Why would CFS symptoms continually worsen overtime ?

[Wishful]

... but never felt an actual improvement, like, distinctly noticeable, a before-and-after type delineation.

Some of us may not have noticeable food responses, but many of us do, and some are quite dramatic. A lot of times I'd think "This feels like I had some <whatever>", and if I checked the ingredients or detailed contents, yes, it had <whatever>. These are mostly negative responses, but I've had a few positive ones as well, such as having a fatty piece of beef and sleeping the whole night through without waking (shocking!). Other responses were more subtle, and I needed to check my journal to verify the correlation.

Cutting out all of a food group or chemical content might be required. If a certain molecule in milk, such as a certain fatty acid, is causing you problems, how can you know that if you insist on 3 cups of coffee a day with milk. My ME started with a type IV food sensitivity, and I had to go on a rotation diet for a while. I was surprised at how few food groups comprise the typical human's diet. It's difficult to make tolerable meals when you have to avoid entire food groups for 5 or more days.

 

[Viala]

@Viala - I agree with you about the Epsom baths, and I find them very relaxing. But if I don't want to take a bath, the magnesium oil provides a quick source of magnesium I can use on targeted areas like my lower back or my knee or just about anything that hurts!

I'll remember it, I haven't used it myself like that but it sounds that it can be really helpful! It makes me wonder now if we are deficient in magnesium, and when we use it like that it helps with pain, maybe by reducing inflammation. I supplement magnesium but it never worked as good and quick as transdermal one. Maybe it's time to retry it again. Nutritional deficiency probably can also contribute to worsening of symptoms over the years.

 

[skandar]

Around what age were you at the time of the infection and start of the symptoms ? How do you know it was a viral infection ?

It was February 16, 1996 when I noticed I had symptoms of “influenza” like infection. URI type symptoms with fever and malaise, severe enuf to force me to bed to recover. I was a tenured professor, living healthily, age 36.8 years. Recovered more slowly than any other infection I’d ever had (15 days). Then would have days that felt 100% heathy. And days where I had malaise for no apparent reason. Had never heard of ME or CFS. Eventually more bad days, and realized it was caused by cognitive or physical exertion. Got diagnosed with CFS at 6 months from initial infection. Slowly got worse over 27 years and had to shut down my lab at age 59.

 

[PhoenixDown]

Mine doesn't, and other PWME reported being able to continue physical activities (including serious bodybuilding)

I cured my PEM, but still have all the other symptoms, so I consider PEM to be a near-universal downstream symptom of ME

Which ME criteria were you diagnosed under? If some body is bodybuilding they certainly don't have the same type of ME that Melvin Ramsey first described back in the 1950s.

 

[Wishful]

Which ME criteria were you diagnosed under?

I self-diagnosed by the Canadian and International criteria. I didn't bother to try to get an official diagnosis. IMO, there are no genuine ME diagnoses, just value judgments from some doctors, and there won't be until we find a reliable marker.

The physical symptoms are very common, but definitely not universal. That's why the criteria have x symptoms from a list of y. We might be missing a pathway to those symptoms, or have some sort of mechanism that counters it.

 

[GreenEdge]

When I started this journey, all I had was over-training syndrome. But my doctor prescribe me an anti-anxiety drug to help me sleep. Then an anti-depressant to help my fatigue. These mind altering drugs appear to work short-term as demonstrated in trials, but our bodies learn to compensate to bring us back into homeostasis. So long term, these drugs actually have the opposite effect.

That anti-anxiety drug I thought was turning me into a zombie was actually turning me into a genius. And that anti-depressant I took was actually turning me into a chicken - Now days, I'm so nervous I can't sleep. And that's how we get locked into this illness.

So what does that make me now?
A chicken , genius.

 

[datadragon]

I think for later stage, it appears that Interferon induced differentiation of dendritic cells such as from infection or heavy exercise or other reasons is irreversible meaning that it persists upon removal of the cytokines. IFN-DCs produced lower levels of IL-12p70 and higher levels of IFN-alpha, IL-4, and IL-10 than IL-4-DCs. As a consequence of this different pattern of cytokine secretion, IFN-DCs induced T cells to produce type 1 (IFN-gamma) and type 2 (IL-4 and IL-10) cytokines, and as expected, IL-4-DCs induced only Th1 differentiation. https://pubmed.ncbi.nlm.nih.gov/14525963/

And this is what is found: IFN-α induces a persistent fatigue in some individuals, which does not abate post-treatment, that is, once there is no longer immune activation. there was a trend towards increased baseline interleukin (IL)-6, and significantly higher baseline IL-10 levels, as well as higher levels of these cytokines in response to IFN-α treatment, alongside concurrent increases in fatigue. Levels increased to more than double those of the other patients by Treatment Week (TW)4 (p =  0.011 for IL-6 and p = 0.001 for IL-10) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/ Further the cytokines interact with orexin to lower levels. On top of that zinc uptake is reduced and zinc is brought into the cell which can cause unavailability to the rest of the body. That leads to the gut barrier problem with changes in the microbiome and short chain fatty acids, a lowering of butyrate and a depletion of normal energy production. B12 also will suffer as you need stomach acid to absorb it normally plus apparently b12 is hit directly by superoxide since zinc is needed for glutathione but of course we may individually have some storage of it. That can lead to undermethylation. Whether people take proper supplements or food to counter that high inflammatory state would also be different among everyone. .

Prenatal LPS as an example also decreased tyrosine hydroxylase levels in the striatum. [Tyrosine hydroxylase catalyzes the conversion of tyrosine into L-DOPA the rate-limiting step in the biosynthesis of dopamine. Tyrosine hydroxylase deficiency leads to impaired synthesis of dopamine as well as epinephrine and norepinephrine etc. Active b6 also goes down with loss of zinc - a big cascade of issues.

These are just some of the thoughts what might be going on.

 

[hapl808]

These are just some of the thoughts what might be going on.

Interesting. I think some of that sounds plausible, although I assume by irreversible you mean that the body can no longer reverse the process, not that the damage is by definition irreversible?

I've always thought that we need something beyond just treating an infection (antivirals) or some neurotransmitter drug (aripiprazole). Although I do always come back to Goldstein's weird approach that seemed effective at 'reversing' some of these effects, even if temporarily. I do wonder if he were effective because he was, unknown to himself, treating maybe 20 different diseases so his shotgun approach worked better than a unified field theory of ME/CFS.

But the levers of gut dysbiosis, neurotransmitter imbalance, pathogen persistence, etc - all seem somewhat plausible, so the question is do you treat one, many, etc?

 

[hapl808]

Things that individually interest me for their potential effects - various mushrooms (I take lion's mane, sometimes reishi, etc), methylene blue (haven't tried yet), clemastine (the MS research is quite interesting), antibiotics (tried and gave me my only remission, albeit extremely brief 10 years ago), antivirals (only tried ku shen - similar to oxymatrine), various neurotransmitter drugs (planning on LDA), stuff like LDN (so promising but just doesn't seem to work for me), Ampligen of course, various forms of CBD (always gave me awful rebound when I tried in the past), etc.

 

[JES]

It intrigues me why it is that as in your case @hapl808 , antibiotics helped briefly, or the same with FMT apparently for some people. Even the prep emptying of the bowel for a colonoscopy has temporary remissions documented on this forum. When I dealt with bad constipation once, somehow my typical ME/CFS symptoms got better even when dealing with the pain from constipation, so even that alone seems to do something.

But the question is are you really treating the correct thing then if all you achieve is temporary improvement and need to redo FMT every month or so, which is unrealistic for 99% of people. I suppose if the gut-focused treatments are easing the symptoms even temporarily, then you are treating the disease if you view the disease as the symptoms and the amount of disability they cause.

However, we are not treating the cause of the disease if the relapse follows after we stop rifaximin or whatever antibiotic or stop doing FMTs, but then again how often do we have medicine or treatments against the deeper cause of any disease? Outside of editing genes and finding some metabolic switch like Ron Davis has been hoping for, maybe there isn't that much deeper we can go with current technology.

 

[hapl808]

However, we are not treating the cause of the disease if the relapse follows after we stop rifaximin or whatever antibiotic or stop doing FMTs, but then again how often do we have medicine or treatments against the deeper cause of any disease? Outside of editing genes and finding some metabolic switch like Ron Davis has been hoping for, maybe there isn't that much deeper we can go with current technology.

Yeah, I really don't know if we're addressing root causes, some downstream effects, or some random unknown aspect. Weird that a lot of people have reported gut-related remission, but usually temporary and brief. Meanwhile LDA would seem to work on something totally different, although I do wonder about neurotransmitters being made mostly in the gut?

I don't have very high hopes for the current technology. My last significant improvement was over 10 years ago. Mostly declining since then. In 2015 I was struggling with more significant moderate and life-limiting symptoms. In 2016 I started having trouble walking. In 2017 I started having really bad immune reactions and sensitivities, and no ability to walk. Around the same time (or just when I noticed), cognitive issues started becoming more prominent and even cognitive exertion would always lead to a crash.

Can't say I've found anything in that time period that has been helpful, just some things that have been harmful and a few things that 'maybe' improve my symptoms temporarily by 5%, like allicin or magnesium or whatever. But honestly small enough improvements that could be entirely placebo effect.

 

[Wishful]

My (vague) theory for gut interactions in my ME is that the gut has various immune activations, which in turn activates glial cells, which affect neurons, and those affected brain cells cause various direct and downstream symptoms. I don't see any major difference between cytokines released by the gut (due to leaks, bad microbes, or whatever) and cytokines released due to viral infections or cytokines released by muscle exertion. It might be one cytokine, or combinations of several. By this theory, treatments that alter gut function or destroy viruses should decrease the offending cytokines, providing a temporary reduction in ME symptoms, usually without completely eliminating those symptoms, which is what we observe from such treatments.

 

[Insomniac]

I feel something close to that in my ME/CFS. If I eat something that triggers my bowel symptoms, my cognitive problems and CFS and general exhaustion worsen. It's not the cause, just one important extra component that worsens things a lot. I had zero bowel problems the first 3 years of illness.

 

[Jo86]

I feel something close to that in my ME/CFS. If I eat something that triggers my bowel symptoms, my cognitive problems and CFS and general exhaustion worsen. It's not the cause, just one important extra component that worsens things a lot. I had zero bowel problems the first 3 years of illness.

Yes, same with me. The symptoms went: sudden brain fog, progressively worsening over 3 years. THEN: gut problems, I started realizing there was actually a connection between food and the symptoms which, at the time, was news, as obvious as it sounds today. THEN physical/body fatigue (when it was only mental fatigue the first years).

 

[Blazer95]

Hi, i got worse. I was able to Work 2 years ago while already being sick. Sometimes in the Gym even. Now all i can do is lying in bed and Go grocery 1-2x per week

 

[Rufous McKinney]

Weird that a lot of people have reported gut-related remission, but usually temporary and brief.

sort of having one now....

I'm recovering from Dengue Fever. Which at some stage, my gut was bloating badly, SIBO was bad, and I was having mild nausea and delayed emptying at the pit of my stomach.

All of that has improved dramatically over the last week.

The question is: how long will this last? I am having "almost normal" bowel movements- a type of miracle.

But this has happened before- after severe gastroperesis type flus, (I call them near death experiences that last 4-10 days) and I starve something out because I can't eat for a few days/ guts improves after this starving...then seems to gradually revert back.

So this time, I'm telling this improvement to stick around.

 

[Rufous McKinney]

various neurotransmitter drugs (planning on LDA)

whats this?

 

[hapl808]

Just meaning drugs that work on neurotransmitters - dopamine, serotonin, etc. LDA refers to Low Dose Abilify.

 

[Rufous McKinney]

Gravity: read about gravity.

Astronauts without gravity can work out all day and that can result in zero benefit, zero new muscles etc.

So Gravity is at work, every moment we are on the planet, pulling down our brains and I think that is a huge factor in continued declines.

 

[Insomniac]

I've always thought that we need something beyond just treating an infection (antivirals) or some neurotransmitter drug (aripiprazole). Although I do always come back to Goldstein's weird approach that seemed effective at 'reversing' some of these effects, even if temporarily. I do wonder if he were effective because he was, unknown to himself, treating maybe 20 different diseases so his shotgun approach worked better than a unified field theory of ME/CFS.

What you just said is fascinating.

I think you are right.

Dr Goldstein's drugs included:

A batch of stuff like midodrine for low blood pressure and POTs or orthostatic intolerance symptoms.

A batch of histamine lowering drugs that are now all used for MCAS .
Some of them are not antihistamines but have anti MCAS activity, he did not know it at the time.

There was migraine type drugs like diamox.
There was a pot pourri mix of drugs thrown in like Gotu Kola, Bee Venom, sleep drugs and pain killers.


If you try a lot of these different things on a group of patients - some who have MCAS, some who have POTs and some who have completely different causes to their CFS, some are bound to improve.

I got little to no help out of him, but he was the best doctor I saw in years. I discovered Baclosal through him. I wish I had the money to stay longer with him.


When I saw him in 2000 the list of what he was using was much bigger than the list at this website

http://www.cfstreatmentguide.com/dr-jay-goldstein-a-z-treatments.html