A Metabolic Trap for ME/CFS?

[mariovitali]

@Ben H

According to my Hypothesis (and experience) Whey Protein is very problematic. I also believe that you went "low fat" when you were working out , is that correct? If you did so, this is yet one more reason for "crashing".

I am not aware of the elements comprising the "Metabolic Trap" hypothesis. Dr Phair (with whom we exchanged many emails) has never discussed any details of this Theory so i am also looking forward to hearing about it.

Needless to say that a lot of Weight Lifters have Liver issues even with simple supplementation of Whey, Creatine and BCAAs.

I believe that you will find the following study interesting. Why do we have increased Liver Enzymes after weightlifting? Is it due to actual strain on the Liver or something else is in play?

The study clearly says about asymptomatic elevations. OTOH we may have an individual with a 90% desctructed liver but despite this no apparent symptoms (...)

Liver function tests are significantly increased for at least 7 days after weightlifting among men used to moderate physical activity, but not used to performing weightlifting on a regular basis. In accordance with these results, and in order to exclude potential exercise-related effects on liver function tests, it is important to impose training restrictions on weightlifting for at least 1 week before the start of clinical trials. Furthermore, the study also illustrates the importance of considering weightlifting and probably other types of intense muscular training as causes of asymptomatic elevations of liver function tests in daily clinical practice. This will reduce the risk of erroneously attributing changes in liver function tests to a drug effect.

The underlying mechanisms of asymptomatic elevations of clinical chemistry parameters caused by muscular exercise are to a large extent unknown and need to be explored further.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291230/


Unfortunately to this day we do not know :

1) What is the prevalence of ME/CFS patients with previous Liver insults (Hepatitis, Gilbert's, Hemochromatosis, EBV, Lyme, Certain Medications) and/or Gallbladder (Stones, Gallbladder removal, Cholestasis) issues vs Controls
2) How many ME/CFS patients have Liver Fibrosis vs Controls.


2 days ago, yet one more patient from Switzerland was found to have F2 Liver Fibrosis.

 

[Wishful]

I'm not at all surprised that weight lifting would cause changes in liver function. Tearing up all those muscle cells means a major clean-up effort. The bloodstream should be filled with extra toxins, protein fragments, etc, which the liver has to deal with. I'm sure it's complex, which is why there isn't a complete understanding of it yet, especially since there's isn't any obvious profit available from the information.

 

[Murph]

For anyone desperate for more info on this hypothesis, you may be able to glean something from this site

https://www.researchgate.net/project/Etiology-of-Chronic-Fatigue-Syndrome

(ht: @pibee for the link)

Robert Phair has put up a bunch of questions, ponderings and theories there, including this picture, which is well above my paygrade but could perhaps yield insights for some of you!!

edit: you can trawl even more of Robert Phair's stuff at this link. Some things show up there that I didn't see in the CFS project, even though they seem to be linked.

https://www.researchgate.net/profile/Robert_Phair2

for example, this question,
What is your experience treating pellagra with niacin?
Textbooks say that pellagra is cured promptly by dietary niacin. But I have not been able to find reports written by physicians or public health officials describing the actual time required for regression of pellagra symptoms after vitamin treatment begins. I'm particularly interested to know if you have encountered any cases of niacin-resistant pellagra or cases where cure was not achieved despite good patient compliance with the therapeutic regimen.

@mariovitali @paolo . Can you see a linkage here? Why might Phair be asking this?? (I see Pellagra can be treated with nicotinamide, and I recall that nicotinamide levels were way out of line in Naviaux's big metabolites study...)

 

[mariovitali]

@Murph

First of all i do hope that whatever Dr Phair's Research brings is a success so that ME/CFS belongs to the past.

I do not know many details about Dr Phair's Hypothesis but allow me to give my two cents :

-Regarding Niacin : I do not know if it is suggested that a high dose Niacin can be tried. I would like however to disclose that i sent to Dr Phair and Prof. Davis the following (October 2017) :

In other words, the techniques i use identify NAD as a "central junction" of the problem. I also hypothesise that both Tocotrienol and Niacin/NADH Supplementation is contra-indicated.

Now, i am not suggesting to ME/CFS patients out there to either take or not take Niacin/NADH. This information was addressed to Researchers, not patients.

 

[pibee]

Haha, i was obsessing on topic and stalking Phair on researchgate few weeks ago but then I just figured it's too complicated to figure it out (especially with my limited knowledge) and will just have to wait for the end of the summer.

 

[Learner1]

@mariovitali Can you please explain your diagram further?

My lab results consistently show huge oxidative stress with depletion of vitamins E, C, A, alpha lipoic acid and glutathione.

Both NAD+ and NADH have given me more energy, while nicotinamide riboside does nothing, and niacin tends to reverse methylation, counteracting the good effects of methyl B12 and other methylation cofactors.

It is unclear to me how your network diagram is relating to actual biochemistry. Can you explain more here, please?

 

[mariovitali]

@Learner1

I will post in the relevant thread so we do not derail this one . I will tag you there

 

[Learner1]

Ok, thanks!

 

[mariovitali]

@Learner1

Just to clarify regarding Niacin : I am not suggesting that one should take or not. What is known however is that to people having Liver Disease, Niacin can cause problems. One might say that since Liver Enzymes are normal, this means that the Liver is fine. This is not true unfortunately. The only way to assess Liver function is through Liver Biopsy. I have a few examples of ME/CFS Patients with F2 - F3 Fibrosis being completely asymptomatic and without having elevated Liver Enzymes.

 

[Learner1]

@Learner1

Just to clarify regarding Niacin : I am not suggesting that one should take or not. What is known however is that to people having Liver Disease, Niacin can cause problems. One might say that since Liver Enzymes are normal, this means that the Liver is fine. This is not true unfortunately. The only way to assess Liver function is through Liver Biopsy. I have a few examples of ME/CFS Patients with F2 - F3 Fibrosis being completely asymptomatic and without having elevated Liver Enzymes.

There is a lot going on in the liver, like Phase I and Phase II detoxification. The various enzymes and pathways use many vitamins, minerals, and amino acids. Picking on niacin seems a bit silly.

One needs sufficient cofactors in good ratios to make these pathways work, as well as the ability to eliminate the toxins they mobilize and process from the body.

 

[mariovitali]

There is a lot going on in the liver, like Phase I and Phase II detoxification. The various enzymes and pathways use many vitamins, minerals, and amino acids. Picking on niacin seems a bit silly.

One needs sufficient cofactors in good ratios to make these pathways work, as well as the ability to eliminate the toxins they mobilize and process from the body.

I agree with everything apart from the "silly" part. Please see here regarding Niacin :


https://livertox.nlm.nih.gov/Niacin.htm

Mayo Clinic :

If you have liver disease, peptic ulcer disease or severe low blood pressure (hypotension), don't take large amounts of niacin. The supplement has been linked with liver damage, can cause hypotension and might activate a peptic ulcer.

https://www.mayoclinic.org/drugs-supplements-niacin/art-20364984

 

[Learner1]

It's a lot more than just niacin.....

https://goo.gl/images/u8PkmT

 

[Learner1]

Taking large doses of anything in isolation is a bad idea. Too much water can kill you.

One needs the cofactors that work with a given nutrient.

Niacin reverses methylation, which can increase toxic problems and cause liver damage. And many ME/CFS patients are short of numerous Phase I and II nutrients.

All of this points to getting good lab work done and working with a practitioner that knows what they're doing rather than taking large amounts of some supplement one reads about on the internet. Not avoiding niacin.

 

[raghav]

Well it is nearly 15 days since the last post in this thread, which i consider the most important in the forum at least for the next few months perspective. Can @Janet Dafoe (Rose49) or somebody give us an update on how much of the testing has been completed, in terms of total effort estimated and whether there were any hiccups along the way. I am not compelling but just want to know whether we have really reached the end of the tunnel. Thanks in advance.

 

[maybe some day]

Well it is nearly 15 days since the last post in this thread, which i consider the most important in the forum at least for the next few months perspective. Can @Janet Dafoe (Rose49) or somebody give us an update on how much of the testing has been completed, in terms of total effort estimated and whether there were any hiccups along the way. I am not compelling but just want to know whether we have really reached the end of the tunnel. Thanks in advance.

Im sure when that happens we will all know.

 

[Sushi]

Hi,
They are working on this as fast as they can and discussing this question. I am unable to answer it myself. Believe me, we are feeling just as urgent as you are. I'm sorry you have to wait even one second longer. But I don't have anything more I can tell you right now. I'm itching to try whatever it is on Whitney, too! We are all just needing to hang in there. Hard.

Can @Janet Dafoe (Rose49) or somebody give us an update on how much of the testing has been completed, in terms of total effort estimated and whether there were any hiccups along the way.

Im sure when that happens we will all know.

I agree. There will be updates when more is known but, as I remember, we were told that that might be the end of the summer.

 

[maybe some day]

I agree. There will be updates when more is known but, as I remember, we were told that that might be the end of the summer.

I dont ever recall wishing summer to end, until now.

 

[valentinelynx]

I dont ever recall wishing summer to end, until now.

LOL! You obviously don't live in Arizona! (I see you live in the SF Bay Area, which was my home most of my life. Wish I could get back there!)

 

[Kenshin]

LOL! You obviously don't live in Arizona! (I see you live in the SF Bay Area, which was my home most of my life. Wish I could get back there!)

I would need air con 24/7, I love the sun, but constant heat makes me feel...Do I even need to use an adjective at this point? I think we are all familiar with the peculier form of torure known as M.E/Cfs.

 

[wastwater]

I think FOXO1A pathway maybe important and possibly the drug Rosiglitazone worth looking at