Dr Markov CBIS Theory of ME/CFS - General Discussion

[Hip]

Thanks. Any verdict on horsetail?

Horsetail does not seem to do much for me now, but it fixed my recurrent UTI when I had that issue.

@Hip...I recall Hip that you have another thread on selenium and that you take that daily too.As there is selenium in horsetail how do you balance that dosage?...Thanks.

I did not know there was selenium in horsetail, but after a quick Google, I see it is only 5 mcg per 500 mg, which is much less than the 400 mcg of selenium I take daily.

 

[Dufresne]

I am interested in hearing any skeptical scientific opinions about Dr Markov's theory. I have been disappointed by the lack of scientific skepticism and scientific discussion on this theory. In particular, the question of whether a set of bacterial toxins leaking into the systemic circulation could really be the cause of ME/CFS, as Dr Markov believes.

I'm pretty sure bacterial translotcation is not the primary cause of my ME/CFS. However I think it interesting that IL-6 seems to be a central cytokine in both sepsis and exercise. It can see increases up to 100x with exercise, and in this context it's working in an anti-inflammatory capacity; on the other hand it's considered inflammatory in diseased states, as it is in sepsis. The following is from the Wikipedia entry for IL-6:

"In general, the cytokine response to exercise and sepsis differs with regard to TNF-α. Thus, the cytokine response to exercise is not preceded by an increase in plasma-TNF-α. Following exercise, the basal plasma IL-6 concentration may increase up to 100-fold, but less dramatic increases are more frequent."

Could it be that our systems are primed by TNF-a or some other aspect of the disease (or even a mild, chronic sepsis) and that IL-6 released in large amounts from physical exercise is acting to increase inflammation and leading to PEM?

IL-6 fits nicely into a model of sickness behavior. Indeed there are rodent studies on the subject. It's also worth noting that IL-6 can cross the BBB without too much trouble.

 

[GlassCannonLife]

I'm pretty sure bacterial translotcation is not the primary cause of my ME/CFS. However I think it interesting that IL-6 seems to be a central cytokine in both sepsis and exercise. It can see increases up to 100x with exercise, and in this context it's working in an anti-inflammatory capacity; on the other hand it's considered inflammatory in diseased states, as it is in sepsis. The following is from the Wikipedia entry for IL-6:

"In general, the cytokine response to exercise and sepsis differs with regard to TNF-α. Thus, the cytokine response to exercise is not preceded by an increase in plasma-TNF-α. Following exercise, the basal plasma IL-6 concentration may increase up to 100-fold, but less dramatic increases are more frequent."

Could it be that our systems are primed by TNF-a or some other aspect of the disease (or even a mild, chronic sepsis) and that IL-6 released in large amounts from physical exercise is acting to increase inflammation and leading to PEM?

IL-6 fits nicely into a model of sickness behavior. Indeed there are rodent studies on the subject. It's also worth noting that IL-6 can cross the BBB without too much trouble.

Yeah, that's very interesting. I just wanted to chime in and say I've had my cytokines tested (was last year though) and the only one that was out of range was IL-6, which was high (30 % above the top of the range or something IIRC).

 

[Hip]

However I think it interesting that IL-6 seems to be a central cytokine in both sepsis and exercise. It can see increases up to 100x with exercise, and in this context it's working in an anti-inflammatory capacity

Interesting that IL-6 is involved in sepsis. IL-6 is definitely one of the three main sickness behavior cytokines, which are IL-6, TNF-alpha and IL-1beta. So high IL-6 could cause some of the symptoms of ME/CFS.

However, this old post details a study which found that in ME/CFS patients, blood levels of the soluble IL-6 receptor were no higher than normal, even after exercise (the soluble IL-6 receptor is what drives the pro-inflammatory trans-signaling IL-6 pathway).


As you say, massive amounts of IL-6 are released via exercise, but the exercise-induced IL-6 pathway is not the same as the infection-induced IL-6 pathway.

I spent some time reading about IL-6 a few years back, as I thought it might be involved in ME/CFS.

I discovered that IL-6 can operate by two pathways: the classical signaling IL-6 pathway which is anti-inflammatory and instigates tissue repair (this is the pathway induced by exercise); and the trans-signaling IL-6 pathway which is pro-inflammatory (this is the pathway induced by infection).

I'm pretty sure bacterial translotcation is not the primary cause of my ME/CFS.

In Dr Markov's theory, it is not actually translocation of bacteria which is taking place. In his theory the bacteria remain in one place (usually in the kidney, though he says in some patients the bacteria are in the nasopharynx).

But Dr Markov says these bacteria are secreting toxins which then leak into the systemic blood circulation, thereby affecting every cell and every organ in the body.


Some bacterial toxins are well studied, and their pernicious effects are known. For example:

Enterotoxin B secreted by Staphylococcus bacteria plays a critical role in the pathogenesis of autoimmune disorders, according to this study.

Another toxin made by Staphylococcus, alpha toxin, interferes with the immune response by polarizing macrophages towards the M2 type. Ref: 1

 

[Dufresne]

Yeah, that's very interesting. I just wanted to chime in and say I've had my cytokines tested (was last year though) and the only one that was out of range was IL-6, which was high (30 % above the top of the range or something IIRC).

I imagine IL-6, because of the correlation to exercise, would be a hard one to draw conclusions from. "Did the subject take the elevator or the stairs on their way in, or even 5 hours ago?" But for this reason might have real implications for ME/CFS research.

It's perhaps interesting to note that IL-6 is involved in Covid and might be an important marker in predicting long Covid.

"Four of the markers, analyzed via a data model, proved to be especially accurate in predicting long Covid: IFN-β, PTX3, IFN-λ2/3 and IL-6. Of these, IFN-β was the single most important indicator of long Covid, present 94% of the time when modeled in a set of four markers."

https://www.forbes.com/sites/willia...longed-inflammatory-response/?sh=4799b74b765c

This is more inline with what I think is happening in ME/CFS; that is, an upregulation of cellular immunity (interferons and such) in the brain that is then getting splashed with gasoline from the periphery. Interferons and cellular immunity in the brain due to infection followed by all kinds of stuff hitting the limbic system, from mast cells to IL-6 (from physical activity), and so on. Both interferons and IL-6 have been at times shown to be correlated with disease severity in ME/CFS. But perhaps where it gets even more interesting is in the individual response to these cytokines. This is where I think limbic health comes in. I like to think of this aspect along the lines of Dr Goldstein's work, where you have channels relating to sorotonin, dopamine, GABA, etc, that are impaired in ME/CFS patients. This is why you have such a myriad of treatments that can produce massive improvements in patients, though they often fall off after a while. It's as if the sickness behavior overturns the intervention. Some people are seeing this with Abilify, which is likely having its effect through the dopamine channel. Consider interferon-induced depression is not universally the case for those on interferon therapy, rather it tends to hit those with a history of mood issues, but that SSRI's and even fish oils can be employed to offset the induction of the syndrome. This would be an example of the serotonin channel.

I think the following is a good review of the cytokines in ME/CFS and I agree with the authors' conclusions:
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-1948-6

 

[Dufresne]

Interesting that IL-6 is involved in sepsis. IL-6 is definitely one of the three main sickness behavior cytokines, which are IL-6, TNF-alpha and IL-1beta. So high IL-6 could cause some of the symptoms of ME/CFS.

However, this old post details a study which found that in ME/CFS patients, blood levels of the soluble IL-6 receptor were no higher than normal, even after exercise (the soluble IL-6 receptor is what drives the pro-inflammatory trans-signaling IL-6 pathway).


As you say, massive amounts of IL-6 are released via exercise, but the exercise-induced IL-6 pathway is not the same as the infection-induced IL-6 pathway.

I spent some time reading about IL-6 a few years back, as I thought it might be involved in ME/CFS.

I discovered that IL-6 can operate by two pathways: the classical signaling IL-6 pathway which is anti-inflammatory and instigates tissue repair (this is the pathway induced by exercise); and the trans-signaling IL-6 pathway which is pro-inflammatory (this is the pathway induced by infection).





In Dr Markov's theory, it is not actually translocation of bacteria which is taking place. In his theory the bacteria remain in one place (usually in the kidney, though he says in some patients the bacteria are in the nasopharynx).

But Dr Markov says these bacteria are secreting toxins which then leak into the systemic blood circulation, thereby affecting every cell and every organ in the body.


Some bacterial toxins are well studied, and their pernicious effects are known. For example:

Enterotoxin B secreted by Staphylococcus bacteria plays a critical role in the pathogenesis of autoimmune disorders, according to this study.

Another toxin made by Staphylococcus, alpha toxin, interferes with the immune response by polarizing macrophages towards the M2 type. Ref: 1

Yes, translocation was the wrong way to put it. I understand it's toxins being released from the bacteria into circulation that is the theory.

So there are two pathways for IL-6, but what I'm wondering is if one pathway could leak over onto the other. Could IL-6 from exercise also inflame a disease process happening at the same time?

 

[Hip]

So there are two pathways for IL-6, but what I'm wondering is if one pathway could leak over onto the other. Could IL-6 from exercise also inflame a disease process happening at the same time?

Yes, that's an interesting idea, and it was what I was pondering in this post: could the IL-6 from exercise become pro-inflammatory, because of some dysfunction in the body? That could well explain PEM.

Basically, it is the amount of the soluble IL-6 receptor floating about in the blood that determines which of its two pathways secreted IL-6 takes.

The more soluble IL-6 receptors are present in the blood, the more the pro-inflammatory trans-signaling IL-6 pathway is activated when IL-6 is secreted. So if you had high amounts of soluble IL-6 receptor in your blood, then I think the IL-6 from exercise might become pro-inflammatory, rather than being anti-inflammatory.

But a study showed that ME/CFS patients have normal levels of soluble IL-6 receptors in the blood.

We can perhaps carry on this IL-6 discussion in that IL-6 thread if you like.

 

[Dufresne]

Yes, that's an interesting idea, and it was what I was pondering in this post: could the IL-6 from exercise become pro-inflammatory, because of some dysfunction in the body? That could well explain PEM.

Basically, it is the amount of the soluble IL-6 receptor floating about in the blood that determines which of its two pathways secreted IL-6 takes.

The more soluble IL-6 receptors are present in the blood, the more the pro-inflammatory trans-signaling IL-6 pathway is activated when IL-6 is secreted. So if you had high amounts of soluble IL-6 receptor in your blood, then I think the IL-6 from exercise might become pro-inflammatory, rather than being anti-inflammatory.

But a study showed that ME/CFS patients have normal levels of soluble IL-6 receptors in the blood.

We can perhaps carry on this IL-6 discussion in that IL-6 thread if you like.

Damn, I should have known you'd already been there.

 

[Hip]

Damn, I should have known you'd already been there.

I have replied to your post here, in order to continue this interesting IL-6 and exercise conversation on that thread.

 

[Dufresne]

I have replied to your post here, in order to continue this interesting IL-6 and exercise conversation on that thread.

Already on it. Thanks.

 

[bensmith]

Update. I went from 1.25 to like 3 to 3.5. That was great, but now i’m back down in severe territory. To be fair he said that is normal and ecpected. Still sucks though.

Not sure if i will finish section 4. Section 1 3 and 4 seemed to make me feel worse.

Overall i think it helped some. The improvements are much more mild than they were though.

Would i recommend the treatment? Probably? But its not going to be as clear a path i dont think.

Just wanted to get these thoughts out to the community, i dont imagine they will change.

I’ll update again later on down the road.

 

[Hip]

Update. I went from 1.25 to like 3 to 3.5. That was great, but now i’m back down in severe territory.

Do you still believe that it was the Staphylococcus vaccine that set you back? I believe you said on Discord that the Staphylococcus vaccine undid the gains you made on the other vaccines prescribed by Dr Markov.


What ME/CFS scale are you using, by the way, when you say " I went from 1.25 to like 3 to 3.5"?

 

[bensmith]

@Hip no i think i would have slid back regardless, although i think it migjt have made it worse with all these other vax that didnt do much.

I dunno about scale, just trying to give y’all an idea about where i am at. The scale hasnt really fit me super well, just saying ive inproved some but not as much as i was before or hoped.

 

[Hip]

I dunno about scale, just trying to give y’all an idea about where i am at.

A useful scale to gauge improvements or worsening on ME/CFS is the Phoenix Rising ME/CFS scale:


Phoenix Rising Severity and Level of Activity Scale

0 — VERY SEVERE: Bedridden constantly, except to go to bathroom.

1 — SEVERE: Bedridden most of day, very rarely leave house.
2 — SEVERE: Leave house once a week, concentrate 1 hour a day.

3 — MODERATE: Leave house several times per week, 2 hours work/activity a day.
4 — MODERATE: 3 to 4 hours work/activity a day.
5 — MODERATE: 4 to 5 hours work/activity a day.

6 — MILD: 6 to 7 hours activity a day, able to do a part-time job.
7 — MILD: Able to do a full-time job but with difficulty.
8 — MILD: Near-normal life activity level, but still symptomatic.

9 — RECOVERY: Normal life activity level, mild symptoms.
10 — RECOVERY: Fully recovered, or in full remission.

 

[bensmith]

@Hip yeah this scale just doesn’t speak to too well. I don’t agree i’m moderate but by this scale i am. But my constant brain pain, that is extremely high.

Like before i started the treatment i wasn’t bedridden, but could never leave the house. I was also in so much pain i thought i might kill myself. Just never really fit that scale too well.

I guess by this scale i went from a one to a five, but i’m in too much pain and too low a quality if life to be considered moderate. Just no way. I’ve heard what other moderates can do, and i’m just not there. I’m severe.

 

[BrightCandle]

@Hip yeah this scale just doesn’t speak to too well. I don’t agree i’m moderate but by this scale i am. But my constant brain pain, that is extremely high.

My preference is the hummingbird scale, not least because it splits out cognitive and physical and its got great descriptions of the various levels.

https://www.hfme.org/themeabilityscale.htm

 

[Hip]

I guess by this scale i went from a one to a five, but i’m in too much pain and too low a quality if life to be considered moderate. Just no way. I’ve heard what other moderates can do, and i’m just not there. I’m severe.

Yeah, patients can have some symptoms which make their situation and quality of life much worse than their level of ME/CFS would suggest.

I don't have any physical pain in my ME/CFS, but I can have substantial mental health suffering. So although I am around 6 - MILD on the Phoenix Rising scale, the mental symptoms that accompany my ME/CFS put me in a worse position.

What I usually say to people is that my ME/CFS is moderate to mild, but that I also have several mental health issues which are also pretty debilitating.

 

[Hipsman]

patients can have some symptoms which make their situation and quality of life much worse than their level of ME/CFS would suggest.

That sounds allot like mine situation, I'm mild, but my brain fog is really bad to a point where I feel like I can do less mentally then someone with severe me/cfs.

 

[Husband of]

That sounds allot like mine situation, I'm mild, but my brain fog is really bad to a point where I feel like I can do less mentally then someone with severe me/cfs.

i would say “activity” can also mean mental activity, similarly work can mean analytical work. So if you can only sufficiently concentrate to do an hour of analytical work, then by the phoenix rising scale you are severe.

despite people having differing experiences of the illness, which is a valid criticism of the scale, I also find the words used to describe the scale to be invalidating - which is a real shame given how much invalidation pwme have to deal with already. While my wife is severe on this scale, the idea that someone who can only do two hours work a day is “moderate” is a bit insulting

 

[Hip]

I also find the words used to describe the scale to be invalidating

The terms mild, moderate and severe are standard ways to describe ME/CFS severity, used by numerous institutions, including the ICC. So it's not just the Phoenix Rising scale. These terms are also widely used throughout medicine to describe disease severity.

Saying something is mild or moderate does not necessarily negate it's severity; a moderate nuclear explosion is still a big event!

i would say “activity” can also mean mental activity, similarly work can mean analytical work. So if you can only sufficiently concentrate to do an hour of analytical work, then by the phoenix rising scale you are severe.

That's right, the activity refers to physical work, and/or mental work requiring concentration.