New study looking at oxidative stress

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because I got ME/CFS after doing those dumb Wim Hoff breathing exercises
breathing? Is that vagal breathing ? I know some swear by all that- how awful- it was too much? Thats a type of exertion..too.

I used to play a flute. Now I just wanna pass out in 30 seconds.

Thanks for posting this, I hope we can discuss and find some help in all this info....

online is discussion of how the study above- links into the collagen degeneration we frequently see in both groups.
 
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Regarding collagen- the comment pasted below mentions how the study above further shows this is going on in both long haul and ME...leading to a link with connective tissue disorders...

Hydroxyproline, a marker of collagen degeneration found to be high in people with #MECFS, was also found elevated in people with #LongCovid.

One possible marker/way to track development of connective tissue disorders in these illnesses?
 
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the study above includes the following statement-

NOS2 is significantly up-regulated in patients with severe and critical COVID-19 (58). There is evidence of nitrosative stress and disordered NO metabolism in people with ME/CFS (38). Levels of NO are higher in ME/CFS patients, which can accelerate nitrosative stress (27). Citrulline, a product of arginine metabolism by NOS, also is increased in ME/CFS (59).

QUESTION:

would taking Nitric Oxide in supplement form- be contra indicated given the statement above?

Not seeking medical advice- just informed opinions...
 

ljimbo423

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This is a diagram they give of what they think oxidative stress is doing in both long COVID-19 and ME/CFS.

1629149271370.png


Fig. 2.
The interactions between redox imbalance, mitochondrial dysfunction, chronic inflammation, and related symptoms. As explained in the text, redox imbalance, mitochondrial dysfunction, and inflammation are bidirectionally related to each other and may cause some of the symptoms of both long COVID-19 and ME/CFS.

The bidirectional connections mean that an initial abnormality in one component can trigger abnormalities in other components and can precipitate a persistent, self-reinforcing pathological process.
 

Pyrrhus

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I found this interesting because I got ME/CFS after doing those dumb Wim Hoff breathing exercises.
Not to worry. The term "oxidative stress" does not refer to breathing or the amount of oxygen in the blood. It refers to the chemical process of oxidation, which does not necessarily involve oxygen.

One thing I've never understood about inflammation is that my markers, c reactive protein and erythrocyte sedimentation rate, are always normal. Is it possible to have inflammation despite this?
Yes, for a number of reasons.
 
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Pyrrhus

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This is the paper:

Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (Paul et al., 2021)
https://www.pnas.org/content/118/34/e2024358118


NB: In this context, the term "redox imbalance" roughly translates to "oxidative stress".

Excerpt:
Paul et al 2021 said:
Although most patients recover from acute COVID-19, some experience postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC). One subgroup of PASC is a syndrome called “long COVID-19,” reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating condition, often triggered by viral and bacterial infections, leading to years-long debilitating symptoms including profound fatigue, postexertional malaise, unrefreshing sleep, cognitive deficits, and orthostatic intolerance.

Some are skeptical that either ME/CFS or long COVID-19 involves underlying biological abnormalities. However, in this review, we summarize the evidence that people with acute COVID-19 and with ME/CFS have biological abnormalities including redox imbalance, systemic inflammation and neuroinflammation, an impaired ability to generate adenosine triphosphate, and a general hypometabolic state. These phenomena have not yet been well studied in people with long COVID-19, and each of them has been reported in other diseases as well, particularly neurological diseases.

We also examine the bidirectional relationship between redox imbalance, inflammation, energy metabolic deficits, and a hypometabolic state. We speculate as to what may be causing these abnormalities. Thus, understanding the molecular underpinnings of both PASC and ME/CFS may lead to the development of novel therapeutics.
(spacing added for readability)
 

Pyrrhus

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From a related article:

Impaired energy metabolism

In his recent review with Dr. Lipkin, Dr. Komaroff also highlighted the findings of impaired energy metabolism. "ME/CFS is characterized by a generalized impairment in energy production, a general hypo-metabolic state, and [oxidative stress] that may contribute to the pathogenesis of fatigue."

Since recent hypotheses have considered the possibility that mitochondrial dysfunction might be behind the impaired energy metabolism, we asked him about any recent advances in our understanding of mitochondrial dysfunction.

"There’s increasing evidence of impairment in producing energy molecules (ATP) from all of the necessary sources: oxygen, glucose, fatty acids and amino acids. But as to what is causing this impaired energy production, that remains obscure," he responded.

If the impaired energy metabolism is not due to mitochondrial dysfunction, what else might be behind it?

Findings from recent studies of metabolomics (the study of all the molecules in the body that are involved in cellular nutrition) may provide some clues.

"[Metabolomics] studies have found evidence of [...] a general hypo-metabolic state characterized by depressed levels of most [cellular nutrients and by-products,]" Dr. Komaroff highlighted in the recent review.

If low levels of cellular nutrients are indeed behind the impaired energy production, then what's behind the low levels of cellular nutrients?

One possibility is oxidative stress — a cellular condition where nutrients might become depleted by the chemical process of oxidation. Specifically, the review notes that studies have found "increased levels of pro-oxidants [...] correlating with severity of symptoms" and "decreased levels of anti-oxidants [...] that correlate with severity of symptoms."

In addition, "brain magnetic resonance imaging (MRI) has shown elevated levels of ventricular lactic acid consistent with oxidative stress."

So if oxidative stress can degrade cellular nutrients, resulting in impaired energy metabolism, then what is behind the oxidative stress itself?

In the field of medicine, the usual suspect in oxidative stress is chronic inflammation. "The [oxidative stress] that is a central feature of ME/CFS may be a marker for [...] inflammation in response to infection or injury," the review noted.

However, Dr. Komaroff and Dr. Lipkin emphasized in the review that the sequence of events is far from clear:

"In addition to defining individual components in the pathogenesis of ME/CFS — chronic inflammation, [oxidative stress], defective energy metabolism — we also need to understand how these components interact. Several are bidirectionally related. For example, inflammation can create [oxidative stress] that, in turn, can damage mitochondrial DNA and membranes. Conversely, mitochondrial dysfunction can generate inflammation, as can [oxidative stress] sufficient to damage tissue."
—Dr. Anthony Komaroff and Dr. Ian Lipkin
 

Pyrrhus

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Just as an example of the above, consider how oxidative stress can deplete the critical intracellular anti-oxidant glutathione, which might then lead to depletion of intracellular vitamin B12:

If you're wondering about the evidence for oxidative stress in ME, here is a paper that documented oxidative stress and low glutathione in the brain of ME patients:

Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology (Shungu et al., 2012)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/

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If you're wondering about the evidence for how oxidative stress leads to low glutathione, here are some papers that describe the relationship well:

Assessment at the Single-Cell Level Identifies Neuronal Glutathione Depletion As Both a Cause and Effect of Ischemia-Reperfusion Oxidative Stress (Won et al., 2015)
https://www.jneurosci.org/content/35/18/7143.long

Glutathione, oxidative stress and neurodegeneration (Schulz et al., 2000)
https://febs.onlinelibrary.wiley.com/doi/full/10.1046/j.1432-1327.2000.01595.x

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And if you're wondering about the evidence for how low glutathione and oxidative stress can lead to low intracellular B12, note that the cobalt ion in B12 is extremely sensitive to oxidative stress. Here is one paper that mentions this:

A new role for glutathione: protection of vitamin B12 from depletion by xenobiotics (Watson et al., 2004)
https://pubmed.ncbi.nlm.nih.gov/15606130/
 

ljimbo423

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Just as an example of the above, consider how oxidative stress can deplete the critical intracellular anti-oxidant glutathione
I think oxidative stress plays a big role in ME/CFS, with far reaching consequences. It seems the amount of glutathione that is needed to suppress this oxidative stress though, is massive!

I take 600mg a day of COQ10, 650mg Alpha Lipoic acid, 1200mg N-acetyl-cystiene, 2 gms vitamin C and many more antioxidants. Which feels like trying to stop a flood with a mop and bucket.

Many people here take much more than I do. It seems to me, until I'm able to lower my chronic immune system activation, antioxidants can only barely mitigate the ROS.

What do you think about this Pyrrhus? Do you think it's mainly chronic immune system activation causing the ROS or something else?
 

roller

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Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (Paul et al., 2021)
https://www.pnas.org/content/118/34/e2024358118
Just as an example of the above, consider how oxidative stress can deplete the critical intracellular anti-oxidant glutathione, which might then lead to depletion of intracellular vitamin B12:
... didnt they mean, there is too much hydrogen sulfide ?

then this protocol would be exactly counterproductive ?
It seems the amount of glutathione that is needed to suppress this oxidative stress though, is massive!

I take 600mg a day of COQ10, 650mg Alpha Lipoic acid, 1200mg N-acetyl-cystiene, 2 gms vitamin C and many more antioxidants. Which feels like trying to stop a flood with a mop and bucket.
all life produces h2s and other gases like ammonia.

if perhaps, some other pathogens create h2s/ammonia or similars, or
the body cant get rid of it properly (e.g. unfortunate change in gut microbiome)
then ... one thing comes to the other ... and - you may easily end up as mecfs ?
 

roller

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in this context, just a "mechanism" from environmental technology...
...to just think about, if similar processes in humans are possible...

Amines have a high affinity for H2S and preferentially absorb H2S into solution. Once the
amines have absorbed H2S, and are considered spent, they are heated to liberate the
absorbed H2S which is then captured as a concentrated gas.
https://stacks.stanford.edu/file/druid:ww988vc1913/Melahn - PhD Thesis - Final-augmented.pdf
(Amines are formally derivatives of ammonia, https://en.wikipedia.org/wiki/Amine)

e.g. for the unexplainable exercise troubles:

a) perhaps a lot of H2S in the body
b) too much ammonia ... for whatever reason
c) too much ammonia binds a lot of h2s
d) one day there is exercise
e) harmful ammonia releases h2s in huge amounts
== person has some h2s poisoning...
 

roller

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in science the effects of too much h2s in animals is compared to "hibernating"

h2s damages olfactory cells
it slows down body functions

mice intoxed with h2s get into a state thats neither wake nor hibernation.
...the mecfs-zombie?
 

seamyb

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I think oxidative stress plays a big role in ME/CFS, with far reaching consequences. It seems the amount of glutathione that is needed to suppress this oxidative stress though, is massive!

I take 600mg a day of COQ10, 650mg Alpha Lipoic acid, 1200mg N-acetyl-cystiene, 2 gms vitamin C and many more antioxidants. Which feels like trying to stop a flood with a mop and bucket.

Many people here take much more than I do. It seems to me, until I'm able to lower my chronic immune system activation, antioxidants can only barely mitigate the ROS.

What do you think about this Pyrrhus? Do you think it's mainly chronic immune system activation causing the ROS or something else?
How does Immune activation cause oxidative stress?

My theory, for me anyway, is that there is a high level of toxic crap coming from a mould/fungal infection and that Phase 1 liver detox is producing all the ROS. Glutathion gets depleted from dealing with the ROS from the increase in phase 1 and also because there's an upsurge in phase 2 where it's used in the detox process.

Have you ever tried just supplementing glutathione and if so, why go about increasing it indirectly with ALA, Vit C etc?

I'm gonna start trying ALA and vitamin C, is there any particular form you take, or will bog standard supplements do the trick?
 

ljimbo423

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How does Immune activation cause oxidative stress?
I'm not sure if I know the whole picture but one way immune system activation causes oxidative stress is because immune cells release toxins to kill pathogens. These toxins cause a lot of oxidative stress and inflammation.

Reactive oxygen species play an important function in innate immune cells

Reactive oxygen species (ROS) are key weapons against pathogenic bacteria and fungi in the antimicrobial defense arsenal of host immunity. Innate immune cells, namely macrophages and neutrophils, release ROS as cytotoxic effectors that can irreversibly oxidize and thus damage cellular structures of the intruding pathogens.

At the same time, ROS are important intracellular mediators that drive the appropriate antimicrobial responses and tune the inflammatory response. The best-recognized source of ROS in phagocytic cells is the NADPH oxidase (NOX) complex [1].

However, mitochondria also contribute to the enhanced ROS generation in these cells. This review focuses on the underappreciated but important roles of mitochondrial ROS (mitoROS) in antimicrobial immune defenses.
Reactive oxygen species play an important function in innate immune cells

My theory, for me anyway, is that there is a high level of toxic crap coming from a mould/fungal infection and that Phase 1 liver detox is producing all the ROS. Glutathion gets depleted from dealing with the ROS from the increase in phase 1 and also because there's an upsurge in phase 2 where it's used in the detox process.
I think glutathione depletion in the liver is another reason ME/CFS causes so much oxidative stress.

Have you ever tried just supplementing glutathione and if so, why go about increasing it indirectly with ALA, Vit C etc?
Glutathione absolutely destroys me. Even just 5-10 mg puts me to sleep within a half hour or so. It also gives me big detox symptoms.

I'm gonna start trying ALA and vitamin C, is there any particular form you take, or will bog standard supplements do the trick?
I take just regular vitamin C and ALA. ALA is suppose to be better absorbed on an empty stomach. Iirc, it's about 20% better absorbed on an empty stomach. I take mine with food because I get heartburn when I take it on an empty stomach.

Vitamin C is best taken 3-4 times a day, to improve absorption and maintain a steady state blood level. I take 500 mg, 4 times a day.