfunction in cation transport is somewhat significant.
    • Trigger points may occur when the ATP depletion and TRP6/7 magnesium lock is even more intense.

    My personal experience which was used to help come up with this theory:
    A few times I've been able to get complete remittance of my CFS with PEMF + Wim Hoff style breathing + Resveratrol + low dose Aspirin + large amounts of magnesium (like 3g), zinc (300mg), copper(15 mg), manganese(50mg). PEMF has been hailed by the owner of selfhacked as the best cure to his fatigue. I am guessing it increases ATP production through some mechanism.

    Basically I take these supplements, lie in bed, and do the breathing while using the PEMF. I breath heavily until I get dizzy, stop until I feel the urge to breath again (signalling that CO2 is raised back to normal levels), then repeat.

    During this process and afterwards, I can take and absorb massive amounts of magnesium etc without getting diarrhea or side effects. Slowly my symptoms start to improve. Normally I can only tolerate 400 mg of magnesium.

    I believe the breathing + PEMF process helps with oxygenation and jump starts atp production. This then activates TRP6/7 and increases mineral absorption.

    One time I did this, and got my best result. I was symptom free for 2 days, and had so much neurotransmitters it was like I was on phenibut + adderall + mdma or something. I had unbelievable energy like my body was a furnace. It was like there was a force pushing my back and every movement and thought was effortless. This wasn't mania, I experienced mania before and I know how to recognize it. I even had thoughts of going over and talking to strangers, getting a girlfriend etc, it was amazing. I also had a near-photographic memory and was very verbally fluent.

    Then after those 2 days ended, I must have had ATP depletion or viral reactivation or something, and I had diarrhea all night, excreting that 3g of magnesium and my symptoms all came back.

    Sadly this process is hard to replicate and keep, I think because it is hard to get the ATP levels started and stay high. Secondly the side effects when the process fails to keep going are fairly bad, diarrhea all day ><. And then that messes up my microbiome and gut health. Also I cannot keep trying to replicate this often because of potential copper/manganese/zinc toxicity.

    EDIT: It is also possible that PEMF stimulated production of some steroid hormones which are known to activate TRPM3. Then I could absorb magnesium etc.

    Things which need testing according to this theory:
    TLDR: TRPM3 receptor dysfunction leads to low intracellular zinc, magnesium, copper etc, leads to poor ATP bioavailabilty and poor methylation. And some other stuff.
    Last edited: Jun 21, 2016
    ebethc, rosie26, Marco and 1 other person like this.
  2. Groggy Doggy

    Groggy Doggy Guest

    Hi @Deltrus

    Thanks for taking the time to put this together. I think we have multiple issues (calcium, sodium, cholesterol, etc). Hoff sounds interesting; do you know if there is any published scientific data as to what changes in the body occur to the participants using his method?

    I think our bodies electrical system is not working correctly, hence the cell signaling issues. So I am curious to know how the breathing techniques work; if they help some illnesses and not others? Do you know why he choose the medium of icy water...does that mean the body's internal temperature rises?

  3. Snow Leopard

    Snow Leopard Hibernating

    South Australia
    The SNP findings are null results. Lack of statistical significance given multiple comparisons and the results were not replicated by those of us who have had 23andme genetic testing.

    The finding in NK and B cells is interesting, but unlikely to be due to SNPs.
    Valentijn likes this.
  4. Deltrus

    Deltrus Senior Member

    @Groggy Doggy The cold water is to do numerous things. For one, extremely cold water heavily stimulates TRPM8. Secondly it causes mitochondrial uncoupling through uncoupling protein which creates heat.

    Aspirin and coffee also cause this process which increases heat. There's also a lot of other possibilities with my theory, for one because TRP receptors can act different due to blood PH, and wim hoff method probably changes blood PH a bit back and forth because breathing heavily breathes off all of a person's acidic CO2, and holding breath causes blood to regain that acidic CO2. Secondly perhaps there is some interaction with mitochondria.

    This is why my theory doesn't really hold as much weight as it could. Also as @Snow Leopard says, the study may have unreliable data.

    But I still think for sure that TRP channels and cation transport are involved.

    I want to try cold exposure but I've been so cold sensitive lately >< . Eventually I'l man up and just go straight to the coldest level shower.

    EDIT: another theory that I've had, is that perhaps acidity sensing TRP channels downregulate cation transporting TRP channels, which is the mechanism of trigger points. Trigger points are highly acidic, and highly excitatory. Perhaps lack of magnesium/calcium etc leads to very high excitation?
    Last edited: Jun 21, 2016

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