Laura Pace brought a rigorous and bracing slant to gut disorders in post-viral illnesses
This has been an Institute of Neuroimmune Medicine and Bateman Horne Center month. We started off with a review of the Institute’s recent Conference, then used Dr. Yellman’s (Bateman Horne Center) overview of mast cell activation syndrome (MCAS), then dug into an exercise study from Nancy Klimas’s Institute of Neuroimmune Medicine, and now here we are with a YouTube talk produced by the Dr. Bateman’s Bateman Horne Center.
It featured Laura Pace MD, Ph.D. a neurogastroenterologist and co-founder of the new and very exciting Metrodora Institute which is focused on neuroimmune axis disorders; i.e. diseases like dysautonomia, chronic fatigue syndrome (ME/CFS), POTS, Ehlers-Danlos Syndrome (EDS) and long COVID. Pace is a Medical Board member for Dysautonomia International and Chair of the Gastrointestinal Working Group for the International Consortium on Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders.
Pace and Metrodora are focused on bringing cutting-edge diagnostics and treatments to people with neuroimmune axis disorders. Health Rising will have more on Metrodora later.
The Talk
Be prepared! Some may find Dr. Pace’s critical approach to the gut problems found in these diseases upsetting. She throws cold water on some of the gut therapies that people with these diseases try. She also illuminates new opportunities that can help patients finally get accurate gut diagnoses and points to future possibilities that should help to greatly improve treatments. Her ultimate goal is personalized treatments that work.
First, she gave us some background on the gut and the neuroimmune system.
Two key things to remember are that in the gut, the tissues, neurons, immune and endocrine cells are in close proximity to each other and are talking to each other; i.e. what affects one may affect the others. With regards to the neuroanatomy of the gut, we’re basically talking about the autonomic nervous system (ANS) – a key system in chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, and others. Ultimately, the ANS affects everything from gut motility (the timely passage of food through the gut), to the integrity of the intestinal barrier, to the makeup of the microbiome, and to how well we absorb nutrients.
Dr. Pace noted that studies suggest that 25% of long-COVID patients have gut symptoms (nausea, bloating, abdominal pain, constipation, early satiety, diarrhea, adverse reactions to foods, flushing, and rashes), but she thinks it’s probably higher than that and it’s going to get higher still. Indeed, a progression of gut problems over time is going to be a major theme in her talk. She warned doctors that early symptoms can be mild, but if their patients get worse, they should be re-evaluated.
Pace does not think much of microbiome studies for the simple fact that 99% of them are focused on the flora in the colon or large intestine. The colon’s main function is to help you pass stool from the body – not to break down food and provide nutrients. After it forms what’s been given to it by the small intestine into a stool that’s then passed out of the body, its work is basically done. Her data shows that the stool microbiome does not approximate what’s found in the colon and doesn’t even come close to approximating the microbiome present in the small intestine microbiota.
The small intestine – the longest part of the gastrointestinal system – is where the real action takes place. It breaks down proteins and fats and then passes the nutrients into the bloodstream. Much of the vaunted immune activity that takes place in the gut occurs in the small intestine; it’s in the small intestine where the gut-brain or gut-neuroimmune axis takes place. If a leaky gut occurs, it’s most likely to occur in the small intestine, where increased gut wall permeability is necessary to allow for the passage of nutrients into the bloodstream.
Gut Motility Problems in ME/CFS, Long COVID, and Other Post-Viral Illnesses
Surprisingly, gut motility – the timely passage of food through the gut – has not been assessed in chronic fatigue syndrome (ME/CFS), fibromyalgia, or long COVID. Our digestive system is designed to systematically break down foods in a timely manner, send the nutrients into the blood, and then get rid of the waste. Problems with gut motility appear to be particularly present in severely ill ME/CFS patients who end up sometimes having to be fed through a tube.
Slowed food transit times can create problems with the absorption of nutrients (malnutrition), constipation, diarrhea, vomiting, abdominal pain, problems with blood sugar, and dysbiosis (unhealthy gut flora). Undigested food in your stomach can harden into a solid mass called a bezoar, causing nausea and vomiting. People with very slow gut motility can’t get enough nutrients and may need to feed through a feeding tube. Interestingly, problems with the vagus nerve – which appear to be common in ME/CFS – can lead to slowed gut motility.
Pace showed several other ways that macrophages and gut neurons interact to maintain gut motility. Both support each other, and loss of either will impair gut motility. What starts this process off – whether neuron damage causes macrophage problems or immune cell infiltration damages the nerves – is a major question that needs to be answered.
Noting that mast cell disorders are common in post-viral illnesses, Pace described a kind of feed-forward process. Gut neurons release neurotransmitters and neuropeptides that cause the mast cells to degranulate (releasing histamine, serotonin, tryptase (actually possibly hundreds of factors), which feed back to the neurons, causing them to release more neurotransmitters, etc., causing more and more inflammation – both in the body and the brain.
Gut issues don’t just cause gut symptoms. Inflammatory substances secreted by the gut microbes, which enter the blood and travel to the central nervous system, can produce many of the symptoms associated with post-viral illnesses including fatigue, brain fog, and headaches.
“Moving Way Beyond Symptom Management”
Cutting-edge Diagnostic Tools Required
Diagnosing what’s going on in the gut in these diseases will require leading-edge diagnostic tools. That’s probably no surprise to the many ME/CFS, FM, and long-COVID patients who have frequently been given a clean bill of health by their doctors.
The good news is that these tools have been developed. The bad news is that it’s not clear how readily available some of them are. The goal, Pace said, is “moving way beyond symptomatic management.” and to identify injuries and damage at the earliest stages – when it is most amenable to treatment.
The Smart Pill – A Game Changer
Dr. Pace calls the Smart Pill a “gamechanger’ for diagnostics.
The SmartPill™ Motility Test does appear to be widely available. Pace noted that traditional gastric emptying tests miss the small intestine and a lot of her patients test normal on them. The SmartPill™ Motility Test, however, captures the motility of the entire gastrointestinal system. The capsule is ingested and uses pH readings to show where in the gut it is. It’s inexpensive, easy to use, and better than the past gold standard – which could only be done in specialized centers. Pace called the SmartPill a “game changer” as a gut diagnostic tool.
She mentioned a young woman with POTS, EDS, and MCAS who was told that she needed to be on solid food because her gastric emptying test was normal. The smart pill indicated that she actually met the criteria for “intestinal failure”. While she had rapid emptying in one part of her gut, her small intestinal transit time was 6 hours and her colonic transit time was over 100 hours (average 59). She was not absorbing nutrients and needed to get her nutrition via an IV (TPN).
Confocal Laser Endoscopy
Confocal laser endoscopy (CLE) has actually been around for a while and may be available. It’s clearly much superior to the former gold standard – which analyzed biopsies using white light endoscopy (WLE). WLE is time- and cost-expensive, has low resolution, often misses things (apparently because it relies on biopsies), and requires anesthesia. Pace said the WLE technique will miss injuries found in the deeper layer of the endothelium protecting the gut.
Eating an allergic food caused leaky gut almost immediately
Compare that to confocal laser endoscopy which uses a laser to optically scan tissues, and “provides a magnified, cellular level view of gastrointestinal epithelia”. CLE allows gastroenterologists to peer deeper into the tissues and can be used as a “real-time” tool; i.e. the gut can be perturbed, say, with foods, and the effect of those foods on the gut can almost immediately be seen.
A recent review reported that “advances in CLE imaging in IBD (inflammatory bowel disease) patients may be used not only to better understand the pathophysiology of the disease but also to guide optimized therapy, and thus allow a completely new, personalized approach to IBD management.” On the downside, confocal laser endoscopy has a “narrow field of view and high capital costs and (requires) specialized operator training”.
THE GIST
- A recent Bateman Horne Center webinar featured Laura Pace MD, Ph.D. a neuro gastroenterologist and co-founder of the new and very exciting Metrodora Institute which is focused on neuroimmune axis disorders; i.e. diseases like dysautonomia, chronic fatigue syndrome (ME/CFS), and others.
- Be prepared! Some may find Dr. Pace throws cold water on some of the gut therapies that people with these diseases try. She also illuminates new opportunities that can help patients finally get accurate gut diagnoses and points to future possibilities that should help to greatly improve treatments. Her ultimate goal is personalized treatments that work.
- Dr. Pace noted that studies suggest that 25% of long-COVID patients have gut symptoms (nausea, bloating, abdominal pain, constipation, early satiety, diarrhea, adverse reactions to foods, flushing, and rashes), but she thinks it’s probably higher than that and it’s going to get higher still. Indeed, a progression of gut problems over time is going to be a major theme in her talk.
- Gut issues don’t just cause gut symptoms, though. Inflammatory substances secreted by the gut microbes, which enter the blood and travel to the central nervous system, can produce many of the symptoms associated with post-viral illnesses including fatigue, brain fog, and headaches.
- Pace does not think much of microbiome studies for the simple fact that 99% of them are focused on the flora in the colon or large intestine. The colon’s main function is to help you pass stool from the body – not to break down food and provide nutrients. Her data shows that the stool microbiome does not approximate what’s found in the colon and doesn’t even come close to approximating the microbiome present in the small intestine microbiota.
- The small intestine – the longest part of the gastrointestinal system – is where the real action takes place. It breaks down proteins and fats and then passes the nutrients into the bloodstream. the immune activity in the gut, the gut-brain axis, leaky gut – they are all most likely to occur in the small intestine.
- Problems with gut motility – the timely passage of food through gut is a major problem in these disorders. Slowed food transit times can create problems with the absorption of nutrients (malnutrition), constipation, diarrhea, vomiting, abdominal pain, problems with blood sugar, and dysbiosis (unhealthy gut flora). People with very slow gut motility can’t get enough nutrients and may need to feed through a feeding tube. Interestingly, problems with the vagus nerve – which appear to be common in ME/CFS – can lead to slowed gut motility.
- Diagnosing what’s going on in the gut in these diseases will require leading-edge diagnostic tools. The good news is that these tools have been developed. The bad news is that it’s not clear how readily available some of them are. The goal, Pace said, is “moving way beyond symptomatic management.” and to identify injuries and damage at the earliest stages – when it is most amenable to treatment.
- The SmartPill™ Motility Test does appear to be widely available. Pace noted that traditional gastric emptying tests miss the small intestine and a lot of her patients test normal on them. The SmartPill™ Motility Test, however, captures the motility of the entire gastrointestinal system. The capsule is ingested and uses pH readings to show where in the gut it is. It’s inexpensive, easy to use, and better than the past gold standard – which could only be done in specialized centers. Pace called the SmartPill a “game changer” as a gut diagnostic tool.
- Confocal laser endoscopy uses a laser to optically scan tissues, and “provides a magnified, cellular level view of gastrointestinal epithelia”. CLE allows gastroenterologists to peer deeper into the tissues and can be used as a “real-time” tool; i.e. the gut can be perturbed, say, with foods, and the effect of those foods on the gut can almost immediately be seen.
- A 2019 CLE study, “Many Patients With Irritable Bowel Syndrome Have Atypical Food Allergies Not Associated With Immunoglobulin“, that 50-60% of people with IBS have “atypical food allergies”. Within 5 minutes of the provocation (!), the CLE test was able to identify a reaction – increased fluid pressure/leaky gut) in the upper part of the small intestine. Interestingly, it took 2-6 hours before the symptoms showed up.
- The IBS patients who removed the offending foods from their diet “showed a highly significant, long-term response… up to the 12 months of follow-up.”
- CLE, then, provides the opportunity to quickly assess the effects foods are having on the gut, and clear up many food allergy issues. With symptoms – many of which may not appear to be gut related – showing up hours later, the test – if available – could be a game changer for people with food allergies. (How available it is for that purpose, I do not know.), Interestingly, it appears that eosinophils, not mast cells, were responsible for the food allergies.
- Wheat was the standout allergen with the majority of the allergic IBS patients reacting to it (60.5%). Next came yeast (20%), milk (9.2%), soy (6.6%), and egg white (4%). The authors suggested that non–gluten-related allergens and amylase tryptase inhibitors probably played a large role in the wheat allergy seen.
- For my part over the past year, I recently added wheat to my diet in a large way. At first, I didn’t notice any changes, but slowly over time, I experienced a huge uptick in pain – particularly muscle-related pain – and fatigue. My muscles had become contracted, tight, and painful. Interestingly, I noticed no increase in gut symptoms. Removing wheat dropped my pain levels substantially.
- Dr. Pace asserted that the diagnosis of irritable bowel syndrome (IBS) and small intestinal bowel overgrowth (SIBO) simply means we don’t understand the biology behind what’s happening.
- Dr. Pace is not a fan of probiotics and prebiotics or fecal transplants. Why inoculate the small intestine with bacteria associated with the colon? Hundreds of millions of dollars have probably been wasted, in her opinion – by looking at the wrong compartment. She felt that altering the microbiota without ways to track it was “dangerous” and could lead to longer-term problems. Until we know what’s happening in the small intestine, we shouldn’t do anything to modify it.
- The histamine ingested from food hits receptors on cells that are meant to receive histamine from the gut. At best, that only produces very local effects. Histamine coming from the mast cells in gut tissues that are in close approximation to nerve fibers, on the other hand, can start a systemic cascade of mast cell and immune effects.
- Besides better diets, she suggested removing obvious food triggers – or obvious combinations of foods – that produce symptoms.
- There’s no harm in starting a trial of mast cell-targeted medication. She employs an H2 blocker 2-3x a day, and oral Cromolyn 4x a day. Some people have problems with tolerating Cromolyn, but she can usually get it to work. Patients should remember to slowly titrate it up as it can cause significant mast degradation (and produce lots of symptoms). She uses quercetin if Cromolyn doesn’t work, as she knows what’s in Cromolyn; not so much with plant-derived quercetin. She also uses leukotriene receptor antagonists.
- Her go-to motility drug is pyridostigmine, and then later she may add on Motegrity.
- Coming up – The Metrodora Institute – the kind of Institute we’ve been waiting for?
It turns out, though, that IgE-mediated allergies aren’t the only type of food allergy present. The large (n=155) 2019 German study used CLE to determine that 50-60% of people with IBS have “atypical food allergies”. (One suspects these food allergies may turn out to be quite typical). None of the patients who tested positive for CLE tested positive using a classical food allergy testing regimen (skin prick, serum IgE).
Within 5 minutes of the provocation (!), the CLE test was able to identify a reaction – increased fluid pressure/leaky gut) in the upper part of the small intestine. Interestingly, it took 2-6 hours before the symptoms showed up.
The IBS patients who removed the offending foods from their diet “showed a highly significant, long-term response… up to the 12 months of follow-up.”
CLE, then, provides the opportunity to quickly assess the effects foods are having on the gut, and clear up many food allergy issues. With symptoms – many of which may not appear to be gut related – showing up hours later, the test – if available – could be a game changer for people with food allergies. (How available it is for that purpose, I do not know.)
Surprise! Mast Cells Not Implicated in IBS
Back to the study. Reduced levels of the occludin enzyme, which plays an important role in maintaining gut barrier integrity, indicated that the food allergy IBS patients were indeed susceptible to leaky gut. An examination of immune cells did not implicate mast cells. Instead, it showed that T-cells and eosinophils were infiltrating the area where the damage occurred. Plus, no increases in tryptase levels (from mast cells) were found in the area.
The authors noted that proteins emitted by eosinophils “have been shown to be toxic to the intestinal epithelium and to rapidly induce epithelial barrier dysfunction” and that other studies have found “that increased eosinophil density and, especially, eosinophil activation are the hallmark of atypical food allergies.”
Wheat Shows Up Big Time
Wheat was the standout allergen with the majority of the allergic IBS patients reacting to it (60.5%). Next came yeast (20%), milk (9.2%), soy (6.6%), and egg white (4%).
Why did wheat take the cake when it came to atypical food allergies? It didn’t all come down to gluten. The authors noted that, while, yes, wheat contains a broad variety of potential gluten allergens, it “especially” contains non–gluten-related allergens and amylase tryptase inhibitors that have been shown to promote intestinal and airway allergies in mice with humanized immune systems.
My recent experience left me a believer in the ability of wheat to massively increase one’s symptoms. During my 40 years with ME/CFS, I’ve mostly stayed away from standard allergens such as wheat, dairy, and soy. I was only sure that soy, though, would immediately cause extreme fatigue.
Over the past year – not noticing any uptick in symptoms after test trials – I added wheat to my diet in a large way. At first, I didn’t notice any changes, but slowly over time, I experienced a huge uptick in pain – particularly muscle-related pain – and fatigue. My muscles had become contracted, tight, and painful. Interestingly, I noticed no increase in gut symptoms.
Finally, a light bulb came on and I rather reluctantly gave up wheat – and my pain diminished dramatically. On the very short scale of interventions that have helped with ME/CFS, removing wheat is at the top.
An ME/CFS Connection
As the German group was doing their thing, Armin Alaedini of Columbia was showing that people who did not have coeliac disease but reported symptoms after eating wheat had damage to the gut lining, systemic immune activation, and leaky gut. Once off wheat, he reported their markers of immune activation began to normalize.
Alaedini next assessed whether the same markers of immune activation he found in the aforementioned wheat study were showing up in ME/CFS. Using data from a past study, his findings suggested that about 15% of the ME/CFS patients fit the profile of having non-coeliac wheat sensitivity.
Questions
Poor Descriptors
In what she said was a pet peeve of hers, Dr. Pace asserted that the diagnosis of irritable bowel syndrome simply means we don’t understand the biology behind what’s happening.
Ditto with small intestinal bowel overgrowth (SIBO). The SIBO test – which measures gas production – tells you something is wrong but doesn’t tell you what it is. Pace clearly believes that these are crude designations that only scratch the surface of a complex problem. Treating SIBO with course after course of antibiotics was a mistake, she felt.
A Really Sick Patient
Dr. Bateman asked her about a really severely ill long-COVID patient who meets the criteria for ME/CFS and experiences severe sensory sensitivity and is clear that a lot of her symptoms are GI-related. Even drinking water (I’ve experienced symptoms from drinking spring water) triggers symptoms and abdominal pain and discomfort. She’s lost a lot of weight and has failed most MCAS treatments.
Dr. Pace proposed that an immune-mediated activation of the autonomic nerves in the gut could be producing her symptoms. The ideal – not easy to do – would be to do deep gut tissue immune profiling and look for autoantibodies. She noted that new autoantibodies such as FGR3 are being identified for systemic pain syndromes.
Small Fiber Neuropathy in the Gut
Dr. Pace’s response regarding problems with the autonomic nerves of the gut brought up the issue, at least in my mind, of small nerve fiber neuropathy (SFN). Small nerve fiber neuropathy is found in the skin and eye – why not the gut or other places? Unfortunately, no one asked about the role small fiber neuropathy may be playing in the mysterious gut symptoms found in many people with IBS, ME/CFS, long COVID, etc.
The problem is that assessing small nerve fiber neuropathy in the gut is difficult “because the nerve plexus of interest lies deep within the muscular layer of the gut, where full-thickness biopsies carry a risk of life-threatening complications such as strictures, perforation, and infection.”
SFN in the gut may be present, though. In a recent case study of a woman with recurrent nausea, vomiting, and fainting episodes who had been diagnosed with postural orthostatic tachycardia syndrome (POTS), small fiber neuropathy (SFN), and impaired gastrointestinal (GI) motility, the authors wrote that “given the current literature and our patient’s history, our central hypothesis is that the small fiber neuropathy contributed to gut immune dysfunction and impaired barrier integrity, leading to increased susceptibility to GI-mediated bacterial infections.”
An SFN in the gut might not be a bad thing to have. The encouraging thing about SFN is that if the cause be identified and fixed, the small nerve fibers can regrow…
Probiotics and Prebiotics
It was not surprising to learn that Dr. Pace is not a fan of probiotics and prebiotics either. Why inoculate the small intestine with bacteria associated with the colon? Hundreds of millions of dollars have probably been wasted, in her opinion – by looking at the wrong compartment. She felt that altering the microbiota without ways to track it was “dangerous” and could lead to longer-term problems. Until we know what’s happening in the small intestine, we shouldn’t do anything to modify it.
Dr. Pace is not alone on this. About five years ago a couple of Israeli studies showed that the gut flora in the colon and small intestine differs dramatically and that a person’s response to probiotics depends on the makeup of their flora and the status of their immune system. While some people did respond well to probiotics people with an autoimmune trending immune system failed to.
The studies also demonstrated that wiping out the gut with antibiotics and then replenishing it with probiotics was the least effective way to produce better gut flora. It was actually more effective to leave the gut alone after using antibiotics than attempting to build a better gut flora with probiotics.
Dr. Pace suggested focusing on a healthy diet that reduces processed foods, additives, and emulsifiers – all of which have been associated with gut problems.
Fecal Transplants
Ditto. You see the pattern emerging. Why populate the small intestine with bacteria from the stool? In infections like C. difficle, where you need to overwhelm the bad bacteria, fecal transplants are fine – otherwise no.
One study which consisted mostly of case reports suggested that fecal transplants may help some people with ME/CFS.
Several fecal transplant studies are currently underway in ME/CFS. Find out more about fecal transplants in IBS and ME/CFS below.
Histamine from Foods vs Histamine From Mast Cells
A doctor noted that a lot of his patients are having pretty good responses to diamine oxidase, which is designed to reduce histamine production from foods. He asked if there was a difference between that and the histamine that is produced by a mast cell in the gut.
Pace said these are entirely separate processes. The histamine ingested from food hits receptors on cells that are meant to receive histamine from the gut. At best, that only produces very local effects. Histamine coming from the mast cells in gut tissues that are in close approximation to nerve fibers, on the other hand, can start a systemic cascade of mast cell and immune effects.
Empiric Therapies (Diet, Mast Cells, Gut Motility)
In the absence of specialized testing, what to do? Besides better diets, she suggested removing obvious food triggers – or obvious combinations of foods – that produce symptoms.
There’s also no harm in starting a trial of mast cell-targeted medication. She employs an H2 blocker 2-3x a day, and oral Cromolyn 4x a day. Some people have problems with tolerating Cromolyn, but she can usually get it to work. Patients should remember to slowly titrate it up as it can cause significant mast degradation (and produce lots of symptoms) if increased too quickly. She does not require that it be taken with or without meals but spaces it throughout the day.
She uses quercetin if Cromolyn doesn’t work, as she knows what’s in Cromolyn; not so much with plant-derived quercetin. She also uses leukotriene receptor antagonists.
Her go-to motility drug is pyridostigmine, and then later she may add on Motegrity.
- Coming up – The Metrodora Institute – the kind of Institute we’ve been waiting for?
Health Rising’s Donation Drive Update
Shedding new light on ME/CFS, FM. Long COVID and other disorders is what Health Rising is all about.
Thanks to the 170-plus people who have contributed to Health Rising thus far! I don’t know where we are at dollar-wise but the drive appears to be going well.
This was a challenging blog as Dr. Pace put thumbs down on some of the gut treatments that people with these diseases try. Dr. Pace, though, is a well-published doctor and researcher who brings a new slant to these diseases and new slants are definitely needed. That’s why this blog featured her. If that’s the kind of focus you want, please support Health Rising in a way that’s appropriate for you.
With regards to the pyridostigmine for gut motility, has the interaction with David Systrom’s research been considered (they may not be even remotely similar doses and it doesn’t matter)?
That really stood out for me. I wonder if he’s seeing gut improvements in his patients on Mestinon.
Yes, interesting question, caught my eye too. Mestinon causes side effects in the gut that make a lot of folks unable to tolerate it. I was one of them. Common side effects include stomach pain, nausea, vomiting, and diarrhea
Fascinating article. I was diagnosed with ME/CFS in 1997 by Dr. Sarah Myhill. I have tried everything like so many others
before and since. Management of my symptoms is now my priority. Two years ago following a heart attack I was also diagnosed completely independently with sensory motor polyneuropathy. Which came first the chicken or the egg?
Regarding the gut that’s here question – since it’s clear the autonomic nerves and motility and gut integrity have been impaired and the immune system is involved – one question seems to be whether it started off an autonomic nervous system problem which lead to immune problems or the other way around.
One of her goals is to look deep into the tissues and understand in detail where the problems are. For the most part, we’re just looking at the surface right now.
Yes, non-celiac gluten sensitivity is a real thing. I was genetically tested earlier this year and I carry a gene for celiac disease and a gene for non-celiac gluten sensitivity. Many people in my family carry these genes and we all have to be on a gluten-free diet.
I mean I still have fibromyalgia and chronic fatigue even though I am on a gluten-free diet, but for others it’s a good thing to test and see if removing wheat from your diet makes you feel better.
What I forget to say was that 3 weeks ago I went down with COVID (double Pfizer vaccinated). I spent a week in hospital on a 6 drug cocktail.
Two weeks later I haven’t felt better in years I’m literally bouncing off the walls driving my long suffering wife crazy. I suppose the crash is just around the corner, but I’m enjoying whilst it lasts.
Peter M – what was the cocktail?!!
Hi sorry only just seen the question. But am now able to put this down almost entirely to Prednisone steroid almost overdose.
Interestingly it’s still ongoing and starting to effect me in possible more negative than positive ways. Still it feels good after 26 years to be a little like my preME self. Unfortunately I know from experience that the inevitable crash is just around the corner.
Other medications I’ll look up and Sen later. They are the Spanish peninsula equivalents as I live in the Canary Islands
Thanks Peter – look fwd to hearing of the others.
I too have had to wean off Prednisone because it produced the same incredible energy and freedom from pain.
Every system in my body seems to crave it.
I now spend over $400 per month(!) on all manner of supplements from i-herb in the USA (I am in NZ and fortunately the freight is free) trying to “fix” my gut and stress response….but stress wins every time.
All the best.
These are the drugs I was sent home with but not what I was on in hospital.
I’ll try and forward those in due course
Ciproflowmax 500mg 2×24
Mucovital Sobres 1×24
Prednisona comp 30mg 2×24
Xumadol Sobres 1×8
Pulmicort Turbugaler 200mcg
Casenbiotic 1×24
Has anyone read the patient-to-patient book ‘The Iodine Crisis’? It explains some of the history of iodine being replaced and how bread changed in the 70s (Kristine Anderson – this may be why you noticed a change in wheat tolerance years ago. Apparently iodine deficiency can cause cancer and unusual anemia.) Bromide in bread is banned in other countries. All new to me.
During my last visit, Dr Chia mentioned they’ve seen good results of Covid treatments on MECFS patients. Chia has petitioned the manufactures to allow these for MECFS patients however it is restricted to use by Covid patients (by the government?). He indicated someone (NIH?) is supposed to be doing a study on this. I’m sorry I don’t have better specifics.
That’s good news and thanks for passing it on. I’m sure we will find out the details at some point 🙂
Hi Nancy, do you know what the Long Covid treatments actually are that Dr Chia speaks about? My daughter has been taking Dr Chia’s Equilibrant medication for past 4 months and is a definite responder as told us. She has gone from severe ME/CFS POTs etc bed bound to studying part time and engaging in life again with no PEM, this is after years and years of PEM. It feels like a miracle has occurred. She got sick at 14 and is now nearly 19…its been a long road to appears to be recovery…
Hi Kim, he was referring to paxlovid or remdesivir for extended periods (longer than the 5 days) as a treatment for MECFS. I am also ramping up on Equilibrant. I’m thrilled to hear of your daughters’ success w/ that treatment. Can you tell me what dose she needed to reach that enables her to avoid pem? I am currently at 2 pills/day and continuing to ramp up. I’m improved at this dose, for energy and brain clarity but am still deeply thrown into a crash by my menstrual cycle or by over doing it.
Peter, I am also really curious what those six medications were. Please share if you can!
“Her data shows that the stool microbiome does not approximate what’s found in the colon and doesn’t even come close to approximating the microbiome present in the small intestine microbiota.” A friend who does as lot of reading about SIBO and other intestinal problems recently told me that the small intestine is supposed to be a sterile compartment, i.e. not contain a microbiota at all. Is this incorrect?
I think the microbiome is less in the small intestine actually but here’s what Harvard page says
“In a healthy person, these “bugs” coexist peacefully, with the largest numbers found in the small and large intestines but also throughout the body. “
Thanks, Cort. I have ME and FM with IBS C, D, and BAM (bile acid malabsorption), which I got from gall bladder removal. My gut is a horrible mess and it gets worse as I age. I’m 70 now. I’m gluten-sensitive and I find it interesting that I was born with a wheat allergy, however, wheat didn’t bother me during my youth and younger adult days. Mysterious! This article brings up a bunch of questions to me. I’m going to send it to my poop doctor to see what he thinks. In addition, I was recently diagnosed with a bad case of iron defficiency anemia. The 4-month stint has been horrible with all of the symptoms. It looked like blood cancer of some type, but luckily, no cancer! I was scanned, poked, prodded, MRI’d and tested everywhere with some 70 blood tests and IV iron infusions. I will ask my cancer doc if any of those blood tests would have shown MCAS. This article has definately helped me in my everlasting search to feel better.
I am 74 and have had FM for over thirty years. I also had my gall bladder removed, and I got FM about six years after the gall bladder surgery. I read that gall bladder removal reduces stomach acid which helps digest food, and people without gall bladders often prone to IBS and SIBO. I found some relief by taking some digestive enzymes after meals. In fact, many doctors today often advise post surgery gall bladder patients take digestive enzymes after meals.
Interesting article – thank you! Do you know how much Quercetin Dr Pace recommends at all? I just ordered the Thorne Quercenase after reading your MCAS article as I identified with a lot of the things it covered – glad to see some of the same suggestions here too!
Thank you, Karen. May I ask what kind of digestive enzymes?
I buy them from Swanson. They contain pancreatin, ox bile powder, diastase, papain, bromelain and betaine HCL.
Hi Karen, I have found the same supplements make all the difference post gall bladder. Bile Acid factors, and a Betain, Pepsin and Gentian root combo.
I have also had ME/CFS for 40 years, am 74 now. My gut issues started long before however. Like Cort, I can’t drink water on an empty stomach without nausea.
My dog developed pancreatitis and I gave him the same digestive enzymes for a while before I found a canine approved supplement for him. Work great!
Thanks for your post.
Thanks, Karen! I also use Swanson. I found a gluten-free enzyme with all the ingredients, and they’ve arrived. I’m hoping for a change.
I’m sorry I don’t think I can isolate each individual drug I was given…well not easily, I’ll maybe give it another go later.
The problem is the report is in Spanish and doing the translation is tricky. Interestingly the treatment and diagnosis changed after 4 days from a severe bronchial.
infection to covid.
Very interesting article Cort! Portraying things from a very different angle. Would be interesting to see what those currently researching the treatments she doesn’t believe in, for example Remissionbiome or those conducting FMT studies, think about this.
Yes, indeed – I was thinking of them as I wrote this. She’s a cautious doctor and they are on the opposite side of the spectrum. Both have their own logic for sure.
Hi Cort, I have also had ME/CFS (or whatever this is) for 40 years. When I first was diagnosed, I was having reactions to everything. I could no longer wear the cologne I had used all my life. I was an advertising copywriter and could no long pick up work from print shops where all kinds of chemicals are used. I couldn’t attend “blue sky” advertising meetings where everyone smoked in those days (not me). And along the way I figured out that wheat was contributing to some of my worst symptoms. In those days, you could only get wheat-free bread from Seattle and it was like styrofoam.
My husband always said he thought my problems started in the gut because the horrible headaches I had for the first few years would be helped by a slushy-icy drink suggesting some kind of inflammation in the stomach. (The headaches would also be knocked out by a shot of heparin which is a mast cell stablizer.)
This past year, I discovered Ther-biotic Digestive Enzymes which seemed to relieve many of my wheat related symptoms: fatigue, bowel irregularity and irritability. So I began to add wheat back into my diet in a big way. Now I have muscle and joint aching and increased brain fog in the afternoon…so it is bye, bye wheat again although I will keep taking the enzymes in case I slip off the wheat wagon and because they are useful for other food intolerance.
If you are going wheat free, I suggest the cookbook, “The Gluten Free Gourmet” and the second version too. Every recipe I have made from these books is very good. You just have to get some ingredients that you wouldn’t normally have around the house.
Interesting how it just kind of slips in there again. It makes me wonder about other foods actually. Thanks for the cookbook recommendation 🙂
Most researchers seem to be on the introverted part of the personality spectrum. They are generally not dynamic speakers. This is unfortunate because the information Dr. Pace presented is so important, but hard to follow because of her small voice and speaking too fast (at least for me). I am so glad I watched her video, however, because I am an introvert also, but will be the luncheon speaker this August at the national conference of Vietnam Veterans of America. I am going to practice projection, eye contact with the audience and a pace of speech that listeners of all ages can comprehend. (My husband who used to be a PR director taught me how to make speeches. Never, never read your speech.) All scientists should take speech lessons, because their future funding depends on engaging with their audiences as does mine.
Also from what I’ve read, stool micribiome tests, probiotics and FMT are not even getting at the real action in the large intestine. As there is another world behind the biofilm that is inaccessible.
Would digestive enzymes help? Too simple?
So many thoughts on this article! Having achalasia which has nerve die-off in the esophagus and in studies has showed some improvement with vagus nerve stimulation (long ago study which was abandoned). I also have Ehlers-Danlos which statistically has at least 50% small fiber neuropathy. In my quest for answers had tests for SIBO, wheat and milk allergens and more, EOE–with no positive results. Is there some sort of a relationship here?
Even though I don’t really have gut symptoms, a doctor put me on a diet avoiding ‘molecular mimicry’ foods such as wheat, milk, tomatoes, potatoes, peanuts, legumes and more. No improvement. Dr. Bonilla is now giving me ketotifen (usually used for asthma)–no improvement.
In my own search I have been using proteolytic enzymes, I am getting astonishing results in tissue response. I have had acne since childhood with the resultant layers of scarring–and still have it at age 70. Since using the enzymes my face has cleared except for a few especially bad areas where old cysts are buried deep under layers of scar tissue. Since taking these enzymes, the skin above these areas becomes ‘mushy’ and then the cystic capsule becomes calcified and works its way to the surface–and very swiftly. These areas are healing rapidly too.
Unfortunately I’m not getting equally noticeable results in energy. However this goes to show the very strong connection of the gut to cutaneous tissue.
I would also like to ask Dr. Pace’s opinion on molecular mimicry–valid or not?
Ooh interesting ( and long ) article ! I have had some strange issues on top of my usual moderate ME/CFS in the past 2 or 3 years and initially the symptoms seemed to suggest mold illness, but now that im living in a tent in my garden, avoiding mold as much as I can, its clear that it only helped slightly. I now suspect the origin of my problems is the stomach and i’m looking at Candida, Leaky Gut and SIBO. I plan to do a test for SIBO soon with a new consumer electronic device that can measure hydrogen and methane for the same price as a single conventional lab test.
Is that electronic test device available now for purchase? Thank you.
Yes its called Foodmarble Aire 2, I was thinking about buying a standard test where you breathe into tubes every 20 minutes then send it off to a lab where they check the gas levels in each tube but then I found out about this device which costs around the same amount as doing one of those traditional tests. I’ve had issues with occasional but consistent bloating and periods of high stomach gas since 2020 which was a bad year for me with a lot of stress, I also took antibiotics and was eating different foods than normal, since then I haven’t felt quite myself but I didn’t know why, eventually this turned into many new symptoms that don’t fit with my ME/CFS, including multiple chemical sensitivity, which I suspect is linked in part to a leaky BBB ( supposedly common if you also have leaky gut ).
Thank you
Dr. Pace won my undying love at a dysautonomia conference years ago when she started her talk by saying “I apologize for my field.” 😂 She brings such a refreshing and sharp viewpoint to the gastroenterology field, which in our experience has been entirely unusual.
Ahh! Good for her!
I am glad to hear there may be a more individual specific diagnostic method available now! Thanks for this report.
I have had IgE and IgG blood testing to get some kind of guidance on which foods might be a problem for me as an individual. The IgG was the most helpful. Dropping 32 foods from my diet made a dramatic difference. But for sustainability the GAPS diet methodology and food preparation is the most likely to help in the long run.
The book Wheat Belly has explanations as to how over the last 60 years the food we still call wheat has in fact been subtantially altered with the addition of 3 major proteins which were not in my childhood wheat of the 1950’s. My allergist (not MD but DO) considered wheat and corn to be the big players in problems like inflammation of the joints. This did not occur because of genetic modification but because of multiple, rapid hybridization with unintentional results.
Do they take medicare for insurance? thanks!
Question is simple: Why is full shotgun microbiome analysis not being done to find the unique changes for each person? Each person’s microbiome was different BEFORE the event…. the response would be different for each person. Trying to kludge all of the data into a single model is simple foolishness.
They cite the microbiome and then proceed to ignore a wealth of existing tools for the microbiome, rather work on a novel (and thus patentable) tool/approach.
I am on the waitlist at the Meteodora clinic and just received a note that Dr. Laura Pace is stepping away from the practice she co-founded, as well as from her career in medicine.
Does anyone know what is going on over there? It looked so promising.