ME/CFS researcher Derya Unutmaz's hypothesis on cause of ME/CFS....

[Learner1]

I agree with you that there is a lot of treatment options missing still.
It’s really hard to change your (leaky) gut and microbiome, even if you keep testing it and checking.

Agreed.

I think one of the problems is that because it is not “mainstream” yet, that we don’t treat it until you have had it for years. I think it gets harder and harder to treat the longer you have it.

I think there's simply not enough science to know all of the dynamics yet. My daughter is a microbiome researcher and we discuss this a lot. No one really knows what interventions will do what exactly, and there are too many variables, through diet, supplements and the many types of creatures in our guts and how they interact with each other.

Another problem is that I think this problem can only be treated by a personalized treatment plan and how do you test that in a protocol.

Exactly. One size fits all solutions simply do not work.

What helped for me is treating the dysbiosis (sibo) constantly, giving the immune system support for getting the LPS out (LDN, immunoglobulins), trying to influence the microbiome (probiotics), treating inflammation in the gut (curcumine, mesalazin, omega 3)
I don’t think any of those things would have worked on their own, so it wouldn’t do well in a study.

So the LDN and Immunoglobulins take care of the LPS? I've been on both for 9 months...

I also am on cromolyn sodium, ranitidine, and ketotifen though I wonder what these drugs do to the microbiome and wonder if they're contributing to the problem. I've never had SIBO, though I know many patients do. And I'm on curcumin and don't need omega 3s.

There needs to be more science around this as most of the studies are testing only one intervention at a time. It's too complex a problem. My family hss been doing stool trsts for 10 years and trying interventions and the results one gets are not always predictable.

But we need to try anyway, as it's important.

 

[ljimbo423]

what - specifically - are NAIOS? do you have a list? thx

Natural anti-inflammatory and antioxidative
substances = (NAIOSs)

Here is a quote from the full Maes paper-

All patients followed the leaky gut
diet and took glutamine, zinc and NAC, in combination
with other NAIOSs, which were given according

to the immune and biochemical status of the patients,
i.e. L-carnitine, coenzyme Q10, taurine and lipoic acid
(in case of carnitine and/or coenzyme Q10 shortage);
or curcumine and quercitine (in case of systemic or intracellular
inflammation).

All I could find in reference to the leaky gut diet they used was this-

and a milk allergic, glutenfree
and low-carb diet, labelled the leaky gut diet

Here is the LINK to the PDF download (Full paper)

I am taking every supplement listed here except taurine, along with a leaky gut diet.

Jim

 

[Wishful]

I agree with you that there is a lot of treatment options missing still.
It’s really hard to change your (leaky) gut and microbiome, even if you keep testing it and checking.

I agree. I had type IV food sensitivity, and all the diet changes, anti-candida treatments, antibiotics, and other things that should affect the microbiome had no long-term effects. Food poisoning (canned coconut milk that was a bit off) apparently flushed out something that was causing problems, because the food sensitivity (due to leaky gut?) went away. I doubt that this will become a reliable treatment option, but it shows that significant positive changes to the microbiome are possible.

 

[ebethc]

I had type IV food sensitivity

what is this?

 

[Wishful]

Type IV delayed food sensitivity is a t-cell mediated reaction to foods. Standard allergies are type I, which don't involve t-cells. Type IV reactions take 48-72 hrs to show up, and is quite precise and consistent (+/- a few minutes).

My guess is that my tetanus booster triggered my ME, which messed up my immune system, resulting in the type IV sensitivity. My microbiome seems to have been involved, but which came first? Was my microbiome causing unnoticed problems that escalated into ME, or did ME cause microbiome changes that caused type IV sensitivity? My guess is the latter. @ljimbo423 will probably argue the former.

 

[ebethc]

Type IV delayed food sensitivity is a t-cell mediated reaction to foods. Standard allergies are type I, which don't involve t-cells. Type IV reactions take 48-72 hrs to show up, and is quite precise and consistent (+/- a few minutes).

My guess is that my tetanus booster triggered my ME, which messed up my immune system, resulting in the type IV sensitivity. My microbiome seems to have been involved, but which came first? Was my microbiome causing unnoticed problems that escalated into ME, or did ME cause microbiome changes that caused type IV sensitivity? My guess is the latter. @ljimbo423 will probably argue the former.

so, I'm guessing that Type IV food sensitivities don't show up on any tests? you would have to find them via an elimination diet?

 

[Wishful]

I couldn't get any testing for type IV sensitivity. The response from several allergists and immunologists was 'Yes, that definitely sounds like type IV sensitivity. Sorry, can't help you.' The alternative medicine allergists response was 'Of course my ($150) scratch test will reveal type IV reactions.', even though the scratch test involves a completely different immune system (immunoglobulin) and supposedly shows results in minutes, whereas the type IV reaction takes 48 hrs. Quackery.

A rotating diet (avoiding foods from the same family for at least five days) allowed me to avoid triggering the symptoms flare-ups. That's a difficult diet to follow, and didn't end the sensitivity, just avoided triggering it. It also didn't avoid my baseline symptoms, which I didn't realize at the time were ME/CFS. I'm very, very grateful that I accidentally cured the sensitivity.

I couldn't do an elimination diet to find out what I was reacting too, because I reacted to pretty much every food other than sugars, starches, and oils so processed that there weren't any other molecules to trigger on. I suppose that was a type IV sensitivity enhanced by ME/CFS.

 

[msf]

LINK

Here is a study that has the same basic hypothesis-



LINK

This is what another leading ME/CFS researcher, Chris Armstrong says about an altered microbiome and increased intestinal permeability (Leaky gut) causing PEM-

LINK


That's 2 leading ME/CFS researchers that have the same hypothesis, so far! It's no surprise to me, that all of the 5 ME/CFS collaborative research teams are focused on the gut, immune system, metabolomics and the brain.

There are also 5 more teams working for the Solve ME/CFS initiative (SMCI). They are also mainly focused on the gut, immune system and metabolomics-

1. LINK

I think many of these researchers have a pretty good idea of what the root cause of ME/CFS is.

That's why they are researching these specific areas. Their challenge is finding the biological bio-markers to connect the gut, immune system, metobolomics and the brain.

I have no doubt they will do it!

Jim

This is encouraging, in that it's becoming quite obvious now to clued up people what the basic problem is. Of course, kdm was saying this 7 years ago. But it's nice having people on board who will hopefully be taken more seriously by mainstream healthcare.
Actually, I would say the harder thing to ascertain now is why the gut is changed in people with ME. I know KDM has his theory, and a recent treatment I tried suggests that he may be right in my case.

 

[msf]

I would bet serious money this is Hanson's hypothesis too, and that lipkin and Davis have at least entertained it.

 

[msf]

None of that shows a strong causal link. It could just as well be that ME/CFS causes the observed changes in the microbiome. I still believe that immune activation, such as from viral infection or vaccination, is the start of ME/CFS for most of us. I'm not expecting a cause or cure involving the microbiome.

The exercise->leaky gut->PEM hypothesis seems a bit weak too. It doesn't seem to fit the precision and consistency of the 24 hr delay I experience, or the fact that some quite strenuous exercise doesn't cause PEM, but muscle-damaging activity does. Muscle damage ->IFN-g -> PEM seems a much better match to observational data.

Wanna bet? Where do you think the muscle damage comes from? If you read my blog I make some guesses about the delay in PEM, which I agree are just guesses at the moment. With regards to your theory , however, you seem to be equating muscle damage and PEM, which I think is misleading in that there is quite obviously a lactic acidosis component too.

Also, I think you are analyzing the types of exercise that cause PEM incorrectly. To me it's not about muscle damaging exercise or not, it's about exercise that pushes you further into glycolysis, so walking is OK for some but running is not. Walking is also better because the muscle relaxes for a moment, unlike say holding a particular position for a long time at a computer, which I doubt anyone would say is muscle damaging exercise.

 

[msf]

Agreed.

I think there's simply not enough science to know all of the dynamics yet. My daughter is a microbiome researcher and we discuss this a lot. No one really knows what interventions will do what exactly, and there are too many variables, through diet, supplements and the many types of creatures in our guts and how they interact with each other.

Exactly. One size fits all solutions simply do not work.

So the LDN and Immunoglobulins take care of the LPS? I've been on both for 9 months...

I also am on cromolyn sodium, ranitidine, and ketotifen though I wonder what these drugs do to the microbiome and wonder if they're contributing to the problem. I've never had SIBO, though I know many patients do. And I'm on curcumin and don't need omega 3s.

There needs to be more science around this as most of the studies are testing only one intervention at a time. It's too complex a problem. My family hss been doing stool trsts for 10 years and trying interventions and the results one gets are not always predictable.

But we need to try anyway, as it's important.

LDN doesn't stop translocation of LPS, but it should stop it activating microglia, as trazodone also should.

 

[Learner1]

LDN doesn't stop translocation of LPS, but it should stop it activating microglia, as trazodone also should.

I'm not sure trazadone would be my chosen solution... Oxidative stress is a huge issue for ME/CFS patients...

Trazodone was cytotoxic and caused cell death with LC50 of 300 µm within 2 h.

Trazodone caused an increase in reactive oxygen species (ROS) formation, malondialdehyde accumulation, depletion of intracellular reduced glutathione (GSH), rise of oxidized glutathione disulfide (GSSG), and a decrease in mitochondrial membrane potential, which confirms the role of oxidative stress in trazodone-induced cytotoxicity.

From

https://www.ncbi.nlm.nih.gov/m/pubmed/24023050/

 

[msf]

I'm not sure trazadone would be my chosen solution... Oxidative stress is a huge issue for ME/CFS patients...

I didn't say it should be your solution or not, I was just pointing out what effect it could be expected to have in ME. My own experience suggests it has this effect. The only study I found on trazodones mitochondrial toxicity suggested it was negligible. Do you know of a study that suggests otherwise?

 

[msf]

I mean at therapeutic levels.

 

[msf]

I see the study you linked to was referring specifically to hepatotoxicity. This is definitely a consideration with trazodone, but the study does not prove anything about its effect on mitochondria in the rest of the body. I might try taurine though, thanks!

 

[msf]

By the way, if you're waiting for a treatment for ME that does not have significant side effects, I think you might be waiting a long time. If you are simply waiting for more evidence as to their effects however, I think that is a perfectly understandable personal decision. Given the list of things that have been tried in ME though, DCA and trazodone wouldn't be anywhere near the top of my list in terms of potential side effects. Rituximab was a lot scarier, for instance, being potentially lethal both directly and indirectly.

 

[Learner1]

I didn't say it should be your solution or not, I was just pointing out what effect it could be expected to have in ME. My own experience suggests it has this effect. The only study I found on trazodones mitochondrial toxicity suggested it was negligible. Do you know of a study that suggests otherwise?

As my mitochondria have already taken a hit by drugs prescribed by doctors without a thought to mitochondrial toxicity, I'm a bit gunshy...

This study indicates impairment in psychiatric patients by trazsdone, tbough I am unable to read the full reference...

or trazodone, which collapses the mitochondrial membrane potential and imposes oxidative stress [13].

From: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511795/#!po=7.14286

Antipsychotics and antidepressants—selective serotonin reuptake inhibitors, mirtazapine, trazodone—inhibit several mitochondrial enzyme complexes

From:
https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp-rj.2016.110705

However, both, trazodone and buspirone also showed some effects on oxygen consumption and OXPHOS activities. Trazodone is also reported to cause liver injury, whereas no liver injury has been reported for buspirone.

From:

https://www.tandfonline.com/doi/full/10.1517/17425255.2014.939628

 

[Learner1]

By the way, if you're waiting for a treatment for ME that does not have significant side effects, I think you might be waiting a long time. If you are simply waiting for more evidence as to their effects however, I think that is a perfectly understandable personal decision. Given the list of things that have been tried in ME though, DCA and trazodone wouldn't be anywhere near the top of my list in terms of potential side effects. Rituximab was a lot scarier, for instance, being potentially lethal both directly and indirectly.

I think it's important to go in with eyes wide open, looking at all the evidence and then weigh whether an intervention shows promise of greater good than harm. And that any potentially harmful effects can be minimized.

Given what we've discussed, LDN might be the safer option, or, if trazadone were the only choice, supplementing with glutathione and phospholipids, in addition to taurine, might be prudent.

 

[msf]

I think it's also important to read the studies we post carefully. What looked like three studies was really only one, in which they said that trazodone had relatively modest effects on hepatotoxicity (not the mitochondria in muscle or anywhere else). I am pretty sure I could find stuff warning against ldn if I wanted, but hopefully my point is made.

 

[Learner1]

My point is that many drugs damage mitochondria. And there are no drugs that fix them. The treatments for damaged mitochondria, if they can be fixed, are expensive oral and IV mito cocktails.

Wanna know how I know?

I also saw several presentations on mito toxicity at the Mitochondrial Foundation Conference, where Robert Naviaux (ever heard of him?) stood up and addressed the doctors and warned them to be wary of causing mitochondrial damage by the drugs they prescribe.

And, in a health system that doesn't cover this treatment and takes absolutely no responsibility for doing the damage in the first place, patients either sit around broken, wondering what's the matter with them, or, if they are lucky, a clever doctor will put 2 and 2 together and help the patient.

It is far better not to damage one's brain, liver, heart, kidneys or immune system in the first place.

Or perhaps your NHS has a better answer for mito damage and they actually help people who have drug-induced mitochondrial damage for free?