Dr. Unger and Dr. Montoya are in the middle of some of the biggest studies ever produced in chronic fatigue syndrome. They talked about their respective programs on the PCOCA call about a month ago.
Here is what my scrambled notes indicated they said.
Dr. Elizabeth Unger
The Multi-Center ME/CFS Experts Study
The CDC went to the ME/CFS experts for its multi-center, multi-year, multi-stage, multi-dimensional, multi……study
Unger’s statement that the seven site ME/CFS experts study will help produce an evidence-based definition makes one wonder how long any definition is going to last. We’ve never, after all, seen a study this big (@470 patients) and this comprehensive looking at the symptoms and characteristics of people with chronic fatigue syndrome.
Moving Slowly
The studies must be very complex. Two years ago, Unger presented some if its findings at the FDA Workshop. A year ago at the IACFS/ME Conference she stated they were “scrubbing” the data. Now she’s reporting they’re beginning to write the papers. Maybe all good things do take time.
Moving Quickly
The delay is also probably in part because they’re moving forward rapidly on the second larger part of the study. She broke the study up into three groups.
Group #1: the Big Tent
Big tent study includes four disease groups and healthy controls
If my notes are right, the first group in the second consists of ME/CFS, fibromyalgia, Lyme disease and hepatitis patients. Nobody has ever jammed this many different types of patients into a major study before, and it’s about time somebody did. Not contrasting ME/CFS patients with other disease groups was a key critique leveled at the field in the AHRQ draft report. Only by contrasting ME/CFS with other similar disease groups can we get at a good definition or diagnostic biomarker. Contrasting ME/CFS patients with a group with an active infection (hepatitis patients) was a great idea.
Most of the ME/CFS patients and over half of the Lyme patients have gone through the first part of the study.
Exercise and Cognition Test
With about 260 people slated to do the one-day exercise test, this is easily the biggest exercise study ever done in ME/CFS. They’ll get their blood taken for gene expression tests and have their cognitive functioning studied.
Yes, it’s too bad it’s not a 2-day test. As difficult as a two-day exercise test is on patients, a two-day study would have nailed the metabolic limits to exercise found in ME/CFS. It could have presented a unique and very disturbing finding to the medical world. I believe it could have broken the doors wide open on this disease, but it’s not to be.
A big study that finds that exercise dramatically alters gene expression patterns and reduces cognition will be big news. In contrast to other studies, this study is big enough to reveal subsets of patients with altered gene expression patterns. Finding reduced cognition after exercise would be another feat, and, of itself, would be an excellent demonstration of post-exertional malaise. Demonstrating that a short exercise session measurably impacts cognition a day later would be big news.
Group #2: the Kids
A big pediatric cohort (130 patients!) is next. You can probably count the number of pediatric studies done on ME/CFS on the fingers of two hands. The kids are less numerous and harder to find, but they had gotten through about 20% of the group as of the time of the call.
Group #3: the Missing Pieces
The CDC is not slacking on this study. They’re going after the “hidden” and hard to get at elements of ME/CFS like no one has before.
The second phase of the study includes many hard to access patients
The third group consists of bedridden patients and patients with recent onset. The bedridden group shouldn’t need exercise to tweak their systems into showing something unusual – they just need to get tested. Studying the recent onset patients just got a whole heck of a lot more interesting after the Lipkin/Hornig Chronic Fatigue Initiative study suggested their different immune signatures differ markedly from later stage patients.
They’ve gotten IRB approval, and this study should begin soon.
Others
Health Care Survey
The CDC has also been able to get ME/CFS questions folded in some very large ongoing medical surveys in five states. The participants will be answering if they’ve ever been diagnosed with ME/CFS, if they still have it, and other questions associated with the quality of the health care they’ve received.
Developing a Curriculum for Medical Schools
The CDC is in the process of finalizing case examples or “scripts” involving ME/CFS patients. These appear to be ways to portray vividly what happens in this disease. The University of Colorado is evaluating how effective they are. They plan to send them to medical schools with the intention of getting them inserted into the curriculum.
Dr. Montoya: Leader of Stanford ME/CFS Program
Dr. Montoya didn’t mince his words. Chronic fatigue syndrome, he said, is a complex, chronic and highly variable disease, and it will take a highly multidimensional approach engage many disciplines to understand it. It can be done, however. Montoya asserted – hold your breath – a 100 million dollars a year in funding would make it possible to conquer ME/CFS in our lifetimes.
A complex disease it’s going to take some big money to figure it out.
Since Montoya is probably around fifty, that would probably include my lifetime but probably at the end of it. Later Montoya asserted, though, that they’d be able to produce good treatments much more quickly than that if they had more money.
Although the timeline for eradication is a long one, Montoya’s statements give one the sense he feels he’s beginning to understand the broad outlines of what’s going on.
They’re also pretty bold statements given the state of current funding. Does he believe $100 million a year in funding is possible? My guess is that he wouldn’t state something like that if he didn’t believe it was in the realm of reality – maybe not this year or next year, but in the conceivable future. Let’s say private sources and other countries can provide $10 to $20 million dollars a year in funding. That would leave the feds kicking in 80-90 million dollars.
Clearly touched by the human dimension of the illness, Dr. Montoya referred to the suffering and isolation experienced by millions of patients.
Some History
His introduction to ME/CFS began in 2004 after he saw one patient with high antibodies to viruses whose life had been devastated by her illness. To his utter surprise, her cognition and fatigue improved significantly on antivirals. (One wonders who was “patient x”? Who initiated that meeting that changed the course of Dr. Montoya’s career and got Stanford into the act? )
One patient not even ten years ago started Dr. Montoya off on his quest to understand and cure chronic fatigue syndrome
In 2006, 9/12 very ill ME/CFS patients in an open-label study improved significantly in a trial of herpesvirus antivirals. Several ended up returning to work after long absences. The next step was a 30 person placebo-controlled double-blinded valganciclovir (Valcyte) trial in ME/CFS patients with high antibody titers for HHV-6 and EBV. They showed significant improvement after six months (but not the dramatic improvements seen in the first study. An analysis suggested, as Dr. Lerner and Dr. Henderson have found, that the longer they were on the drug, the better they tended to do.
The results opened the possibility that long-term use of valganciclovir or another antiviral could be helpful in a subset of patients. Widespread skepticism from infectious disease specialists about the use of antivirals in ME/CFS dates, however, back to 1988 antiviral trial by Stephen Strauss. Despite the different drug and short duration of the trial, the failure of the Straus trial has apparently loomed over this part of the field for decades.
The Montoya/Kogelnik trial indicated valganciclovir had produced a surprising and never seen before immunomodulatory shift that increased Th1 functioning in the ME/CFS patients. The antiviral drug had somehow strengthened their antiviral defenses. Dr. Montoya suggested that this unexpected immunomodulatory shift may be crucial and could help explain the benefits the patients received. The cytokine data they’re currently gathering supports their conclusions.
But why would herpesviruses and not other viruses be such a big deal in ME/CFS? Because of the balky NK cells typically found in ME/CFS: people with poor functioning NK cells are highly susceptible to herpes virus infections.
Three Implications
Montoya is starting to look for pathogen in natural killer cells
Montoya drew three broad implications from his findings.
- Herpesviruses – A more in-depth look at herpesviruses themselves is needed. Only eight (eight is not enough?) herpesviruses have been found. Sounding like he knew of some efforts in this area that will bear fruit, Montoya stated it was “very possible” more herpesviruses will be discovered in the next couple of years.
- NK cells – More focus on NK cells is critical.
- NK cell infections – Montoya is beginning study to see if NK cells are the target of known or unknown viruses. Looking for pathogens in NK cells appears to be an entirely new endeavor in ME/CFS. Some attempts have been made to get at the cause of the NK cell problems in ME/CFS, and others are ongoing. Isabel Barao, Ph.D. at the Simmaron Research Foundation is looking at possible genetic underpinnings of NK cell dysfunction.
Why is Dr. Montoya able to do stuff like this? Because of an anonymous donor who gave him unrestricted funds for five years starting in 2009. (If memory serves he gave him $8 million to spend as he wished – and the five years is up.)
Current Work
25 million data points: big, big, BIG data!
Montoya created a large biobank of 200 ME/CFS patients and 400 corresponding age and sex matched healthy controls. He’s also currently working on a mega immune study that consists of having hundreds of patient samples being tested in Mark Davis’s Human Immunome Project. Ultimately producing more than 25 million data points, this will easily be the most comprehensive overview of immune functioning in ME/CFS ever done. Gene expression, cytokines, pathogens, immune cell makeup – it’s all apparently there in the study.
Jared Younger was one of the stars of the program and Montoya said they missed him greatly. Besides Younger’s groundbreaking studies on low dose naltrexone (LDN) and fibromyalgia, his Good-Day/Bad Day study suggested that leptin could play a major role in ME/CFCS.
It looks like Stanford’s loss may be our gain, however. Younger was quickly able to put a team together in his new Fatigue and Pain lab at the University of Alabama and is engaged in more studies than ever.
An Inflammatory Disease
“Our cytokine data contradicts the erroneous conclusion that ME/CFS is not an inflammatory disease and supports that not only an inflammatory state exists in these patients but it also opens the door for the use of anti-inflammatory drugs or biologics, as it has been done for other inflammatory diseases whose aetiology is still unknown, including in rheumatoid arthritis and systemic lupus erythematosus.” Dr. Montoya
For many years, investigators believed inflammation was not present in ME/CFS, but the tests they were using (SED, CRP) are outdated and do not pick up the kind of inflammation present. Increased levels of IFN-y, IL-7, IL-17 and other cytokines indicate that an inflammatory process is feeding symptom severity in ME/CFS.
ME/CFS’s Kissing Cousin: Systemic Inflammatory Response Syndrome (SIRS)
A gene expression study indicated that the disease ME/CFS looked most like was “systemic inflammatory response syndrome (SIRS)”. In fact, at the gene expression level, ME/CFS doesn’t look somewhat like SIRS – it looks almost exactly like it.
First described in 1983, SIRS is an inflammatory state that affects the whole body. Sometimes it’s produced in response to an infection and sometimes not. Related to sepsis, SIRS contains both pro and anti-inflammatory elements.
Was Berg ahead of his time?
The pathways leading to this condition have been highlighted in ME/CFS before. Fifteen years ago, Dr. David Berg proposed that the same coagulation problems preceding SIRS (fibrin deposition, platelet aggregation, and coagulopathies) characterized ME/CFS as well. All but forgotten now by most practitioners, Dr. Holtorf is still putting Berg’s findings into practice. At the recent LDN conference, he called heparin one of his favorite treatments for ME/CFS/FM.
As ME/CFS gets worse, the inflammation present in it worsens. Montoya asserted that the inflammatory state found in ME/CFS opens the door for the use of anti-inflammatory drugs being used in autoimmune disorders such as lupus and rheumatoid arthritis. Herpesvirus suppression is just one component – an important one – but just one of apparently, a well-rounded and holistic program for fighting this disease. He suggested that there will never be a drug for ME/CFS.
But what about the recent Lipkin.Hornig study? That studies results suggested that ME/CFS in it’s later stages is a disease of reduced immune activation. How does that fit the picture of an inflammatory disease? Montoya stated Lipkin found evidence of both increased and reduced inflammation.
Could targeted treatments aimed at reducing IL-17 work – at least in recent duration patients? It’s (hopefully) significant that IL-17 has popped up in three important and impressive research groups; Columbia and Stanford and although he didn’t mention it, Dr. Klimas’s group. Montoya said it’s still too early to tell how IL-17 is.
Montoya said one thing about the longer duration patients that made sense in light of the Lipkin/Hornig results: a complex network of changes takes place as the disease gets worse.
MEANINGFUL Treatment Options
Montoya then asked “the question” – what will it take to find meaningful treatment options? Options that consistently move the bar for patients? Given a hundred million dollars a year in funding, he believed consistently effective treatment options could be developed in a few years.
The IOM Report
Critics of the IOM report have not been in short supply, but Dr. Montoya was clearly a fan. As a doctor and researcher working in a well-respected academic institution, he felt this report coming from “serious institution” was going to help him at Stanford.
He stated:
- The report has the potential to change the narrative of the disease in the US.
- So far, every one of his patients at Stanford has met the criteria.
- He appreciated the calls made for funding but was disappointed they did not come with a number. (Neither did the P2P (yet). Nor did CFSAC. Why is everyone letting the federal government pick a number?) .
Q &A
Is ME/CFS or SEID is contagious?
Montoya said there is no good evidence that it is transmissible. Patients are not passing it on to their loved ones.
He agreed that there have been well-documented outbreaks and noted that an infection can have both epidemic (easily spread) and endemic (not easily spread in its later stages) characteristics. He suggested that an undetected infectious agent able to reactivate other infectious agents such as EBV and Q could be present in an epidemic environment. In its endemic form –which is the form we almost always see it in – patients should not worry about ME/CFS being transmissible….
Will the CDC follow the recommendations of the IOM report on the definition and alter the CDC toolkit?
Dr. Unger simply said revisions will take time to be developed and posted. [Note that the CDC is a member of the DHHS, and it will, of course, follow DHHS guidelines or outcomes coming out of the report. [It’s possible that the CDC’s multi-site study may end up changing the Tool Kit the most.]
Is the CDC Testing Dr. Chia’s samples?
Yes, they are. Dr. Chia’s samples are finally getting beyond his laboratory. The CDC Picornavirus laboratory has received 30 samples from Dr. Chia and began in March. It’s taken, what a decade, for another laboratory to finally examine Dr. Chia’s samples – an unbelievably long time for a good hypothesis not to get examined. Good for the CDC to take this on.
Wrap Up
The big news for me was
- The next stage of the CDC multi-site study includes a very wide array of disease groups and ME/CFS subsets
- The CDC is trying to get ME/CFS into the curriculum of medical schools
- Dr. Chia’s samples are finally getting tested
- Dr. Montoya is looking for pathogens in natural killer cells
- He’s convinced herpesviruses play an important role and that new herpesviruses may be found in the next couple of years
- He believes immunomodulation is going to be key
- ME/CFS is an inflammatory disorder
Very good article as usual. I just can’t get over that the CDC isn’t doing a two-day exercise study. I am perfectly fine the first day and even half way through the second day. Then it hits and OH BOY.
It makes me question the CDC’s knowledge and motives when I see something like a one day exercise test. But doesn’t surprise me that they would continue to stand in the way of getting real answers about our illness.
It wouldn’t surprise me if some of the clinicians didn’t want them [2-day exercise tests]. If you’re somebody trying to help a patient improve (and they’re often paying you quite a lot to try to do this), they might not feel like asking their patients to do it.
I imagine there was considerable worry about significant relapses. I could handle a two-day test – it wouldn’t be pretty but I would come out of it – but some people might have real problems.
Yes, a one day test is a waste of time and money. Although i used to be able to work out for 3 hours, now i can only go for like 10 minutes…but the next day not being able to move, i doubt any of the patients would even be able to show up…
I know a lot of people are disappointed in not having the two-day test done. I am as well but I disagree that a one-day test is a waste of money. The Light’s only needed a one-day test to produce their fascinating results that showed huge alterations in gene expressions. Dane Cook found that a one-day test significantly impacted cognitive functioning the next day. Other studies have found complement activation. Dr. Klimas is using one-day test to uncover what goes wrong first in the body. One day tests can show us a lot – they just don’t as readily show the dramatic metabolic breakdowns that occur during the two-day tests.
One would hope that if they ever do a scientific study they wouldn’t mind if patients have a relapse after a two day exercise test.
I have to agree that not doing a two-day test seems to be an oversight. If the CDC set the standard at a two day test perhaps that would become the norm…followed by the doctors who administer Social Security disability exams as well as long term disability insurers who remain loathe to acknowledge and help those impacted by Chronic Fatigue.
I was diagnosed with CFS in 2011 after becoming ill in 2010 and have never been able to resume a regular workload. After several very rough years I am thankful that I can now work a couple days a week but not in a row…and not without paying the price mentally and physically for days after if I push through and “tough it out” to finish a task or project.
Thanks as always, Cort, for your terrific write-ups. It’s so encouraging to know that studies like this are coming down the pipe, gives a lot of hope.
Thanks Alex
I, too, am dumbfounded (but not surprised) that the CDC will not do a 2-day test, and please do not list too much on the patients as a reason for not doing it. The CDC has consistently dropped the ball with this disease for decades. For Pete’s sake, if the patients are willing to participate in the study, they are going to be very ticked off if all of the effort they put into showing up and doing the study are dismissed later simply because it was not extended another day. At any rate, I would be. If you’re going to do something, do it right…the first time. Would it be possible for another entity to step in and do the second day test? The subjects will already be on-site and the information gathered will prove invaluable. Why would one put everything together for a casserole then not bake it?
We have waited long enough. I would like to be able to enjoy a few of my ‘golden years’.
What I heard from someone who said he knew what was going on was that the physicians didn’t want to do the 2-day test. Just what I heard – do with it what you will.
I imagine the logistics of having someone else step in would be daunting and then you would have two different groups doing the test – which researchers would frown upon and probably use to poo-poo the results.
As a long time (4+ year patient of Dr. Montoya’s) I can tell you he often says things that he later denies. He told me he thought ME/CFS very well could be infectious (after I shared my wife had it and I was infected 10 years later). I remember the interesting report during the Incline Village outbreak of the 6 teachers, 5 of which shared a lunch room all coming down with ME/CFS, the 6th that instead took long drives to eat his lunch and smoke, remained the only one unaffected?
So we’re only 95 million short………
When you speak of little pediatric studies. I still think Janet Huber at Tufts, is on to something studying the thousands of teenagers that get mononucleosis and comparing them to the approximately 0.5% that end up with ME/CFS each year(nearly all female)! She’s studying some HERX gene (extraneous DNA) that causes down regulation of our immune systems in some situations. Unfortunately I think her funds are always threatened by the NIH.
Yes, we’re a little short 🙂
If I remember correctly Huber’s study unfortunately did not work out.
It seems the hopeful news just keeps coming these days! Or, at least, you are making a concerted effort to keep is aware of all recent sources of hope. In any case, thank you Cort!
Quick question – what are ‘Dr. Chia’s samples’? I know he is particularly interested in the possible role of enteroviruses. Is it a sample set from his patients that will be tested? From stomach/GI biopsy, or….?
I’ve always held out special hope for Dr. Chia’s work, not only because of my own experience with sudden onset CFS triggered by an infection that clearly disrupted/attacked my GI, but more generally, because the poliovirus – the virus that was most closely implicated/studied in the development of ME historically – is an enterovirus. So, any formal study of the enteroviruses is a huge win in my mind, especially for those of us who most closely identify with the historical definitions of ME. It’s like the research is finally coming full circle…thirty years later.
Of course, those of us who have been sick for many years may have something more akin to post-polio syndrome, rather than the active stage of infection. (Possibly reflective of that ‘three year shift’ found in the recent Hornig/Lipkin study.) In any case, this new round of interest and rigor that you describe sounds hopeful, as a start to finally sorting those details out.
And, thank God someone is finally going to study people just as they fall ill. Such a long time coming….so much needless suffering.
I believe it must be enterovirus in stomach samples. With regards to other gut stuff – we’re waiting on the Solve CFS Initiative’s exercise/gut flora results to be published, the Lipkin gut study is underway, I think Hanson has a gut study going and Pridgen has scoured FM patients guts for herpes viruses. So more gut stuff coming down the pike 🙂
Good deal. Thanks Cort! Hopefully someone will turn something up!
Do you know if any of that interest is leftover from the much older debate on ME? Meaning, do you get the feeling that the doctors/reaerchers that currently show the most interest in the gut do so, at least in part, because of the historical accounts of ME (atypical polio, etc.)? Or do you think it’s more that they’ve just coincidentally found themselves there because of the general increased interest in the gut, microbiome, and its role in the immune system (inflammation, energy production, etc.)?
Fine if you don’t know/care. 🙂 Just curious if you had an impression one way or the other.
Thanks!
I’m pretty sure it’s the second. There is just so much more understanding about the effects the gut can have on health now. I think the whole medical profession is learning.
I see.
Makes me with there was a lot more coordination/communication between these mainstreamers and the Naturopathic field. They, of course, have been adamant about the importance of the gut (and mircrobiome, in particular) – for so many conditions – for so long! Science certainly moves in mysterious ways.
Thank you for your thoughts – always interesting!
I must be totally out of reallity… When I read stuff like that 100 million/ year to solve it in a lifetime it makes me so so so fucking sad.
I keep seeing 2015 with this new promissing breaking through studies and get so hopeful, than I read something like that is like a ice bucket dropping on my head (with no challenge, and no money :\)
When I see those Lipkin/Hornig studies I feel like they’re o the verge of finding the key… how can I understand we’ll need a lifetime?… Damn…
BTW, Cort, Are you planning on writing about those new spinnal fluid findings from Lipkin and Hornig?
Amazing text, as always
Yes. They’ll be out soon.
Ron Davis, by the way, thinks if you give one big team $5 million dollars a year that in ten years they could figured this out…
“He suggested that there will never be a drug for ME/CFS.”
Is this right? Or was it something else e.g. there will never be a single drug for ME/CFS? (I didn’t listen so have no idea).
Sorry – he very much believes there will be drugs for ME/CFS – just not a single drug that helps everybody or I imagine a single drug that by itself cures people; i.e. other treatment may be needed. That was what I read into his statement.
Thanks
I have had ME/CFS or over 30 years; after getting a swine flu shot. Had gotten to the point where I was able to function again somewhat and if I paced myself. Then I fell and fractured 4 ribs; which sent me into full-blown ME again. It is much harder the second time around and I get very angry when it prevents me from functioning like I want to. My NK cells were on a ratio of 500 to 1 when I first became ill. I no longer get tests and go to the doctors cause I know there really isn’t anything they can do to help me. I have become very guarded around other people and don’t reveal my illness to many people cause 30 years ago when I first became ill ME/CFS was considered “psychosomatic” illness and I sure didn’t want people thinking that of me. I doubt anything will happen in my lifetime as I am already 74 years old.
It’s rough…you get better and then some sort of unforseen trauma pushes you back again. Our systems are just not as resilient as they should be. If there’s no benefit to saying what you have – and you get only distress from it – why do it?
Oh and by the way, the lyme group wasn’t chronic lyme was it? Or how would they know that?
Excellent article, Cort! Thank you! Do you know of any connection between Dr. Chia’s search for enteroviruses in the gut and Small Intestine Bacterial Overgrowth (SIBO) in Dr. Chia’s or anyone elses’ work?
Dr. Younger isn’t doing any clinical work at U of A but he said he’d be willing to come up to Vanderbilt for some kind of symposium onf ME/CFS. I hope to contact Dr. Clayton, chair of the IOM ME/CFS Committee, here in Nashville to see if that might be a possibility in the not-too-distant future. We need to develop some clinicians to treat us in Nashville. One possible entre into the Vandy clinical community is what Dr. Peter Rowe at Johns Hopkins University told me is the premier center for testing for POTS and other forms of autonomic system dysfunction. The only research out of Vandy mentioning CFS is one or more on orthostatic intolerance.
Dr. Rowe was the first one as far as I know that made the connection between OI and CFS maybe 22 years ago. I went on florinef at that point based on his research and a doctor who believed CFS was real. What was amazing to me was that when I called the pediatric CFS clinic he runs at Johns Hopkins to get direction, he immediately jumped on the phone to talk to me himself and emailed me information. I had a chance to personally thank him for the help he gave me two decades ago.
Recently I read that SIBO is also an autonomic system dysfunction as well as OI. If anyone knows anything more about that, I’d love to hear about it.
As far as research funding, I am of the opinion that we are owed “compensatory” funding for the neglect for 3 decades in addition to Dr. Montoya’s suggestion. I don’t really know if this is feasible or even wise, but I can’t help but think a class action suit against HHS for neglecting and even stealing our funding would be in order and would get lots of publicity to push for more funding. I think we need a bad cop as well as a good cop to drive up funding. No conflict = no drama = no publicity = no outrage = no sharp boost in our funding.
To Lacey: My heart goes out to you. I’ve been sick for almost as long as you and don’t expect any miracles at this point. I’m grateful and hopeful of finding ways to modest improvements. Now we have to fight for the young people who may be saved from having to go what we’ve had to endure.
Esther,
I love your idea of a class action lawsuit and compensatory funding! I’ve had this for more than 20 years and wonder if I would have had a better chance at health if more had been done in the beginning. I’m guessing most lawyers would not want to expend the time, energy and $ it would take to go up against HHS. 🙁
Thank you Cort again for keeping us updated on all this!!
Kira
Shoot yeah I’d vote for a pain and suffering lawsuit for my 24 years of illness. So, would it be based at from time of onset or from time of diagnosis?
As far as research funding, I am of the opinion that we are owed “compensatory” funding for the neglect for 3 decades in addition to Dr. Montoya’s suggestion.
I don’t know if its going to happen but I heartily agree
Hi Esther,
Re: SIBO and enteroviruses…
I am not aware of any clinicians/researches who are directly taking this on. (But that by no means that there aren’t any!) But from my own information gathering I know this:
SIBO is most often referred to as developing in the wake of a “stomach bug”, a “stomach flu”, and “food poisoning”, so one would think that any specific enterovirus could be included in that group. Usually little explanation for this association is given, though it is often proposed that the infection causes some sort of “damage” to the gut that allows the bacteria to spread and overpopulate. Maybe it’s somewhere in the TH1/TH2 shift hypothesis – where the viral invasion distracts the body’s bacterial defenses, and therefore bacteria is allowed to overrun the system? Maybe the healthy balance of of the micro-biome is disrupted by the infection, or the immunological war that follows? On an even more basic level, when the ileocecal valve (the vale between the small intestine and large intestine) is swollen for any reason (i.e. infection), it is less able to do its job of keeping nicely sealed, and can therefore allow bacteria to leak back into the small intestine, where it is not really supposed to be.
Also, if a viral invasion can trigger an autoimmune response (in susceptible individuals), as is thought to be the case in many types of autoimmunity, an enterovirus could theoretically trigger auto-immune mediated SIBO. (I guess that’s the T1/T2 shift again.) For example, Dr. Mark Pimentel is working to connect autoimmune-mediated poor gut motility, to an overgrowth of bacteria in the small intestine. (As explained to me by my naturopath…) …he believes that in SIBO patients, the immune system mistakingly attacks the motility centers in the enteric nervous system in its attempt to rid the GI of invaders, thereby slowing motility and allowing the system to “back up”, i.e. into the small intestine. Which creates a self-feeding cycle of disease.
So, basically, there appear to be all sorts of ways that the two might be connected.
Mostly conjecture and piecemeal logic there, but that’s all I got! (I’d love to know if you turn up anything more official on the subject.)
Re: SIBO and Autonomic Nervous System Dysfunction…
(Same caveat as above applies here.)
The only connection I know is that almost every un-conscious function in your body – including the movement (peristalsis) of your intestines, the opening and closing of your digestive valves, etc. – is in large part dictated/controlled by your autonomic nervous system. So any disruption/dysregulation in that system could have all manner of effect on your ability to properly digest and keep various bacterial populations where they are supposed to be.
(Also, that same relationship between Nervous System function and SIBO proposed by Pimentel loosely applies here too.)
Hope that helps. Wish I had more “official” sources to offer you! Martha
Again why the virus obsession…I know I am a broken record but it’s a futile and wasteful path
I hope you’re wrong Matthias – it has the grace of simplicity but we shall see. I think things that affect immune functioning may be the key in the long run..
I’m a broken record too… “finding the mythical virus”
A single exercise test will almost show nothing wrong. Maybe the gene study will help. The 2-day test would make a big difference for ME/SEID and will end the discussion that GET/CBT is effective. I don’t understand why the CDC doesn’t ask some patiënts to do this. Tehy can do both a one day- and 2 day test. Then you can compare the data. I did a 2 day test it was heavy but if it is important you must do it.
Cort, what is so special about dr. Chia’s samples? I don’t understand.
Over the past ten or fifteen years Chia has found high rates of enterovirus in his stomach samples again and again. He believes an enteroviral infection – an atypical one I believe- is what is causing ME/CFS. Despite all the work he has done on it, no one has tested his hypothesis. IF the CDC finds high rates of enterovirus in his samples – that will be an unusual finding and would I imagine finally get the research community engaged in his work.
Females have enhanced immunoreactivity compared to males. ME/CFS is about 2 to 4 times more common in women, than in men. I’ve never heard of a virus that preferred women, over men. This is why, ME/CFS is more likely to be an autoimmune illness with many different environmental/stressors causes, rather than chronic low-grade infection from a virus, that can’t be defeated. Autoimmune diseases affect about 10% of the population, 75% are women.
I have the classic signs of ME/CFS/SEID. Cognitive dysfunction, post exercise crash, coma like fatigue, etc, etc. and have been diagnosed with it from an MS specialist at Georgetown. However, I was diagnosed with my first autoimmune illness at age 8 – rheumatoid arthritis. They didn’t have RH factor tests back then, they just looked at symptoms. For me it was excessive tiredness. They had no idea about CFS so I was given the RA label. I then was diagnosed with Hashimoto’s Thyroiditis, adult onset autoimmune diabetes, I have psoriasis which is autoimmune, autoimmune hearing loss, I had miscarriages they claimed were autoimmune related, and a neurologist said I had atypical MS (now thought to be CFS). So I’ve been looking at factors involved in autoimmune diseases for probably 50 years. I’ve tried HRT and bioidentical progesterone, pig adrenals for adrenal fatigue, Rituxan, Embrel and every class of that drug, guaifenesin, antidepressants, methotrexate, Armour thyroid, more supplements than I can remember- you name it I’ve tried it. After much research, discussion and thought, I have come to the conclusion that in autoimmune diseases, the body is not attacking itself for no reason. It is attacking something that we have yet not discovered but is in there. Based on that, I took antivirals for two years and by six months into it I went from bedridden to 80 percent of normal and stayed that way. I was at 80 percent for years but had to pace myself. Then a major trauma in my life left me bedridden again re activating whatever it is. I’m back on antivirals and again about 80 percent of normal. My point is that just because we haven’t yet found a virus that some how is associated primarily with women, doesn’t me there isn’t one. I have tried literally everything and only antivirals have helped me. This isn’t science. This is just my opinion based on my own experience.
What a story ShewolfDC! Convincing stuff 🙂 I hope you’ll consider put your experiences with antivirals on the review section of the Forums. http://cortjohnson.org/forums/reviews/products/
shewolfdc said: “I have come to the conclusion that in autoimmune diseases, the body is not attacking itself for no reason. It is attacking something that we have yet not discovered but is in there.”
***************************
I will never be convinced that ME/CFS is caused only by a virus, especially one that likes women. It may be one of many triggers in susceptible people, but it is not the only cause of ME/CFS. ME/CFS is an autoimmune illness. My immune system is totally upregulated; I never get colds or flues. My body eats viruses for breakfast. I overreact to chemicals, meds, alcohol (anything and everything my body deems foreign); all my symptoms are caused by my hyper-immune response. Exercise makes my symptoms even worse because it further boosts my immunity. When your immune system goes into overdrive (like mine has) you are going to be allergic or highly sensitive to from one to over five hundred different things.
I have had ME/CFS for 30 years and also tried literally everything. I am about 80% back to normal also, but what worked for me was immune suppression, sedating antihistamines, antiinflammatories and raising my dopamine levels. Dopamine is the major neurotransmitter that puts the brakes on prolactin, which is an immune-stimulating peptide hormone. Prolactin enhances the progression of the immune process in autoimmune diseases. I don’t have a virus lurking somewhere in my body; I have an autoimmune illness ME/CFS caused by an immune system in overdrive.
Many of us have very different ideas about what our illness is. Mold, hormones, viruses, chemicals, tick bites, etc. Bottom line though nobody knows. It’s all conjecture. My conjecture though is the same as yours; that it is autoimmune related. I too never get colds etc. I too had my dopamine levels regulated and was taking anti-inflammatories. When I went to the ME antiviral doctor he said I should get off the anti-inflammtories. I told him I couldn’t possibly get off them. He said, they only treat the symptom, not the cause. The antivirals will slow down the cause, he said and you won’t need them. The antivirals have allowed me to leave behind all of my other symptom related meds. The idea that ME is autoimmunity of the central nervous system rings very true to me. I have brain lesions and had a lumbar puncture and they found in my spinal fluid much the same things as recent published studies found. We completely agree that ME is an autoimmune related. Where we differ is the cause of autoimmunity. But as we know, our opinions are only opinions. They can’t even come up with a freakin’ definition for what we have, so how can we say what causes what we can’t even define? The only thing I hope for is that in our lifetimes we find out. And find a treatment. And when that happens it won’t matter to me whose theory was dead on, just as long as I can be healthy, I’ll be a happy camper. For now, I’m so happy that both of us have found a way to be 80 percent ok. We’re so much better off than so many others on here. I have a horse and I can ride him again and to me that pretty much is all that matters. 🙂
shewolfdc: Yes, I suppose as long as we have both found ways, to somewhat deal with this terrible illness, that is a good thing. I wish all others with this unfortunate illness the same. That’s why I comment. I am hoping that someone might see similarities between my experience with ME/CFS and their experience with the illness. I hope that my observations, over the past 30 years, and what has helped me, may somehow help others. Waiting for the medical establishment to come up with answers has been beyond frustrating. Plus, when I see how different this illness presents in each of us, the frustration just grows. I truly don’t believe we all have the same illness, so how can antivirals possibly cure us all? Some seem to have immune systems that barely function, while others seem to have immune systems, that are on fire (like mine). I have absolutely no faith, that antivirals would cure my case of ME/CFS, or make me any less allergic, or sensitive to the environment around me.
Hi Rachael,
What do you use to increase dopamine ?
Jill, I use tyrosine, along with other supplements and over-the counter meds to help build depleted dopamine/endorphin neurotransmitters. I am not a doctor; I don’t like to tell people exactly what I do because it has the ability to considerably raise blood pressure. I wouldn’t want to cause anyone harm. Let’s just say tyrosine is a good start, but make sure you monitor your blood pressure.
“Dopamine is a neurotransmitter that is associated with emotions, movement, and the brain’s pleasure and reward system. Investigators now provide a broad overview of the direct and indirect role of dopamine in modulating the immune system and discuss how recent research has opened up new possibilities for treating diseases such as Parkinson’s and Alzheimer’s disease, schizophrenia, multiple sclerosis or even the autoimmune disorders.”
“Permanent dysfunctions of either the central (CNS) or the peripheral (immune) dopaminergic system are frequently associated with immune malfunctions. Current dopamine replacement or receptor blocking therapies are based on the supposed action of these drugs at the target site, and they often only relieve disease symptoms.”
http://www.sciencedaily.com/releases/2012/10/121011123740.htm
Here is an excellent article on a THEORY as to how autoimmunity is caused by a virus and why women may be predominately affected.
I have seen similar theories over the years which is where I developed my way of thinking on this and spurred me to antiviral therapy. As I mentioned, I take almost no other drugs at this point – I still take a thyroid drug and a statin and various vitamins.
I’m not trying to sway your opinion, just wanted you to see an example of the type of research that led me to mine.
http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/43797
Rachel,
What anti-inflammatories do you use? Are they otc or rx?
Thanks.
Kira: While, I would rather not say which antiiflammatories I use, they’re OTC, and so is the antihistamine I use. If pharmaceutical drug companies think you can solve your own medical problems, in regards to illness, you can bet they will try to take these agents off the market. I’m not a doctor and I am also protecting myself, in regards to what works for me. However, the reason these over-the-counter drugs work is because I have been able to successfully restore depleted dopamine neurotransmitters with tyrosine and other supplements. Drugs that require a dopamine source now have a something to work with; I’m no longer running-on-empty and I can successfully calm my hyper-immune response..
Rachael,
I totally understand. It’s just the only anti-inflammatories i know are nsaids, which give me gastritis. I can work with my doc on supplements. Used to do l-tyrosine. Will give it another try perhaps.
Thanks!
Shewolfdc – which antivirals have you used?
Famvir and Valcyte. Valcyte (sp) this latest time. Also the latest time, my doctor added an antacid. He said he found it heightened the affect of the antiviral. I think the combo did a great job.
Antivirals only work if you have high antibody titers.
I wrote a tutorial on how to tell if you need antivirals and what to do.
http://www.carolwolfmedia.com/#!think-you-have-cfs-seid/csnm
Shewolf,
Thanks for the info!
Kira
Agree!!! The infectious agent causing all these symptoms is key to real treatment. Agree about auto-immunity too. A virus in only mythical until it is found.
It seems that CFS has a number of subsets.
I know for certain in my case that estrogen plays a role. So my cfs is probably in the subset that has a higher percentage of women.
After having this illness about 14 years, some of the changes i made began to help (diet, supplements, rest, sleep, etc) and i began a painfully slow process of reconditioning my body. It took another 5 years but i was finally able to play doubles tennis 2-3 times a week. I didn’t do much else but it was heaven! I was able to do this for about a year or so.
Then menopause began and WHAM! Within months i was back to as sick as i ever was. Back in bed. No tennis. No life.
I’ve been taking HRT (estrogen and progesterone) but it hasn’t helped the fatigue very much (just the night sweats and hot flashes). I’ve started with an alternative doctor to do a more thorough investigation of my thryroid and adrenal glands. I may try low dose hydrocortisone again. I tried it years ago but the anxiety it gave me was worse than being sick. We’ll see.
If Lacey or any other gals who have had this when they hit menopause, i’d love to hear your experience. Thanks!
Kira
Fascinating Kira. I just have to say it – with all the different subsets this disease is so interesting! Good luck with your search…
Thank you, Cort, for this somewhat promising article regarding Drs. Montoya and Unger. Happy to see Dr. Unger so on board and that she is still working toward having ME/CFS added to the medical school curriculum. I pray for sufficient funding to move these studies forward. After 20 years of a lowgrade fever, it is now just as suddenly gone. I can only attribute it to Valcyte though I am uncertain as I’ve never seen a CFS/ME specialist but rather “con” MD’s into working with me by showing them research articles such as Dr. Montoya’s. And I can see where I’m into the more “mature” end of this disease in that my viral titers are not nearly as high as they were, my adrenal burnout seems to be recovered, and my fever gone. Now I have secondary hypothyroidism from HPA axis dysfunction wherein my TSH is normal but my free T3/4 is low but I receive Armour Thyroid for this and my numbers are within normal limits with the medication. The lack of fever has increased my ability to tolerate stressors although I remain largely housebound and thankfully receive state and federal disability which allows me to remain independent financially though still dependent on individuals for assistance. I am such a stereotypical case that it’s a shame that I’ve never been able to become part of any ongoing study though I have always been more than willing but possibly not able if it involved long distance travel. I’m more at peace now with this being my daily reality after railing against it for so many years. I’ve much to be thankful for and try to focus on what is positive and allow it to beneficially affect my immune system and general sense of well being. Your years of information regarding this disease has helped enormously and for that in itself I’ll always be most grateful. With love. marcie myers
Hi Marcie,
I, too, had a low-grade fever every day for 20 years. However, I can’t attribute my now-normal temperature to anti-viral medication. In my case, the timing coincided with menopause (almost six years ago) — the only possible reason I’ve come up with. But, at the same time, I developed Rheumatoid Arthritis and worsened digestive problems (gluten/grain intolerance), so obviously something changed in my immune system. I’m also on Armour Thyroid, and taking bio-identical hormones, without which my hormone levels would measure “zero”.
I haven’t linked my increased ability to handle stress to the lack of fever — that’s an interesting thought. But, like you, I am largely (but not completely) housebound.
Hi,
no 2 day test! how stupid is that, I mean it is not an expensive test to do.
Why is it not to be then? Why not point out it needs to be a 2day test and make it happen, why is it too late already?
Tim
I think a sort of autoimmunity (or infection) against Lipid raft could explain everything especially caveolins they are widely expressed in the brain, micro-vessels of the nervous system, endothelial cells, astrocytes, oligodendrocytes, Schwann cells, dorsal root ganglia and hippocampal neurons.
I asked my doc last year to run a test to see if I had herpes virus from reading many articles. Turns out I had one in my gut. She told me I must of had in long ago. Don’t have any symptoms of herpes elsewhere. Anyway, I have had many issues with my gut, such as IBS, bloating, lactose intolerance, etc. I bought some KeyBiotics which has really helped with the IBS issues. I would not go to bathroom on a reg basis.. Maybe going sometimes not going up to a week. Miserable but with the Keybiotics, I now go on a regular basis. Makes me feel much better in the gut but my fatigue still lingers on. I was diagnosed with Fibro/CFS in 1998. Such a relief to find it had a name at the time even though I could not even dress myself and go. Eventually, after a year off from work, I went back. One of the hardest things I did in my life. Worked for about 7 more years but everyday I had to drag myself to get there. Could take it no longer and stopped working in 2006. It was fine at first being home and getting rest. Doing things at my leisure but then in got worse. I am in bed right now typing this message. I will need to get up and take my husband, who was diagnosed with chronic renal failure about 4 years ago, to dialysis. I am trying to care for him as much as I can but between the 2 of us, it really sucks. I think the reason I am bed now maybe to rest up while I can in between taking him to doctor appts, hospital and dialysis. Needless to say, I think stress is always a factor with CFS/ME. Hate to ramble on, just wanted to say that I think the gut and immune system may well have something to do with the cure. I think the spinal fluid is a link as well. One doc I had back in 1998, went with a needle in my spine to get rid of scar tissue from a bad car accident I had back in 1986. He did this with saline solution and did it five days in a row. I have no idea if that means anything or not to doctors but it did not help me at all. Instead it made me worse. Can you Dr. Connect any of these dots together? I know it is a lot of info but just wanted your ballpark input. Thanks.
I asked my doc last year to run a test to see if I had herpes virus from reading many articles. Turns out I had one in my gut. She told me I must of had it long ago. Don’t have any symptoms of herpes elsewhere. Anyway, I have had many issues with my gut, such as IBS, bloating, lactose intolerance, etc. I bought some KeyBiotics which has really helped with the IBS issues. I would not go to bathroom on a reg basis.. Maybe going sometimes not going up to a week. Miserable but with the Keybiotics, I now go on a regular basis. Makes me feel much better in the gut but my fatigue still lingers on. I was diagnosed with Fibro/CFS in 1998. Such a relief to find it had a name at the time even though I could not even dress myself and go. Eventually, after a year off from work, I went back. One of the hardest things I did in my life. Worked for about 7 more years but everyday I had to drag myself to get there. Could take it no longer and stopped working in 2006. It was fine at first being home and getting rest. Doing things at my leisure but then in got worse. I am in bed right now typing this message. I will need to get up and take my husband, who was diagnosed with chronic renal failure about 4 years ago, to dialysis. I am trying to care for him as much as I can but between the 2 of us, it really sucks. I think the reason I am bed now maybe to rest up while I can in between taking him to doctor appts, hospital and dialysis. Needless to say, I think stress is always a factor with CFS/ME. Hate to ramble on, just wanted to say that I think the gut and immune system may well have something to do with the cure. I think the spinal fluid is a link as well. One doc I had back in 1998, went with a needle in my spine to get rid of scar tissue from a bad car accident I had back in 1986. He did this with saline solution and did it five days in a row. I have no idea if that means anything or not to doctors but it did not help me at all. Instead it made me worse. Can you Dr. Connect any of these dots together? I know it is a lot of info but just wanted your ballpark input. Thanks.
Julie,
I’m sorry to hear about your husband’s health. I’m no expert but in my own experience, even minor medical procedures have always made me worse. The spinal procedure: I never recover from procedures that serious.
How do you test for herpes in the gut? Is it a gut-specific type of herpes?
I asked my doc last year to run a test to see if I had herpes virus from reading many articles. Turns out I had one in my gut. She told me I must of had it long ago. Don’t have any symptoms of herpes elsewhere. Anyway, I have had many issues with my gut, such as IBS, bloating, lactose intolerance, etc. I bought some KeyBiotics which has really helped with the IBS issues. I would not go to bathroom on a reg basis.. Maybe going sometimes not going up to a week. Miserable but with the Keybiotics, I now go on a regular basis. Makes me feel much better in the gut but my fatigue still lingers on. I was diagnosed with Fibro/CFS in 1998. Such a relief to find it had a name at the time even though I could not even dress myself and go. Eventually, after a year off from work, I went back. One of the hardest things I did in my life. Worked for about 7 more years but everyday I had to drag myself to get there. Could take it no longer and stopped working in 2006. It was fine at first being home and getting rest. Doing things at my leisure but then in got worse. I am in bed right now typing this message. I will need to get up and take my husband, who was diagnosed with chronic renal failure about 4 years ago, to dialysis. I am trying to care for him as much as I can but between the 2 of us, it really sucks. I think the reason I am bed now maybe to rest up while I can in between taking him to doctor appts, hospital and dialysis. Needless to say, I think stress is always a factor with CFS/ME. Hate to ramble on, just wanted to say that I think the gut and immune system may well have something to do with the cure. I think the spinal fluid is a link as well. One doc I had back in 1998, went with a needle in my spine to get rid of scar tissue from a bad car accident I had back in 1986. He did this with saline solution and did it five days in a row. I have no idea if that means anything or not to doctors but it did not help me at all. Instead it made me worse. Also have low grade fever everyday but doc says tests are normal. Can you Dr. Connect any of these dots together? I know it is a lot of info but just wanted your ballpark input. Thanks.
I agree on a class action lawsuit for those of us who have lost our most productive yearz to a disease and then repeatedly mistreated by the medical profession. 20 years for me. I had some improvements , recently had an severe adverse reaction to a “safe” drug and my health has declined. I am now also diagnosed with Mast Cell Activation Disorder. This is so very difficult . I would like to know more about natural anti inflammatories…. Tumeric? Boswellia ? Any others people like? I know prednisone helps me of coutse there are adverse effects and short term use is recommended. I have also recently tested POSITIVE for SIBO but what now? I modified my diet years ago, no gluten, grains, no sugar, no processed foods, no artificial ingredients, etc etc . Sometimes I am really frustrated. Either help us , offer a clinic which should be free after we have wasted our money for 20 to 30 years, or offer euthanasia.
Has anyone successfully treated SIBO and who can help me with that? I am taking probiotic, I do have severe motility malfunctioning. I do meditate, use the alpha-stim microcurrent stimulator daily, use tappi g / EFT , exercise as I can. I know I have tested positive for lots of the herpes viruses and I eadily get recurrances of shingles. It’s a mess !!!!! I don’t even know where to focus at this point….SIBO or something else….do I go visit Dr Chia? Bless us all for what we have endured.
Thank you so much, Cort, for this encouraging article!
Many thanks for highlighting all of these issues.
Ehlers Danlos Syndrome ‘types’ with incomplete partial Habitus Marfans Syndrome with Syncope/P.O.T.S. & MCAD Mast Cell Activation Disorder…Some have full Marfans no EDS or
another type called Beals…Genetic born conditions deficiency in Collagen not a Virus not Lymies either…Runs through Families…Dr. Rodney Grahame Hypermobility Unit London