Glutamate/GABA – Related Damage

Also as I continued my research, I eventually came to believe that many of my problems were also glutamate related, either via glutamate receptors directly or via GABA receptors.  This hypothesis of FQ’s damaging or affecting these receptors has been in existence for a while now, and has been studied in research studies to some extent as well.  In my case, what struck me was how similar my symptoms, in particular my “flaring” symptoms, were like an extreme version of MSG (monosodium glutamate) symptoms described by people with MSG sensitivities.  This is what ultimately sold me on the “glutamate/GABA hypothesis”.  It also became quite clear early on that taking a GABA agonist, whether a traditional medication such as benzos, or alternative supplements (such as Kavinace) really helped my symptoms overall – it was NOT simply an “anti-anxiety” med in that regard.  GABA and Glutamate receptors are found throughout the body, not just in the CNS, and I would imagine that providing excessive GABA would drive down glutamate, which may be one of the reasons it helped me so much.   I tried to use these sparingly, but there was no doubt they helped tremendously during the worst of times, and I could easily feel the draw to addiction occurring.  In my case, I built up tolerance pretty quickly, and could feel it occurring, so I had to be careful.  Tolerance – and withdrawal – will occur with either medications or supplements – there really is no difference as the same or similar receptors are targeted.   I don’t think I could have gotten through the worst of the flares or survived as long as I have without taking a GABA agonist.

Interestingly enough, when I was on a fully suppressive dose of TH replacement, I not only didn’t feel the need to take a GABA agonist, but the few times I tried thinking it might help me sleep, I essentially felt no effect what so ever.  It seemed like the only time GABA worked was when my thyroid hormones were out of whack.

I have done a few neurotransmitter (NT) tests as well.  Given that these are single point tests (versus serial measurements), and there are questions regarding their validity in terms of accurately representing levels of neurotransmitters in CNS or other areas of the body, I wasn’t confident of exactly what meaning, if any, my measurement results had.  However, having said that, there was an interesting difference in values when I was on TH meds vs. when I was not.  When I was ON TH meds and feeling pretty good, my glutamate levels were low normal, and GABA was high normal.  In Year 4, when I was OFF TH meds, and symptomatic, both Glutamate and GABA were a little above normal range.  As to what, if any significance I can place on this, I don’t know.  I really wish I could have done serial monitoring of selected NT’s along with the TH monitoring; perhaps some patterns would have emerged, not only increasing my confidence in the test methodologies, but providing additional clues to my situation as well.  Unfortunately, the current NT testing available to the public is usually in the form of full panels and is cost prohibitive for doing serial monitoring at this point in time.  I think with a bit of searching, one might be able to contact some of the NT-testing labs and perhaps set up panels for serial monitoring with price discounts in the interest of research.  At this point in time, almost 5 years post, I don’t have the energy or financial means to do this for myself anymore, but it would be an interesting project and might shed further light on where some of the floxing issues lie.

Had the NT testing I mentioned above been available and affordable, I then would have tested some NT’s and correlated them with my symptoms.  It would have been good to test this hypothesis when I was on an appropriate dose of TH meds; however, I didn’t think of it then, as I was very “TH focused” (and very TH responsive) at that point in time.  In Year 4/5 post, when I was not on TH meds and was highly symptomatic with increasing neurological issues, is when I started reviewing the “glutamate/GABA hypotheses”, and I was too afraid to try MSG for obvious reasons.  I also had a question about MSG potentially having iodine in it, due to the salt content.  I knew that I was very sensitive to iodine, and was able to test this sensitivity in many ways on many occasions because I was able to isolate iodine from TH or foods or supplements.  I wasn’t sure if I could separate out iodine completely from MSG.  I also wanted to test for a number of “anti-glutamate receptor” antibodies, and I tried to at least get the anti-NMDAR test while I was highly symptomatic, with no success.  (Update:   I was able to test for anti-NMDAR(1) and was negative).

One of the ways I wanted to test the “glutamate” theory was by taking glutamine supplements, or better yet, a trial of MSG if I had the guts to try (which so far, I haven’t).    However, I did try adding an organic non-MSG bullion broth to my typical chicken meal once.   I was desperate for more flavoring, anything to try and provide some variety to my taste buds, after years of being on such a limited diet.   I looked carefully at the ingredients in the bullion before doing so, making sure there was no MSG in it, and didn’t see anything else that I thought looked alarming.   Yet, I could tell that I was having a reaction within 30-60 minutes of eating my first meal, which presumably had about 1/8-1/4 of this bullion cube in it.   I also could taste a familiar salty taste that I hadn’t had in years, and it tasted different than just the sea salt I had been using.  Well, it turns out one of the ingredients in this bullion is “Yeast Extract”.  So I looked it up and found out that Yeast extracts (and fermented foods) contain glutamic acid, which, in solution with sodium ions, is the same as monosodium glutamate.    And in the same way, yeast extracts are often used to create savoury flavours and umami taste sensations, and are found in a large variety of packaged foods.   So this added further data to my belief that I had developed a glutamic acid/glutamate sensitivity post floxing.    If any flox victims are reacting to chicken, chicken soups, or any other foods etc., which you think are organic, this is something to consider.    Along with the iodine, it could be glutamic acid/glutamate or MSG/ MSG equivalents as well.

I never had any food allergies or intolerances that I knew of prior to being floxed, and this included MSG.  I’m sure I was exposed to plenty of it during my lifetime, as it is a ubiquitous additive in processed foods, restaurant foods, and of course Asian foods.  So I’m pretty confident I was not “MSG sensitive” prior to being floxed.  But given my symptoms now (Year 4/5 post Cipro), it wouldn’t surprise me if “glutamate toxicity” is coming into play, and that I probably would react to MSG, based on my current symptoms and the available research.

Magnesium is an antagonist of the NMDA glutamate receptor and is an integral part of the receptor’s function.  This may be one potential reason Magnesium appears to help many flox victims.  If FQ’s bind up Magnesium, creating a transient Mg deficiency, which would be amplified in already Mg-deficient people, less Mg would be available for this antagonism.  Perhaps this is one mechanism of potentially increased susceptibility to FQ’s in some people.

There are numerous references implicating glutamate/NMDA-R/GABA-R in FQ-Induced CNS damage.  There are also references of the piperazine derivative (which is part of the structure of Ciprofloxacin) targeting NMDA-R’s.  Research also implicates Glutamate/NMDA-R’s playing a role in tendon pathologies and tendinosis.  Here are some of them:

References NMDA GABA ACh


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