Woah woah woah there
@joshua.leisk, you know we’ve worked well together and spent a crap ton of time trying to figure this out....but please don’t overstate what has happened. We haven’t “resolved 50 percent” of my symptoms. We got the burning to go away for a period of time, and it has come back (because I chose to go off the sodium benzoate, EGCG etc because of the fainting episodes I had)...but even at its best I wouldn’t say we resolved 50 percent of my symptoms — I have a laundry list...not just dizziness and burning. I have severe cogntibe issues, fatigue, akathesia, anxiety, depression, issues w my menstrual cycle, headaches and head pressure, insomnia, food intolerances.
You are working incredibly hard for me and you know I eternally grateful for it...but I also don’t want people to get the wrong impression.
Sorry, that's very fair - I should have been more clear. 50% of the "primary issues" which have been discussed as the "goalposts".
There's all of the secondary cascade / reflex, which are downstream from low a-KGDH : high GDH.
In the model:
1. severe cognitive issues, akathesia, anxiety, depression
These primarily relate to issues with
- tyrosine depletion, which comes from phenylalanine overuse for phenylacetylglutamine synthesis issues from excess ammonia production, further causing acetyl-coa depletion.
- resulting dopamine and thyroxine deficiency (phasic), thanks to tyrosine low-availability.
- excess metabolism of myo-inositol, causing inositol deficiency.
- excess metabolism of other B vitamins, causing deficiency / cycle impairments (used for maintaining succinate, during a-KGDH impairment, once aspartate runs low).
- serotonin homeostasis, as a see-saw from dopamine and antibodies (lytic)
- antibodies for dopamine receptors, adrenergic receptors (lytic phase) and excess catecholamines produced which cause anxiety. These are created to primarily compensate for the beta-oxidation insensitivity.
- inflammation from hepatic encephalopathy, ROS.
- inflammation from phosphatidylcholine pathway impairment.
- sphingolipid synthesis impairment via cofactor depletion.
- GABA reduction (used for maintaining succinate, during a-KGDH impairment, once aspartate runs low).
2. fatigue
This is more complex, however the fatty acid oxidation pathways are affected in two places.
- Beta-adrenergic signalling dysregulation thanks to acetyl-coa depletion (latent) and antibodies (lytic). This also relates to orthostatic intolerance. This causes cortisol dysregulation, also.
- cAMP being impaired.
- Low thyroxine
- There's also the issue from the sleep deprivation / unrefreshing sleep, which relates to GABA:glutamate balance and melatonin signalling. This can be an additional factor for the head pressure, also.
We've recently found a small number of people who appear to have (some confirmed with serology) a co-infection to T.gondii and benefited from an additional plant extract that kills that efficiently parasite. (I suspect other parasites will have similar behaviour / response.)
3. issues with menstrual cycle
This one has a few factors, also.
- There are complications with the tissue health, which relates to HIF-1a, which relates to the hypoxia, low a-KGDH.
- There's also issues with e2 : DHT balance, caused by DHT metabolism issues and 3-HSD. The 3-HSD issue we further address in 3.3 with sulforaphane and related compounds.
- There's also a feedback loop for blood pressure / RAAS as part of the cycle, via hormonal signalling and blood volume reduction.
4. headaches and head pressure, insomnia
The main causes of encephalopathy and insomnia in this model relate to glutamate:GABA and ammonia.
- Normally, this relates again to a-KGDH low : GDH high and accumulated nitrogen. NMDA blunting from ammonia.
- There may be additional causes for this, with co-infections, such as T.gondii, HPV, other.
- Melatonin synthesis issues.
5. food intolerances
This one is multifactoral, also.
- HIF-1a signalling breakdown leading to skin, gut barrier issues via collagen synthesis impairment, prolyl hydroxylases.
- Zonulin overexpression, thanks to gut microbiome dysbiosis, SIBO from gall-bladder / bile metabolism issues.
- LPS-positive bacteria, causing gut barrier inflammation and leakage.
- Immune system dysregulation / mast cell activation, downstream of Platelet Activating Factor increases from the increased LDL (produced by lytic phase) coupled with low acetylhydrolase (from low acetyl-coa) and sphingosine-1-phosphate issues downstream of the P5P issues, plus cortisol dysregulation.
There are hundreds of other impacted pathways. Having had the pleasure of recently working with Metabolon data, it becomes very clear how broad the impact is and follows the model as downstream factors from the cascades we've described.
CFS/ME is highly debilitating, when untreated.
