It took Tony Komaroff over thirty years to get this done but it may have been worth it. Komaroff, Harvard doctor, researcher and ME/CFS advocate, has been studying, writing about and advocating for ME/CFS research since at least 1987 when he was the senior author on no less than four studies.
Over his long research history, he’s examined pathogens, the immune system, brain scans, hormones, the autonomic nervous system, cognition and others. His huge 1996 “health status” study demonstrated that people with ME/CFS were more functionally inhibited than people with congestive heart failure, type II diabetes mellitus, heart attack, multiple sclerosis, and depression. All in all, Komaroff has co-authored over 80 studies on ME/CFS.
Only three times has he been able to get something published in JAMA. Ironically, his first “ME/CFS” study – on chronic Epstein-Barr virus – way back in 1987 landed in JAMA. Except for a comment he got published in 1997, that was it until this year when he got “Advances in Understanding the Pathophysiology of Chronic Fatigue Syndrome” article published.
It took Tony Komaroff over thirty years to get another ME/CFS paper published on JAMA. This new paper, though, is a hit…
Komaroff’s been doing overviews of ME/CFS for years. In 2015, he scored a coup when he got “Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Real Illness” published in the most widely read general internal medicine journal – the Annals of Internal Medicine.
This is different – this is JAMA, the flagship journal of the American Medical Association – “the professional organization for physicians in the United States.” Reportedly “the most widely circulated general medical journal in the world”, JAMA is not a specialty journal; it doesn’t focus on neurology or immunology – it’s a general medical journal aimed primarily at doctors and medical students.
It gets around. JAMA states that its Impact Factor (51.3) is one of the highest in medicine and science, that its website gets almost 25 million visits a year, and that it has more than 750,000 followers on Twitter and Facebook.
Getting this article published in JAMA means more than quite a few doctors and medical students are getting a new view of ME/CFS. It also means the editorial staff of JAMA believes Komaroff’s message – that ME/CFS is a real disease – has merit and that doctors should be exposed to it – a good sign. Komaroff wrote:
JAMA’s “published very little about ME/CFS over the years, but are warming to the subject. They probably are the most widely read English language medical journal in the world, and so their interest is important. The implicit message of the article is that there is a complex underlying biology to ME/CFS and that health authorities are taking it very seriously—which will probably come as a surprise to many readers.”
JAMA now knows that it has good reason to “warm” to ME/CFS. Komaroff’s article is not just beating the competition – it’s blowing it away. The 27,000 plus views it’s had over the past four days are far and away the most of any recently published article. Right now, Komaroff’s article is about 10,000 page views ahead of its closest competitor with most JAMA articles getting around 3-5K views.
- Update: as of July 19th the article has received over 57,000 page views, which according to an analysis of the articles appearing on JAMA in 2018, would – just two weeks after its publication- would put it in the top ten most viewed articles of that year.
This is despite the fact that the article is not easy to find. It was published online on July 5th (not in the official JAMA editions on July 2nd/9th) yet readers are still flocking to it. The article is now highlighted in a box marked “trending” – which will undoubtedly get it more views.
The Article
The article is not long but it is impactful. Komaroff smartly refers to the 2015 Institute of Medicine report on ME/CFS, produced by an institution that the doctors/medical students reading this article will know, appreciate and presumably trust. Komaroff has the doctors and medical students know that this report concluded that “ME/CFS is a serious, chronic, complex systemic disease” that affects up to an estimated 2.5 million people in the United States, and causes from $17 billion to $24 billion in economic losses annually in the U.S.
As to the idea that ME/CFS is not a real disease – well, many of the tests doctors used in the 1980’s when ME/CFS first leapt onto the scene in a big way (and the tests that doctors still use today) couldn’t find anything wrong. Many doctors concluded that meant there really was nothing wrong, but Komaroff asserts that the results of the next 3 decades indicate that it was the tests that were wrong (and the doctors who put too much faith in them) – not the patients.
The overwhelming weight of scientific evidence over the past three decades suggests that something has gone wrong biologically in ME/CFS. Most of the tests, which have done that, though, cannot be accessed in doctors’ offices.
Komaroff then quickly spins through the abnormal findings – the autonomic and central nervous system, metabolic, immune, hormonal and exertion findings. Thankfully, he includes the inability to repeat energy production levels on the second day of a two-day exercise test. (Unfortunately, the uniqueness of that finding did not make it into the paper.)
Unifying Models
Komaroff presents two models of ME/CFS – both of which result in a hypometabolic state.
It’s in the Unifying Model section that things gets really interesting. Komaroff has always been conservative. He’s careful, he doesn’t go out on limbs – and that’s been helpful at times and at times not. Komaroff, for instance, signed off on the chronic fatigue syndrome name in 1988 (it was called chronic Epstein-Barr virus syndrome), he voted against approving Ampligen for ME/CFS (he wanted more studies – which he must have known were not likely to happen – and six years later, haven’t happened and aren’t likely to), and his support of Bill Reeves and the CDC when they were under attack all showed just how conservative he can be. That innate conservatism, however, has also probably enabled him to be a bridge to the outside research world. It’s possible Komaroff is the only figure that could have gotten this paper into JAMA.
That made the first part of the first sentence in the unifying hypothesis section really surprising:
“What if ME/CFS reflects the activation of biologically ancient, evolutionarily conserved responses to injury or potential injury, a pathological inability to turn these responses off, or both?”
Komaroff – our conservative liaison to the medical community – has clearly bought into Naviaux’s dauer hypothesis. Two paragraphs later, he devoted a full paragraph to it, and overall, about 10 percent of this short paper – Komaroff’s outreach to the medical community – is focused on it. He clearly wants doctors to know it’s possible ME/CFS patients are stuck in some kind of hypometabolic, hibernation-like state.
The other model Komaroff presents ends up in a similar state. In that model, neuroinflammation activates a fatigue nucleus in the brain which basically tells the body to shut down. That neuroinflammation could be triggered by any number of things – a herpesvirus infection in the brain, autoimmunity, neurotoxins, a breached blood-brain barrier, inflammation in the periphery that’s tweaking the vagus nerve (aka VanElzakker), gut inflammation and/or chronic stress. Each of these may be present in ME/CFS but in different individuals.
Or, the worm may be in play. Komaroff suggests people with ME/CFS may have gotten stuck in the ancient biological state of metabolic shutdown seen in the state of dauer that the Caenorhabditis elegans worm enters into, or the state of hibernation that some animals enter into during times of stress. Functionality flies out the window as the animal hunkers down and simply tries to survive.
(As the same end point is reached in both the neuroinflammation and the dauer hypothesis, who’s to say (other than perhaps Bob Naviaux :)) that the activation of the fatigue nucleus that Komaroff presents in the first model doesn’t also occur when humans, if they do, enter into a dauer state.)
If Komaroff was aiming at perking up some eyebrows, he surely succeeded. His neuroinflammation hypothesis will undoubtedly ring bells with many of the doctors, etc. who’ve read Komaroff’s article over the past couple of days. Few, on the hand, will have heard of dauer, or will have ever thought to possibly connect ME/CFS with a state of hibernation. (Compare the 27,000 plus views Komaroff’s article has had to the 4800 views the last JAMA publication on ME/CFS in August, 2018 had.)
The article’s Altmetric social media score shows that Komaroff’s ME/CFS JAMA article is scoring in the top 5% of all research articles. JAMA, like all medical journals, likes to know that its articles are being read. The more attention given to a subject, the more likely JAMA will revisit it again – and, of course, with its wide reach into the probably the most ignorant branch of our medical establishment – doctors – JAMA is one place that we really want ME/CFS studies to show up on. Please visit the original article here (no need to read it if you don’t want to) and share it via tweets, Facebook and other social media outlets.
In another sign that JAMA is coming around, on July 9th in its Biotech Innovations section, JAMA also published a short review of the ME/CFS nanoneedle study “Biomarker Test for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome” that was recently published in Proceedings of the National Academy of Sciences. Please visit that article and pass it around as well.
Health Rising – a Vital Source of Information
Keep Us Rocking As Well
I printed this article and brought it with me to my PCP today who has never engaged with me on fighting this disease.
When I handed to her she said she had printed it out herself and that she had it on her treadmill to read. I was surprised to say the least.
Finally.
There you go – that’s the JAMA effect I imagine :).
It’ll be interesting to see how she reacts to it
Not replying to this comment directly, but wedging in. Low Dose Naltrexone (LDN) is quite helpful for many conditions, one of which is CFS (also M.S., hashimotos, thyroid issues, and many others.) I’m putting this here because many comments below ask about treatment, and as we all know, most people are unable to get much treatment due to the VILE mislabeling and misinformation spread about he medical community about M.E./CFS.
Now this condition has reached non-deniability all are due fair treament, as we have been gouged out of insurance plan money, cost for excessive appointments, and turned away from emergency rooms with nothing but confusion.
LDN should not be administered clumsily, and should be learned about before taking – staring at a low 0.5mg dose, and slowly over weeks working up by 0.2mg at a time. If you can find a rare doctor who even knows to prescribe it, insist on this method, as it will reduce side effects. Some doctors will try to give you 2.0mg or even 4.5mg immediately and it can wreck havoc for some. LDN can restore energy somewhat (not back to normal though) but have a dramatically positive effect on brain fog. If side effects arise, take a day or even two off. Learn more about LDN online, and in various facebook groups dedicated to the medicine.
Cort, I am sitting here crying with relief that { my} Dr. Komaroff has finally been recognized for the expert in this arena for over 30 plus years. This man saved my life when I entered Albany Medical Center in the early 80’s my body was shutting down. With help from Albany Medical, a nurse I knew immediately went on high alert to find anything that would save me, and she read journals and contacted my Dr.’s Albany Medical and told them they had to reach out of Dr. Komaroff, which they did immediately.
He was the only expert at the time and thank God he was available. He told them to give me three different medications, one was an antibiotic, and two were anti- depressants, his simple words to them was this” she will either flourish in 2-3 days or she won’t but none of the med’s will hurt her”, He zeroed in on exactly what I needed. The long journey started there and continues to this day, many doctors, tests and years of struggle now have me in my aged years to 68. Now the ugly BEAST RETURNS just as the Infectious Disease Specialist who worked with me for 12 years that followed Albany Med. Once we had this is a dormant state I could survive with many changes to my life, but at least I had a life. He said this is only temporary, when this decides to wake up you will know it, with a vengeance. Well in May of this year I became as ill as I’ve ever been in my life and I knew what I needed. With much persistence and against the Dr. on my second visit in 2 days to emergency help I said if you will only try to listen to what I am saying, you will see I am correct, well a steroid later and antibiotics along with my antidepressants I started to pull out of it, the minute I ran the course of med’s with in 24 hours I was back telling them to repeat these steps again. They did and that started me on the road to healing. However, I didn’t stop there as I was having many problems surfacing, memory loss, cognitive issues and now it is believes I have Executive Brain problems so I am going through many test, Dr.’s etc. and I keep telling them all the same thing, this is what the Dr. told me would happen. Well now you can rest assured I am printing this out to distribute to each and every one of them, Primary, Neurologists (2), and now a Center for Excellence on Alzheimer disease. I can’t wait to deliver this news as each one of them are a aware of Dr. Komaroff from my initial discussions with them. I will end up reaching out to Dr. Komaroff with my current history as I am so afraid I could fall between the cracks at a very fragile time of my life, I had to fight to heard for 35 years with this illness and now I am in the fight of my life as new developments of Brain functions etc. are now surfacing. Thank you for reading this and I will be glad to hear from you when you get time. You to are a life saver Cort, thank you for all you do. Adrienne Hull
Why bother with your PCP if they never engaged with you? Go to a CFS specialist and get treated.
Many CFS specialists do not take medicare..she may have no choice., or may be unable to travel to one.
Hi. I’ve been to several professionals for this disease for a lot of years and none of their protocols worked for me. But I have to see my PCP for my medications for sleep and occasional anxiety. It’s no treat but I have to go.
Very few people have the energy or financial resources to get to the ?6 specialists who largely do the accepted tests and, regardless of results, simply kindly wish the patients good luck as there is no real treatment or an accepted diagnostic test. As well,no name or definition for clinical diagnosis or research diagnosis had yet to be agreed on. Neither medical students nor current practitioners are receiving any education and to my knowledge no particular specialty has been designated to see ME/CFS parients.
I am very grateful to Dr. Kamaroff for continuing to support us and thrilled that his article is at the top of what’s trending on JAMA. Much thanks to you, Dr Kamaroff. Matter of fact, a big hug to you and all participants. Highest regards,
Marcie Myers,BSN diagnosed in 1994 at age39.
What is “dauer?” I believe it means quite serious in German. M
Very few people have the energy or financial resources to get to the ?6 specialists who largely do the accepted tests and, regardless of results, simply kindly wish the patients good luck as there is no real treatment or an accepted diagnostic test. As well,no name or definition for clinical diagnosis or research diagnosis had yet to be agreed on. Neither medical students nor current practitioners are receiving any education and to my knowledge no particular specialty has been designated to see ME/CFS patients.
I am very grateful to Dr. Kamaroff for continuing to support us and thrilled that his article is at the top of what’s trending on JAMA. Much thanks to you, Dr Kamaroff. Matter of fact, a big hug to you and all participants. Highest regards,
Marcie Myers,BSN diagnosed in 1994 at age39.
What is “dauer?” I believe it means quite serious in German. M
There is no treatment Fred. If there were an effective treatment protocol, many of us would be recovered.
The German word “Dauer” means “permanence”, Andrea, ongoing…
I’d love to see a CFS specialist but there are non in my area of Australia. (If anyone know of one in Adelaide, South Australia, please let me know)
There used to be 3 but they retired. Now there is nobody so I’m stuck with a GP who doesn’t really understand, as the Gp I had that received newsletters from the CFS specialist also retired.
There are very few specialists who treat ME/CFS. I was on a waiting list for Dr. Petersen for a year and was then told they were not taking any new patients. Now they don’t even return phone calls. When I contacted Stanford I was told I was too old. If only it was as simple as you think it is.
This is the first article out of hundreds that I actually feel. This guy has come onto something that I feel. I was laying the other day thinking about how deep I fade. I lay down close my eyes and I feel like I’m lapsing into the deepest depths of darkness. My heart rate falls very low and there is hardly breath. It fascinates me that I even wake up. I’ve often felt that one click and I’m gone into a dark thoughtless nothingness where my brain rests quiet and very deep while my organs lightly function continuing life processes. The cognitive factors are unbelievable. They seem to exist as overlays on the brain. Like my brain is wrapped in a cloak that won’t let feelings in. I actually don’t feel during times when I’m flaring worse than usual. I loose feeling and certain senses like I’m shutting down. Yes I think he has it. At least his theory on hyper nation rings very true with what my body wants to do. My body wants to shut down and keep breathing. i had real fight and flight issues. I was under severe stress that I couldn’t get away from. I had to stay in an abusive situation and couldn’t get away from it. Then the switch flipped and my body said hey, your going to shut down cause you’ve exhausted every cell and now it’s over. Yes he is onto something. And yes I have an underlying infection. Chlamydia pnemoniae that I cannot seem to wipe out. I think between my bad life and the infection, my immune system tanked. Now I’m gone. I’m in a dark unfeeling world fighting a body that really wants to go into a healing coma. I need recovery. I need help as we all do. Hope that the research yields solutions soon.
Eat healthier, including anti-viral dark colored vegetables, greens, fruits, berries, and herbs.
Eat a little fruit every 1.5 to 2 hours to heal your overstressed adrenals and balance blood sugars. You will see a noticeable difference within a couple weeks.
Read ‘Life Changing Foods’ by Anthony William.
And his other books.
If you are unable to read & comprehend more than a few pages, the Soundcloud App carries the author’s weekly radio show. Half of the episodes have to do with EBV or CFS, and the other things you mentioned.
Find a holistic doctor familiar with AW’s work.
I just read Renae’s comment to my daughter who has ME. She agreed. That need to sleep is so totally overwhelming and consuming that nothing else matters. It’s a ‘sleep’ like no other, very deep. A state of hibernation? Plausible to me!
I hope they prescribe some very good antibiotics for you to take along with prednisone! Change your diet to natural foods if possible while you’re on those drugs. Have them put you on it for 3 weeks! I know it sounds weird but try to eat a pickle every day to help gut flora with a probiotic! Good luck!
Wendy, Check out Griffith University on the Gold Coast.
5G will cause millions to have ME
What lol?
I’m curious, Paul. Why will 5G cause millions to have ME? Thanks!
Yep. Our immune systems can’t handle it. Not to mention the increase in tinuttitus and neurological overstimulation, etc, etc. We think we can just be electrically charged with no effects.
5G is now what Big Tobacco was in the 40’s and 50’s. Bad news all around, IMO. This guy is *not* my rep by the way. https://www.youtube.com/watch?v=hkDDQqDVsbk&t=173s
Please check the link to the original article. Many thanks for your brilliant journalism in this field.
Thanks! Just fixed. 🙂
Note the comments at the bottom of Komaroff article. One person suggests that the “malaise” appears to be the same as dissociation from PTSD in early childhood. ? Hopefully someone will straighten her out. This PEM term is a mess.
I agree that the PEM term is a mess. I think that patients shoot themselves in the foot when they cling to the word “malaise.” You can’t blame psychiatrists for latching onto the word when Merriam-Webster defines it as “a vague sense of mental or moral ill-being.” Other definitions are no better.
oh I wish that stupid Dutsh speaking docters would read it to! Here, you get the comment, if they do the effort to read it at all what is: no in 99,9% of the cases. Oh, but that is in the US! 🙁 as if it would not count here. Now for years 99% bedridden and getting worse and worse, who should I show it to? My homephysicion who comes once in a while does not read it. Also many equipments to test, they just do not have here. Also for other deseases. Here the goverment still says:GET and CBT. At the latest conference from OMF, at the end, the closing remarks, anthony komaroff says on an question from someone that they rejected ampligen because of some serious side effects. Oh, not that it is all perfect, far from that, but I wished that I lived in the US because there are at least things moving! thanks court! feel 3 days in a row like dying, even heart and breath and swollowing. Thanks for a glimp of hope!
It’s actually possible that Dutch doctors will read this piece. The AMA association made it clear that the journal is read worldwide.
My recollection isn’t that there were a lot of side effects with Ampligen. The studies didn’t show that and ME/CFS experts who have used the drug for years presented a great deal of evidence that side-effects weren’t a problem. As I remember the FDA wanted huge studies to be sure they hadn’t missed something – and Komaroff went along with them.
Other members of the panel – who had no experience with ME/CFS did not. They seemed pretty staggered by the suffering that the patients presented. They pointed to the more immediate need for effective drugs in this population. Given that need they felt it was worth it to give Ampligen a try. That argument apparently did not sway Anthony Komaroff. As I remember he voted against Ampligen on both the efficacy and side effect issues. I can tell you that people in the room were utterly shocked.
We all knew that this was it for Ampligen. The company didn’t have the money to do the big studies the FDA wanted. If it didn’t get through, then, it wasn’t going to get through. That argument apparently didn’t sway Komaroff either. Not long afterwards I was told that the FDA dropped its concerns about side effects.
That’s not to say that Komaroff hasn’t done a lot of good and is continuing to do a lot of good for ME/CFS. He’s quite bravely supported people with this disease from the beginning. Those votes were really something, though…
And he was right.
People can be pushed into talking drugs by punitive social security measures. Having had my illness precipitated by twenty five years of ‘safe’ asthma medication I don’t want to take any more drugs. The drugs destroyed my immune system and left me vulnerable to this illness. But if I can’t work =(currently one day a week after two years off), I’d have to take whatever is recommended in order to qualify for any government support. That’s the only thing that’s more scary to me than staying sick or even worsening. I know that others are on different situations and I respect that — I don’t speak for others.
I remember that; I spoke to the committee advising the FDA. The issue wasn’t safety for those adults who had been taking it. The issue was not whether it was effective for some patients. The issue was how to identify who wpuld have the positive effect.
The definition for the disease was not reliable enough to say it would be effective for all who met Fukuda. There wasn’t a big enough study to prove that. And the research done did not identify what subset, biologically speaking, would benefit.
Plus, there were some comments that this novel agent is messing with the RNA. And although it has been shown safe in adults, there has been no research to show the side effects and possible benefits for pediatric cases, which may still be developing their immune system. And if they approved it, despite the labeling, it would end up being tried on children with ME/CFS.
I think Komaroff’s requiring any drug to meet same requirements of robust research is to help bring our disease in the mainstream. Why should the standards be lower for our disease? I remember the representative on the committee that was for drug industry even said that the studies for Ampligen were not industry standard.
The FDA has certainly relaxed and does relax its standards win diseases where a special need exists. Ironically if Ampligen had been approved the money would have been available to find out who benefitted. While the FDA was on the panel, it’s not their vote which is under discussion ‘ it’s Dr. Komaroff – ME/CFS expert.
Neural Brain Retraining. Ashok Gupta, London. Had CFS, cured. Many being helped. No drugs. Even mentioned in this article, It comes from deep in the brain, check it out, google.
Wow, really 100% cured?
Why isn’t this news spread all over the world so all patients can be cured?
He’s also been done by the UK advertising standards authority for making false claims about success rates of his treatments and he is not medically qualified in any discipline. In any case CFS is not necessarily M. E. and there is evidence that circa 5 percent of sufferers do recover for unknown reasons. See https://www.meassociation.org.uk/2018/04/advertising-standards-uphold-complaint-against-gupta-programme-for-me-cfs-and-fibromyalgia-11-april-2018/
Didn’t Komaroff vote against Ampligen January 2012? I was 70% better on Ampligen and Komaroff voted against it based on efficacy I believe. To hell with whoever it’s helping right Dr. Komaroff? One of Unger’s minions at the time. So instead of working and having a normal life I lay in a bed and take anti- depressants, heart meds, thyroid meds and can barely walk since off Ampligen. I could only afford Ampligen and living in Charlotte for a year. Three weeks off Ampligen I was home bound and sick unable to work. My employer was holding my job for a year. Did y’all forget that Komaroff did that along with Unger? Now he’s a great guy? He’s the reason the FDA wouldn’t approve Ampligen so fuck Komaroff and Unger there not doctors they are demons!
I don’t know why you say we forgot that since it’s clearly reported in the blog!
To everyone’s shock, Komaroff voted against Ampligen moving forward. We thought that at least the ME/CFS experts -those who knew the cost of the disease – would vote for Ampligen going forward. Two of them – Tony Komaroff and Beth Unger – voted against Ampligen. Komaroff’s vote was particularly egregious since he is a doctor who has seen ME/CFS patients and knows what they go through.
Meanwhile two people on the FDA panel who had connection to ME/CFS were persuaded enough by the studies, the doctor’s reports and the patients to move Ampligen forward.
Truly a bizarre situation.
I wrote that komaroff said on the last conference from OMF that there where serious side effects. Just as a remark. I do not know what to believe. But would ron davis let that happen if it was not true? I do not think so. I know I was treated a half year for a so called active chlamydia pneumonia infection with antbiotics and it made me a total lot worse. Many others on antibiotics got worse to. And a few got better or stayed the same. Although so ill, I wished I have never taken the antibiotics. And I even did not have an active infection I heard later, it where anti boddys. But in my half year antibiotics, I got a real infection!I have decades ago lost everything and anything but wished someone had warned me for antibiotics.
Didn’t IV Ampligen cease to be effective shortly after it was discontinued? That’s no good. And extremely expensive. Fido’s to those of you who had the money and support to live in Charlotte fora year or longer. I was not one of them. Much of this is for highly financial solvent patients who have mega support. I do not. Marcie
To everyone: where is Ampligen now?
So far as I know Ampligen is dead in the water. Hemispherx nixed the patient connection that brought so much – that really brought them as far as they – a company the FDA loved to hate because of all their shenanigans – loved to hate.
There is some good news though. Dr. Peterson and Simmaron, Maureen Hanson and the CDC are teaming together to dig into how effective Ampligen is and how does what it does. I don’t know if this will be enough for Ampligen to move forward – the FDA still wants big studies so far as I know – but it will surely be helpful.
Hope to report on that soon.
Really, what do you see in ampligen Cort? Results have been very mixed. I am not saying it doesn’t help some people but the same could be said about several drugs.
I thought they are testing Ampligen on cancer now with good results.
They need to start running these tests & they are not doing these at all. HATS Hereditary Alpha Tryptasemi Syndrome, Alpha Gal Meat Allergy component testing &
full panels of EDS traits & also GSD panels Genetics for Glycogen Storage Disease all types testing
What on earth is a full panel of EDS traits??
Ehler Danlos Syndrome – a connective tissue disease. many of the symptoms from that are ones that I suffer with.
This is a huge breakthrough for all patients with ME/CFS. Having this article published in JAMA gives the illness a legitimacy that will make it accepted by the majority of doctors a patient may see. With an estimated 2.5 million patients affected, the pharmaceutical industry will also turn their attention to treatments that may be even better and less toxic than Ampligen like Viralym M developed at Baylor.
Thank you for the report Cort! Wonderful that there may be some real consensus emerging!
It seems to me that this newest, most focused-seeming round of ME/CFS research (slowly coming into focus over the last few years), including the evidence pointing to a dauer-like state, may be describing what all of us (or many/most of us) with ME/CFS have most in common. (Just as a condition like MS appears to have one end-point in common: demyelination.)
While the more scattered-seeming research (and various clinical observations) from over the years, highlighting various “causes” and “contributors” to the condition, may be locating the various factors that can trigger that state (genetics, viruses, GI dysbiosis, mold exposure, etc.), as well as the primary mechanism of damage (inflammation, neuro-inflammation, autoimmunity, etc.). (Just as a condition like MS also appears to have many various triggers: genetics, viruses, stress, diet, etc., and, a primary mechanism of damage: autoimmunity.)
In other words, the “full” condition of ME/CFS, in total, might turn be a trigger, or triggers (likely a different collection in each person), plus a primarily mechanism of damage (may also be variable from person to person)…resulting in a common “dauer” state: i.e. the “central” condition of ME/CFS.
Theoretically, a holistic solution would therefore be to minimize/resolve the triggers (assuming they are ongoing), minimize/resolve the primary mechanism of damage (assuming it is ongoing) and concurrently help minimize/resolve the dauer state. (Just as in a condition like MS, a holistic approach is to minimize/resolve the triggers, minimize/resolve the autoimmunity, and restore the function/health of the damaged nerves.)
On the other hand, it’s also interesting to think that a state of “dauer” might also just be the most effective way for an organism to survive and attempt to heal from ongoing/stubborn illness/inflammation. In that case, one would need to only (“only”!) help minimize/resolve the ongoing triggers, and the mechanism of damage, and the “dauer” may theoretically release on its own.
(Further spitballing on a side note: Maybe this could even be why someone like Dr. Komaroff might not support a powerful drug solution like Ampligen, as it may not target what he sees as the “central”, or “shared” state of ME/CFS?…only some aspects of some specific versions of it…which might only make it appropriate/safe for some people, and not all with the condition…?)
In other words, a dauer-like state in humans might be another way to describe a “deep concentrated state of healing”. (Or, maybe the only way that we have to describe it! I know of no other.)
Maybe it should only viewed as “pathogenic” when it becomes chronic, and when there is strong evidence/suspicion that the original trigger (and any ongoing/opportunistic triggers/perpetuators) are all fully resolved. Theoretically, an organism could get “stuck” in such a state through some mechanism (like brain plasticity, or some other unknown mechanism), just as we can get stuck in states of chronic pain and chronic stress (both of which serve powerful life-saving functions, and are only “problematic” when the actual injury/situation is fully healed/addressed, but the signaling appears to be still stuck “on”).
Maybe some common and hotly-contested treatments (such as CBT and GET) do successfully release some states of stuck “dauer” (just like a comprehensive modern pain clinic can help resolve some cases of “stuck” chronic pain signaling), but are largely ineffective (even enormously harmful) if they are inappropriately applied to systems that are still struggling to fight the original trigger (infection, SIBO), and/or heal the resulting damage (tissue damage, neurological damage, etc.).
Just my 20 to 30 cents for the day!
Insightful analysis Martha.. lots of good points there.. Your suggestion that similar dauer states might happen as a healthy, short-term/ non-chronic healing response to a stressor made me think again of how, following an initial acute triggering event (pesticide neurotoxin plus possible EB virus exposure plus excitement around new school/move to London – excitement can be a stressor too, apparently and IIUC, any stress can weaken the blood-brain barrier), and long before getting worse and subsequently diagnosed, I had decades of sporadic, brief flu-like illnesses in which all I wanted to do was sleep, almost coma-like, without interruptions, and I somehow knew I would be OK, so long as I could have that total rest/ shut-down time. (Once, in a bizarre sort of Keystone Cops episode, a team of grim-faced doctors arrived in Jeep and tried to drag me out of bed and make me walk around, because someone was convinced I’d taken a drug overdose!)
But these ‘mystery illness’ episodes always resolved within a couple of days; I never bothered with doctors or medication other than perhaps a dose of over-the-counter painkillers. I recall a friend too, who described having occasional bouts of unexplained ME/CFS- like symptoms, similarly taking time off to just zone out for a day or two, and being fine again afterwards.
Maybe this is all irrelevant, or maybe, as you suggest, it’s only when our body/brain’s healthy healing response to some actual neural virus/ toxin/ or other stressor somehow gets stuck, that it morphs into a serious, chronic disease.
That’s so interesting, Elizabeth. My ex, with whom I am still in regular contact, has experienced episodes of acute ME/CSF-like episodes for decades exactly as you described. She calls it being in a ‘conscious coma.’ Episodes generally last 3-5 days. Occasionally longer.
One curious aspect of this is, compared to me (who, when stressed, defaults neurologically to a rather severe anxiety state) she is naturally wired for a much lower anxiety state, whatever her circumstance. This plays into Dr Sharon McGlathery’s RCCX theory: overly empathetic people attract (to grossly simplify) and when under extreme stress they often tip into any number of conditions that fit under the mutable CYP21A2 gene rubric. My ex has rheumatoid arthritis btw, even without the anxiety aspect, but it is intriguing wondering whether she has been protected from full on Me/CFS by not having the gene for extreme anxiety so common to the type described by McGlathery. Incidentally I have a daughter who is nearly disabled with a condition called Mal de Debarquement Syndrome, a balance disorder. When stressed by ill health she also shifts into the same anxiety pattern.
In any case, I finally have what might be an answer to her mysterious episodes. Thanks.
Hi Elizabeth,
Yes, it is interesting to wonder where the line is between illness and healing, because one always goes hand-in-hand with the other.
I may be (in fact most likely am!) totally off-base in all of my specific theorizing above, but this subject of “dauer” always stimulates the thought in me that we (as a collective culture) have no real words to describe directly any states of “deep healing” (no one speaks of convalescence, for instance, or even recuperation…except after something like major surgery). We don’t even have any set way to identify symptoms of healing. (Except that severe fatigue does appear to be the most commonly shared symptom of all illness, and therefore probably of all healing too.)
If any such state were to prove itself able to settle in permanently…leaving us perpetually thwarted in our efforts…then the line between illness and healing would become all the more important to formally locate, and learn how to influence.
But, yes, this was all pure conjecture on my part! Only time will reveal the full truth!
Best wishes,
Martha
Great job reporting, Cort. Thank you so much for continuing to keep us informed. JAMA! Wow! This is huge.
Thanks!
If anything to inform medicos their routine Lab test are inadequate at best!
Do Not Ever EVER tell someone,
“labs are normal, you are just Depressed”
Karma will get you***
Wow up to over 30,900 views. That’s over 3,000 more views in 7 hours.
There will be some humble pie eating going on about now. And hopefully guilt for professional neglect and malpractice.
Am I bitter… after 30 years of eye rolling, snide remarks, and being dismissed… yes I’m bitter.
Actually nurses, they’ve been the worst! I only meet one nurse in all that time who believed me and that was only in the last year. She told me recently she ended up having an argument with her colleagues on whether or no ME/CFS is a biological disease.
So this article is fantastic
Just curious if anyone has seen the Netflix series “Life Overtakes Me.”
Here’s the synopsis:
“In the grip of trauma, hundreds of refugee children in Sweden withdraw from life’s uncertainties into a coma-like illness called ‘Resignation Syndrome.'”
I have fibromyalgia and heavy fatigue issues. My doctor has mentioned CFS/ME but I don’t think I fit the post-exertional malaise category so I’ve told him I wanted to investigate other possibilities (turns out my grandfather is diagnosed with narcolepsy and I apparently have some alleles that increase my genetic risk).
I wish you all the best. I’m sorry that you’re struggling.
Great article, good job by Komaroff to get this published.
I’m just wondering about the meaning of the following statement:
“Provocation studies seek to clarify whether challenges that make
people with ME/CFS feel worse also make a biological abnormality
worse.”
What does he mean by biological abnormality here? That if you don’t have this biological abnormality, you are just assumed to be mentally wrong because you’re unable to walk?
Yes, I think that is what it means, pretty much. It’s basically saying they’re looking to see if there is a correlation between PwME subjectively ‘feeling worse’ (including claiming to be unable to walk!) and an increase in some objectively explanatory, measurable pathophysiology.
Insulting for us, maybe, but absolutely essential for all such correlations with biological abnormalities to be clearly demonstrated, to convince the ME sceptics NOT to chuck us all into the ‘Medically Unexplained Symptoms’ garbage can, where psychologists in many parts of the world are still being enabled to play at trying to make us better with CBT et al, to correct those ‘unhelpful illness beliefs’ of ours….
Before putting Komaroff on a pedestal one might want to recall that he co-authored the despicable Fukuda 1994 “CFS” definition, along with our “friends” Strauss, Sharpe, and others.
We know for a fact that Strauss and Fukuda intended to bury us and the illness, because Strauss put it in black-and-white, on official NIH stationery, no less:
“I predict that fatigue itself will remain the subject of considerable interest but the notion of a discrete form of fatiguing illness will evaporate. We would, then, be left with Chronic Fatigue that can be distinguished as Idiopathic or Secondary to an identifiable medical or psychiatric disorder.
I consider this a desirable outcome.”
http://www.cfidsreport.com/News/14_Chronic_Fatigue_Syndrome_Definition_IOM_Straus.html
There is a much simpler explanation than invoking some unknown ancient evolutionary mechanism. Namely, hypersensitivity to exertion -> neuroinflammation -> fatigue, sickness behavior, and whole slew of neurological symptoms.
People suddenly develop hyper-sensitivity to all kinds of things: allergy, PTSD, MCS, IBS to name a few. It’s not a leap to imagine hyper-sensitivity to myokines and resulting bodily inflammation.
As for the inability to generate energy on the second day, getting sick will do the same thing. CFS patients are getting sick after exercise and therefore unable to perform on the 2nd day at the same level as the first. No metabolic abnormality required.
The key interesting thing about CPET, though, is that it’s a gold standard, reliably reproducible *standalone* medical test. By definition, if the test is repeated, there is an accepted 7% degree of variability for anyone — with or without a medical condition.
However, Staci Stevens’ discovery that ME patients cannot reproduce (within that accepted 7% degree of variability) their Day 1 results on Day 2 demonstrates a metabolic abnormality seen in no other disease.
ME patients essentially “break” the CPET.
Imagine getting a flu on the second day before the CPET test. You wouldn’t be able to perform at the same level. That doesn’t mean you have a metabolic abnormality in general, it just means you got sick.
PEM is often described as flu-like symptom. (I describe it as feverishness without fever). And the exercise-induced sickness is a simpler explanation than some exotic metabolic abnormality for the inability to perform on the second day. The metabolic abnormality does not explain either, at least in a straightforward manner, the neurological symptoms like light sensitivity.
I wonder if Dr.Komaroff could be referring to the ancient metabolite hydrogen sulfide, the earliest gas that drove evolution? See https://www.mdpi.com/2076-3921/8/2/48/htm and
https://www.bioscience.org/2016/v21/af/4407/fulltext.htm.
Is there anyway to know how many medical professionals alone read it? I would bet a fair number of those clicks are from patients.
I had brain scans done at NYU and they came back grossly abnormal. I was told I had widespread neuroinflammation or clinical encephalitis. IVIG and other major treatments did not help so I’m stuck wondering what to do. I support this theory. But what can be done?
Probably nothing other than rest.
https://www.ncbi.nlm.nih.gov/pubmed/24669820 suggests that Curcumin is effective in reducing microglial activation in brain inflammation. I tried a supplement, but didn’t have any effect on my CFS.
Christians – I was diagnosed with CFS in 2008. Two years ago I was also diagnosed with a muscle disease and in Feb., Mar., and Apr. of this year I had IVIG therapy for the muscle disease. This in fact made me more sick. My rheumatologist posited that it may have caused intracranial hypertension. I had a brain mri done last week. I will get results today. It is discouraging when once again I can’t “tolerate” what is classified as “well tolerated.”
Ouch! Good luck TKKS!
I read the article and was relieved to see that it was an “opinion piece” not actually a scientific article. It would be just another appalling example of how far Human medicine has fallen if such speculation had been accepted in JAMA as an actual peer reviewed article! Still it’s great to see anything on CFS get into the mainstream medical community for discussion.
MarthaLauren… “Maybe it should only viewed as “pathogenic” when it becomes chronic …” I and most people I know who have this disease have had their lives decimated by it for years if not decades. I get your point about the body trying to keep itself alive in the best way it can. I just have to say, it’s chronic!
I agree with Matt, f*** Kamaroff. He has an awful lot of making up to do for that damning Ampligen vote. In that one vote, so many of us were consigned to a lifetime of disability. I’m glad about the JAMA article. Its just that I’m 66, and I don’t have much hope of a cure happening in my lifetime. If Ampligen had been approved, I might have had a decade or so of decent quality of life before the end.
Hi Sarah,
Absolutely, ME/CFS is a chronic condition. (I know that all too well myself.) I’m sorry if that point was unclear in my wording. (I was trying to portray a complex set of ideas and may have come up short.)
I was really only intending to speak to the specific state of “dauer” (which, as I understand it is still mostly theoretical, with some points of data surfacing in the research that seems to support it), not to ME/CFS, generally.
I was mostly wondering aloud (because I find it both interesting and confusing)…if dauer, or any kind of “system shut down” proves to be a player in the disease, if it will – in and of itself – prove to be mostly pathogenic, or mostly protective…? In the part of my comment that you reference, I was wondering if a dauer state will ultimately be considered mostly pathogenic only if it is found to be chronically active outside the ongoing influence of a “good” reason for it to continue (such as infection, inflammation, autoimmunity, etc.)
…But, on the other hand, maybe it will turn out to be a combination of equal parts both (both protective, and pathogenic). (Autoimmunity can be viewed that way, too: as our immune system attempts to protect us, it hurts us too.)
Hopefully that is more clear. If not, please excuse my remaining blunders: I do find this a difficult format for complex subject matter. (And ME/CFS is certainly that.)
Best wishes,
Martha
ME/CFS recovery stories with Ayurveda and Panchkarma can be found here.CFS from Ayurveda Perspective.
http://ayurveda.alandiashram.org/ayurvedic-treatment/chronic-fatigue
I have been ill with ME/CFS for 37 years and I have found enormous benefit from Ayurvedic medicine over the past 9 years. If I do an annual panchkarma at a very reputable clinic, take my herbal medicines daily, watch my diet, and don’t over-exert, I can be somewhat functional, working 2-3 hours a day, able to run short errands, even travel occasionally. If I do a too-short panchakarma, try to do too much, or lapse in my diet, I end up house-bound or even bed-bound, as I was for most of the month of April. I just got home from my annual treatment and am already feeling a lot better. It’s a bit of a difficult process and I realize it might not work for everyone. It’s also not a cure for me, but it continues to be very helpful.
However, the linked article above is offensive and belittling and I don’t recommend reading it. I’m commenting only because I don’t want readers here to think that all Ayurvedic practitioners are like the one at the link. My doctor is very supportive and understanding, she knows that I am severely ill, and has been very helpful to me.
Thanks for passing that on Don. Glad to hear that you’ve been getting some relief. We don’t hear a lot about Ayurvedic medicine.
Hi Don, thank you for posting this. I have never come across anybody who has tried Ayurveda for ME/CFS. I have been ill for 33 years, also a very long time. I have been three times to India and did panchakarma treatments, and I hope to be able to go again, next year. I live in Austria. Obviously traveling that far is exhausting in itself. I am wondering where you do the panchakarma, Do you ind sharing the name and place of the clinic and the practitioner you refer to, or is that not allowed here?
Almost 51,000 views! I haven’t checked but I imagine that nothing else is coming remotely close.
MarthaLauren, if you check back here, thanks for your response. A good bit more gracious than my crabby one. Thanks!
Read Spinal Cord Medicine : Principles and Practice, editor in chief Vernon W. Lin , MD, Ph.D. With 8 MD associate editors. ( 1,043 pages) Every single symptom/lab test anomaly we have can be found in people who have had spinal cord trauma of some degree – including multiple immune , inflammatory, hormonal anomalies, dysautonomia. About 1/2 of SCI patients have problems with thalamus ( brain) dysfunction. So, the brain is also involved. Also there is disordered sleep and fatigue in SCI people. Remember that spinal cord trauma does not always result in paralysis.
So what could be causing spinal cord trauma : overt injury, various viruses ( remember what the polio virus did), various microorganisms, abnormal CSF pressures due to craniocervical issues, tension on the spinal cord by an unstable sacrum with/without connective tissue issues. It was neurosurgeon Shokei Yamada who demonstrated dysfunctional mitochondria (cytochromes ) in spinal nerve cells which were under tension, ie Tethered spinal cord.
Would love to write more about this, but just too tired. ❤️
If there was a SCI what do you suggest for a patient with ME?