The wind blew like mad all four days of the conference. Maybe those are winds of change…
A sense of excitement and hope I hadn’t seen before pervaded this conference. More than anything else, this was a conference of possible beginnings. Fields of inquiry such as metabolomics are being opened up that promise much. Time, of course, will be the great arbiter, but right now hope is in the air.
Dr. John Whiting, who’s been attending these conferences for years said it rather feels like the Berlin Wall falling – things seem to be dropping into place. Let’s hope so. One thing seems sure; the next year or two are going to be exciting. Dr. Fluge’s statement, “We’re just scratching the surface. Give us a year.” suggested much more is to come.
As new possibilities for understanding the energy problem in ME/CFS emerge, using exercise as a stressor to characterize the effects of energy depletion in ME/CFS are on the rise. Those studies continue to underscore not just how impaired the energy production system is in ME/CFS, but how many ways it can be impaired.
Before that – a note of thanks to an organization we probably too often take for granted. This conference – the 12th conference the IACFS/ME has hosted – brought patients, doctors and researchers from around the world to discuss and collaborate on this disease.
It didn’t have to be. Fibromyalgia, with several times the number of patients, several drug approvals, and much greater public recognition, doesn’t have conferences like these. For whatever reason, that field hasn’t had two figures like Daram Ablashi and Orvalene Prewitt, who, way back in 1990 (when ME/CFS prevalence figures were ridiculously low), declared that this disease deserves a professionally produced scientific conference.
Twenty-seven years later, a still perennially cash-strapped organization run entirely by volunteers keeps finding ways to put them on, giving patients a chance to meet up, doctors to learn and researchers to collaborate. Relationships have been forged that would never otherwise have occurred.
So thanks to the volunteers, now and past, of the IACFS/ME for believing in ME/CFS and devoting your time and energy to ensuring that the community has a place to come together.
(Now let’s do it every year :))
The IACFS/ME 2016 Conference Overviews #1: Energy and Exercise
Metabolomics and Energy
Dr. Fluge : Plenary Session – B-lymphocyte depletion and disease mechanisms in ME/CFS
Dr. Fluge, it turns out, was onto the metabolomic connection in ME/CFS well before most of us were. Struck by the McGregor/Armstrong group’s past work in Australia, he initiated a metabolomics study sometime in the past year. Then he appears to have initiated another study (a gene expression study) based on that study. Plus, he’s been examining the effects of ME/CFS patients’ serum on the energy production in their muscle cells. The man is nothing if not busy.
Fluge stated that symptoms in ME/CFS could easily be caused by defects in the energy production process, and cited both the anaerobic exercise work done by Workwell and Naviaux’s metabolomics work. Like Naviaux, Fluge asserts there’s nothing wrong with the mitochondria; they’re not broken or damaged – they’re simply turned off. That’s probably good news given how complex the mitochondria are.
But how does the success with Rituximab fit into this energy breakdown? Very easily it turns out. It simply requires an immune attack on the mitochondria. Rituximab could, by knocking down B-cell activity, be stopping the production of the antibodies that are whacking the mitochondria in ME/CFS.
Something in the blood could be causing ME/CFS
How did Fluge figure out that the mitochondria are not to blame? The same way Ron Davis did. Both exposed cells from healthy controls to the serum from ill ME/CFS patients – and watched those healthy cells poop out. Then when they put ME/CFS cells into healthy people’s serum, they turned into healthy cells. Something in the serum of ME/CFS patients is knocking the heck out of their cells.
Ron Davis will begin bombarding those cells with different factors to see if he can figure out what in their own serum is causing their energy production to poop out.
Neither Fluge nor Davis knows what that is. It could be autoantibodies or it could be something else. Fluge suggested that a subset of aberrant B-cells producing these antibodies could do the trick. Fluge and Mella have apparently been searching for autoantibodies for quite a while, but Davis isn’t surprised that they haven’t found them yet; it’s not that easy to do.
The key may be something called the pyruvate dehydrogenase complex (PDC). Both the Davis Open Medicine Foundation and the Fluge/Mella groups appear to be looking intently at the process of pyruvate metabolism. The end product of glycolysis is pyruvate which then gets altered by the PDC complex so that it can be used in citric acid cycle and aerobic energy production. It’s essentially the bridge between anaerobic energy production and aerobic energy production.
Glycolysis is the part of the energy production process the Australian 2015 metabolomics study suggested was broken in ME/CFS. If pyruvate doesn’t get produced or isn’t broken down properly, aerobic energy production gets stuck in first gear; it’s simply won’t have the resources to get moving. Looking at a diagram, Christopher Snell of Workwell poked a finger at the point where energy production makes its rather momentous shift from anaerobic to aerobic energy production, and said that’s where we always thought the problem occurred.
If I have this right (hopefully), then problems with glycolysis then – not aerobic energy production per se – but the part of the energy production cycle that provides the resources for aerobic energy production may be a key in ME/CFS. It’s possible that the aerobic part of the energy production process is not damaged in ME/CFS; it’s just starved for resources.
Pyruvate dehydrogenase is a main player in carbohydrate metabolism; if carbs aren’t available or something is wrong with PDH, it gets down-regulated and fatty acids are used as an energy source. That’s what the Australians’ data suggest is happening in ME/CFS.
It’s also, as the Aussies pointed out, similar to what happens in starvation. In starvation, the level of PDK enzymes (pyruvate dehydrogenase kinase) increase as the PDH complex stops muscles from using glucose as a fuel and shifts towards using fats and amino acids. Fluge and Mella’s unpublished gene expression study suggests a similar pattern is happening in ME/CFS. It also found that men were more likely to grab amino acids from their muscles to fuel glycolysis but women had more trouble breaking down pyruvate to acetyl-CoA.
Genetic problems with pyruvate dehydrogenase do suggest that something like ME/CFS can occur. They are associated with an abnormal buildup of lactate, low energy and severe lethargy. Pyruvate dehydrogenase has also been pegged as a possible factor in primary biliary cirrhosis – a disease Julia Newton has studied extensively – which shares similar fatigue characteristics with ME/CFS.
Fluge warned that the results are preliminary. We certainly have to be careful. We’ve had several instances of very promising work not pan out recently. Some of Dr. Newton’s very promising work was apparently recently upended, and ten years of Dr. Natelson’s work went down the drain as well. Both published several studies with positive findings until a larger study indicated the work was all for naught.
It’s encouraging that both Fluge and Davis, the Aussies, Hanson and Naviaux are finding similar broad patterns of hypometabolism. Much more is to clearly to come. “We’re just scratching the surface”, Fluge said. “Give us a year…” and we’ll know much more.
POSTER: A Metabolomic and Genetic Analysis of Post Exertional Fatigue in ME/CFS
Neil McGregor was clearly in demand at the conference. His fingers danced in the air as he described the metabolic breakdowns present in ME/CFS.
This serum, fecal matter and urine metabolomics study found that post-exertional fatigue with an adenosine product called hypoxanthine in the serum and uracil in fecal matter. Hypoxanthine should not be showing up in high levels in the serum; its presence there suggested that it was not being transported from the gut to the kidneys where it should be reabsorbed.
An assessment of the genes that transport hypoxanthine found five-fold increases in some of the polymorphisms associated with them.
The McGregor abstract focused on the kidneys but hypoxanthines also affect the muscles. In fact, serum hypoxanthine levels are considered to be a biomarker for the muscle fatigue that occurs as a result of intense exercise. With serum hypoxanthine levels significantly increasing after intense exercise, hypoxanthine is considered to be a good indicator of muscle stress.
ME/CFS patients, of course, are not engaging in intense exercise but, the Australians ME/CFS metabolomics data suggests ME/CFS may be similar to starvation, and similar kinds of muscle breakdown occur in intense exercise and starvation. During intense exercise or starvation – if I have this right – purine compounds are broken down to provide ATP for the muscles. That process leaves behind hypoxanthines in the muscles which are then used to reconstitute purines and keep the flow of ATP going. The hypoxanthines should be used up before they have a chance to reach the blood.
High levels of hypoxanthines in the blood or serum means the muscle cells no longer have a base with which to reconstitute their ATP, and have to start that process over again from scratch. That’s a recipe, of course, for lower energy production. Hypoxanthine levels in the blood have become such a hot topic in athletics that some believe they will replace more traditional training measures such as VO2 max and lactate threshold.
The Mitochondria
POSTER: Marian Dix Lemle – Hydrogen Sulfide Redux (Understandng ME/CFS through the systemic actions of the bioenergetics mediator hydrogen sulfide)
Marian Lemle’s 2007 paper proposed hydrogen sulfide (H2) could be driving ME/CFS patients into a hypometabolic or hibernation-like state. At the Institute for Neuro Immune Medicine’s pre-IACFS/ME conference conference, her work took center stage as Dr. Deth discussed mitochondrial functioning.
In her poster Lemle began the process of updating us on the enormous strides in understanding the role H2S plays in the body. H2S regulates the production in the mitochondria, DNA replication and more. Recent evidence suggests it also plays a role in inflammation, blood vessel functioning or “tone”, neurotransmission and cortisol production.
Children with POTS have been found to have increased levels of H2S and breath tests for H2S may be a biomarker for small intestinal bowel overgrowth (SIBO). H2S may also be involved in mast cell activation, muscle problems and disturbed sleep.
Exercise
Cooking With Less Fuel – the CDC/ Dane Cook Multi-site Exercise Study
As Fluge and Mella were digging into the causes of the energy problems in ME/CFS, other studies were uncovering more physiological evidence that they exist. Dane Cook’s CDC multi-site exercise study should go a long way to convincing naysayers that vigorous exercise is a no no in chronic fatigue syndrome (ME/CFS). The worries about the one-day test were for naught; the ME/CFS patients showed significant declines in almost every parameter tested.
The Gist
- An immune system attack on the mitochondria could be causing the energy problems in ME/CFS
- Putting healthy cells in ME/CFS patients blood causes their energy production to drop suggests that what’s causing ME/CFS could be in the blood
- Problems with the pyruvate dehydrogenase enzyme complex could explain much about the energy problems in ME/CFS
- Thirty minutes of submaximal exercise caused reductions in ME/CFS patients brain activity and cognitive capability the next day.
- High hypoxanthine levels suggest ME/CFS is in some ways similar to starvation
- lncreased lactate levels during exercise indicate the more toxic, inefficient and far less powerful anaerobic energy production pathway is used more in ME/CFS
- Reduced heart rates during exercise indicate an inability to appropriately engage the heart during exercise
- Many different types of exercise dysfunction are found in the ME/CFS community
- Problems with hydrogen sulfide could explain many of the mitochondrial and other issues in ME/CFS
- Exercise triggered sympathetic nervous system activity caused about half the ME/CFS patients in a small study to temporarily come down with POTS
- Dr. Fluge asserted that we will learn much about ME/CFS in the next year
Cook found that the point at which ME/CFS patients meet their anaerobic threshold (percentage of VO2 max) was similar to that found in controls (they didn’t go into anaerobic energy production earlier) but every other test for energy production was impaired.
The key check in this test is something called “peak effort”. Peak effort refers to the ability to reach an expected heart rate and a desired C02/O2 use rate (RER). Exercising hard causes O2 levels to drop as muscles snatch up oxygen to produce energy, and levels of CO2 – a byproduct of exercise – to rise. When the correct peak heart rate and C02/O2 are reached, peak effort has been achieved. Not reaching peak effort puts the other exercise findings in doubt; it suggests that a person is simply not trying hard enough.
More of the ME/CFS participants in the study achieved peak effort (81%) than the healthy controls (78%). Their significantly lower peak oxygen consumption (peak VO2) suggested they weren’t able to produce as much energy. Their reduced ventilatory equivalent or volume (VE) suggested they may have had problems getting oxygen to their tissues. Their lower heart rates indicated they weren’t able to get their heart up to speed. The lower lactate levels indicated problems with energy production. The higher RPE levels indicated they were really exhausted by the effort.
Poor physical fitness alone cannot account for these changes. Sedentary people typically have reduced anaerobic thresholds and increased heart rates and ventilatory exchanges but ME/CFS patients displayed the opposite pattern; they had reduced heart rates, reduced VE and normal anaerobic thresholds. That suggests that their reductions are due to biological limitations.
That was a good result, but that wasn’t the main finding. Cook also found that exercise produced significant cognitive issues the next day in ME/CFS patients. That’s not what is supposed to happen; exercise is supposed to improve cognition, not reduce it. In fact, the healthy controls did better on the cognition tests the day after the exercise and the brain imagining tests showed why. Their brains – apparently freshly invigorated after that exercise – were more active during the cognitive testing the next day, but the ME/CFS patients brains were not; one part of their brains was actually less active. Cook indicated that that meant they had to work harder to produce the same result.
If energy depletion is a big part of this disease, then one would expect it to show up in the biggest user of energy in the body – the brain – and it did.
This study has the potential to be a game
Thirty minutes of exercise caused both cognitive declines and reduced brain activity in ME/CFS patients the next day. It did the opposite in healthy people.
changer, I believe. It’s large (n=84), it includes multiple sites, and it’s got the CDC’s stamp on it. It shows that a mere 30 minutes of submaximal exercise can whack ME/CFS patients’ ability to think and reduces their brain activity the next day.
Plus, it shows that despite trying as hard as healthy controls, people with ME/CFS can’t produce as much energy and or get their hearts engaged properly. The lower lactate findings are intriguing; some researchers are finding higher lactate levels but the Australians found lower lactate levels – suggesting that even the anaerobic energy production process is blunted in ME/CFS.
Something New From the Norwegians
The Norwegians’ contributions to ME/CFS – already immense – continue to expand. Katarina Lien of the University of Oslo took exercise testing a step further when she inserted an arterial catheter to assess the levels of lactate – a toxic by-product of anaerobic energy production – every thirty seconds during a two-day exercise test in ME/CFS patients and healthy controls.
Her small study (n=33, all female) added another twist to the exercise testing results in ME/CFS. Lien did find reduced peak oxygen consumption – an indication that ME/CFS patients were not producing as much energy as the healthy controls – on both days, and did find ME/CFS patients’ V02 max drop on the second test, but did not find the drop statistically significant, as other studies have.
Lien did, however, find greatly increased lactate accumulations in the ME/CFS patients during both exercise tests (p<.001). The fact that in the controls lactate appeared at a later time point during the second exercise test suggested that healthy controls actually benefitted from the first exercise session. Lactate’s appearance at an earlier time point on the second exercise test in ME/CFS patients suggested that they were relying more on anaerobic energy production than before.
A similar “left shift in the lactate curve” is found in over-trained athletes.
Not Working Well – Heart Rates Fail to Match Demands
The more researchers dig into energy production and exercise in ME/CFS the more they seem to find. First, problems with V02 max and anaerobic thresholds showed up. Then they found problems with ventilation, and at the conference Mark VanNess of Workwell demonstrated that heart rate is an issue as well.
We know that, particularly at night, resting heart rates can be elevated in ME/CFS, but VanNess asked a very different question: what happens to the heart rate during exercise? It should quickly increase and in the first exercise test it did, but on the second day the peak heart rate the ME/CFS patients were able to achieve was significantly lower than the healthy controls (165 bpm -180 bpm), plus it appeared that the strain of the exercise on the first day caused the ME/CFS patients’ resting heart rate the second day to significantly increase (100-89).
This inability to ramp up one’s heart rate sufficiently in response to exercise – which is called chronotropic incompetence (CI) – is associated in people with cardiovascular disease with reduced quality of life and functioning.
Another exertion problem; ME/CFS patients’ hearts cannot keep up with the demands of exercise.
Because the testing was done on fairly functional people, VanNess suggested that it probably underestimated the true extent of the CI in ME/CFS. He indicated that it’s not due to reduced blood volume.
The Workwell Foundation Presentation at the NIH on Exercise Testing – We’ve heard a lot about Edward Shorter’s unfortunate presentation – apparently initiated by the Nursing Institute (not Nath’s Special Interest Group (SIG) on ME/CFS) on the “history” of ME/CFS. The SIG’s presentations have been decidedly different: Dr. Komaroff, Dr. Peterson, Lenny Jason and the Workwell group have all presented thus far.
Mark Van Ness said he was very pleased with the reception the Workwell Foundation got. He felt that the interest expressed, the questions asked, and the level of expertise regarding exercise present, suggested that the NIH is indeed interested in figuring this disease out. He was also quite impressed with Brian Wallit who emphasized that this disease is biological.
Beyond VO2 Max – Keller on the Other Exercise Intolerant Subsets
The recent emergence of Betsy Keller demonstrates just how important it is to enroll more researchers into working on ME/CFS. In the last three years Keller has published three studies which have validated and expanded upon Workwell’s stunning exercise findings. Like Maureen Hanson, Keller has become a force of her own in this field, and we’re lucky to have her.
In this talk she shed some light on the variability we’ve seen in these studies. Her findings suggested that just about everything that can go wrong in this test does go wrong, at least with someone somewhere in the ME/CFS community. Keller’s evaluation of almost 100 patients indicated that ME/CFS patients can and do respond very differently to two-day exercise tests.
Researchers have generally focused on ME/CFS patients’ inability to reach similar levels of VO2 max or VO2 max at the anaerobic threshold on a second exercise test. Keller’s analysis indicated that these tests are important: 34% and 39% of ME/CFS patients, respectively, showed declines on the next day exercise test in their VO2 max or V02 max at the anaerobic threshold (VO2/VAT). But there’s more to the exercise problems than that.
Problems with autonomic nervous functioning (43%) and ventilation (47%) were prominent as well – plus almost a third of those tested (29%) didn’t display any abnormalities. VO2 max, then, is not the be all and end all in ME/CFS – problems exist in different facets of the energy production process in different patients.
Keller’s more intensive examination of an identical twin pair, one with and without ME/CFS, suggested that exercise probably affects many factors including inflammation, leaky gut and gut microbiome diversity. Plus increased lactate dehydrogenase (LDH) levels suggested – in line with what Fluge/Mella and the Australians are finding – a dysfunction in the pyruvate dehydrogenase (PDH) complex is present.
Keller’s and Cook’s findings suggested that the massive amount of testing done after exercise in the NIH’s Intramural study including immune and autonomic studies, brain imaging and others may reap big dividends indeed.
When Autonomic Nervous System Failure Causes Exercise Problems in ME/CFS
The Baraniuk group at Georgetown University in Washington D.C. is doing some fascinating work. Some people with POTS do quite well with exercise, but Madison Keefe of the Baraniuk group discovered that exercise can have the opposite effect in ME/CFS; it can actually induce a temporary case of POTS.
Postural orthostatic tachycardia syndrome (POTS) occurs when one’s heart rate increases abnormally rapidly upon standing.
Exercise induces temporary cases of POTS in about half of those tested
Rather remarkably, almost half of the 19 ME/CFS patients temporarily developed POTS after exercising. They probably experienced things like dizziness, heart pounding, fatigue, etc., upon standing after exercise. Autonomic nervous system testing indicated that increased sympathetic nervous system activity was probably responsible. (The ME/CFS patients who did not exhibit increased sympathetic nervous system activity didn’t come down with POTS). None of the ME/CFS patients had been diagnosed with POTS prior to the exercise test.
Exaggerated sympathetic nervous system activity, then, is yet another thing to look for in exercise studies. Because POTS simply requires measuring heart rate when going from resting to standing, it’s an easy test to do. It’s a bit surprising that we don’t see more heart rate variability measures done within exercise studies; hopefully this is the first of many to come.
- Coming up next: the Immune System and Brain Overviews, ME/CFS Experts on the Conference and, The Future..
Thanks to the IACFS/ME for their support and to Adria and Karen for their help with housing.
Cort,
Can you do an informal study of ME/CFS readers to see if anyone is has had their CPK tested and share the results. Creatine phosphokinase (CPK) is an enzyme in the body which is usually associated with muscle break down. Mine tends to be slightly elevated around 500 where normal > 200. Based on the cannibalism of muscle theory above, this could be an easy test to see if a similar process is happening.
My CPK levels have been checked three times over the last 3 years, and have been in the normal range.
CPK 143 IU/L (REF: 26-174)
CPK 157 U/L (REF: 55-170)
CPK 170 U/L (REF: 55-170)
p.s. I believe you meant “normal < 200"?
Thanks Erik and you are correct below 200.
I *think* my doctor tested these several years ago.
What I know for sure is that my doctor tested for muscle enzymes that show up on overtraining and that the result was normal (no problem with it).
Had mine tested by neuro doc (not immunologist who did diagnose ME) pre diagnosis & was told it was normal.
Is this the same as serum creatine kinase? I was high on that on a bad myalgia day not on a low pain retest:
510 painful day (no ‘exercise’ or injury)
51 retest
Chris, I had slightly raised CPK (low 200’s) and was referred to an Immunologist who said I probably had CFS after MRI came back normal. I did have a weakly positive ANA at the time also.
Thanks for reporting back on your CPK tests. While we are on the subject of tests, has anyone done the mold panel tests recommeneded by Dr Shoemaker? If so, what were your levels. I did this tests which indicate I have biotoxin illness, but they also seem lower than the scant amount of data I have seen about people with mold illness. He does for example, ATCH, MSH, VEGF, TGEF-B1. Anyway, since Brewer and now the Rey/Klimas offices are testing for mold mycotoxins, I am wondering if some of his treatments could be beneficial. Maybe, this needs to be another article so we can discuss it more fully.
Cort, you do such an amazing job reporting all this for us.THANK YOU!
Thanks Jeanie and thanks for your support 🙂
Cort said:
“Fluge and Mella have apparently been searching for autoantibodies for quite a while, but Davis isn’t surprised that they haven’t found them yet; it’s not that easy to do.”
My money says they have found them and we will hear about it shortly!
I sincerely hope you’re right. You could be – they must be searching for antibodies that effect mitochondrial functioning..That narrows it down.
Oh my goodness, would this be amazing!
How do you make this conclusion? Do you know anything more?
Once again I am happy for you CFS folks but feel doomed as an FM person. It is pretty ironic that a disorder characterized by fatigue has mobilized immensely as you point out, while FM, perhaps keeping a lot of us largely landlocked at home in pjs and bathrobes in pain, is so under researched that we will die with it. The only positive thing for me is that though in retirement I can do none of the things for which I’d planned, I was fortunate enough to have a decent life with tolerable pain for 65 years with only the last three almost intolerable. I feel like a broken record posting this lament but seeing almost zero high power focus on FM is just depressing and there is no where else to complain. My wife is beyond tired of hearing about FM.
Don’t underestimate the power of ME/CFS research to elucidate what is happening in FM, Steve and we shouldn’t underestimate the opposite either. I’ve been diagnosed with both and I think there’s a huge overlap. I’ve been concentrating on ME/CFS recently but there’s definitely interesting stuff going on FM…
I got CFS when I was 26 years old. I am now 65. I was also diagnosed with FM when I was about 35. Fatigue was truly terrible, but I was desperately sick with low grade fever, golf ball sized swollen glands, shooting pains in legs, burning sensation on arms and face, and all the rest that goes with CFS. I felt many times that I was truly dying. And when I got CFS, it didn’t even have that disgusting name I, like many long term sufferers, have been tossed around from Doctor to Doctor, most telling me I just needed to get more involved with life, even though I had two babies to take care of. So, fatigue us just the tip of the ice berg for many of us with CFS. Plus ,like many , I dealt with FM, and Interstitial cystitis. That goes along with CFS many times and it is truly a miserable disease. So , Steve, not to dismiss your suffering, but CFS is much more than being extremely fatigued! So I would count myself pretty lucky if I had only FM to contend with.
I was not trying to minimize CFS symptoms, just found it ironic that CFS patients have apparently mobilized more. I’m afraid that FM, also, has many more symptoms than awful musculoskeletal pain, you can find them enumerated by others in Cort’s forums. It’s easy to think that the financial research pie is is Limited that we are all competing for it the biggest slice…and unfortunately, that’s the truth LOL!
Steve, may I point out that many researchers are beginning to think tha FM and CFS are two sidez of they same coin. It is likely that they are subsets of the same illness. Therefore any progress made on the CFS front are actually made on the FM front as well.
Let’s hope you’re right.
Are there people with FM who have no fatgue, no trouble sleeping, and wake fully refreshed?
From what I have learned, the low ATP causes most the symptoms. It affects the hypothalmus, which disturbs temp.regulation, sleep, thyroid, hormones. In the muscles, it basically causes mild rigor mortis.
The swollen lymph nodes and slight fevers are from the smouldering underlying viruses.
I am so grateful for this site. It is a constant source of hope for me. Thanks!!
Glad to hear it Karen! The research is a source of hope for me as well 🙂
Thank you Cort! My brain would never be able to sift thru the info & summarize it so well! Without your hard work we simply would not realize how exciting the research is getting & without that, hope of science solving this mystery soon would diminish. Instead, it is very alive & kicking!! Big thank you to you & to all the researchers & volunteers that are making solving this beast their top priority!
Thank you so much for the summary. Has the Dane Cook exercise research been published yet? If not, do you maybe have aproximate ETA on it?
I’m afraid I don’t have an ETA on it. It does appear from what I can tell to be finished though.
Hi Cory,
I,too,appreciate everything you do!I have a question about kidneys. I’ve had kidney pain for quite awhile,but never an infection or Dr couldn’t find reason. They’re getting so much worse here lately. Should I be worried? Is there another test they should be doing that they may be unaware of?
Thank You so much☝?
Tracy
I wish I knew Tracey but this was the first time I had heard of the kidneys being possibly connected to ME/CFS. I wish you the best of luck getting an answer. I just encourage you to keep looking – perhaps see a different doctor? – until you get an answer.
Thank you Cort! As always☝?⚞☮⚟
Hi Tracy,
Have they checked for kidney stones? Have you considered parasites? Have you checked to see if your blood is too thick? Hypercoagulation? Have you checked your heavy metal levels? Just some areas to investigate.
Yes! Not sure about the pesticide? I was at Cleveland Clinic this time last yr,I would think they’d check, but the last 19yrs, I would’ve thought alot of things! I have so many problems about EVERYWHERE, this kidney pain has been off and on for quite a few yrs. When it 1st started I had my husband get me cranberry pills, it seemed to help, at least some! Now nothing helps, and it’s been about 2- 3 mths straight? I seriously dont have a concept of time anymore. I’m bedridden/ housebound 90% of the the time (when I have good days, WATCH OUT…I GET A LOL FROGGY ?)…In one yr, I went from 150lbs? down to 134lbs..no reason..now out of nowhere, I’m 172lbs!! There’s something wrong!I have a strong feeling it’s my kidneys. Since my tests are normal? I don’t know what to do??PRAY!! LOTS AND LOTS OF PRAYING☝☝☝
I also feel I’m supposed to help others with this!! My “feelibgs” are usually correct..I can’t help anyone if I’m dead! They’re missing something and I don’t know what it is? I also get meningitis 1 to 2 times a yr! I don’t even go to hospital anymore. I’d rather suffer at home! We’re always in so much pain, when is it serious and when is it not? Sorry this is so long!!! Any suggestions, I’d greatly appreciate it. I’m a wife,a mother of 3 and just became a MeMaw for the 1st time. I watched my kids being raised by the people God blessed me with, if at possible, I Want to be there for my grandbaby.
Thank You!
God Bless
Hi Tracy,
Is it perhaps on top of your kidneys and quite localized? If so, it could be the adrenals. They are located just on top of it. Many people have pain in it with intense adrenaline production and so do I. It increases sharply with increased overexertion and can last quite long if too overexerted for a long time. It can also produce the most intense painshoots I did ever experience.
The type of pain can change in them. They can feel like somebody is trying to remove them, with own hands, to kinda a heartbeat, electricity..like a big snapper!!! You remember those? but must the humming part…just waiting for the shock!! Does that make sense, AT ALL?
Also, what triggered mine was a staph inf in 1998, in my bladder! I’ve never had a bladder Inf And my bladder has been, just not right. I happened to see in the Dr notes of 1998, interesting she says increased urination in flare up! My dad is also sick btw, last 21yrs. Pneumonia triggered his, 13days after an eye surgery. He woke up one day, sick? I woke up one day, sick! His sister is 100% bedridden, can only move her eyes. She was diagnosed with MSA. His baby sister passed at 49yrs old, his baby brother is a mess. My grandma was sick (We did think it was in her head, I’m not going to lie? She didn’t get to hear, I BELIEVE EVERY WORD GRANDMA, I BELIEVE YOU. Because I know how important that is! Her mother was also sick.
My dad doesn’t get the meningitis, I don’t think sore throats? But we’re so much alike. I’m the only One whose been diagnosed with Myalgic Encephamyalitis/ chronic pain syndrome, it was also the 1st time hearing the words M.E. a yr ago last week! I haven’t been able to find a Dr who has even heard of it. When I’m desperate enough to go to a hospital, just for them to look at me like I’m an idiot, I also have seizures, they want to know, WHAT AM I ON? I’m not on ANY pain meds, but I can def sound like it. They ask me, well what do you want us to Do? And judge me for being in and out of hospital since I was 23yrs old. I’m 42. I’m tired, really tired!
Hi Tracy,
You might want to check your environment for toxic molds, because kidney pain is one symptoms that many of us ME/CFS patients have when we are exposed to them.
Does the pain ever go away when you are in a different environment?
Tracy – I had kidney pain for a while, particularly on waking. I discovered I was very dehydrated, and haven’t had issues with that since drinking lots more water + salt.
Tracy Duncan,
Hope you see this. Yes, I have suspected kidney involvement for some time. I have pain on the left flank. Just recently got dx with chronic medical kidney disease in left kidney only – via ultrasound.
It is very important to be checked for reflux from the bladder up the ureters to the kidney. This takes a sophisticated urodynamic study.
Dr. Paul St. Amand wrote about kidney issues in FM years ago. He thinks that we have some kidney issue that prevents the proper excretion of phosphates by the kidney into the urine. Supposedly his theory was disproven, but I think he may have a point. long story.
Also, in my support group ( led the group 13 years) there were many reports of kidney differences: polycystic kidneys, one kidney, horseshoe shaped kidneys and so on. I think I may have a floating kidney on the left – i.e.one that was not attached perfectly during fetal development and moves around too much.
I spoke with many patients and families, and looked carefully at my own relatives. I concluded years ago that many or most of us have multiple structural glitches in ourselves and families. It is as if the fetus did not have quite enough metabolic energy to complete the various soft tissue systems. Example: missing lateral sections of vertebrae, hemangiomas in liver/vertebrae, small holes ( foramina in sacrum- called hypodevelopment of sacrum), incomplete rotation of the gut ( expressed as long, redundant colon), hypoplastic maxilla ( upper jaw), and do much more.
WOW!!! Yes,I’m seeing it! I’ve got sick butterflies! Ive known there had to be something wrong! Nobody will listen. I’m seeing a new Dr finally Jan 4th.TY for taking the time to write this.
God Bless!
Tracy, I’ve heard of rare cases of kidney failure or kidney problems associated with POTS/NMH/autonomic dysfunction (frequently goes w/ ME?CFS) causing greatly lowered blood volume. Seek out standard kidney tests from your primary care physician and if no answers there I’d ask for a referral to a nephrologist (kidney issues, diseases and structure) and maybe an endocrinologist…can check all the hormone levels that kidneys act on and need for normal function. Hope that helps!
Thank you!Everything helps!!
I believe very much a Study on hereditary fructose intolerance (HFI) is warranted I have seen countless People Positive with this in CFS/EDS it
would explain the Glucose issues…Also it would explain why the reaction to foods, medicines is so high plus also I here countless
People saying MRI contrast or the Colonoscopy cleansing agent makes one worse even the medicines given prior to this procedure…I even reacted
bad to simple Calcium I switched the medicine also to one with Lemon it made my bowel much worse…If (HFI) is involved it is actually
treatable on an elimination diet lifestyle & avoiding certain medicines or vitamins..One would have to wear a Medic Alert bracelets always
neck/wrist plus put red flags in all Medical files…I know (HFI) is there no doubts the question is what percentage actually has this…
These all jibe with my personal experience. I get dizziness after an “intense” exercise and I always felt that PEMS is an overtraining syndrome for CFS patient. They are all symptoms, however, including metabolomic abnormality. We still need someone to stitch it all together and lead us to the cause. Unfortunately I’m not seeing much activity on that front.
One thing I’m thinking, if we can correlate the blood biochemistry to the symptom levels by monitoring metabolites and cytokines every hour after an exercise for 4 days, that might lead us to pinpoint particular biochemicals, or the sensitivity to them, causing us all the havoc. That was done for athletes, so it could be done with CFS patients as well.
I will volunteer myself ??
PEM doesn’t much resemble overtraining syndrome in my opinion. PEM = symptoms of immune activation, i.e. acute flu-like symptoms; sore throat, muscle pain, fever, malaise, headache, swollen lymph nodes. None of these occur in overtraining as far as I know. It’s hard to see how hypometabolism would lead to these symptoms. Fever alone requires a decently large increase in metabolic activity to sustain.
Hi Weyland, do you have fever as part of PEM? I get a temperature drop and sometimes hypothermia instead.
Maybe it has to do with less or more than 3 years of disease difference Lipkin found? I’m past this one, related to immune under activation according to Lipkin. Are you under or over 3 years of ME?
I get a low grade fever, then it will drop into the 95’s? I get the flu, sore throat, swollen lympnodes, etc. I get horrible bruising..mostly on my legs, but now my arms, sometimes it looks like I have a black eye. It’s crazy ?
It may be true that ots does not involve fever or ache as much. But both pem and ots are more about complete exhaustion and weakness. In my case, fatigue and ache are rather constant, and then I get bed-ridden when I get pem. No fever for me tho.
If you look up the symptoms of ots and cfs/pem, the lists are strikingly similar, including the ans dysfunction.
Studies have shown that swollen lymph glands -once thought to be a core symptom of ME/CFS – are not common; I doubt that fever is as well. ON the other hand muscle pain, post-exertional malaise, increased resting heart rate, insomnia, problems sleeping and concentrating are common to both.
Signs of overtraining syndrome
Jennifer is overtraining. Along with persistent fatigue and a loss of interest in her friends, she may be also experiencing these symptoms of overtraining.
Persistent muscle soreness
Elevated resting heart rate
Increased susceptibility to infections
Increased incidence of injuries
Irritability
Depression
Loss of motivation
Insomnia
Decreased appetite
Weight loss
Experiencing a loss of interest in what you once
Interesting that swollen glands and low grade fever are not a common symptom of CFS. Then why was it described early on as a horrible flu that never went away? Flu has those symptoms.
Those symptoms certainly are important and many probably experience them but studies indicate that other symptoms are more common. It may have been that the early cohorts of patients had more of these symptoms and they became kind of embedded in the ME/CFS gestalt. (I had sore throat for years without having fever or swollen lymph glands; for me now it would be fatigue, PEM, muscle pain, cognitive issues, some orthostatic intolerance, unrefreshing sleep and sensitivities. Then again, I didn’t have a flu-like onset).
The IOM report lists these symptoms as the core symptoms of ME/CFS – Fatigue and impairment, post-exertional malaise, unrefreshing sleep, cognitive impairment and orthostatic intolerance. Other symptoms include pain, immune impairment and infection (fever?) and less commonly, gastrointestinal impairments, Genitourinary impairments, Sore throat, Painful or tender axillary/cervical lymph nodes, Sensitivity to external stimuli (e.g., foods, drugs, chemicals)
Cort, thank you for keeping us updated on the latest information and for always being an encouraging voice on our journey.
“Neither Fluge nor Davis knows what that is. It could be autoantibodies or it could be something else. Fluge suggested that a subset of aberrant B-cells producing these antibodies could do the trick. Fluge and Mella have apparently been searching for autoantibodies for quite a while, but Davis isn’t surprised that they haven’t found them yet; it’s not that easy to do.”
Seems like it would be trivial to start by isolating the IgG from patients blood and introducing that to healthy cells. If that didn’t have the noted effect then it’s unlikely to be an autoantibody affecting the mitochondria. I guess we can assume the Norwegians have already done this if they are spending any time on isolating autoantibodies.
Can any of you knowledgeable people tell me if any of this fascinating research explain why one of my worst symptoms are daily headaches with a tendency to migraine.
I am moderately affected and can walk for a maximum of 25 minutes each day but can feel the energy run out at the end and then need to rest for many hours to get some energy back. Often I don’t have any sign of a headache in the evening and then I sleep quite well mostly but the head pain will start up usually within a couple of hours of waking.
Pam, I’m not very knowledgable as far as the science goes, but when I first got sick, I had horrible, migraine type headaches. I was part of a study at Georgetown University with Dr. Barinuick (sp?) and he was very interested if migraines were a component of CFS and Gulf War syndrome.
My doctor (with CFS experience) gave me a medicine against migraine once he diagnosed me with some form of Orthostatic Intolerance. The medicine was supposed to stimulate the vagus nerve and stimulate blood flow to the head. I got much worse however.
Apparently some for of migraine would be caused by poor or badly regulated blood flow to the brain. Google shows many links with “migraine blood flow”. Many experiments have shown poor blood flow for a prolonged time after exercising with ME too. It could be a potential link?
When i try to walk a while i have to stop before i get to zero energy or i too would need a long rest due to post exertional malaise. I can definately feel worse the next day in some way or other, especially in the am. So maybe you are overexerting? Do you get the migraines if you dont walk till out of energy? For myself i would explore that.
Pam,
Do you know about Chiari malformations. Persistent headache is sometimes the only symptom. Also, persistent headache can be from a misalignment of the atlas/ upper neck and skull base. Lying down changes the spinal curvatures and can stress the upper neck. A traditional osteopath may be helpful.
I read with interest the part about ME/CFS patients cells failing to utilise carbs and glucose but instead utilise ketones and fat.
As a few months ago I read about an interesting ketone drink that was designed for the US
Military to give soldiers extra energy.
Since then athletes have been tested on it with extended endurance, but importantly the metabolites (byproducts like lactate) of exercise in their muscles are greatly reduced. (I have a feeling it could be a metabolite that the body’s own immune antibodies could be mistakingly targeting).
I wondered then if it would be any good to us ME/CFS sufferers. My understanding is the drink works best is for endurance athletes, for a longer release of sustained energy because ketones need oxygen to convert to energy over time, so maybe a nitrate combination with the keytone drink would work well for ME/CFS.
Anyway after reading Cort’s post, I’m now really thinking this combo could well be a help, As to get any extra energy supply would be fantastic!!!
I thought it would be best to post here publicly before anyone greedy says they thought of the combo idea for use in ME/CFS first. Hopefully there’s no patent on it for use in ME/CFS yet and it’s only aimed at athletes. Im not sure how patents work, but I hear if it’s already public knowledge it can’t be patanted?
If that’s the case then we all get to benefit without more added patent costs
Here’s a link to the athlete study. (Imaging it combined with a oxygen increasing drug like a nitrate)
http://www.ox.ac.uk/news/2016-07-29-ketone-drink-gives-competitive-cyclists-boost-altering-their-metabolism#
Hi Cort, what a terrific piece, thanks for bringing it all together, and for putting so much effort into the conference.
I have a pile of questions and hope you might be able to answer some from your notes.
First, a clarification. I wouldn’t normally bother with geeky detail like this, about pyruvate, but will make an exception since it may well prove a key in our illness. Some people might want to skip this biochemistry section:
************** biochemistry alert
Pyruvate isn’t really ‘broken down’ into Acteyl-CoA. Co-enzyme A (CoA) is a separate molecule, that carries most of the pyruvate (the “Acetyl” part of Acteyl-CoA) to the Citric Acid cycle as the fuel that ultimately produces ATP.
The Pyruvate Dehydrogenase complex adds most of pyruvate to CoA, generating Acetyl-Co. Acetyl-CoA then carries the Acetyl group to the citric acid cycle which drives the energy cycle. Plain old CoA is released, which returns to pick up more acetyl from the next sacrificed pyruvate molecule. And so on.
The reason the enzyme is called pyruvate “dehydrogenase” is it takes hydrogen from pyruvate. That hydrogen is donated to NAD to create the high-energy molecule NADH, which itself can be used to generate more ATP, or used as a fuel molecule itself. The reaction also releases CO2, which we breathe out.
Note that this all takes place in mitochondria – pyruvate is produced in the cell cytoplasm through glycolysis, then enters the mitochondria to meet its fate (ultimately, water and carbon dioxide).
******** end of biochemistry
On the subject of pyruvate, you wrote:
“Fluge warned that the results are preliminary. We certainly have to be careful. We’ve had several instances of very promising work not pan out recently. Some of Dr. Newton’s very promising work was apparently recently upended”
Warning noted. Julia Newton had previously talked about her cell culture work that found the problem was in Pyruvate dehydrogenase (PDH) -which would back up these other findings, but this doesn’t seem to have been published. Do you know if this was one of the findings that didn’t check out?
Her key finding was that due to problems with PDH, pyruvate was converted to lactate instead of entering mitochondria to power aerobic respiration. It would fit nicely, but..
OK, going to stop there as I’m out of gas, but I’m afraid I’ll be back with many more Qs. Though no biochemistry, I promise.
Thanks for clearing up the biochemistry part. The chart I saw showed pyruvate going into acetyl COA so I assumed it was transformed into it but nature has other ways of using it 🙂
I didn’t know she had fingered PDH as well. Here are the unfortunate results of some of Dr. Newton’s muscle studies. The grant to fund them began in 2012. I’d really like your take on what this means. It did say that “novel means” were used – so perhaps there was a problem with those “means” ????
https://www.actionforme.org.uk/resources/questions-and-answers/what-is-the-understanding-muscle-dysfunction-study/
Project summary: By Gina Rutherford, Newcastle University
Studies have demonstrated that when CFS/M.E. patients complete relatively low-level repeat exercise, they experience profound muscle dysfunction which is accompanied by acidity in the muscle. This has been speculated to be due to abnormalities within the muscle.[1],[2]
These abnormalities may lead to patients using anaerobic energy-producing pathways, rather than aerobic energy pathways that enable the muscle to function for longer without excessive fatigue. Studies that have reported abnormality have used magnetic resonance spectroscopy (MRS) to measure internal pH of the lower limb musculature in patients.
In this project, muscle samples were obtained from CFS/M.E. patients in an attempt to investigate muscle function in more detail. This involved using novel approaches to measure pH at rest and following electrical impulse stimulation which functioned to experimentally mimic muscular contraction and simulate exercise. Furthermore, other approaches were used to investigate specific energy producing pathways such as glycolysis (anaerobic respiration) and mitochondrial oxidative phosphorylation (aerobic respiration).
During each experiment, the cells were treated with key drug compounds to test the capacity of new drugs to modulate cellular energy production and to investigate the capacity of these drugs to treat peripheral muscle fatigue in CFS/M.E.
Fluorescent dye was used to measure the pH inside the muscle. Interestingly, there was no difference in pH when CFS/M.E. muscle samples were compared to healthy control sample, which contrasts previous work conducted when CFS/M.E. patients performed an exercise intervention .
When specifically measuring glycolytic (anaerobic) activity there was no significant difference in lactate which is produced at a rate comparable to glycolysis or any of the glycolytic parameters measured.
Mitochondrial (aerobic) function was also assessed using a technique called extracellular flux analysis, which measures the rate of cellular oxygen consumption. Data revealed there to be no differences in the mitochondrial function of CFS/M.E. muscle cells compared to healthy control samples. Thus, it can be determined that mitochondrial dysfunction is not the cause of muscle fatigue symptomology experienced by CFS/M.E. patients.
Free radical generation in CFS/M.E. muscle samples was also investigated in this project. Briefly, free radicals are atoms that contain an unpaired electron in their outermost ring, this results in a highly reactive configuration which will readily interact with other molecules to become stabilised, which is potentially damaging to key components of the cell and could lead to cellular dysfunction.
However, the results demonstrated there to be no evidence of elevated free radical generation when compared to control samples. This would suggest that the muscle fatigue phenotype exhibited in CFS/M.E. patients is not related to elevated oxidative stress at the isolated muscle cell level.
This research project did not find any evidence of biochemical or metabolic dysfunction in muscle cell samples obtained from CFS/M.E. patients. This contrasts previous work that has reported muscle dysfunction in CFS/M.E. patients following exercise. Further investigations are required to determine the biological basis of fatigue in CFS/M.E. patients.
Hi Cort,
I read your summary and followed the link. I can’t be 100% certain, but the quote “In this project, muscle samples were obtained from CFS/M.E. patients…” plus the 25000 $ budget led me to believe they did the tests in a petri dish.
If true it was done in a petri dish, that leaves following problem you mentioned earlier: if our cells are put into the blood of healthy people, they are OK. If cells of healthy people are put in our blood, they fail. Putting them in a petri dish may be likewise. Hard to crack disease :-(.
Excellent point Dejurgen! If they were taken out of the blood -they might be fine! I hadn’t thought of that but I imagine that Newton is:)
Thanks for pointing out the AfME write up by Gina Rutherford. The model is taking mecfs muscle cells by biopsy (ouch) and not just growing them in culture, but stimulating them elctrically so that they form myotubles, a kind of crude muscle-in-a-dish system. I think Julia Newton has called this a muscle gym system.
The original pyruvate dehydrogenase finding came from that work, I think. However, Rutherford’s conclusion:
“This research project did not find any evidence of biochemical or metabolic dysfunction in muscle cell samples obtained from CFS/M.E. patients… Further investigations are required to determine the biological basis of fatigue in CFS/M.E. patients. ”
is premature,not least because it was a novel system.
In fact, last year NEwton and co published using this muscle model and found differences
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122982
“Method: Skeletal muscle cell cultures were established from 10 subjects with CFS and 7 age-matched controls, subjected to electrical pulse stimulation (EPS) for up to 24h and examined for changes associated with exercise.
Conclusion: EPS is an effective model for eliciting muscle contraction and the metabolic changes associated with exercise in cultured skeletal muscle cells. We found four main differences in cultured skeletal muscle cells from subjects with CFS; increased myogenin expression in the basal state, impaired activation of AMPK, impaired stimulation of glucose uptake and diminished release of IL6. The retention of these differences in cultured muscle cells from CFS subjects points to a genetic/epigenetic mechanism, and provides a system to identify novel therapeutic targets.”
So here the problem was mainly AMP-activated protein Kinase (AMPK) a key enzyme in the cell that regulates overall energy levels
https://en.wikipedia.org/wiki/AMP-activated_protein_kinase
Which again sounds interesting. Though note the tiny sample and as ever replication is needed.
ps Easy to miss the biochemical nicities – they’re usually/always very dull, and I missed out 90% of the detail as it was.
“I hadn’t thought of that but I imagine that Newton is:)”
Well, I believe she is a very good scientist that does a lot of good work. But she is also a professor, meaning that:
* She became a professor on a different main topic. That is likely still her strongest domain.
* She has to split her time over doing plenty of administration, be a director in a hospital, take care of patients, teach students, go to many comities, write plenty of research proposals to attract funding or prepare them, guide many Phd students, read their publications…
* In practice, when I was a Phd student in a non medical field, my professor had exactly zero hours time to do research himself anymore. He likely had very few time reading new literature himself apart from what his Phd students let him read and correct for sending for publication. Conferences he attended were likely another major source of new information for him.
* So, the actual work on this specific paper is quite certainly done by Phd students Gina Rutherford and Philip Manning. So far there only paper seems this one (google scholar search): https://www.hindawi.com/journals/jar/2016/2497348/abs/. It is a review study with over 100 of references, but at first glance I do not see the paper you mentioned (don’t know exact title/author). If it is not there, it likely wont be taken into account.
Important: they did not seem to have published their research yet. That might still allow for there conclusion “Thus, it can be determined that mitochondrial dysfunction is not the cause of muscle fatigue symptomology experienced by CFS/M.E. patients.” to be changed to “Thus, USING OUR METHODLOGY, …”. Why? Once such a strong statement is made as a main conclusion, it is VERY hard to withdraw or go against it. Mailing the paper you spoke of may help them if they were potentially not aware of it and may leave this road open for us patients. If you dislike to mail them, please post a link to the paper. I don’t mind asking them polite if that conclusion remains when feeding the cells with the patients blood.
Once again, sorry for too long… Fail to be both brief an clear with mindfog.
Thanks DeJurgen – I think you make some good points. A lot of academic researchers have to split their time many ways. Plus some are doctors as well. I imagine that Montoya, for instance, is juggling many different plates including ME/CFS research, toxoplasmosis research, the clinic and probably classes as well.
One wonders how doctors with their heavy patient loads keep up with the research as well.
@Simon: Fig2A shows something else: Phospho-AMPK/native AMPK (= actived AMPK?) is about 40% HIGHER at rest in CFS. Activated AMPK is higher and protective during oxidative cell stress: https://www.ncbi.nlm.nih.gov/pubmed/23688501. Also, alcohol reduces AMPK activity. Many people with CFS react poorly to alcohol = react poorly to less extra activated AMPK at rest?
The lack of increase after exercise may be because activated AMPK already works at top capacity during rest?
Also interesting, there is a link to another suspect in ME, NO: https://www.ncbi.nlm.nih.gov/pubmed/20349036
I have been wondering if the antibodies could be directed against the bacterium Midichloria Mitochondrii and the mitochondria of the patient’s cells are also attacked, because they are so similar. No autoimmunity, but collateral damage…
Thanks Cort. Is there any chance that mold is causing the mitochondria to turn itself off?
In the US Rituximab didn’t have the same results as in Norway. Makes me wonder if there are different environmental factors at play.
Thoughts?
Naviaux has proposed that some sort of insult has caused ME/CFS cells to turn themselves off and hunker down. I would think that mold -given how debilitating it can be – could do that in spades actually.
Cort is right on. The body is like a spinning top that needs to stay in balance; so many processes starting with taking in nutrition and oxygen to make energy and then detoxify the waste products of that energy production. What I haven’t been able to understand is why use Rituximab to KILL B cells when Vitamin D can fix them. By adding Vitamin K2 and magnesium glycinate hypercalcemia can be avoided and the toxin of a chemotherapy drug is not added to the body.
Have you found Vitamin D and K2 to be a cure for your CFS? I haven’t. Also, I don’t believe that anyone says the B-cells are broken and I believe I read where they are not sure why Rituximab works even though it is used to kill off B-cells. One theory could be that latent viral type (retrovirus, virus, enterovirus) have hijacked the B-cells and by eliminating them for long enough the immune system or returns to homeostasis and can then fight things off on its own again.
If free radicals are expected, they can affect cell membranes and evolve hydrocarbons in exhaled breath. Hope NIH or others might fund MenssanaResearch.com in NJ that has looked at hydrocarbons in exhaled breath, and found useful to diagnose lung cancer, breast cancer, radiation exposure. Non invasive test so no blood draws, just exhale into a silver looked bag like a balloon and send to lab for GC-MS analysis.
Similarly, people talk about nitrosation errors, so should look at NO, nitric oxide in exhaled breath, to see if it goes from normal 20-30 ppbv to high, such as in some asthma, or low. Handheld low cost instruments are available for this. High NO might dilate blood vessels and contribute to POTS. Low NO might have other effects. Worth looking at exhaled breath, incl also H2S as mentioned by others, perhaps other compounds.
It’s really interesting how findings about energy are beginning to converge. At the same time, the findings also conflict to some extent and I wonder if that was disucssed at the conference?
Clearly there’s a lot of variation in 2-day results as Betsy Keller pointed out. (Just to clarify “plus almost a third of those tested (29%) didn’t display any abnormalities” – does that mean 29% had no day 2 abnormalities in VO2 peak, AT or any other measure?)
But for me the biggest question is how most studies find that differences with controls show up in the second maximal test, but not the first. This is at odds with patients’ experience is PEM after single, much lesser stressors than a max exertion test, and also with this intriguing finding:
“How did Fluge figure out that the mitochondria are not to blame? The same way Ron Davis did. Both exposed cells from healthy controls to the serum from ill ME/CFS patients – and watched those healthy cells poop out. Then when they put ME/CFS cells into healthy people’s serum, they turned into healthy cells. Something in the serum of ME/CFS patients is knocking the heck out of their cells.”
That’s amazing, and could be a great model for studying what’s going wrong (Nath said months back he wanted to try just this approach in the NIH’s study of using serum to see if it carried something that invoked problems).
But if problems are triggered straight off, and Naviaux and others find metabolic energy problems in ‘normal’ mecfs blood, and maybe glycolysis is up the spout – then why don’t we see big problems in the initial exercise test?
I’d love to know if this was discussed formally or informally at the conference.
I believe the 29% was ANY abnormality at all but we’ll see when the paper comes out. Keller provided a really interesting analysis that the tweets really couldn’t do justice to.
Some studies do find problems in the initial exercise test and others don’t. It doesn’t seem to be as fine-tuned a test as one might want. Keller suggests looking for other abnormalities as well.
Thanks for the 29% clarification, hope won’t be too long before it is published.
Most studies, inc I think all the published 2 day ones, find little on day 1 beside the obv one that patients are less fit than controls. This jars with the recent findings of problems in energy metabolism, and seems a bit more than a fine tuning issue.
Just to be clear, I’m not saying, “study X must be wrong”, but “huh,these results don’t square up, what’s going on?” Could be pretty interesting, but I think it deserves attention.
@Simon: It could be what is measured / how numbers are processed.
If I understand well:
* max exercise means for example 15 min at 2 km/h for ME and 60 min at 8 km/h for control (both must reach anaerobe?)
* metabolites are measured as % of blood volume
Now let’s calculate with fictive easy numbers for lactate:
* let’s call 15′ at 2km/h 1 unit of work; so ME 1 unit work, control 16 units of work
* let assume ME makes 25 ml lactate per unit of work, healthy 10 ml lactate per unit of work
ME: 3l blood, 0.5% lactate = 15 ml initial; produces 25 ml extra; total after exercise 40 ml or 1.33% or 0.83% increase
Control: 5l blood, 1% lactate = 50 ml initial; produces 160 ml extra; total after exercise 210 ml or 4.2% or 3.2% increase
=> So total % and increase in % worse for control, but increase per work much worse for ME in this fictive example.
=> The other tissues, 10’s of kg, also act as buffer to take up lactate.
=> In order to see strong increase in ME, increase per unit of work must be sky high (second day, altered processes due to PEM?)
Just a thought, much depend on actual methods.
Hi,
On the discussion of blood from ME/CFS causing healthy mitochondria to poop out, is anyone aware of any ME/CFS patients who have tried Plasmapheresis, Plasmapheresis is a process in which the liquid in the blood, or plasma, is separated from the cells. In sick people, plasma can contain antibodies that attack the immune system. A machine removes the affected plasma and replaces it with good plasma, or a plasma substitute.
Plasmapheresis was used with early HIV patients with good results but still did not prevent AIDs or death.
thank you once again cort