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Have the results of Dr Chia's ME/CFS interferon treatment actually proven enterovirus causes ME/CFS?

mrmichaelfreedmen

Senior Member
Messages
156
Location
Australia
I was recently reading some of Dr John Chia's findings, and it suddenly occurred to me that his work and observations may have proved that enterovirus causes ME/CFS. The following explains my logic of why his observations provide proof.



Numerous studies dating back to the 1980s have demonstrated an association between enteroviruses and ME/CFS.

However, as we know, association does not by itself imply causation, and proving that enterovirus actually causes ME/CFS requires going further.

Research that has come tantalizing close to proving enterovirus causes ME/CFS is the data from interferon treatment studies. For ME/CFS patients with high antibody titers to enterovirus, intravenous interferon often results in major improvements in ME/CFS symptoms, and some patients experience full remission for up to a year or so (but most of these patients eventually relapse). And crucially, along with these symptomatic improvements and remissions, enteroviral load (enterovirus antibody titers and enteroviral RNA) goes down after the IV interferon treatment when symptoms improve; and enteroviral load goes back up again simultaneously with the relapse.

This suggests (but does not yet prove) that the ME/CFS improvements and remissions after interferon therapy are the result of the reduced enteroviral load, and that a high enteroviral load can cause ME/CFS.



There have been three published ME/CFS interferon therapy studies: one in 1993 (full paper here), one in 1996 (full paper here), and Dr John Chia's study in 2004. Some details of Dr Chia's further experiments with IV interferon are given in this 2011 article.

All of these studies found IV interferon treatment provided significant benefit in a subset of ME/CFS patients, and there were several cases of patients completely recovering (full remission) from ME/CFS after interferon treatment, and remaining in full remission for at least a year after the treatment.

In the 1993 study, 18 patients were treated with interferon alpha, and out of these, 5 patients improved. Of these 5 improved patients, 3 went into complete remission, and 2 of these 3 were still entirely recovered when checked 1 year later (they may have relapsed further down the line, but the study only followed them for a year).

Significantly, 4 out of the 5 patients who recovered or improved from interferon treatment had elevated coxsackievirus B IgM antibodies. Only one of the patients who did not improve had elevated coxsackievirus B IgM antibodies. So this study gives some indication that interferon often works for ME/CFS patients with active chronic enterovirus infections, but generally does not work for ME/CFS patients who do not have enterovirus infections. We will use this fact later.

In the 1996 study, 26 patients were treated with interferon alpha, and out of these 7 patients improved.

In Dr Chia's 2004 study, 5 patients who had chronically high antibody titers to CVB3 or CVB5 were treated with interferon alpha and the antiviral drug ribavirin. This combined interferon + ribavirin therapy resulted a significant symptomatic improvement in 4 of 5 patients. Concomitant to their symptomatic improvements was a disappearance of enteroviral RNA in all patients, and a decrease in enterovirus antibody titers in 4 of 5 patients.

However, relapse occurred about 4 months later in most patients, along with their antibody titers rising again to pre-treatment levels, and reappearance of enteroviral RNA.

The 2011 article details more of Dr Chia's experiments with interferon: for example: 8 of 14 severely ill ME/CFS patients with enteroviral RNA in their blood returned to part-time or full-time work after interferon-alpha plus interferon-delta combined therapy. Most however relapsed several months later (heavy exertion was a common trigger of relapse).



So we see in these interferon studies a general trend: patients improve or go into full remission as a result of interferon therapy, along with a concomitant reduction in enteroviral load (ie, reduced enterovirus antibody titers and disappearance of enteroviral RNA) while the patients are experiencing major improvements or full remission. Then when the patients relapse, the viral load also goes back up.

However, suggestive though it is, this evidence does not as it stands prove that enterovirus causes ME/CFS, because again, correlation does not imply causation, and there are alternative interpretations.

One alternative interpretation is if we assume ME/CFS is caused by an immune dysfunction or weakness, rather than a virus (let's say the viral infections in ME/CFS just arise from immune weakness, but do not cause ME/CFS): in this scenario, it is conceivable that interferon might rectify the immune dysfunction, and in that way ameliorate ME/CFS symptoms or bring on remission.

In other words, it is a logical possibility that the beneficial effects of interferon for ME/CFS come from its modulation of the immune system, rather than from its antiviral effects in reducing enteroviral load.



Thus the crux of the issue here is trying to determine whether interferon's highly beneficial effects for ME/CFS are the direct result of its antiviral action on enteroviruses, or the result of its immunomodulatory effects (or the result of some other disease-modifying effects interferon may have, that are unrelated to viruses).

If we can prove that the beneficial effects arise from interferon's antiviral action on enteroviruses, then we have more-or-less proven that enteroviruses can cause ME/CFS. So I am now going to attempt to prove this.

The proof starts with a statement made by Dr Chia in his presentation at the Invest in ME 2009 London Conference. At timecode 42:31 of this video, Dr Chia talks about his interferon-alpha + ribavirin combination therapy for enterovirus-associated ME/CFS. Dr Chia says:


Dr Chia is saying that he has found interferon-alpha is ineffective for coxsackievirus B4, ie, that interferon-alpha does not reduce CVB4 viral loads, although interferon is effective for other coxsackieviruses, such as CVB3.

Now Dr Chia has noted that CVB3 and CVB4 are the two most common enteroviruses he finds in ME/CFS patients as active infections (then less frequently, he finds CVB2, EV6, EV7 and EV9 as active infections).

So Dr Chia finds both CVB3 and CVB4 are strongly associated with ME/CFS; yet interferon is effective for fighting CVB3, but not CVB4.



Now comes the logical climax to my proposition that Chia's observations prove enterovirus causes ME/CFS:

If it were the case that interferon ameliorates ME/CFS not by any antiviral mechanism, but through modulating immune function (or via some other disease-modifying mechanism), then you would expect interferon treatment to have the same success rate for all classes of ME/CFS patient, irrespective of what active viral infections the patient has.

In particular, if interferon ameliorates ME/CFS via a non-antiviral mechanism, then you would expect interferon to work equally well for patients with active CVB3 and for patients with active CVB4. And indeed, equally well whether the patient has an enterovirus infection, or an infection with some other virus (or no viral infection at all).

However, Dr Chia found that interferon-alpha works for patients with CVB3, but not for patients with CVB4.

And furthermore, the 1993 study found that by and large, interferon-alpha only worked for patients with enterovirus infections. They found interferon-alpha rarely worked for ME/CFS patients without enterovirus infections.

So these findings clearly contradict the idea that interferon ameliorates ME/CFS by a mechanism unrelated to its antiviral effect. Because where interferon is ineffectual against a particular virus, it does not help ME/CFS patients with that virus.

Therefore we have to accept the explanation that interferon ameliorates ME/CFS via its antiviral action, an action which has been shown to significantly reduce enteroviral loads.

Thus this leads us to the conclusion that chronic active enteroviral infections are a cause of ME/CFS.



Note that in the above, I am not arguing that enterovirus is the only cause of ME/CFS. Other pathogens may well also cause this disease; and there may be non-pathogenic causes as well.

I am just suggesting that the status of enterovirus as merely an association of ME/CFS might be re-examined: I am questioning whether enterovirus can now be upgraded to a probable cause of ME/CFS.

Of course, there could be flaw in my argument. Please point it out if you find one.


Note also that Dr Chia does not use interferon much these days, due I believe to the cost (around $15,000 for a course of treatment), and the fact that relapse is the norm.

Virii and Cancer cells produce Nagalase(research it) - this would cause a self perpetual infection. I believe this is true for EV and has also been mentioned by Dr Chia as one of the reasons oxymatrine only works in 50% of cases.

I never visit these forums anymore. Good luck
 

Hip

Senior Member
Messages
17,824
@Hip how did your dihydroquercetin experience go??

(I think you may have posted your question on the wrong thread, so I am answering it on this thread.)



Even with just 6 x 45 mg dihydroquercetin capsules a day (I used Swanson Russian Rejuvenator dihydroquercetin), I felt mentally overstimulated, which is unpleasant, so I stopped taking it.

Interestingly, the closely-related compound quercetin also caused similar overstimulation when I tried it a few years back.

I really want to get up to a dose of 1,000 mg of dihydroquercetin, so this overstimulation is a problem for me.

I think the overstimulation may be due to the fact that quercetin, like caffeine, is an adenosine receptor antagonist, and I suspect that's how quercetin and DHQ produce their stimulatory effects. If I can block or counter this adenosine receptor antagonism, I may be able to prevent the overstimulation.
 

Hip

Senior Member
Messages
17,824
Virii and Cancer cells produce Nagalase(research it) - this would cause a self perpetual infection. I believe this is true for EV and has also been mentioned by Dr Chia as one of the reasons oxymatrine only works in 50% of cases.

Would you have a link or reference to where Dr Chia said that nagalase levels explain the success or failure of oxymatrine?
 
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mrmichaelfreedmen

Senior Member
Messages
156
Location
Australia
Would you have a link or reference to where Dr Chia said that nagalase levels explain the success or failure of oxymatrine?

Regarding Nagalase:

By disabling MAF, nagalase prevents macrophage activation for phagocytosis and antigen presentation, leading to immune suppression.

Elevated nagalase is indicative of either tumor activity or an active viral load in the body. With suppressed macrophage activity, viruses can become highly active and create fatigue, low grade fevers, muscle aches, joint pains and continued immunosuppression. This is often an underlying cause of many chronic illnesses such as chronic fatigue syndrome, fibromyalgia and Lyme disease.

http://drklinghardt.com/what-is-nagalase-by-dr-nicol-giandomenico/

It was both GSH deficiency and/or elevated Nagalase where he believes Oxymatrine fails 48% of the time. I can not find the specific link, however I think Patrick W. Calvin wrote this in regards to an appointment with Dr Chia??

Nothing I have read has indicated that Oxymatrine alone will overcome elevated Nagalase levels.
 
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Hip

Senior Member
Messages
17,824
I can not find the specific link, however I think Patrick W. Calvin wrote this in regards to an appointment with Dr Chia??

I Google searched, but could not find anything on Patrick's blog about nagalase and oxymatrine. If you do come across the webpage where you read this, please post it, if you could.

I was one of the 48% who got no benefits from oxymatrine, even though I have high titers to coxsackievirus B4 (I have an active ongoing infection to CVB4), and I am interested in why oxymatrine benefits some but not others.
 

jepps

Senior Member
Messages
519
Location
Austria
I was one of the 48% who got no benefits from oxymatrine, even though I have high titers to coxsackievirus B4 (I have an active ongoing infection to CVB4), and I am interested in why oxymatrine benefits some but not others.

Maybe it depends of the microbiome, and you have microbes, that neutralize the dosage oxymatrine you take. So increasing the dosage could improve the efficiency, to feed the microbes, and leave enough oxymatrine to do its job.

Justin Sonnenburg describes in his book, that various reactions to medicaments depend on this fact. As each person has its own microbiome, dosages of the medicaments vary from person to person. One may respond to a tiny dosage, another needs a huge dosage. In every case part of the medicament feeds your microbiome, the rest is for you.
 

Hip

Senior Member
Messages
17,824
Maybe it depends of the microbiome, and you have microbes, that neutralize the dosage oxymatrine you take.

In case there may have been some bioavailability issues, I also tried taking pure oxymatrine powder transdermally, but still no effect in my case.
 

jstefl

Senior Member
Messages
250
Location
Brookfield, Wisconsin
I was an early user of Oxymatrine. I started on White Tiger, and switched to Equilibrant several years later after it became available. After a year on Equilibrant, I gave up due to the expense and lack of progress.

Two and a half years ago, I started on resistant starches. After six months of RS use, I again tried Equilibrant, and this time found that it made a difference in the way I feel. It is a noticeable, but not great improvement. I am happy with any improvement that I can get, so I will continue taking it.

This may be a case that applies only to me. I was tested by Dr. Chia and ARUP many years ago, and I can't find any doctor that will repeat the tests, so I can't give you a measure of any changes that may have occurred. What I do notice is that I have less of a tired, brain fogged, headachy feeling while I am taking RS and Equilibrant.

John
 

mrmichaelfreedmen

Senior Member
Messages
156
Location
Australia
I Google searched, but could not find anything on Patrick's blog about nagalase and oxymatrine. If you do come across the webpage where you read this, please post it, if you could.

I was one of the 48% who got no benefits from oxymatrine, even though I have high titers to coxsackievirus B4 (I have an active ongoing infection to CVB4), and I am interested in why oxymatrine benefits some but not others.


@Hip

Just did the Nagalase blood test, results in a couple weeks time. The outcome will be interesting. I believe there may be more then just one or two reasons why oxymatrine only works in 52% of patients Dr Chia has treated.

600mg White tiger oxymatrine/day.
2000mg Inosine/day. *The addition of 100mg/day Epivir this past week has done nothing apart from causing slight nausea and mild headaches.

Will replace Epivir with Amantadeine in due time.


@jstefl

RS may be affecting the microbiome in a positive way and improving immunity in ways we do not fully understand yet??
 
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JES

Senior Member
Messages
1,320
A bit off-topic, but still concerning enteroviruses. According to a recent Swedish CFS/ME blog post, 26 out of 27 patients tested at ArminLabs, Germany, reported that their results were positive for "active coxsackievirus infection" on a Swedish CFS/ME Facebook group.

If this is a reliable test, it could become a new piece of evidence supporting the coupling between enteroviruses and CFS/ME, since so far any patient data on enteroviruses has mainly come from one source only (Dr. Chia), or at least I wasn't aware of any enterovirus statistics from European CFS/ME patients before this. Sadly Swedish healthcare doesn't have a test for enteroviruses, so these patients cannot get any official diagnosis or treatment either.
 

Hip

Senior Member
Messages
17,824
so far any patient data on enteroviruses has mainly come from one source only (Dr. Chia), or at least I wasn't aware of any enterovirus statistics from European CFS/ME patients before this.

Interesting, though I am not sure just how reliable the ArminLabs coxsackievirus test is. I'd like to see it validated using the coxsackievirus B neutralization tests used by Dr Chia and in other ME/CFS studies.

By the way, there are numerous studies finding enterovirus in ME/CFS patients that date back as far as 1970. There is no other virus that has been so closely linked to ME/CFS, in terms of the sheer number of studies on enterovirus and ME/CFS.
 

actup

Senior Member
Messages
162
Location
Pacific NW
Dr Ian Lipkin's world class microbe discovery project is all about enterovirus as well as 1000's of other potential pathogens. A tremendous bang for your buck donation. His microbiome results will be almost impossible to refute given his reputation and a lab with some of the most sophisticated equipment in the world (no exaggeration). The patient samples are ready for analysis but the nih has refused funding for completion of this project. It's cruel beyond words for a very sick poverty stricken patient population to have to fund research on their illness but that's the reality for now. Please donate: http://www.meaction.net/2016/08/10/ciis-mecfs-monster-study/
 

Hip

Senior Member
Messages
17,824
Dr Ian Lipkin's world class microbe discovery project is all about enterovirus as well as 1000's of other potential pathogens.

I am not sure whether the new VirCapSeq-VERT technique Prof Lipkin will use for detecting viruses in his study can detect chronic enterovirus infections in the blood of ME/CFS patients. With the previous methodology Lipkin used, high throughput sequencing, he said he was not able to detect chronic enterovirus infections in the blood of ME/CFS patients (but could detect them if a virally-infected tissue sample was used, rather than a blood sample).


Evidence for an enterovirus association to ME/CFS has already been amply demonstrated in numerous studies conducted over the last 45 years.

What we really need to understand is how and why enterovirus appears to be able to trigger ME/CFS in some people, but not in most others who catch the same enterovirus. For example, is ME/CFS only triggered when enterovirus breaches into the brain? Or when enterovirus breaks into and infects certain critical immune organs, such as the thymus or spleen?
 
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actup

Senior Member
Messages
162
Location
Pacific NW
@Hip most of these studies are older with small patient numbers and a lack of replication. All I'm saying is we need the completion of the microbediscovery project which is a well designed study run by a world class scientist in a world class lab. I expect the funding dam to break when Dr Lipkin's study results are published.

Found this information on the microbediscovery.org site re: sensitivity of the VirCapSeq-VERT
sequencing platform. A 100-10,000 fold increase in viral matches sounds impressive.

Pathogen hunt
VirCapSeq-VERT, is the Virome-Capture-Sequencing platform for Vertebrate viruses. This is powerful new technology invented by CII and hailed by Scientific American as one of the “world changing ideas” of 2015. It is a system to broadly screen for all viral infections in vertebrates including humans. This test has much greater sensitivity than the current standard molecular techniques, and increases viral matches from 100 to 10,000-fold compared with conventional high-throughput tests.

This testing identifies any virus that has ever been found to be in a person – 1.7 million agents are reported to be tapped through this testing. This work would clearly increase the yield of viruses detected in people with ME/CFS.
 
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Hip

Senior Member
Messages
17,824
@Hip most of these studies are older with small patient numbers and a lack of replication.

No, many of these original British ME/CFS studies were large, for example: 337 patients, 420 patients, 60 patients, 158 patients, 121 patients, 88 patients, 48 patients.

And Dr Chia's research (on 165 patients) replicated these original British studies; but the British studies all replicated each other anyway.

So no, these studies were not small, and there was lots of replication.



Of course Prof Lipkin's new study will be very interesting; but we already have lots of evidence for enterovirus involvement in ME/CFS.
 

bertiedog

Senior Member
Messages
1,738
Location
South East England, UK
A bit off-topic, but still concerning enteroviruses. According to a recent Swedish CFS/ME blog post, 26 out of 27 patients tested at ArminLabs, Germany, reported that their results were positive for "active coxsackievirus infection" on a Swedish CFS/ME Facebook group.

I had this when tested 2 years ago by Infectolab in Germany. This was when Armin S was the Director before setting up his own company. I believe the result was something like 1:1000 whereas my result was 1:10.000.

Pam
 

jepps

Senior Member
Messages
519
Location
Austria
What we really need to understand is how and why enterovirus appears to be able to trigger ME/CFS in some people, but not in most others who catch the same enterovirus.

If healthy gut microbes regulate the nervs according to this study

https://www.theguardian.com/science/neurophilosophy/2016/apr/05/gut-bacteria-brain-myelin

And according to a new study from researchers at University College Cork, your gut microbes might affect the structure and function of the brain in a more direct way, by regulating myelination, the process by which nerve fibres are insulated so that they can conduct impulses properly.

Less healthy microbes in the gut could mean less protection of the nervs from pathogenic viruses. This could result in viral infection of the nervs: to much pathogenic viruses, less healthy microbes in the nervs.
 
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Hip

Senior Member
Messages
17,824
Less healthy microbes in the gut could mean less protection of the nervs from pathogenic viruses. This could result in viral infection of the nervs: to much pathogenic viruses, less healthy microbes in the nervs.

It could be something like this, that tissue compartments like the brain and nervous system in some people are less protected or more vulnerable, allowing ME/CFS-associated viruses like enterovirus and EBV to break into and infect these tissue compartments.



Dr Chia observed that giving immune-suppressing corticosteroid drugs (such as prednisone) to the patient during the initial acute enterovirus infection was a recipe for triggering ME/CFS. So it seems from Chia's observation that if there is some immunosuppression at the time you catch your acute viral infection, this may be a crucial factor that determines to whether you go on develop ME/CFS or not from the virus.

See this thread: Corticosteroids (Steroids) Such as Prednisone Given During an Acute Viral Infection May Cause ME/CFS

This may explain why stress has been reported as a factor associated with the onset of ME/CFS: stress raises cortisol, which then has an immunosuppressive effect. Dr Chia mentions this in a video interview here.

But other factors might also be immunosuppressive, such as exposure to mold toxins or pesticides. So these factors, if they are present at the same time as the acute viral infection, may be a recipe for triggering ME/CFS.
 

mrmichaelfreedmen

Senior Member
Messages
156
Location
Australia
Maybe it depends of the microbiome, and you have microbes, that neutralize the dosage oxymatrine you take. So increasing the dosage could improve the efficiency, to feed the microbes, and leave enough oxymatrine to do its job.

Justin Sonnenburg describes in his book, that various reactions to medicaments depend on this fact. As each person has its own microbiome, dosages of the medicaments vary from person to person. One may respond to a tiny dosage, another needs a huge dosage. In every case part of the medicament feeds your microbiome, the rest is for you.

Some bacteria also produce Nagalase. I think this is where Dr Chia has found 7 days of Rifampin has made a huge difference in patient response to treatment. Some patients with Lyme have "turned a corner" after introducing this antibiotic to there protocol, some believe it has antibiofilm activity.
 

eljefe19

Senior Member
Messages
483
Some bacteria also produce Nagalase. I think this is where Dr Chia has found 7 days of Rifampin has made a huge difference in patient response to treatment. Some patients with Lyme have "turned a corner" after introducing this antibiotic to there protocol, some believe it has antibiofilm activity.

So the typical length of a Rifampin cycle is 7 days? I've been taking Oxymatrine for several months now, using gcmaf to try and lower nagalese, didn't know of any other way to do this, but have been considering Rifampin for its synergy with Oxymatrine.

In fact, my nagalese was the highest my doctor had ever seen, well over 3 iirc.