A Metabolic Trap for ME/CFS?

M Paine

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I've recently had to change primary care doctor. It would be really helpful to me to have a one or two page article, readable by a GP, which outlines the case for the metabolic mature of ME/CFS. Aimed at practitioners, not general public.

Has anyone seen a round-up of the current state of ME/CFS aimed at practitioners? Specifically looking at the findings of the more recent metabolomics data?
 

Kenshin

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Near the beggining of the illness I used to get remmisions every evening.
Meaning I would be in bed for most of the day, but get a few hours of being completely normal in the evening.

My body still follows the pattern, but I am always ill, never feeling normal, just improved at certain times.
 

Wishful

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The type IV delayed sensitivity is far from well-understood. My symptoms started as a type IV delayed food sensitivity (to oranges), and then spread to pretty much everything but highly processed starches (I didn't eat plain sugar, so I'm not sure about that). It started with a precise, consistent 48-hr +/- a few minutes delay, which fits type IV. A few months later, I started a rotating diet, which did avoid triggering flare-ups, but it also abruptly switched the delay to a precise and consistent 17.5 hrs, which doesn't fit what's written about type IV sensitivity. A couple of years later, I ate some cherries, had a bad reaction to them, and my delay abruptly switched to 23 hrs and thirty-some minutes. I didn't refine the time delay, because soon after that, I had food poisoning and that seemed to cure the type IV reaction. I never found any research mentioning abrupt switches in the time delay, or even delays under 48 hrs. An immunologist agreed that this was a type IV delayed food sensitivity, but of course, didn't have any clinical test to verify it.

I think that my ME triggered a few weeks or months before that, from a tetanus booster, and the type IV sensitivity was a result of the ME messing up my immune system. The multiple daily immune activation probably then pushed my cells into the metabolic trap. The symptoms of the sensitivity were the same as those of ME, so it took me a couple of years to actually realize that the sensitivity had stopped. I thought that the time delay had just switched to 20 minutes (way outside the known limits for type IV sensitivity), but later found that it was a boost in tryptophan transport across the BBB 20 minutes after eating a starchy meal.

We really shouldn't be surprised by complex interactions in our immune systems. The amazing thing is that it doesn't get messed up more often.
 

FMMM1

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I've recently had to change primary care doctor. It would be really helpful to me to have a one or two page article, readable by a GP, which outlines the case for the metabolic mature of ME/CFS. Aimed at practitioners, not general public.

Has anyone seen a round-up of the current state of ME/CFS aimed at practitioners? Specifically looking at the findings of the more recent metabolomics data?
Check out the transcript of Chris Armstrong's talk at the OMF Symposium in September 2017. I found it on the Melbourne University website.

I also found this [https://totoneimbehl.wordpress.com/...omf-symp-stanford-19aug2017/comment-page-1/]; I assume this is the same.

May be of some interest.
 

M Paine

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Thank you @FMMM1, lot's of interesting information in there. I have not been keeping up it seems, I have not seen any of the OMF videos from that time.

A transcript might not be suited as a printout for a clinician. I think that their time is so valuable, or perhaps another description is that their time is limited. It might need to be some sort of bullet point list of findings, or something like that in order to give a doctor a lot of information, quickly.

My new doctor is young, and honestly I doubt has any expirience with ME/CFS. Which actually, is kind of a good thing if you ask me. We live at a new point in ME/CFS history, where there is really good evidence for the biological basis of the disease. Metabolomics data seems like the best source of information in my oppinion, and a one-page document outlining the metabolomics and other relavant proteomics, genetic, and immune signalling data would be really valuable as a patient.
 
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It’s all very interesting and very puzzling. Some people feel that the ketogenic diet might have triggered their ME while others are using it specifically because they believe it aids recovery. By bypassing a blocked energy pathway? And then there is Dr Naviaux who saw a metabolic similarities with ME and starvation.

I wasn’t dieting but I was very physically active and experiencing acute sustained stress for several years previously. And then I caught a virus. And followed the same pattern of deterioration described by others. Falling further down the well. It took about 18 months to find myself right at the bottom.
I would find it odd for ketogenic diet to cause ME after reading about the history, evolution and studies around it. Can you link me on here to a post where this is discussed? I just went full Keto a week ago and am interested in studying all experiences from our community regarding the diet.
 

TreePerson

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I would find it odd for ketogenic diet to cause ME after reading about the history, evolution and studies around it. Can you link me on here to a post where this is discussed? I just went full Keto a week ago and am interested in studying all experiences from our community regarding the diet.

Ben H higher up the thread referred to having been high protein mainly keto prior to onset. There may have been one more? I don’t think he or anyone has said categorically that they believe this to be the cause of onset. People who did a lot of training prior to onset have been commenting because this was mentioned in the original article about the research.
 
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I would find it odd for ketogenic diet to cause ME after reading about the history, evolution and studies around it. Can you link me on here to a post where this is discussed? I just went full Keto a week ago and am interested in studying all experiences from our community regarding the diet.
yeah i was just in a thread where someone said keto gave them problems.
 

ebethc

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The first biochemical (not exactly metabolic) trap theory of ME I encountered was the eicosanoid theory. In this eicosanoids, very short range fat based hormones, drive inflammation and other processes to create more eicosanoids, perhaps involving a wider range of chemicals than just these hormones alone. It was only a theory, and not proven, but you can look up Grey and Martinovic on PubMed. Dr Martinovic was my treating doctor from 1993. I knew I had to do something or drop out of my PhD.

How do u lower arachidonic acid (which, I believe, is a product of eicosanoids)?

I think AA is what causes inflammation and pain (I believe it’s linked to prostaglandins)

Last, Maureen Hanson is studying lipid metabolism, so I have a hunch that she might come up w some interesting insights..
 

FMMM1

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Thank you @FMMM1, lot's of interesting information in there. I have not been keeping up it seems, I have not seen any of the OMF videos from that time.

A transcript might not be suited as a printout for a clinician. I think that their time is so valuable, or perhaps another description is that their time is limited. It might need to be some sort of bullet point list of findings, or something like that in order to give a doctor a lot of information, quickly.

My new doctor is young, and honestly I doubt has any expirience with ME/CFS. Which actually, is kind of a good thing if you ask me. We live at a new point in ME/CFS history, where there is really good evidence for the biological basis of the disease. Metabolomics data seems like the best source of information in my oppinion, and a one-page document outlining the metabolomics and other relavant proteomics, genetic, and immune signalling data would be really valuable as a patient.
Possibly ask the Melboune group if they have anything. If you watch Neil McGregor's presentation at the symposium you'll hear that they work closely with medical doctors.
 

boolybooly

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Speculating, the article mentions ME epidemics and the existence of these suggest that if there is a metabolic trap it must have a cause which can explain this epidemiological pattern. This is not necessarily contagion but anecdotally this is how many people describe onset, as virus symptoms and failed recovery, which suggests an immune trigger activated by an infection.

This is why I feel it is likely that there are metabolic aspects to ME as a consequence of an immune trigger but unlikely that nutritional deficit alone is responsible for the condition or that supplements alone can rectify it. However given the histories of scurvey and rickets its not something that can be dismissed and is worth investigating.

It strikes me the link between immunological activity and metabolism might involve the activation of the Dauer state genes being investigated by Dr Naviaux. These pathways which originally evolved as hibernation and aestivation responses could potentially have been coopted by evolution among our vertebrate ancestors as antiviral strategies to alter the cellular environment to make it as alien and hostile to viruses as possible, at the same time making life difficult for the host, requiring withdrawal from activity, usually temporary while surviving on body reserves. My guess is this is not unique to ME and most infections that make one want to curl up in bed and sleep involve this kind of response but there would seem to be a problem with chronic activation and cumulative severity in ME.

There may be a "trap" at work here such as Dauer type activity which impedes viral reproduction but makes it harder for the immune system to clear viruses so that it ends up in a never ending cycle of defence and this might relate to metabolic blockages, like the biotin deficiency which I am convinced is real, which could involve a metabolic trap in the prolongation of infection and response.

What I am saying is that it seems possible to me that if there is a metabolic trap involved that there is an immunological trigger springing the metabolic trap and maintaining it.

It follows that if an immune response involving Dauer states is the basis of the metabolic disruption, evolution would favour the battle against viruses and would tend to leave immune cells in a more competent state than hibernating cells. So by that logic white blood cells might be the least likely to show a metabolic trap.

If that makes sense to anyone but my poor befuddled self. :confused:

2c
 

ebethc

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I
I just learned that Phair stumbled on this metabolic trap last December. We're so lucky that the Pineapple fund stepped in with that funding - now we will know if the hypothesis has legs or not by the end of summer. That's certainly not par for the course for ME/CFS. Van Elzakker came up with his vagus nerve hypothesis over five years ago and we're still waiting to hear about that.

The Davis team seems pretty excited about this hypothesis
Thanks for sharing this... good to know where the pine money is going, and good to know one research track
 

alex3619

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How do u lower arachidonic acid (which, I believe, is a product of eicosanoids)?

I think AA is what causes inflammation and pain (I believe it’s linked to prostaglandins)

Last, Maureen Hanson is studying lipid metabolism, so I have a hunch that she might come up w some interesting insights..
The strategy was indeed to lower AA, arachidonic acid, but via polyunsaturated fat restriction, though of course AA is high in many animal foods. AA is not a product of eicosanoids, its the primary precursor for most of them, specifically the series 2 eicosanoids, which includes the most inflammatory of these hormones.

You can start lowering it by avoiding butter, tropical fish, and organ meats, as primary sources. However most meats and dairy contain some.

Then you need to avoid AA precursors, but not consume so little as to induce deficiency problems. These are mostly of plant origin, and includes mostly seeds and nuts. Some nuts are very low in these primarily omega-6 fats, such as macadamia nuts, olives and I think avocado. These particular nuts are very high in monounsaturated fats, especially the macadamia nuts.

Deep sea fish also typically dominate in omega-3 fats, though this is not anti-inflammatory but just very weakly proinflammatory, and will competitively compete for the same enzymes, resulting in series 3 eicosanoids.

However this needs to be done with medical supervision, as too low an AA and precursor intake can be fatal or have dire consequences.

Prostaglandins are a subtype of eicosanoids.

Alcohol releases free arachidonic acid. Free arachidonic acid inevitably is metabolised into eicosanoids. Its very likely this is the primary mechanism for alcohol poisoning, and why PWME have such an issue with alcohol. However we also often have a restriction on synthesis, another deep topic, and a boost to utilisation, resulting in lower AA levels than normal. Diet does play a role in this too.

Cortisol is, if I recall correctly, the primary suppressor to the release of free AA.
 

alex3619

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I think the metabolic trip is triggered by the immune system. It seems to happen when a number of stressors happen together.
Such immune function will put a high demand on certain metabolites. It may also lower energy production for most of the body. Low energy plus depleted metabolites might cause issues. So while cytokines or other immune signals might be involved, its also possible that metabolite drain is a big part of the issue.
 
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I believe I depleted my lysine, which led to reactivation of EBV. I was an athlete with high BCAA and arginine intake at the time I got sick. When I attempt a high-protein diet now, I just pee a lot of the protein out (as evidenced by bubbles in urine) unless I maintain a high B6 and zinc intake.

I have trouble maintaining an adequate appetite, but when I'm able to stimulate an appetite, I'm always ravenously hungry for protein. I'm also really prone to edema, which I believe is from burning the albumin and other proteins from my bloodstream. Not horrible edema, but noticeable puffiness in my face, indentations from my socks and waking up with wrinkles from the sheets marked into my skin. This edema also goes away with high B6 and zinc.

I don't understand what prevents me from repleting my B6 and zinc. I have been taking them both to prevent edema and proteinuria since about March 2017, and I still need them daily.