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The ME/CFS 2-day exercise test results are unique.
Every once in a while in the chronic fatigue syndrome (ME/CFS) world, we get a really big study, and this is one. For one, it validates and expands upon the findings of past, smaller 2-day exercise studies, and that’s a big deal. The 2-day exercise studies, after all, occupy a unique place not only in ME/CFS but in the medical research world – and that means trouble.
It’s tough overturning paradigms, but that’s what the 2-day exercise studies that the Workwell Foundation initiated in ME/CFS over two decades ago aimed to do.
THE GIST
- Every once in a while in the chronic fatigue syndrome (ME/CFS) world, we get a really big study, and this is one. For one, it validates and expands upon the findings of past, smaller 2-day exercise studies and that’s a big deal. The 2-day exercise studies, after all, occupy a unique place not only in ME/CFS but in the medical research world.
- These types of studies were largely abandoned decades ago after researchers concluded that even people with serious medical conditions were able to duplicate the results of their first day on the second day. It seems that human beings, even when they are very ill, can produce the same amount of energy from one day to the next.
- At least that was the thinking until Staci Stevens and the Workwell Foundation showed, in a landmark study, that was not true for ME/CFS. The results were so shocking that the exercise physiology world essentially ignored them. Since then smaller studies have been done, but what we really needed was a NICE, BIG STUDY, and that’s what we have.
- Thanks to Maureen Hanson and her NIH-funded ME/CFS research center, we have a nice big, well-funded (NIH funded), rigorously produced 2-day CPET study.
- These 2-day CPET studies are crucial because they are the only studies that have definitively shown that intense exercise one day somehow knocks down energy production the next day in people with ME/CFS; i.e. they validate the post-exertional malaise symptom in ME/CFS.
- The study comes at a good time. Another exercise physiologist, Dane Cook, found that after controlling for aerobic fitness, all the problems with energy production that the other studies found disappeared – potentially giving a death blow to a core understanding of ME/CFS.
- This study, which used sedentary healthy controls, took up Cook’s challenge, but after controlling for aerobic fitness, it found the same energy production problems that the studies Cook dismissed found. That is, when asked to engage in an intense but short exercise bout, people with ME/CFS couldn’t produce as much energy, use as much oxygen, last as long, nor do as much work as the sedentary healthy controls.
- The authors also proposed that Cook’s study, which matched some of his female with male participants, underestimated the energy production problems that were present.
- The “pulse pressure” findings suggested that impaired blood flows and oxygen delivery to the muscles probably play a major role in the exercise problems in ME/CFS.
- The findings from the second CPET exercise test followed on the findings from the first. It indicated that the first exercise test had indeed damaged ME/CFS patients’ ability to produce energy in a number of ways. Contrast that with the sedentary but healthy controls who displayed a normal recovery from the exercise and no change in energy production (peak oxygen consumption or peak work).
- The study also found that the first exercise session damaged the ability of the hearts of ME/CFS patients to respond normally during the second exercise session; i.e. the ME/CFS patients (but not the healthy controls) demonstrated chronotropic incompetence.
- The authors also took a shot at the conclusions of the Nath Intramural study, stating that the effort preference findings should not have been applied to the exercise test results and that muscle problems in ME/CFS (rather than the brain) could have contributed to the low exercise results.
- This large study validated, hopefully for the last time, the findings of all the 2-day CPET studies that have gone before. I still remember being gobsmacked at the implications of Workwell’s 2009 2-day CPET finding. As I wrote the blog, “A Crack in the Foundation”, I thought this will change everything. It has been changing everything but much more slowly than I would have thought.
- Now that we have a big, rigorous study whose results cannot be denied, thanks so much to the pioneers who have led the way over the past 25 years. They are courageous people who have bucked the system, perhaps at a cost to themselves. So, thank you so much Staci and Jared Stevens, Chris Snell, Mark Van Ness and Todd Davenport (Workwell), thank you Betsy Keller and her Ithaca group, and Maureen Hanson (Cornell), thank you to the Van Campen, Rowe and Visser team, thank you Ruud Vermeulen and your group, and thanks, more recently, to Jong-Han Leem and his Korean group.
- Thanks as well to over 250 people who have brought Health Rising about 80% of the way to its goal as we look to wrap up the drive shortly!
At least that was the thinking until Staci Stevens and the Workwell Foundation showed, in a landmark study, that was not true for ME/CFS. The results were so shocking that the exercise physiology world essentially ignored them.
Since then, though, ME/CFS researchers have, in mostly small studies, been working at validating Workwell’s initial findings, although one has the sense they’ve really never taken hold outside of ME/CFS. Then again, we’ve never had a big, really rigorously produced 2-day CPET study that’s seemed guaranteed to turn heads. That is, until now.
The Study
The “Cardiopulmonary and metabolic responses during a 2-day CPET in myalgic encephalomyelitis/chronic fatigue syndrome: translating reduced oxygen consumption to impairment status to treatment considerations” study, led by exercise physiologist Betsy Keller, is easily the biggest (and best) 2-day ME/CFS cardiopulmonary exercise study done to date.
The 2-day CPET test is unique in that, while 1-day CPET and invasive cardiopulmonary exercise studies can tell us what happens during exercise, the 2-day CPET studies have been able to show us how exercise one day impacts the ability to produce energy the next day, i.e. it validates postexertional malaise at a core level.
These studies – which require that patients to exercise to exhaustion twice over two days – must be amongst the most difficult to pull off. Not only does the patient have to engage in two short but intense exercise sessions over two days – a big commitment for a person with ME/CFS – but if they’ve traveled, they’ll probably have to book some rest days before they can leave.
Those restrictions made the size and scope of this study (n=151 over 3 locations – Ithaca College (Gerald Moore MD), Weill Cornell Medicine (Susan Levine MD), and Dr. John Chia – unusual. The reason this complex study – which took place over four years – was able to get so large was simple: it got some very nice NIH funding via Maureen Hanson’s Cornell ME/CFS Collaborative Research Center.
Maureen Hanson’s decision to regularly employ exercise stressors in her NIH-funded Center has paid off in spades with this study and others that have moved the ME/CFS field forward considerably. Once again, we see how valuable the NIH-funded research centers and NIH-funded studies can be. Few groups fund studies of the size and complexity that the NIH regularly funds.
Rigorous Effort
Canadian criteria – check; sedentary healthy controls – check; CPET calibration – check.
The authors went to great lengths to dot their i’s and cross their t’s. The patients met the Canadian Criteria for ME/CFS and, importantly, the healthy controls were sedentary. The lead author, Betsy Keller, met with the exercise technicians to “practice the test protocol, confirm calibration and long-term quality control and assurance with biocalibration of metabolic measurement systems.”
This is important as CPET machines can be touchy. AI CoPilot reported that CPET machines require “careful handling and proper calibration” and can be sensitive to things like “patient movement, improper sensor placement, and environmental conditions”. CPET machines, for instance, have to be calibrated for altitude. For Betsy Keller and the exercise physiologists at Workwell (Staci and Jared Stevens in this study), calibration usually requires having the machines tested using a human subject with known readings to make sure they are reading accurately.
In short, we can assume that the ME/CFS patients were real ME/CFS patients and that the cardiopulmonary exercise test was done properly.
A Little Controversy
The two main ME/CFS exercise groups in the U.S. – the Workwell/Keller group working with Maureen Hanson, and Dane Cook’s group that’s been working with the CDC – have been at loggerheads for years.
Early on, Workwell asserted that Cook’s submaximal testing procedure was: a) ineffective at uncovering the aerobic impairments found in ME/CFS; and b) exposed ME/CFS patients to increased levels of stress. For his part, for almost 20 years, Cook has asserted that Workwell, Keller, Vermoulen, (everyone except him, actually) have been assessing their exercise results incorrectly. Their results, Cook asserted, needed to be matched for aerobic fitness.
Cook got similar results to the other studies until he controlled for aerobic fitness. Once he did that – most notably in a recent large CDC exercise study- all the problems with energy production disappeared…
Cook had an explanation for exercise problems in ME/CFS, but it was markedly different. He proposed that metabolic problems at the cellular level were throwing ME/CFS patients’ breathing patterns off. His assertion that the early entry into the anaerobic energy production, the reduced oxygen consumption, the reduced ability to do work, etc., seen during exercise were all incorrect struck at the heart of what we thought we knew about ME/CFS.
On both a physiological and personal level, these findings seemed to make so much sense, but here we were with an issue that needed to be addressed – and which this study finally did by controlling for aerobic fitness.
Were the energy impairment findings during exercise findings a statistical fluke, or were they real?
Results
The First CPET
This study found they were real after all. Even after controlling for aerobic fitness, the Keller group found that during exercise ME/CFS patients overall had a lower capacity to do work, took a shorter time to reach peak effort, had reduced ventilatory function, O2 consumption, CO2 production, and oxygen pulse compared to the healthy controls.
In other words, in contrast to Cook’s results, this study found that ME/CFS patients couldn’t produce as much energy, use as much oxygen, last as long, or do as much work as the sedentary healthy controls.
What gives? Keller et. Al proposed that Cook had his own matching problem. Noting that about 10% of Cook’s samples matched males with females, they proposed that sex differences in oxygen-carrying capacity, blood flows, blood volume, etc., could have caused Cook to miss the reduced levels of oxygenation and energy production that were present.
Pulse Pressure
Decreased blood flows appear to be a major problem.
Next, the Keller group focused on pulse pressure: the difference between the diastolic and systolic blood pressures during peak load; i.e. the point at which the participants’ systems were most stressed. Pulse pressure is an important indicator of cardiovascular health. While an increased pulse pressure can reflect hardening of the arteries, a narrowed pulse pressure can indicate problems with blood flows.
The narrowed pulse pressure found in the ME/CFS patients suggested that “total peripheral resistance” (i.e. resistance in the blood vessels to blood flows) was present. A variety of past findings could help explain why that might be so in ME/CFS. Hypoperfusion (the inability to provide adequate blood flows), endothelial dysfunction (blood vessel problems), reduced stroke volume (blood outflows from the heart), preload failure (inability to load the heart with enough blood), and smaller heart size could all be contributing to problems with blood flows.
This suggested that impaired blood flows and oxygen delivery are contributing to the reduced energy production during exercise they found in the ME/CFS patients. With the focus on energy metabolism and blood flows, we’re right back where we started prior to the publication of the Cook study.
Effort Preference?
With the Cook study apparently out of the way, they took on Nath’s Intramural study next. Noting that the results of the small CPET portion of the study were in line with others, they agreed with the author’s conclusion that autonomic nervous system problems contributed to the results, but there the similarities ended.
Keller et. Al. called the use of the Effort Preference Reward Test (EPRT) used, and the conclusion that reduced “effort preference” contributed to the CPET findings, “misguided”. Noting that the EPRIT test was developed for depression, and that the findings have never been highly associated with oxygen, they also asserted that the small CPET study (n=19) suffered from its own patient matching problems (!).
The jump from the Effort Preference findings to the study’s conclusion that the problem lay in broken pathways in the brain and that nothing was wrong with the muscles was one of the more dicey parts of the study. It seemed to fly in the face of several studies that have found muscle problems in ME/CFS.
Keller et. Al. proposed that problems in the muscles (poor signaling due to vagus nerve problems, accumulation of muscle metabolites, damage to the brainstem) could also explain the reduced muscle activation the Nath study found. Looking at things more systemically, they proposed that both low blood volume and blood vessel dysfunction could signal the brainstem to put the brakes on exercise in ME/CFS.
Plus, their CPET studies don’t show reductions in peak effort. Instead, they propose that ME/CFS patients’ early entry into anaerobic energy production during exercise naturally makes things more effortful for them.
2nd CPET Exercise Test
The sedentary but healthy controls were not affected by the short, intense exercise session; the ME/CFS patients were.
The findings from the second CPET exercise test followed on the findings from the first. From the already low 1st exercise test, the results (further reductions in peak Work (− 5.5%), time to peak exercise (− 6.6%), ventilatory measures (− 4.9% to − 7.8%), heart rate (− 2.6%), O2 pulse (− 4.0%), and rate-pressure product (− 3.4%) indicated that the first exercise test had indeed damaged ME/CFS patients’ ability to produce energy.
Contrast that with the sedentary but healthy controls who displayed a normal recovery from the exercise and no change in energy production (peak oxygen consumption or peak work).
The study also found that the first exercise session damaged the ability of the hearts of ME/CFS patients to respond normally during the second exercise session; i.e. the ME/CFS patients (but not the healthy controls) demonstrated chronotropic incompetence.
In contrast to Cook’s focus on peak VO2 – which assesses the maximum aerobic capacity present (or one’s peak ability to produce energy) – Workwell and Keller have always emphasized the importance of assessing ME/CFS patients at their ventilatory/anaerobic threshold. This is the point at which a person relies more and more on anaerobic energy production. It’s also the point at which toxic by-products from anaerobic energy production start producing pain, fatigue and other symptoms. In other words, it’s the point at which people stop exerting themselves. In their study, ME/CFS patients reached that point at lower levels of energy production, workload, and heartrate.
Cook has been more focused on peak aerobic capacity – the point in the test where someone produces their peak energy levels. That focus makes some sense with healthy controls but ignores the possibility that some people with ME/CFS can produce normal or even high peak levels of energy at some point in the test but can’t maintain them. I know an ME/CFS patient who had abnormally high peak aerobic capacity but who is very low functioning. She can temporarily produce high amounts of energy, but her aerobic window fades quickly – leaving her very impaired.
Conclusion
The largest and most rigorous 2-day cardiopulmonary exercise done to date did a couple of significant things. For one, it validated, hopefully once and for all, the highly unusual problem with exercise that afflicts people with ME/CFS. Exercise almost always makes people stronger, but in people with ME/CFS, intense exercise, in particular, does not. Instead, it damages them. In no other disease to date has a short but intense bout of exercise knocked a person’s energy production system for a loop.
This finding, of course, potentially explains so much about a disease that’s been characterized as a “systemic exertion intolerance disorder”. It helps explain why studies have indicated that people with ME/CFS are significantly less functional than people with other serious illnesses.
I still remember being gobsmacked by Workwell’s first 2-day CPET study way back in 2009. It is still probably my most exciting ME/CFS moment and I vividly remember the title of the blog I wrote “A Crack in the Foundation“. I thought, my god, this is it! Everything is going to change after this study. Legitimacy was just around the corner and we were going to see massive studies to learn about this strange finding – and that didn’t happen. The rest of the world did not sit up and take notice.
Things have been changing, though. ME/CFS researchers took it upon themselves to do more 2-days studies and now we finally have the big study to lay all the objections to rest. Will it change things? I’m sure it will. How quickly? I have no idea.
I think it’s time, though, to say thank you to all the pioneers who plugged away for so many years at resurrecting these difficult tests, and in doing so, paved the way for this study to happen. They are courageous people who have bucked the system, perhaps at a cost to themselves. So, thank you so much Staci and Jared Stevens, Chris Snell, Mark VanNess and Todd Davenport (Workwell), thank you Betsy Keller and her Ithaca group, and Maureen Hanson (Cornell), thank you to the Van Campen, Rowe and Visser team, thank you Ruud Vermeulen and your group, and thanks, more recently, to Jong-Han Leem and his Korean group. (Thanks also to Yvette to alerting me about this study and so many more…)
We’ll see what happens from here.
- Coming up Pt. II – the authors’ treatment recommendations given the low energy state people with ME/CFS find themselves in.
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I think the person’s name you quoted as Vermuelen and Vermolen a few times in this article is most likely “Vermeulen”. I would check and adjust it if necessary. Nothing worse than having your name incorrectly spelt.
Until Betsy Keller did my 2-day CPET testing last year I still questioned if everything was in my head after being gaslit for many years. My results were eye opening and validating. I re-read my results when I start questioning myself again. It still means nothing to my pcp but I’m happy to have found some amazing doctors (neurologist, cardiologist and integrative) that have an understanding of what my body is facing. I desperately hope and pray for a cure one day even though it’s not looking like it’ll be just one thing that does the trick. I am so thankful to Betsy and all who have swam against the tide of the medical system. I’m amazed and brought to tears that there are people out there fighting for people like me and others with ME. Thank you thank you thank you.
Vermeulen was misspelled twice (Vermuelen). (Since we’re striving for accuracy there was no Vermolen in the blog.) I was going to go back and check and forgot.
While I always hope to get the names right, I hope Mr. Vermeulen understands how easy it is for a non-native speaker to misspell a difficult name such as his and accepts my apology and takes to heart my thanks to him for working in this field.
Vermoulen is still there
There is something glaringly obviously worse than having your name misspelled and that’s living with ME/CFS. Please don’t shame Cort when he puts so much work and effort into keeping the community up to date. We all have a level of cognitive impairment. Show dome empathy; be kind.
This double exercise test objectively validates the severe limitations that ME patients have. Disability insurance companies are not happy about that. the correct name is Ruud Vermeulen -:)
My apologies to Ruud for Americanizing your name! 🙂
The other really important of this study is that it hopefully once and for all validates the 2-day CPET as tool for assessing disability. I worried that Cook’s findings would impact that.
That is a relief, as my 2dCPET from Workwell was instrumental in winning my disability case, without even having to go before a judge at a hearing. (That and recording a NASA Lean Test on my HR monitor to show proof of POTS and its effects). Not to mention in clarifying my own understanding of what was happening to me when I did what I’ve always done, push through the pain and symptoms because I thought that was the only acceptable thing for a ‘tough hardworking girl’ to do or way to get stronger again. It was having the opposite effect of course, but so many people are so judgemental and lacking empathy, or are ‘tired too’ or said ‘yeah getting older stinks eh, suck it up we all go through it’. As if they have a clue!
Its hard, especially with my own self-driven workaholic nature, to overcome those voices, thoughts, and patterns, but my CPET results put all of that to bed. I am unspeakably grateful to WW and all the others; with the trajectory I was on of rapidly increasing severity and loss of function, but no understanding of why or what was happening or ability to survive without income, I know I’d likely be in very severe state or dead by now. It was expensive and the travel was tough (I did have to spend a whole week there so I could rest for days before and after the test), but it has been a literal life-saver for me. Thank you all!! And thank you, Cort!
And a big thank you to the patients who took part in these studies and coped with days and weeks of recovery!
I have had this horrible illness for 24 years and I am also very grateful to all the patients who took part in this groundbreaking study (I sincerely hope). And of course to the researchers and doctors too.
I know from having fibromyalgia for 40+ years and being a former athlete in my younger days that this is absolutely the truth when it comes to exercise. My body shuts down after doing any exercise and has over the years. The next day, the next day and the next day, I truly paid for doing any exercise. My husband would say let’s just go for a little walk but after that little walk, I couldn’t walk anymore and my body was in pain. I told myself I’m just out of shape, but I simply couldn’t continue to make the effort to exercise. I always thought it was in my head and could never , understand why I simply couldn’t get “back in shape” without being in pain. Thank you so much for restoring my sense of sanity and all your hard work. Please continue we need your help.
It’s great to see Nath’s and Cook’s studies have been dealt a death blow. Hopefully this large study attracts much more attention globally than the 1st CPET study.
I have always had low pulse pressure since having ME and this gets lower when I’m in PEM. I had sent some measurements to my cardiologist a few years ago but he never got back to me about them.
I look forward to part ll and hearing what they recommend for treatment.
🙂 I was very glad to see that Keller, Stevens, Hanson et al. were able to respond to Cook’s findings and bring back energy production problems front and center. With regard Nath his study had a lot of good findings as well so I wouldn’t say the whole study has been dealt a death blow but obviously there are many questions about the effort preference finding and the use of that test in this disease.
I do think that central fatigue is involved in ME/CFS and there’s evidence of muscle problems as well. My guess is that both the brain and the muscles are involved. To produce the kind of debility that’s often involved in ME/cFS and long COVID – I think it’s going to take a lot!
Yes! A very big thank you to this wonderful group of medical professionals, especially Staci Stevens – a true pioneer who discovered this phenomenon in ME/CFS.
We really owe them a debt of gratitude for continuing to educate, advocate and publish.
Even other exercise physiologists disbelieved it – right up until they witnessed it with their own eyes.
Certainly, the Nath study needs to be understood on a granular basis – some important research in there.
I’m pretty sure Ron Davis said the Nath study’s effort preference findings were “dangerous” (I think they were his words). Given that the grip test was N = 8 (if I recall correctly) making up a new ME/CFS aetiological theory that was in conflict/incompatible with existing research findings was a bold move. And then the patient community copped some flack for being resistive to the theory. Given the dubious history of ME/CFS research (e.g. GET/CBT) I really can’t understand why more questions weren’t raised before publication.
Many thanks to you, Cort. Always you are there informing us of the newest research. We are inspired and given hope because of you.
I hope this paper means the American Heart Association will take notice. I’d like to see plans for this group to be part of the next ACA conference.
I hope this news is published widely in mainstream media, and brings us the validation we have all so long needed from doctors as well as family and friends. I plan to print out the paper and bring it to all of my doctor appointments for the foreseeable future.
Now this is the kind of study that we need! Big enough to be relied on, funded by the NIH, and with sensible conclusions that look at both sides of the picture and consider the whole patient!
Looking forward to part 2 on this, thanks Cort!
Betsy Keller also produced my favourite ME/CFS researcher quote: “Given what we have learned in the past eight years about this illness, it is intellectually embarrassing to suggest that ME is a psychological illness.” (2015).
Said 9 years ago, so it’s even more embarrassing to anyone who still has this view given the 17 years of learning this quote now applies to, and the jump in research since she said it.
Have any tests on just heart rate recovery over 2 days, been done in this context, or does it always take an extended period of exercise on each day, to show a measurable difference between the 2 days?
I don’t know of other tests on heart rate recovery over 2 days, but I just wanted to say that this exercise test (on a stationary bike) typically only takes 8-12 minutes, then repeated the 2nd day.
Each test is the metabolic equivalent of carrying a box of groceries up 1 flight of stairs.
I’m thinking the whole time reading this: Who in Europe should be alerted of theese studies? Having worked at the same clinics as some doctors and reseachers that later involved in long covid … And we have so little research in ME and long covid here in my country.
Recently there was a study published here that exercize could be recommended to long covid patient and that the recommendations should be changed. They found also negative changes in the muscles in those patients with exercize, but no PEM.
We are but a small country in northen Europe, but how I wish we were better of in research on this topic!
LOLA supplement arrived today. Taken first dose. Will report back in 4-5 days.
What supplement is that? Any more info would be appreciated. thanks
Wondering what brand of LOLA you are taking.
Thanks.
Bulk supplements
Thank you for this, Matthias. I wish you well in using this and hope you will keep us posted. I asked about the brand as many are flocking to Bulk Supplements. It seems that it’s probably because it is readily available and not expensive. I’m a bit leery given that many reputable sources have tagged Bulk Supplements as being of questionable quality, poor oversight and at times, not containing the strength of the ingredients it claims to contain. That said, I hope it serves you and that you will offer updates on your experience.
Seeing a few other options including this (capsules):
https://navafresh.nz/products/trexgenics-lornithine-stable-form-as-laspartate-500mg-urea-detox-protein-metabolism-liver-support-60-vcaps-1?gad_source=1&gbraid=0AAAAAoSHFfi5trFE-aDn_0DgT3V6W8MmZ&gclid=CjwKCAjwqMO0BhA8EiwAFTLgIIAOJxy7Rm7u94ZlVxZzpqP_FMOwYZKyREimS_TKMrwWcqq-dUsCeBoCvrMQAvD_BwE
My understanding is that powders are a well used delivery system for amino acids. Would be interested to hear whether people think capsules are more effective.
I just took my second dose. At least no adverse effects! I am not sure how long it would take for positive effects to start showing up. I wouldn’t have thought it would be weeks. I would have thought a few days, since it’s a metabolic process rather than a fundamental system rehabilitation
Yes. I believe powders are best integrated into the body. My reticence is less about the question of adverse effects than whether the anticipated positive effects might be compromised by a product that is not always quality controlled and therefor does not allow for an accurate gauge of its efficacy. Again, wishing you well and do keep us posted.
Fair enough. Have you or anyone else heard of Nutricost?
https://nz.iherb.com/pr/nutricost-l-arginine-l-ornithine-750-mg-180-capsules/139409?gad_source=1&gclid=CjwKCAjwqMO0BhA8EiwAFTLgIOUi5xdrFhWYQ_q8FZiOZW-Wd2BoPwUx_-bLlvoYCaMf6lUeZhVmQhoCT7MQAvD_BwE&gclsrc=aw.ds
I’ve heard of Nutricost. I find it a bit dispiriting when a company receives mixed reviews and, additionally, class action law suits related to at least one of their products (as is the case with one of their magnesium products). That can be googled. Things always get complicated when one is having to juggle the dollar cost of supplements and their quality. Thorne, Pure Encapsulations, Jarrow are very reputable. The first two unfortunately can be considerably more expensive in terms of dollars.
Regarding the link you posted – the product listed is l-Arginine l-Ornithine not l-aspartate l-ornithine, as was noted in the study though. I’ve noted the Thorne listing of l-arginine (https://www.thorne.com/products/dp/perfusia-sr-reg?gad_source=1&gclid=CjwKCAjwy8i0BhAkEiwAdFaeGN4jOviYB0Bm8U_O5nNqSCfO7te2n_knORaPlfUDUxtBNrVlw-I56xoCiMsQAvD_BwE) which seems to be useful but this all seems to be a bit like going down a rabbit hole without further guidance.
I too have gotten my LOLA and have been on LOLA for a week. It’s definitely doing something….but….at the same time my daughter couldn’t get any company over to vacuum and mop her basement floor so I obliged….and been paying ever since.
my pain and inflammation has jumped into the driver seat and left any noticable LOLA benifits way back in the trunk
Is LOLA specifically for CFS? I’ve never heard of it, how does it help?
See Cort’s “Rescuing the Metabolic Problems in ME/CFS and Long COVID? The LOLA Possibility” posted the end of June.
If you didn’t see life’s reply…it’s down below….
Cort did a blog on it a few days ago.im not too good at finding and posting links etc. Sorry Tanya
I ordered from Bulk Supplements and received it a couple of days ago but I am really very concerned to use it based on the numerous bad comments found on the web about this company (unfortunately after I passed my order). I am actually trying to decide if I take the chance to try it or if simply throw it to garbage and reorder from Allergy Research Group which seems an extremely serious company. However, the price is about 4 times higher. I think it is better to pay more than get sicker than we already are.
It’s certainly a tough call. And the circumstances all the more egregious that this occurs in relation to those wanting deeply to get well. I wish you well moving forward.
Would it make sense to theorize, based on these findings, that people with ME/CFS might be able to muster some adrenaline initially to get going, but that other metabolic or cardiovascular processes don’t function well enough to keep things going—sort of like a gas stove that has an electric starter to light the flame, but not enough gas (amount/volume/pressure, etc.) to sustain a constant fame?
I suppose so. Based on the findings on the Nath study which, if I understood it correctly, found some central fatigue process in the brain, I suspect that, also, the body produces this central fatigue to protect from runinng into PEM which I think happens somewhere else in the metabolism, and adrenaline can override that central fatigue, explaining why adrenaline can mask exertion limits and lead to bad crashes.
5 days in, and ZERO benefit from LOLA. Will give it another 4-5 days.
I am keen to give curcumin another go. It really helped me with PEM a couple of years ago, and there are now formulations with improved bioavailability. I would like to try a bit more light exercise but need some support for the PEM.
There’s a form of curcumin with fenugreek that is supposed to more readily cross the blood brain barrier. Interested to see if that means it potentially helps with mental fatigue as well as PEM (when I previously took curcumin it helped with PEM but not really with mental fatigue). Mental fatigue and PEM are my only CFS symptoms.
On curcumin and PEM, this is interesting:
https://www.aging-us.com/article/204614/text#:~:text=Because%20of%20the%20antioxidant%20and,and%20tissue%20protection%20%5B23%5D.
I hope I’m not gazumping Cort’s next planned post, but the Workwell Foundation just did a proof of concept using the Stat Health earpiece to measure cerebral bloodflow during PEM.
https://lumiahealth.com/blogs/news/reduced-supine-blood-flow-to-head-in-post-exertional-malaise-pem
A proper study is planned.
When I worked as an editor, we would make a mini reference guide for each document we worked on with names, acronyms/initialisms, unusual terminology or spellings and so on.
So you would look up a name in a reputable source and cross check it in another, copy and paste it into your reference guide, and then always copy and paste the name from there each time you used it.
Blowed if I can remember what it was called, even though I made hundreds of them. I want to say style sheet.
Having said that, I noticed that a major journal printed an article with the main author’s name wrong all the way through. I don’t know how they managed that, as it wasn’t even a spellcheck boo-boo. So even a Springer journal may not be a reputable source for checking someone’s name.
Effort preference is ludicrous to even be in an ME/CFS study
Whitney Dafoe more accurately describes it as ‘Harm Avoidance’. Because if we actually had a preference option that doesn’t worsen us later (which we don’t), we’d choose to do a massive amount of things. Unfortunately we are punished with physical harm for it.
Even if the effort tests aren’t appearing to cause harm. Like the lever tapping sounds innocuous enough. The neurons of ME patients poop out much faster than healthy controls do. That will be another reason why ME patients may ‘appear’ to be ‘preferring’ to reduce or stop the amount of effort. When neurones are depleted in energy, they try to conserve it. And in turn will be likely by not being able to reward the patient for the effort. So one would expect the ability to utilise effort would reduce.
It’s much like the unrelated ‘willpower testing’ in healthy people. It turned out that ‘willpower’ was directly related to blood sugar levels. When subjects hadn’t eaten, their neurones didn’t have enough energy to function optimally, so pooped out much earlier, causing the subject to give up (or give in to temptation) earlier in the willpower tests compared to when they were allowed a glucose drink. Similar will be what’s happening in the ‘Effort Preference’, simply not enough fuel being converted to energy by the neurones themselves.
The fact that this test is even in an ME/CFS study shows the utter ignorance, and arrogance of those who insisted it be in the study.
Hi Cort, is part 2 still on the way? Looking forward to it! Thanks!
That’s hilarious! I forgot all about it. Thanks for the reminder 🙂
Haha, glad I asked 🙂