Chris Armstrong and the Hunt for the Metabolic Underpinnings of ME/CFS

SWAlexander

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Chris Armstrong and the Hunt for the Metabolic Underpinnings of ME/CFS
https://www.healthrising.org/blog/2021/10/17/chris-armstrong-chronic-fatigue-syndrome-metabolism/


Conclusion
Chris Armstrong and the 5th Open Medicine Foundation-funded research center in Australia are on something of a roll. Armstrong is continuing his focus on energy metabolism as he and his team try to understand the metabolic underpinnings of ME/CFS. If all goes well, we should learn more about why people with ME/CFS are so susceptible to crashes, why their cells may be starving (and what they are starving for), and if excess ammonia is wreaking havoc on cellular energy production. Plus, the eye study could potentially provide a cheap and accessible diagnostic test.
It probably comes as no surprise that excess ammonia can be a problem. When a dysfunctional liver fails to break down nitrogen, excess ammonia can produce neuroinflammation and encephalopathy. Nobody, until now, has applied the excess ammonia issue to cells.
Armstrong glommed onto his cellular ammonia accumulation hypothesis when metabolomic studies suggested that people with ME/CFS were using amino acids for fuel at a faster rate than healthy controls.

atp production in mitochondria
Most of the adenosine triphosphate (ATP) synthesized during glucose metabolism is produced in the mitochondria through oxidative phosphorylation. This is a complex reaction powered by the proton gradient across the mitochondrial inner membrane, which is generated by mitochondrial respiration.
https://pubmed.ncbi.nlm.nih.gov/16945388/

Amino acids are usually used for fuel at an elevated rate during a stress response or starvation. When you’re starving, for instance, your body will save your carbohydrates to make sure your brain and immune system are getting them. The rest of your body will use fats and amino acids in greater proportions. The long-term use of amino acids for energy will reduce digestive enzyme production and break down muscles and connective tissues.
For some reason, people with ME/CFS also appear to be preferentially turning to amino acids to power their cells. That presents a potential problem because amino acids have this pesky nitrogen atom attached to them that needs to be taken care of. The body usually eliminates the nitrogen from amino acids in a variety of “safe” forms, but the ME/CFS metabolomic studies are not finding as much of these “safe” forms as expected.
That suggests that all that nitrogen is being eliminated all right – but in “unsafe” forms such as ammonia or peroxynitrite – two highly reactive compounds that can wreak havoc in our cellular energy production system.

Why is ammonia highly toxic?

When excessive amounts of ammonia enter the central nervous system, the brain's defences are severely challenged. – A complex molecular chain reaction is triggered when the brain is exposed to excessive levels of ammonia. We have found that ammonia short-circuits the transport of potassium into the brain's glial cells.
What removes ammonia from the body?
Your body treats ammonia as a waste product, and gets rid of it through the liver. It can be added to other chemicals to form an amino acid called glutamine. It can also be used to form a chemical compound called urea. Your bloodstream moves the urea to your kidneys, where it is eliminated in your urine.
What does it mean when your breath smells like ammonia?
Chronic kidney disease (CKD) is one possible cause of having an ammonia taste in your mouth, sometimes called “ammonia breath.” Some people describe ammonia breath as having a metallic taste, while others have reported that it smells similar to urine.
Does high ammonia levels cause brain damage?
If your body can't process or eliminate ammonia, it builds up in the bloodstream. High ammonia levels in the blood can lead to serious health problems, including brain damage, coma, and even death. High ammonia levels in the blood are most often caused by liver disease.
What causes ammonia?
High ammonia levels sometimes point to either liver or kidney disease. But several other things can cause higher ammonia levels, like: Bleeding in your stomach, intestines, esophagus, or other parts of your body. Alcohol and drug use, including narcotics and medicines that take extra fluid out of your body (diuretics)
What are the symptoms of low ammonia?
Early symptoms may be mild and include:
Breath with a musty or sweet odor.
Changes in sleep patterns.
Changes in thinking.
Mild confusion.
Forgetfulness.
Personality or mood changes.
Poor concentration and judgment.
Worsening of handwriting or loss of other small hand movements.


(text in Italic from diff sources)
 
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SWAlexander

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this is drfinitely what is going on with me, Urine tests show issues with kidney and liver and action against ammonia and changing energy sources all ease symptoms.
Me too. The smell of ammonia, bleach, gasoline, cow dung and everything that is composing is a warning to me. If I ignore the signs, I faint and have many bad down-days ahead.

We need urine tests. Do we have too much or not enough ammonia (chlorophyll)?

What are the symptoms of chlorophyll on the brain?

Elevated concentrations of ammonia in the brain as a result of hyperammonemia leads to cerebral dysfunction involving a spectrum of neuropsychiatric and neurological symptoms (impaired memory, shortened attention span, sleep-wake inversions, brain edema, intracranial hypertension, seizures, ataxia and coma)
 
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This was Joshua's theory
These acute elevations of nitrogen levels are directly related to any energy use - movement,
brain activity, metabolism[1].
The virally-induced excess nitrogen accumulation quickly leads to a crisis state, which triggers
each affected cell to reach critical levels of some “nitrogen” metabolites - glutamate, glutamine
and ammonia->urea, prioritising an equally urgent purging process to run, at a metabolically
expensive cost of also proportionally sacrificing / depleting some “absolutely essential
metabolites”[2].

“Elevated glutamate and/or urea is the catalyst for the primary symptoms
observed in CFS/ME[2].”

Alcohol extracts of Reishi are known to contain large amounts of unique
triterpenes, such as ganodermic acid, which have a demonstrated ability to
ameliorate viral alterations, induce apoptosis in Epstein-Barr Virus (EBV) and
cancer cells, while providing normalisations to mitochondrial function and
metabolism
He said that when you disable some features of the viral infection with the mushroom it causes a metabolic shift which will produce or suddenly release excess amounts of nitrogen compounds, which causes a pressure headache, it is counteracted with sodium benzoate and glycine. I've found that this is consistently the case for me, I've started the reishi pills twice, I ran out so I stopped taking any for a week or 2 and I had to start retaking them recently. I neglected the careful approach I used last time and ended up with a really bad headache and I felt my eyes were bulging out. I'm curious does anyone else have this reaction to the Reishi mushroom ? sadly I wasn't able to prove that HHV had any influence on my symptoms or disease process. I wonder if there could be an alternative explanation for why the mushroom causes that effect.
 

SWAlexander

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This was Joshua's theory

He said that when you disable some features of the viral infection with the mushroom it causes a metabolic shift which will produce or suddenly release excess amounts of nitrogen compounds, which causes a pressure headache, it is counteracted with sodium benzoate and glycine. I've found that this is consistently the case for me, I've started the reishi pills twice, I ran out so I stopped taking any for a week or 2 and I had to start retaking them recently. I neglected the careful approach I used last time and ended up with a really bad headache and I felt my eyes were bulging out. I'm curious does anyone else have this reaction to the Reishi mushroom ? sadly I wasn't able to prove that HHV had any influence on my symptoms or disease process. I wonder if there could be an alternative explanation for why the mushroom causes that effect.
Maybe this helps:
Neurometabolic Effect of Altaian Fungus Ganoderma lucidum (Reishi Mushroom) in Rats Under Moderate Alcohol Consumption: Background:
The medications produced from natural products are widely used as prophylactics for sickness induced by alcohol consumption. One such prophylactic is produced from the Reishi mushroom, Ganoderma lucidum. Because of the antioxidant properties of these preparations, we expect neuroprotective prophylactic effects of Reishi-based medications in alcohol-treated animals. https://pubmed.ncbi.nlm.nih.gov/26058418/
Also:


Is reishi mushroom toxic?
Use of powdered reishi mushroom has been associated with toxic effects on the liver. Reishi mushroom can also cause other side effects including dryness of the mouth, throat, and nasal area along with itchiness and rash, stomach upset and diarrhea, dizziness and headache, nosebleed, and bloody stools. https://www.rxlist.com/reishi_mushroom/supplements.htm

BIO: Potential of a Wild Medicinal Mushroom, Ganoderma Sp., as Feed Supplement in Chicken Diet: Effect on Performance and Health of Pullets
Proximate and chemical composition of a wild mushroom, Ganoderma sp was evaluated. The phytochemical analysis showed it contained carbohydrates and reducing sugars, steroids, cardiac glycosides, saponins and resins. Proximate analysis revealed crude protein (13.3%±0.2), crude fibre (34.7%±6.4), fats (2.6%±0.3), calcium (0.4%±0.1) and phosphorus (0.3%±0.0). Acidic amino acids (glutamic and aspartic acid) (6.2 g%±1.4 and 5.6 g%± 0.1) and sulphur containing amino acids (cystine and methionine) (1.5 g%±1.3 and 0.7 g%±0.1) were also detected. https://www.researchgate.net/public...t_Effect_on_Performance_and_Health_of_Pullets

 

Boba

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Starving of cells reminds me of low T3 Syndrome, which is also caused by starvation. I developed low T3 after contracting covid. Another link that supports this hypothesis.