Exercise, Reactive Oxygen Species, and Fatigue.

[Croatoan]

There is ample evidence that the fatigue that occurs after exertion in ME is the result of either the creation of too many Reactive Oxygen Species (ROS), or the inability to remove them properly through the antioxidant pathway.

It is also well know that after stressful life events, high protein diet, high calorie diet, heat stress, exogenous toxins, and viral or bacterial infection and the inability to remove ROS.

I believe that the ROS in genetically susceptible people (nature) becomes to much to handle after any combination of these environmental issues (nurture).

Your whole life should be focused on limiting the creation of, and reducing ROS if you want to feel better. High ROS is the cause of all the many different symptoms of ME. What needs to be done will be different for everybody, but the root cause is the same; too many ROS. The one thing that all ME patients have in common is fatigue after exertion, so this article is a great place to start:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909187/

It is my belief that the fatigue ME patients have originates in a disruption the Electron Transport Chain:
[bimg=no-lightbox]http://www.nature.com/cdd/journal/v10/n5/images/4401225f1.jpg[/bimg]

When electrons are not "transported" to be used they attach to oxygen and lipids and produce free radicals as well as limit the amount of ATP created. ATP is what is used for energy.

I feel this is why NADH has worked for some people in the past, and why Riboflavin works for me, and why CoQ10 works for others:
[bimg=no-lightbox]http://chemistry.elmhurst.edu/vchembook/images/596electransport2.gif[/bimg]

[bimg=no-lightbox]http://www.nature.com/nrm/journal/v3/n3/images/nrm762-i2.gif[/bimg]

 

[Remy]

One good way to know for sure if you have oxidative stress damage is to get an Organic Acids test.

If 8-hydroxy-2' -deoxyguanosine (8-OHdG) is elevated, there is a good chance that you will benefit from interventions designed to reduce oxidative stress.

 

[Croatoan]

One good way to know for sure if you have oxidative stress damage is to get an Organic Acids test.

If 8-hydroxy-2' -deoxyguanosine (8-OHdG) is elevated, there is a good chance that you will benefit from interventions designed to reduce oxidative stress.

Do you have a source for this? Becasue I do not beleive it but I am too lazy to prove it.

 

[Remy]

Do you have a source for this? Becasue I do not beleive it but I am too lazy to prove it.

Of course I have a source for it. Once again, Google is your friend.

Also, polite requests work wonders too rather than just disbelief and self-proclaimed laziness.

 

[weyland]

What needs to be done will be different for everybody, but the root cause is the same; too many ROS.

ROS isn't the root cause. It's the reaction to the root cause.

 

[Who Me?]

Of course I have a source for it. Once again, Google is your friend.

Also, polite requests work wonders too rather than just disbelief and self-proclaimed laziness.

Well said @Remy

 

[Croatoan]

ROS isn't the root cause. It's the reaction to the root cause.

But ROS creates all the symptoms. The causes of increased ROS are in the hundreds.

What do think is the root cause?

Plus, I am not saying this to be snarky, but I am better, and all I did was reduce ROS, that was my only focus.

 

[Croatoan]

Of course I have a source for it. Once again, Google is your friend.

Also, polite requests work wonders too rather than just disbelief and self-proclaimed laziness.

So, I could Google for a long time but not come up with the same source. Sources, your sources, are extremely important. This is about collaboration and if you do not site your source we both do the same work and that is a waste of time.

You read to much into my comment. Note that I put a smiley face on the end. That means I was smi!in, not pissy faced or frowning.

 

[weyland]

What do think is the root cause?

Depends on the person. Most commonly in ME it is an infectious process I believe. Production of ROS is an important part of innate immune defense.

I recommend reading this paper for an interesting perspective.

 

[Croatoan]

Depends on the person. Most commonly in ME it is an infectious process I believe. Production of ROS is an important part of innate immune defense.

I recommend reading this paper for an interesting perspective.

I read the whole thing. What in there is a new perspective? It is common knowledge that infections cause oxidative stress. But at the end he is just silly: "Treatment of oxidative changes in chronic disease with antioxidants is similar to treating a fever with aspirin instead of treating the pneumonia."

If the ROS are produced by infection, yes treat the infection. But whit if the ROS is created by a cofactor deficiency? A deficiency in riboflavin will cause excess superoxides. How does he suppose we treat that? With antibiotics?
http://journals.cambridge.org/actio...e=online&aid=9260125&fileId=S0007114514000178

And how about the ROS produced by pollution, do we treat that with antibiotics as well?
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241427/

And look here how pollution makes influenza worse:
http://particleandfibretoxicology.biomedcentral.com/articles/10.1186/s12989-014-0057-1

If ROS were defensive against infection then the child would be better off, not worse off.

I do not doubt that any environmental stressor can start the cascade of ME, but if it is caused by an infection why does the illness continue when there is no sign of disease? It is possible that the initial stressor fully depleted an anti-oxidant cofactor in a gentically susceptible population.

after years of investigating viral/bacterial causes for ME there is zero evidence there is an agent that is common among patients. what is common? Excess oxidative stress.

[Drops Mic]

 

[weyland]

If the ROS are produced by infection, yes treat the infection. But whit if the ROS is created by a cofactor deficiency? A deficiency in riboflavin will cause excess superoxides. How does he suppose we treat that? With antibiotics?
http://journals.cambridge.org/actio...e=online&aid=9260125&fileId=S0007114514000178

That paper doesn't really provide any proof that riboflavin deficiency alone causes excessive ROS production as far as I can tell. Most of the evidence reviewed is on fish or murine studies. One of the human studies reviewed is in the context of infection and notes the opposite of what you're saying:

In a case–control study(43) on Indian children, it was found that plasma MDA levels of malaria patients with riboflavin deficiency were significantly higher than those of malaria infected children with normal riboflavin status. However, in healthy children without malaria infection, no difference in MDA levels was observed between riboflavin-deficient and riboflavin-sufficient children. Furthermore, in this study, ribo- flavin status was found to be inversely correlated with plasma MDA levels in malaria patients but not with those in healthy subjects

And how about the ROS produced by pollution, do we treat that with antibiotics as well?

I fear you missed the point of the paper I linked.

If ROS were defensive against infection then the child would be better off, not worse off.

The child mouse yes.

after years of investigating viral/bacterial causes for ME there is zero evidence there is an agent that is common among patients.

That's not really true. There is evidence implicating several viruses and bacteria. What's common is persistent immune activation.

 

[Croatoan]

That paper doesn't really provide any proof that riboflavin deficiency alone causes excessive ROS production as far as I can tell. Most of the evidence reviewed is on fish or murine studies. One of the human studies reviewed is in the context of infection and notes the opposite of what you're saying:

Read more of the studies then.
http://www.ncbi.nlm.nih.gov/pubmed/15115116

The child mouse yes.

I forgot the link for that one, but here you go. I fail to understand how you do not see the connection.
http://bmb.oxfordjournals.org/content/68/1/95.full

But mice studies are useful and you dismiss it not to further our understanding, but only to try to appear intelligent.

That's not really true. There is evidence implicating several viruses and bacteria. What's common is persistent immune activation.

Listen, if you think that people with ME do not have enough oxidative stress to kill a virus or bacteria in the body show me some links to back up your hypotheisis.

Or, you can test this yourself by increasing your oxidative stress, because that is what you and the other researcher are saying, that oxidative stress exists to kill bateria and virii. so go ahead and deplete you selenium and riboflavin, and maganese and copper and zinc, live near a hiway, get a high stress job, etc.

I have a strong feeling I know you from PR.

 

[Remy]

Sources, your sources, are extremely important. This is about collaboration and if you do not site your source we both do the same work and that is a waste of time.

I have no problems providing sources when people are genuinely interested in something I've posted. However, I have zero interest in carrying on a discussion with someone who has already made up his mind and stated it plainly.

So how about this one, for just one example. It's pretty definitive. Bold emphasis is mine.

Clin Chim Acta. 2004 Jan;339(1-2):1-9.
Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics.

Wu LL1, Chiou CC, Chang PY, Wu JT.
Abstract
Reactive oxygen species (ROS) produced either endogenously or exogenously can attack lipid, protein and nucleic acid simultaneously in the living cells. In nuclear and mitochondrial DNA, 8-hydroxydeoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, is the most frequently detected and studied DNA lesion. Upon DNA repair, 8-OHdG is excreted in the urine. Numerous evidences have indicated that urinary 8-OHdG not only is a biomarker of generalized, cellular oxidative stress but might also be a risk factor for cancer, atherosclerosis and diabetes. For example, elevated level of urinary 8-OHdG has been detected in patients with various cancers. In human atherosclerotic plaques, there were increased amounts of oxidatively modified DNA and 8-OHdG. Elevated urinary 8-OHdG and leukocyte DNA were also detected in diabetic patients with hyperglycemia, and the level of urinary 8-OHdG in diabetes correlated with the severity of diabetic nephropathy and retinopathy. We have discussed various methods for determining 8-OHdG in the tissue and urine, including HPLC with and without extraction, and ELISA. Using the ELISA we developed, we found that the normal range of urinary 8-OHdG for females was 43.9 +/- 42.1 ng/mg creatinine and 29.6 +/- 24.5 ng/mg creatinine for males, respectively. We found that the normal value between females and males is significantly different (p < 0.001).

 

[RuthAnn]

This is interesting topic. It starts to make more sense of reactivation of viruses.
Look at this with respect to EBV.
http://www.ncbi.nlm.nih.gov/pubmed/24376853

Here, we address the role of ROS in induction of EBV reactivation under MNNG treatment. EBV reactivation was induced in over 70% of EBV-positive NA cells and the promoter of Rta (Rp) was activated after MNNG treatment. Inhibitor experiments revealed ATM, p38 MAPK and JNK were activated by ROS and involved in MNNG-induced EBV reactivation. Significantly, ROS scavengers N-acetyl-L-cysteine (NAC), catalase and reduced glutathione inhibited EBV reactivation under MNNG and H₂O₂ treatment, suggesting ROS mediate EBV reactivation.

 

[RuthAnn]

Here is a list of common symptoms of oxidative stress if you don't feel that you can afford expensive testing.
https://doctordoni.com/2014/10/5-signs-of-oxidative-stress.html

So, how can you tell if oxidative stress is occurring in your body? Here are five signs to look out for:

1. Fatigue
2. Memory loss and/or brain fog
3. Muscle and/or joint pain
4. Wrinkles and grey hair
5. Decreased eye sight
6. Headaches and sensitivity to noise
7. Susceptibility to infections

 

[RuthAnn]

Statin induced myopathy, in case anyone's CFS/ME was statin induced and your doctor didn't tell you it was a possible side effect.
Statins interrupt the mevalonate pathway, interrupting production of CoQ10, an important transporter in the electron transport chain.

http://www.spacedoc.com/articles/my-statin-story

 

[RuthAnn]

http://bsherman.net/freeradicals.htm

"A long and disturbing list of diseases is now linked to oxy radicals and ROS (see Box 8.1). The onslaught of free radicals and ROS also contributes to many of the less serious but still troubling symptoms of aging, such as wrinkled skin, gray hair, balding, and bodily stiffness. Oxy radicals have also been linked to such minor but bothersome conditions as dandruff and hangovers. One of the most experienced free-radical researchers, the Japanese biochemist Yukie Niwa, estimates that at least 85% of chronic and degenerative diseases result from oxidative damage (Niwa & Hansen, 1989, p. 9)"

 

[Croatoan]

This is interesting topic. It starts to make more sense of reactivation of viruses.
Look at this with respect to EBV.
http://www.ncbi.nlm.nih.gov/pubmed/24376853

Here, we address the role of ROS in induction of EBV reactivation under MNNG treatment. EBV reactivation was induced in over 70% of EBV-positive NA cells and the promoter of Rta (Rp) was activated after MNNG treatment. Inhibitor experiments revealed ATM, p38 MAPK and JNK were activated by ROS and involved in MNNG-induced EBV reactivation. Significantly, ROS scavengers N-acetyl-L-cysteine (NAC), catalase and reduced glutathione inhibited EBV reactivation under MNNG and H₂O₂ treatment, suggesting ROS mediate EBV reactivation.

Yes! That is exactly what I am saying. It is not that we have these virii any more than anyone else, it is just that for whatever reason we have higher levels ROS or they trigger more ROS production.

This clicked with me years ago, a friend of mine had herpes, and everytime she got stressed she had an outbreak. That led me on my first investigation regarding ROS and disease symptoms.

I want to add, that for the first time in my life I have gone the longest every without a cold or a flu. It is not that I do not get the flu, but my ROS burden is so much lower I can handle the ROS burden from influenza.

 

[Veet]

If the ROS are produced by infection, yes treat the infection. But whit if the ROS is created by a cofactor deficiency? A deficiency in riboflavin will cause excess superoxides.

During the past year my primary focus was on oxidative stress and antioxidants. This was based on my understanding of Martin Pall's NO/ONOO theory, and my symptoms. I've come to recognize a cluster of symptoms as symptomatic, presumably, of peroxynitrite. (light-jeadedness, shortness of breath, increased sensitivity to sound,noise, general feeling of yuk). Taking, or more to the point in my case, eating, antioxidants resolves those symptoms.

Adding B2, in the activated form of FMN, definitely reduced my need for antioxidants, as well as eliminating myt need for antihistamines and mast cell stabilizer.

Infection provoked my initiation into chronic fatigue, but has not been one of my ongoing issues. Stress can also provoke herpes outbreak for me. But one of the things that eliminates my herpes, olive leaf extract, is also a strong antioxidant, one I've just put back into daily use.

 

[RuthAnn]

There is ample evidence that the fatigue that occurs after exertion in ME is the result of either the creation of too many Reactive Oxygen Species (ROS), or the inability to remove them properly through the antioxidant pathway.

It is also well know that after stressful life events, high protein diet, high calorie diet, heat stress, exogenous toxins, and viral or bacterial infection and the inability to remove ROS.

I believe that the ROS in genetically susceptible people (nature) becomes to much to handle after any combination of these environmental issues (nurture).

Your whole life should be focused on limiting the creation of, and reducing ROS if you want to feel better. High ROS is the cause of all the many different symptoms of ME. What needs to be done will be different for everybody, but the root cause is the same; too many ROS. The one thing that all ME patients have in common is fatigue after exertion, so this article is a great place to start:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909187/

It is my belief that the fatigue ME patients have originates in a disruption the Electron Transport Chain:
[bimg=no-lightbox]http://www.nature.com/cdd/journal/v10/n5/images/4401225f1.jpg[/bimg]

When electrons are not "transported" to be used they attach to oxygen and lipids and produce free radicals as well as limit the amount of ATP created. ATP is what is used for energy.

I feel this is why NADH has worked for some people in the past, and why Riboflavin works for me, and why CoQ10 works for others:
[bimg=no-lightbox]http://chemistry.elmhurst.edu/vchembook/images/596electransport2.gif[/bimg]


[bimg=no-lightbox]http://www.nature.com/nrm/journal/v3/n3/images/nrm762-i2.gif[/bimg]

@Croatoan, what happens to all those H+ 's coming off the electron transport chain?