Every once in a while a study comes along for which terms like “seminal” or “groundbreaking” seems appropriate. The 2020 Van Campen/Rowe/Visser study, “Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: A quantitative, controlled study using Doppler echography“, is, for me, one of those. It’s a large study which carves out new diagnostic territory, clears up a mystery, and makes us look at chronic fatigue syndrome (ME/CFS) newly.
Visser, the senior author, is a well-published cardiologist who has been publishing studies for decades. Prior to his first exercise study on ME/CFS in 2010, he’d been pumping out study after study on all sorts of aspects of cardiology. After 2010, though, he’s devoted himself almost exclusively to ME/CFS research focused on exercise intolerance, orthostatic intolerance and dysautonomia. In 2013, he did a series of video interviews on ME/CFS.
Huge Study
The first thing to notice about the study is its huge size – over 400 patients. The study began with 714 possible ME/CFS patients seen from 2012-2018 at Stichting CardioZorg clinic in Hoofddorp, in the Netherlands. All 429 ME/CFS patients were given the opportunity to do an orthostatic stress (tilt table) test and/or an exercise stress test.
During the tilt table test (TTT), the patient lay supine for 20 minutes and then was tilted up to 70 degrees for a maximum of 30 minutes. During that time, their heart rate, blood pressure, and blood flows to the brain were measured. They were asked a wide variety of questions about their symptoms during the test.
In contrast to the “intracranial doppler” usually used to measure blood flows, something called “extracranial doppler” was used. Intracranial doppler doesn’t actually measure blood flows to the brain – it measures the velocity of blood flows to the brain.
Are narrowed blood vessels leading to the brain choking off blood flows in ME/CFS and POTS?
Because extracranial doppler, on the other hand, measures velocity and takes into account blood vessel diameter, it’s able to give a more accurate assessment of blood flows. This technique, which is rarely used, may be critical in ME/CFS because reduced CO2 levels in ME/CFS may be narrowing the blood vessels – resulting in reduced blood flows even when blood flow velocity is normal.
This isn’t the first time CO2 levels have been assessed in ME/CFS during a tilt table test. In a smaller 2007 study, Dr. Natelson found hypocapnia in about 20% of people with ME/CFS. Low CO2 levels were also found in POTS patients in 2006, and way back in 1999, Novak found them in orthostatic intolerance.
In 2018, Novak found that a considerable number of possible postural orthostatic tachycardia syndrome (POTS) patients had normal hearts rates but reduced CO2 levels and reduced blood flows to the brain. He called this form of orthostatic intolerance hypocapnic cerebral hypoperfusion. Only Novak assessed blood flows to the brain in POTS.
This study has four things going for it: its size, its accuracy (the first-time use of extracranial doppler), its combined testing of CO2 levels and blood flows to the brain, and finally, its focus on chronic fatigue syndrome (ME/CFS).
The Gist
- Containing over 400 people, this is surely the largest orthostatic intolerance study done in ME/CFS.
- Virtually everyone with ME/CFS has a form of orthostatic intolerance characterized by low blood flows to the brain and low blood CO2 levels.
- At the end of the 10-minute tilt table test, the blood flows to the brain were on average reduced by 27% in ME/CFS and 7% in the healthy controls,
- People with the lowest blood flows to the brain were the most symptomatic.
- People with ME/CFS who did not have symptoms associated with orthostatic intolerance still had reduced blood flows to the brain.
- People with a diagnosis of POTS or orthostatic hypotension (OH) also have low blood CO2 levels. In fact, POTS patients had the lowest CO2 levels of all.
- Low blood CO2 levels can produce a narrowing of the arteries that reduces blood flows to the brain.
- The cause of the reduced CO2 levels and the impact they are having is unclear. They could be caused by a number of factors (baroreceptor problems, problems with signaling, metabolic acidosis, etc.).
- The success phenylephrine had in removing all symptoms of orthostatic intolerance during a tilt table test is a bit hard to understand given that the drug is a vasoconstrictor. It may have helped with baroreceptor activation or with blood vessel problems in the body.
- ME/CFS patients without a diagnosis of POTS or orthostatic hypotension should, if possible, have a tilt table test done using extracranial doppler – a more precise method of measuring blood flows to the brain.
Results
As so often happens, at baseline – when both the healthy controls and ME/CFS patients were lying supine – no differences in cerebral blood flows were seen.
Once tilted, though, things radically changed. At mid-tilt, blood flows to the brain dropped by about 23% in the ME/CFS patients and just 5% in the healthy controls (HCs). By the end of the test, the ME/CFS patients’ blood flows to their brains has taken a 27% hit, while the HCs had declined by just 7%.
It wasn’t surprising to see dramatic declines in blood flows to the brain in the ME/CFS patients with POTS or orthostatic hypotension. While it’s not exactly clear how, those conditions are believed to reduce blood flows to the brain.
But what about the chronic fatigue syndrome patients without a diagnosis of orthostatic intolerance (OI)? Why did so many of them (78%) report symptoms associated with orthostatic intolerance in their daily lives if they didn’t have it?
This was not a small group. They actually made up the bulk (57%) of the large study. Eighty-two percent of the ME/CFS patients without POTS (postural orthostatic tachycardia syndrome) or OH (orthostatic hypotension) still had abnormally low brain blood flows. What was causing the decline in brain blood flows in them?
The low CO2 levels (hypocapnia) found in these patients may be the cause. Low blood CO2 levels are associated with narrowed blood vessels and hyperventilation.
One website reported that the hyperventilation associated with low CO2 levels is associated with many conditions we hear a lot about in ME/CFS: cellular hypoxia, chronic inflammation, lactic acid accumulation, anaerobic energy production, overactive nerve cells, shortness of breath, and others.
The low brain blood flow/low CO2 problem was not relegated to the non-POTS/non-OH patients, however. CO2 levels during the tilt were reduced in all the ME/CFS patients – including the POTS and OH patients – compared to the healthy controls. In fact, CO2 levels were lowest in the POTS patients.
More work on CO2 needs to be done, but low CO2 levels could be reducing blood flows to the brain. Lowered CO2 levels were found throughout the ME/CFS group. (Image by Gerd Altmann from Pixabay)
It’s possible, but certainly not certain, that the low CO2 levels are playing a major role in reducing blood flows to the brain found throughout ME/CFS and in POTS. The patients with the lowest CO2 levels (<30 mmHg) had the lowest blood flows to the brain.
Plus, a symptom assessment indicated that the lower the blood flows to the brain, the more OI symptoms a person had – something that makes total sense.
More work needs to be done with the CO2 issue. In particular, the authors stated that dose-response data was necessary to pin down the effects the lower CO2 levels might be having.
The detailed symptom assessment taken found a voluminous and heterogeneous mix of symptoms showed up in the ME/CFS patients. Surprisingly, the chronic fatigue syndrome patients with just reduced brain blood flows (another form of OI) had more symptoms than those with orthostatic hypotension. It was the POTS patients, though, who really stood out: they had significantly more symptoms than either group.
One takeaway is that if you have symptoms of orthostatic intolerance – that is, if you experience symptoms of dizziness, fatigue, nausea, pain, cognitive issues, etc. while standing or sitting, but don’t meet the criteria for POTS, OH or other forms of orthostatic intolerance – you likely have a form of OI characterized by reduced blood flows to the brain. I fit in this group. I “passed” a tilt table test but felt awful while doing it.
The study also suggested that even if you don’t experience symptoms associated with orthostatic intolerance, you may still not be getting normal amounts of blood flows to the brain. ME/CFS patients who did not report symptoms associated with orthostatic intolerance still experienced, on the mean, double the drop in blood flows to their brains as did the healthy controls. Some patients without symptoms of OI experienced very high drops in blood flows, indeed, when tilted up (<46%).
Causes?
No one knows why brain blood flows are commonly reduced in ME/CFS and POTS. Novak suggested that baroreceptor problems interfering with “respiratory drive”, compensation for metabolic acidosis, orthostatic ventilation-perfusion mismatch, problems with the respiratory centers in the brain and others (reduced blood volume) could be in play.
A POTS Option
A fascinating 2014 paper by Pozzi and Stewart, “Reduced Cerebral Blood Flow With Orthostasis Precedes Hypocapnic Hyperpnea, Sympathetic Activation, and Postural Tachycardia Syndrome“, (thanks to Peter Rowe for the tip). Every few minutes, this study tracked changes in HR, BP, CO2 level, sympathetic nervous system activity, etc. as POTS patients engaged in a tilt table test.
The researchers knew that when people with POTS stand up, blood tends to pool in the abdomen and lower body, thus reducing blood flows to the brain. They also knew that in healthy people, the very early stages of standing results in a short period of low blood pressure. After the arterial baroreflex and the autonomic nervous system kick in, all returns to normal.
The POTS patients (all suffering from shortness of breath) remained stuck in a state of low blood pressure – which caused the blood flows to their brain to plummet. That resulted (without their being aware of it) in their breathing more deeply than normal (hyperpnea), a reduction in their CO2 levels, and an uptick in sympathetic nervous system activity. The reduced CO2 levels further reduced their blood flows to the brain. The authors believed that the deep breathing and reduced CO2 levels resulted in a brain-wide narrowing (vasoconstriction) of their blood vessels and a state of hypoxia-ischemia (low oxygen levels/restriction of blood supply).
In this scenario, low CO2 levels are initially a reaction to reduced blood flows to the brain – not a cause of them. Once they show up, they make things worse, but they don’t start the process.
Communication Breakdown?
Another option may be a communication problem with the brainstem. When less blood (and oxygen) starts reaching your brain and/or your CO2 blood levels go squirrelly, chemoreflex receptors in your blood vessels tell your brainstem – a possibly problematic organ in ME/CFS – to increase your breathing rate. When CO2 levels get too high, those chemoreceptors tell your brainstem to decrease your breathing rate.
Both these auto-correction processes may be off in ME/CFS/POTS. The chemoreflex system in ME/CFS may be increasing breathing rates too much when brain blood oxygen levels fall, and then failing to reduce breathing rates enough when CO2 levels tank. The upshot of that could be hyperventilation and reduced CO2 levels.
The Phenylephrine Question
While treatment options are unclear, one small study funded by the National Institutes of Health (NIH) and the Solve ME/CFS Initiative (SMCI) used a drug called phenylephrine to attempt to increase blood flows to the brain. Phenylephrine stimulates the α-adrenergic receptors, leading increased in blood pressure, baroreflex stimulation, and a deep vagal stimulation with a reduction in heart rate.
When the ME/CFS patients were given phenylephrine, every physiological measure normalized during their tilt table test. Their heart and breathing rates, CO2 levels and blood flows to the brain all returned to normal levels. Even their performance on a cognitive test returned to normal. Their brain fog was gone.
Interestingly, phenylephrine is a vasoconstrictor – just the wrong drug one would think for a condition where low CO2 levels may be reducing blood flows to the brain. Because phenylephrine, though, does not make it to the brain, it could be vasoconstricting blood vessels in the body, thereby reducing blood pooling in the abdomen and legs, and increasing blood flows to the brain that way. It may also activate the baroreceptors.
Whatever it’s doing, it produced a fantastic effect.
Recommendations
The authors of the recent NASA Lean Study called this study “very important” and concluded that its findings were consistent with their own (very considerable) clinical findings.
Most tilt table tests do not assess blood flows to the brain, and when they do, they usually use intracranial doppler – which is likely not accurate in ME/CFS.
The authors of this study asserted that cerebral blood flows should be assessed during tilt testing in ME/CFS using extracranial Doppler – particularly in patients who have symptoms of orthostatic intolerance assessment, but normal heart rate and blood pressure results on a tilt test. This is the only way to show that orthostatic intolerance exists in people who do not test positive for POTS or OH on a tilt table test.
Dr. Peter Rowe, one of the study’s co-authors, stated that he believed that “extracranial measurement of cerebral blood flow will soon become the gold standard test for orthostatic intolerance”. Rowe reported that 90% of adult and pediatric ME/CFS patients have orthostatic intolerance and the study “helps us understand why people with ME/CFS are so symptomatic when upright”.
Extracranial Doppler measurements do not appear to have been widely adopted and Rowe said it will likely take some time for labs to adopt them as a standard practice. Rowe did say that labs which do vascular ultrasounds and carotid artery studies should be able to learn how to do them without great difficulty.
Just What is ME/CFS?
This huge study begs the question of what is ME/CFS? Could it be a circulatory disorder? There are so many tantalizing findings in ME/CFS right now, but the blood vessel / blood flow issue must be near the top of the list.
The question remains: what is causing the low blood flows to the brain?
David Systrom believes that n theblood loss issue may be occurring between the arterial and venous systems. (Blood has also been found to collect in the abdomen and lower body in POTS patients.) Wirth and Scheibenbogen propose that clamped down blood vessels, plus a rather nasty compensatory response involving vasodilators play a role. Barnden has documented problems in the brainstem which it appears could affect blood vessel functioning, breathing, heart rate, etc.. Other studies suggest reduced blood flows to the muscles are occurring as well.
At the end of the paper, the authors asked whether the orthostatic intolerance found in ME/CFS is similar to the circulatory dysfunction found in autonomic neuropathy. Autonomic neuropathy signifies damage to the nerves of the autonomic nervous system. Systrom, Oaklander and Scheibenbogen have all speculated that an autoimmune process may have damaged the small nerve fibers that carry sensory and autonomic nervous system signals; i.e. that ME/CFS could be an autoimmune-induced autonomic neuropathy.
Other possibilities, of course, are present, but it does feel like we’re getting closer.
Conclusions
Containing over 400 people, this is also surely the largest orthostatic intolerance study done in ME/CFS. This study used an unusual technique (extracranial doppler) to clear up a mystery, introduce a new diagnostic category and possibly identify a fundamental issue in ME/CFS (low blood CO2 levels upon being tilted).
The study explained why so many people with ME/CFS with symptoms of orthostatic intolerance (OI) have not tested positive for it, and suggested that virtually everyone with ME/CFS has a form of orthostatic intolerance. That may come as a shock to some doctors, but will probably not come as a surprise to most of us. We’ve just been waiting for the right technology to uncover what’s going on.
The study found that virtually everyone with ME/CFS had a form of orthostatic intolerance characterized by low blood CO2 levels and low blood flows to the brain. While the study was not able to show that low CO2 levels are contributing to the low blood flows, low CO2 levels can produce a narrowing of the arteries that reduces blood flows to the brain.
At the end of the 10-minute tilt table test, blood flows to the brain were on average reduced by 27% in ME/CFS and 7% in the healthy controls.
The fact that people with the lowest blood flows to their brains were the most symptomatic suggested that low blood flow to the brain is the key factor in OI. Even some people with ME/CFS without symptoms associated with orthostatic intolerance still had reduced blood flows to the brain.
ME/CFS patients with a diagnosis of POTS or orthostatic hypotension also have low blood CO2 levels. In fact, POTS patients had the lowest CO2 levels of all.
ME/CFS patients without a diagnosis of POTS or orthostatic hypotension should, if possible, have a tilt table test done using extracranial doppler to measure their blood flows to the brain. That is the only way that most people with ME/CFS will get diagnosed with OI.
The cause of the reduced CO2 levels is unclear but could be due to a number of factors (baroreceptor problems, problems with signaling, metabolic acidosis, a result of low blood flows to the brain, etc.).
The success phenylephrine had in removing all symptoms of orthostatic intolerance during a tilt table test is a bit hard to understand given that the drug is a vasoconstrictor, but the drug may have helped with baroreceptor activation or with blood vessel problems in the body.
- We’re not done at all done withthe Van Campen, Rowe and Visser team. Coming up: overviews of studies on blood volume, exercise intolerance, tilt tests for the severely ill, and brain fog.
- Plus coming up – a way to increase blood volume that’s as effective as saline.
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Wow. So I’ve had CFS for like 30 years, and on-and-off OI symptoms. After reading this, I thought, well, if the brain is not getting enough blood flow only when I am upright, then simply lying down should resolve my brain fog? Lied down for a couple hours. Didn’t help 🙁 I also wake up tired most days, after 7-8 of sleep (lying down, obviously) so this doesn’t seem to apply to me. Or am I missing something?
It probably does apply to you as the study found it in almost everyone. It’s just that there’s more going on. Like with sleep – you’re supine but most people with ME/CFS don’t get refreshing sleep. I would bet something around poor blood flows period – not just to the brain – but everywhere is part of the problem. Things just get magnified when you stand up.
Do other pots/Cfs sufferers find that acupuncture helps (by apparently increasing blood flow through the body) ? It has been my experience that regular acupuncture is very helpful. Just a shame it is so costly.
Yes. I get relief for a couple of days from acupuncture
It very likely does apply to you.
The blood has to flow towards the brain AND back from the brain to the heart.
When getting from the supine position to standing upwarts, the pressure of the blood at the height of the head drops immediately. That reduces the inflow of blood to the brain quick and immediately. That causes plenty of quick acting symptoms like feeling slow and dazed.
When laying down *for a longer time* blood doesn’t flow that easy back from the brain to the heart. When standing upwarts, gravity does help that. When laying down, that extra help is lost. As a result, the combination of easier inflow to the brain of fresh blood (going easier when laying down) and more difficult return of blood from the brain to the heart while lying down increases the amount of blood pooling in the brain. This effect isn’t as obivous as blood pooling in the legs. But it very likely is there.
This results in increased pressure in the brain, a common observation in ME/FM… studies. The increased pressure is IMO caused in part by a buildup of intracranial fluid from blood not returning well enough.
The extra pressure, building up over time, does help blood return from the brain to the heart over time. That (only) *limits* the extra buildup of fluid and pressure in the brain. It sort of puts a halt or maximum on blood pooling in the brain as when too much blood pools in the brain, brain pressure increases to the point inflow reduces and outflow increases. I hope I explained this clear enough.
The increased intracranial pressure sort of compensates for the free drop down from the brain to the heart when standing up. Unfortunately, that increased brain pressure has a whole range of side effects too.
So I see two aspects of my personal OI:
* a rapid decrease in blood flow to the brain when standing up
* a slow increase of brain pressure when laying down too long
* I try and solve the first by only slowly getting from the supine to the upright position with sitting for some time as an intermediate step. That should allow the body to addapt better I hope.
* When awaking at night I often tend to get up and go for a small walk to the bathroom and some leg-pump work to let the blood circulate better. That seems to break these prolongued periods of laying down and blood accumulating enough to make a clear difference for me. When trying this one out, don’t start with doing so when it’s early morning, then it’s too hard to fall asleep again. Do so when you still feel sleepy enough.
I recently found a further study, in which the CFS patients continued to be monitored after tilt table testing had finished.
Their cerebral blood flow remained depressed for some time after they were lying down again:
https://pubmed.ncbi.nlm.nih.gov/34667909/
To Vlad’s comment, this might sound off the wall, but I often lie down and try to listen to the radio to catch up with the news but find it much harder to concentrate and follow the discussion when lying down than when sitting up. Not from getting drowsy and falling asleep, but just more trouble paying attention. But sitting up brings all the attendant problems you’re discussing here.
Maybe there’s something else at work too? A separate “systemic” problem?
Just a comment.
I’ve noticed that too. There is also a symptom exacerbation when lying down at times – at least at first. I always thought that was really weird (lol).
Lately I’ve noticed a new odd symptom – I now bleed very little when cut. I’ve been diagnosed with OI. Wondering if narrowing of the arteries might have something to do with reduced bleeding?
I also bleed less now! I feel like I am a zombie haha! It does seem like reduced blood flow could be a factor and possible narrowing of vessels?
Vicki and Katie, as a multi-decade sufferer from CFS, I noticed a marked improvement in my ability to stay standing when I started taking a blood-thinning drug. It turns out I have genetic mutations of the blood which cause it to clot too readily. It was causing slow bleeding and eventually clotting in leg veins. I imagine I had micro-clots formed in vessels feeding my brain, although I have no proof of this, of course. Nevertheless, before taking the blood-thinner I could only stand for 5 minutes, at most, before feeling faint, but with the drug, 30 mins or more was no problem. Just thought I would pass this along. Perhaps you could be tested for the mutations. I think they are risks for strokes.
One possible explanation, which does NOT mean its right, is missed here. The blood flow problems are secondary and more a complication than the underlying problem.
Consider the two findings of “something in the blood”, one of which involves energy deficit, and the other mitochondrial suppression. Combine that with evidence of hypoxia, low blood volume, and too much oxygen in the blood.
IF there is a factor in the blood suppressing mitochondrial electron transport chain usage of oxygen. There will be more oxygen and less CO2.. Adaptive changes over time may mean that there is less microcirculation. When supine the blood flow is more or less normal, but oxygen utilization and CO2 release will be low. Being upright compounds this with the usual stressors, even though OI may be subclinical. Given that oxygen use is low then even small changes in the blood flow could have a bigger impact.
As usual, too many possibilities, not enough proven explanations. More data is always welcome though.
I am hoping further evidence of low blood volume alluded to can clarify some of this.
Interesting! I had never thought of reduced mitochondrial activity leading to a buildup of oxygen in the blood. That seems to make sense, though. Is there evidence of increased O2 in the blood?
Could you please reach out to Patrick Mckeown regarding Buteyko Method and his book “Oxygen Advantage”? It’s based on this premise, that over breathing decreases carbon dioxide and oxygen exchange at the cellular level. I started practicing these breathing methods recently and wonder if over time it will affect POTS and exercise intolerance. I also started getting Barnes Myofascial release and after my first session treating the chest and abdomen i have less resting tachycardia, less bounding pulse, and quicker recovery of resting baseline pulse 65-75 after activity. I think fascial restrictions can decrease venous return.
Thanks Sandra. I will check it out. I recently got Breath by James Nestor.
Yes, there was as study using invasive CPET that showed oxy levels were too high, but only in a small number of patients. Harvard study I think.
I would estimate that looking for “increased O2 in the blood” will be difficult and not very fruitful as most people do get to max saturation. We have to go the other way around – look at the drop rate of saturation. If your sub-population have reduced O2 consumption (relative to general population) then the drop in saturation upon breath holding should be later to a certain extent. I am certain this will work out for populations. interpretation for specific subjects is not easy as there may be many contributing factors. Therefore I do not expect to see a regular scientific study – still, this just may be workable for citizen scientist project, preferably conducted with scientists experienced with such collaboration.
Thanks Alex, yes, I think the oxygen is not getting to my brain as it should as I was very excited by this study. Thanks for mentioning this – as I had forgotten what Systrom found – which could directly bear on the present findings.
Systrom found venous blood oxygen levels were too high. The oxygen was not being taken up by the muscles as it should’ve. The study involved about 70 patients.
From the blog:
https://www.healthrising.org/blog/2019/12/11/oxygen-extraction-post-exertional-malaise-chronic-fatigue-syndrome/
Cheney had people breathe into paper bags to increase their CO2 levels. I’ve tried that during certain kinds of crashes with sometimes almost instantaneous success. Something definitely is broken in the mitochondrial/cell energy oxygen/redox/CO2 etc. balance.
I recently had a SEVERE crash from injecting a small amount of MOTS-C peptide, a substance that’s produced naturally by the mitochondria from exercise. I took some cellular antioxidants – alpha lipoic acid, and I think some NAC – and it reversed that day almost immediately. The next day I was back to “normal.”
After that, I tried a supplement called “MitoPure,” (aka urolithin A, derivative of pomegranate ) which aids in recycling mitochondria via mitophagy (clearing out old/damaged mitochondria to produce new ones), and again crashed as if I had done a lot of exertion. That one lasted longer and wasn’t alleviated by antioxidants, but after about a week and doing Buteyko breathing (which has helped other crashes before), and the paper bag method, it finally reversed. I can literally feel it just reverse, and then it might take a day or so to fully come back to “normal.”
I also developed really bad acid reflux during that crash, in fact, that aspect started right away, right before the crash, and it diminished along with the crash alleviating, so I think there is something going on with blood and body acidity related to oxygen, CO2, cell energy production, etc. I wish someone could figure this stuff out because it really gets old having “oxygen crashes” (as I call them) just from talking sometimes! Don’t ask me why it happens, apparently again the O2/CO2 balance gets out of whack and leads to a crash. I go right for the paper bag in those cases, but sometimes even then it takes a few days to reverse or kind of “get out of it.”
Thanks for writing this summary and for all of your hard work keeping us informed, Cort. This is a very exciting study. I have ME/CFS and POTS. I have always noticed that I can think a lot better when lying down since I got sick in 2016.
I have been telling doctors for over 30 years I feel as if my brain is not getting oxygen/blood. I have to live from my bed and lie down 98% of the time. If I stand or sit up my symptoms late exacerbated and I may end up crashing for weeks if I go to a doctor, or clean for a couple of hours etc. this is getting worse over time.
I use to be able to stand up for longer periods of time but was always mostly bedridden.
I also have low blood pressure high heart rate especially when standing up etc. this low blood flow to the brain is there when I lie down too sometimes very bad it worsens to extreme levels when I am upright, This study proves what I have been telling doctors since age 23 I am now 57. They all think I am crazy.
Well Lynn, we know you’re not crazy 🙂
Is it ok for me to pass this link onto my GP here in England? The study actually mentions symptoms such as small nerve fibre problems which I have read about before;it is satisfying to encounter such a neat tie-in. Thank you so much for publishing this study. Regards, MA Wilson.
yes i have had CFS for 8 years and i too have told the doctor it has FELT like im not getting enough oxygen to my brain. theres even times when im lying down ( not always ) but sometimes i feel like i almost have a mini stroke…like my brain goes unconscious for a split second. scary. among all the other symptoms that go along with this illness. 🙁
Sit up as much as you can. Raise the head of your bed about 5 inches. The more you lay down the more your blood flow gets worse. Your body adjusts to what (it thinks) you need. It’s called de-conditioning. I slept for 2 years!! I have POTS, Chronic Fatigue. Ritilin helps me more than anything. Well, and Water!! I get dehydrated easily, which decreases blood volume. Keep ritilin and water by your bed, take in the morning. You will slowly get up. I wish you the best.
How interesting – Ritalin. I talked to someone it really helped.
Another thing people should keep in mind is soft mattresses just end up exacerbating the de-conditioning/circulation issue, especially if you have ended up bed bound for a long period of time, it can completely distort your whole system or your brains connection to the rest of your body. I have spent years laying outside on the ground and on firm surfaces inside to gradually help correct all this, in the very least people should consider making sure there mattress is firm enough to give more solid feedback to the body/brain. As you say raising the head of the bed slightly to help circulation can help too, laying too flat for me tends to be more uncomfortable and on a bed that is too soft is horrible, you especially notice this after going more firm for sometime, how bad soft mattresses are.
Lynn, have you done a “lie, sit, stand” test? This can reveal some types of orthostatic intolerance by abnormal changes in the pulse or blood pressure.
https://www.healthrising.org/blog/2020/08/25/bateman-nasa-lean-test-chronic-fatigue-syndrome-orthostatic-intolerance/
If no abnormalities show up, ask for transcranial Doppler testing for hypoperfusion. An autonomic specialist should be able to arrange this.
i’ve eaten salt so that i could feel better but now i have high BP so no more salt. Also just diagnosed with Parkinsons, talk about MISERY! does ANYONE feel terrible PRESSURE in your head everyday? awoke with ME/CFS 22+ yrs. ago.
Yes, I have pressure in my head also. I also have high blood pressure that I had before ME/CFS and have always taken a beta blocker (Bystolic). It keeps my heartrate down and if I don’t take it, I WILL crash. Seems weird to me that those of us with high bp would also have OI. Someone, please explain that one.
When BP is high, more blood will flow from the heart *towards* the brain.
When blood vessels toward the brain are narrowed, less blood will flow towards the brain. Increased BP in part can compensate for that.
The blood however HAS to return from the brain to the heart. Most people and even doctors see that happening “automatically”. Nothing is further from the truth. If blood vessels from the brain to the heart are narrowed then gravity alone wont fix all. Blood / liquid will accumulate in the brain and pressure in the brain (intracranial pressure) WILL go up.
Compare it with inflating a tire, that has a small whole (puncture) in it, with a compressor. Now see that compressure having two settings: Low and very high.
On low settings, a modest amount of air is pumped into the tire per second. The small whole is enough to let escape an equal amount of air per second and the pressure of the tire will be low.
On high settings, a far higher amount of air is pumped into the tire per second. After the first few minutes of inflating the tire will have its final shape and pressure and as much air has to leave the tire through the whole as the compressor pumps into it each second.
That will increase the pressure in the tire a lot more then in the low settings. That has two effects:
* As the pressure of the tire increases, the compressor will be able to pump in less air per second as the difference in pressure between the compressor and the tire decreases.
* As the pressure of the tire increases, more air will escape through the puncture.
=> After a few minutes after starting to inflate the tire, inflow of air from the compressor will reduce a bit and outflow of air through the puncture will increase a lot untill both are equal. Then the pressure and inflated volume of the tire stays constant.
It’s a bit technical but I hope I managed to symplify it enough this way. Something similar but worse happens when laying down for a longer time (sleep), see a post of mine above.
IMO this is the “hidden” part of OT in ME patients. I strongly suspect that narrowed *returning* blood vessels from the brain to the heart are very problematic in ME/FM/…
Had me/cfs for 31 yrs. Lots of salt helps. So does acupuncture 2x wk. Would Phenylephrine be a good thing to take? I believe i took it yrs before I had me/cfs for sinus problems that it helped. fyi-re full head, i often have a woozy full head.
Dr. Visser in the tape said there was no treatment. He mentioned wearing compression stockings. Kind of discouraging.
I don’t know if his recommendations have changed but that tape was 7 years old. Certainly increasing blood volume could help and there are many other options for orthostatic intolerance. They will be digging into this more deeply. When the cause is determined then they’ll be able to go after it…What I like is that things seem to be coming together.
Tried that but didn’t help
If the blood vessels returning from the brain to the heart are too narrow, increasing blood volumes can backfire badly (even more increase in intracranial pressure). Please be carefull.
Thanks. I hadn’t heard of problems resulting from increasing blood volume but this just shows how complicated this all is. What we really need to do is to identify and fix the root of the problem. Intracranial hypertension – something we haven’t mentioned much recently, after all, is a real thing.
https://www.healthrising.org/blog/2019/12/23/intracranial-hypertension-fibromyalgia-chronic-fatigue-migraine/
How does THAT fit into all of us?
There’s a genetic condition called hypophosphatasa, affecting ALP (enzyme). “On the surface of the brain at the blood/ brain barrier, ALP converts a form of vitamin B6 (pyridoxal 5′ phosphate) to another form of vitamin B6 (pyridoxal) so that it can cross into the brain and help to form neurotransmitters in the brain”
One of the traits is intracranial hypertension.
Interesting, na?
It is also characterized by fatigue and pain upon mild exertion… doesn’t it sound familiar? Some do get an ME/FMS diagnosis before being correctly diagnosed with HPP.
High B6 plasma levels (what’s measured in labs is PLP) is a marker, usually together with low ALP (per a range set for HPP, not the lab’s).
Not always though. ALP is sometimes seen in the low normal range, and in one of the rarer forms, normal ALP levels.
There are two other substances that can be measured, I gather testing is not as easy as the above. Molecular testing would confirm diagnosis.
I have been finding people in the hEDS / FMS / ME community with slightly elevated B6 levels. For some, it goes up when very sick, and back to normal when recuperating.
Perhaps it is HPP, or perhaps our own peculiar disfunction.
It may share something with HPP, in mechanism of pathology stemming from PLP disfunction. We are somehow not able to utilize it, maybe intermittently, maybe as a baseline conditions.
What does it say about intracranial hypertension that is related to B6?
There is also Chiari malformations…
I posted a thread on the forums with information on HPP and how to go on about figuring out if one has it.
There is another condition in which PLP can build up. I’ll be posting about it at some point.
We need researchers looking into B6 in ME/FMS/hEDS!
I am happy to collate info from people that have high B6 and get interest going from the research community.
Or maybe a significant number of us have HPP or Classical Homocystinuria and are not being properly diagnosed…
This is way too late haha 🙂 but very interesting!
I came across HPP some days ago. In 2017 I was tested for high parathyroid hormone. Doctor didn’t even mention it. 2022 I had low ALP levels, they took more tests which seemed normal? Now I was tested for low ALP again. I will talk to my doctor about parathyroid hormone as well as HPP.
Maybe sth will come out of it, but likely that it is just the millionst thing that is slightly wrong with my body but doesn’t lead anywhere… We all know it too well.
I have severe SFN which is frequently connected to parathyroid problems as well as B6 toxicity.
Hi. I’ve learned stuff too.
Low metabolism/thyroid function can also cause low ALP in the blood.
Many with HPP ‘adult’ onset diagnosis are really just not having their hypothyroidism recognized.
“When vitamin D or calcium is deficient, or when phosphate is excessive, and in hypoglycemia and stress (Ljunghall, et al., 1984), parathyroid hormone increases. This can lead to softening of bones, and hardening of soft tissues, especially arteries, sometimes brain, skin and other organs. Parathyroid hormone increases blood pressure, even before the calcium stiffening is detected.”
“A deficiency of either calcium or magnesium can stimulate the parathyroid glands to produce more hormone (parathyroid hormone, PTH)…”
https://raypeat.com/articles/articles/calcium.shtml
Small fiber neuropathy = hypothyroidism.
My comment should be a direct reply to @Meirav
Thank you for replying!
My thyroid levels do always fall in the normal range, so I dont think this would be the case for me.
It is all so complicated and interconnected.
Have you measured your heart rate and temperature?
These are reliable ways of assesing metabolic function.
It’s biology 101 – if your body doesn’t reach 37°C, your proteins don’t fold, your enzymes don’t work, you don’t produce enough CO2 to offload O2 into tissues, etc.
Many things can suppress TSH and they are usually not measured in tandem. Lab results can be misleading. They do not measure metabolic function.
https://raypeat.com/articles/articles/thyroid.shtml
You can read Broda Barnes too.
It also lists breathing insufficiencies, in toddlers though.
But little is known about HPP in adults, as usual….
The difference between the official medical literature and what doctors see in clinical practicer.
Could breathing patterns be affects in adults as well?
Interesting, na? 😉
I just read the link you provided on IHH.
The way you describe feeling after the lumbar puncture –
that’s what I get with taurine.
Memory problems (word finding difficulties and forgetting what I was about to do, etc) = gone.
Taurine does a number of things to the osmolarity of the cell and oxidative stress and calcium. I did find something on it used to treat IHH.
https://pubmed.ncbi.nlm.nih.gov/27156064/
I think there might be something about the relationship of potassium/sodium/magnesium/calcium that is affected.
So looking at blood test results: not necessarily wether any of them is high or low – more the relationship between them.
Maybe the intracranial hypertension is due to toxic levels of substances/byproducts?
“Cerebral blood flow is determined by a number of factors, such as viscosity of blood, how dilated blood vessels are, and the net pressure of the flow of blood into the brain, known as cerebral perfusion pressure, which is determined by the body’s blood pressure. Cerebral perfusion pressure (CPP) is defined as the mean arterial pressure (MAP) minus the intracranial pressure (ICP). In normal individuals, it should be above 50 mm Hg. Intracranial pressure should not be above 15 mm Hg ( ICP of 20 mm Hg is considered as Intracranial Hypertension.) [6]) Cerebral blood vessels are able to change the flow of blood through them by altering their diameters in a process called autoregulation; they constrict when systemic blood pressure is raised and dilate when it is lowered.[7] Arterioles also constrict and dilate in response to different chemical concentrations. For example, they dilate in response to higher levels of carbon dioxide in the blood and constrict in response to lower levels of carbon dioxide.[7]”
NOTE: I advise to carefully study one’s amino acids before embarking on using nutraceuticals. Taurine was very low in my test, and after researching and looking into it, decided it was OK to try. I work with family doctor to monitor the health of my internal organs. That it works for me, doesn’t mean that it will work for everyone the same way. I also took other steps before going for the taurine. I also track blood pressure and heart rate to monitor the effect of substances.
sodium/potassium/magnedium/calcium = electrolytes
There is also something about the charged state of the cell in our disfunction.
With oxidative stress – acidic I believe?
when there is less oxygen, also – I can’t remember which way it goes.
the mitochondria problems..
This person uses potassium/sodium mix works on her POTS symptoms.
Note that she also uses aspirin = blood thinner. That also helps the POTS (and IHH if you have it…)
While she started this treatment to address her MCAS, it helps with the dysautonomia as well.
https://www.mastcelldisease.com/my-new-all-natural-rx/
The sodium/potassium mix would make the cell basic, changing the charges?
This changes redox reactions? an effect on oxidative stress then?
I don’t have the biochemistry of these things down yet…
I’m sure others here do.
https://www.saeure-basen-forum.de/en/acid-base-balance
@Meirav:
A quick search told me that ALP deficiency is rare, but many diseases are thought to be rare by lack of diagnosis on the other hand.
I did find a few things relating to ALP you might find interesting:
* A paper on NCBI with title “Neutrophil alkaline phosphatase activity increase in bacterial infections is not associated with a general increase in secretory vesicle membrane components.” from “ANNA KARLSSON,1* LAILA KHALFAN,1CLAES DAHLGREN,1TORGNY STIGBRAND,2ANDPER FOLLIN3,4” (not linked as WordPress bloks these links with plenty of numbers):
-> Neutrophils, immune cells of the innate imune system, contain vesicles (private stores with concentrated specific chemicals in their cell) with ALP if I got it right.
-> A lot more of it is found in saliva during bacterial infection.
-> The paper has a graph relating ALP, myeloperoxidase (a marker of neutrophil activity) and Vit B12 binding protein.
-> It seems that “defective ALP” has a change to change innate immune system functioning; you mentioned a relation with infection.
You also mentioned the effect of taurine; you might want to look at the paper with title “Activation of Rat Intestinal Alkaline Phosphatase by Taurine May be an Alternative Mechanism of Endotoxemic Injury Protection”
Kind regards,
dejurgen
Hi @Dejurgen. Thank you.
I’ve been working on another reason that B6 may be high, connected to 1-carbon metabolism. I’ll get to posting it on the forum when I have enough on it.
There is also a problem with calcium with defective ALP in HPP.
Taurine regulates calcium in neurons
https://link.springer.com/article/10.1023/A:1014890219513
I wonder how that connects with the studies you pointed out
I think the language I used I was confusing:
By sick, I meant that some have found that if they test for B6 and ALP when they are more symptomatic (i.e. crashing?), b6 up ALP down.
If they test when they regain a bit of health (but not normal yet, just better functioning), the B6 and ALP go back to being within normal ranges.
Thank you for replying!
My thyroid levels do always fall in the normal range, so I dont think this would be the case for me.
It is all so complicated and interconnected.
Sorry, I dont know why my reply appeared here.
I reposted as direct reply to @Meirav.
Sorry for the confusion.
Would hyperbaric chambers be of any use to relieve these symptoms?
Tried that but didn’t help
I’ve had dozens and dozens of HBO2 treatments over the years. It never affected anything to do with ME that I could tell.
How do these findings relate to those of us with hyper (high blood pressure) POTS?
I passed out on a tilt table test at 7 minutes – the neurologist said it was due to hypoperfusion of the brain…
I’m wondering the same thing. I also passed out on the NASA tilt test.
Now that is some orthostatic intolerance!
Thanks Cort for putting this edition of your blog together. It’s chock-full of good stuff, and I feel we should all be encouraged by it.
Very constricted blood vessels towards the brain, reducing blood flow to the brain more then high BP can increase it compared to healthy people?
Wow. Just Wow.
Interesting piece of the puzzle. Phenylephrine is a selective α1-adrenergic receptor activator, and this receptor has been implicated as having a role in modulating the immune system.
see: Modulation of Immune Cell Function by α1-Adrenergic Receptor Activation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624728/
and: Adrenergic regulation of innate immunity: a review
https://www.frontiersin.org/articles/10.3389/fphar.2015.00171/full
I don’t understand these studies at all, but this may explain the effects of phenylephrine beyond just increasing blood flow. I agree with Alex Young that the blood flow problems in the brain are symptoms of a wider problem, not the cause of all symptoms.
Yep I agree. I think this is a secondary factor in the illness, not a primary one.
That this drug works makes perfect sense to me. A shot of adrenalin always makes my body work albeit only temporarily.
As described my heart rate lowers (I can see this from fitbit) pulse becomes very strong and I briefly feel normal. I can stand walk etc and am not in pain. Brain is alert.
I do not have POTS or OH but I do have severe ME and the classic purple legs on standing and have always felt that my circulatory system is severely affected.
These adrenergic receptors have been implicated before and it is very interesting that stimulating them artificially normalised measurements.
Unfortunately once an adrenalin burst has subsided I will feel worse and it can cause further permanent long-term deterioration.
I have sometimes wondered if somehow the ME body will only work in a high stress, high adrenalin situation. As if it has forgotten how to function with normal hormone levels. Or possibly shuts down hard in a way not yet understood unless very high hormone levels are present. And that this can become a downward spiral. Maybe something to do with cell danger response?
Hi Penny, I wonder about the same ideas as you. I’m lucky – I’m not severely affected but I find if I rev up my nervous system a bit, then I function better. However, this is not sustainable on a continuous basis.
A few years ago I was extremely stressed and was hyping up my nervous system by eating chocolate (?) – I wasn’t sleeping restoratively and I was absolutely wired.
Underneath the charged up, artificially propelled system, I was deteriorating. I could tolerate less and less food and my available energy was becoming increasingly depleted. I knew this, on one level, but didn’t know how I could break out of it, without plummeting down – which I really feared.
Anyway, I did manage to do that and I’m still working on it now. I feel really fed up at times, living within my energy means. I basically have to live on energy saving mode. So, I try to resolve any unfinished business, as they say, not take on too much, pace myself – have a rest every afternoon etc. Anyway I shouldn’t grumble, so many people are much less fortunate than me. But I was struck by your thinking.
The chocolate issue is a bit of a puzzle to me. A few years ago, I had become fairly thin, pale, cold and my blood pressure was on the lower end – I was barely ticking over. Over the winter of 2017/18 my legs were tending to collapse under me on occasion. I sometimes felt like all of me would collapse.
However, in desperation, I remembered that having delved into the Christmas chocolate, it had given me a bit of energy. So I found some chocolate I could eat and I became a fat person, with rosy cheeks… I did notice the feeling of warmth in my cheeks, that had disappeared for a while.
I wonder whether I am having some sort of intolerant reaction to the chocolate and that is what is putting my blood pressure and heart rate up? Now, it did became totally out-of-control and my blood pressure went dangerously high.
I’ve settled down now, I’m different and can tolerate more food and am generally much better. Still have colour in my cheeks and am not so fat or thin. I do eat a very controlled diet and lead a very controlled life…, which if I think about it, drives me mad – so I try not to think too much!
one possible cause of the low CO2 could be a subtle, unconscious and continuous hyperventilation (which has been shown to be quote common in me/cfs).
hyperventilation leads to low CO2. and if it’s chronic, it’s gonna change the CO2- receptors (in the carotis arteria and in the brainstem) tolerance for CO2. every little increase in CO2 will then lead to an increase of breathing (because signal to breath is regulated by CO2). this increased breathing leads to even more hyperventilation. a vicious cycle has established. the good news though is, it can (and has to) be addressed! one factor, which contributes to hyperventilation ist the chronically activated stress response (which by the way leads to whole bunch of problems, including metabolic acidity; which in turn can reinforce hyperventilation). a chronuc state of fight or flight can be addressed in several ways (e.g. MBSR, mindfulness based stress reduction by jon kabat-zinn; rewiring stressful patterns; trauma therapy if necessary, erc. which helps finding a permanent state of security and calmness etc.). and then, of course, the chronic hyperventilation has to be addressed directly by normalizing bad breathing patterns (search for patrick mckeown). another indirect way is to normalize the metabolic acidity by eating a healthy, basic diet (adding more veggies! search for dr. michael greger, dr. will bulsiewicz, dr. mark hyman) ideally diary free. supplementing with electrolytes (esp. magnesium, may be potassium) and taking basic baths like e.g. an epsom salt bath.
Thanks Enrico – I think the hyperventilation issue and breathing issues in general are fascinating. Stewart also found a predominance of deep breathing in the POTS study mentioned and Systrom has found an almost universal hyperventilation during exercise.
For me I notice that my breathing is quite irregular and I have the feeling that any stressor throws a normal breathing pattern – which should be quite light – off. I often suddenly take deep breaths.
The autonomic nervous system can be retrained to some extent and I am trying to do that.
Here’s a resource page on breathing and ME/CFS and FM.
https://www.healthrising.org/forums/resources/breathing-techniques-for-chronic-fatigue-syndrome-and-fibromyalgia.495/
I remember Dr. Jarred Younger’s presentation a couple of years ago about the presence of inflammation in certain parts of the brain. Could inflammation restrict in some way blood flow or is it the low blood flow over a long period of time that causes inflammation?
That said, these recent findings seem to fit my case quite well. I had severe orthostatic intolerance as well as cardiac compression due to pectus excavatum. I had surgery to resolve the cardiac compression, and my orthostatic tolerance improved dramatically.
The authors cited inflammation, metabolic issues and something else as possible factors. Interesting about pectus excavatum – another way to cause OI! I assume that connective tissues are involved in that – another huge factor for a subset of people with ME/CFS.
Inflammation can go hand in had with high oxidative stress.
NO, nitrogen oxide, is a main dillator of blood vessels. Oxidative stress (ROS) rapidely can react with NO reducing NO levels (constricting blood vessels) and creating extra toxic reactive nitrogen stress (RNS) from that NO.
Just trying to increase NO production to increase blood vessel dillation is tricky as, in a situation of plenty of ROS, that would also increase toxic RNS a lot.
Short answer: plenty of oxidative stress alone can narrow blood vessels. It also can make RBC less flexible hampering blood flow even worse.
Your experience with the pectus excavatum interests me as I have the same skeletal abnormality. Have not had it surgically corrected because it’s been deemed not severe by the cardiologist. But would a fibro/CFS researcher or expert dismiss it? I do have orthostatic intolerance but have not explored the tilt tables, etc. Had not really considered it enough in terms of my symptoms. Thanks for the input.
I believe Dr. Bergquist’s findings were autoantibodies against adrenergic receptors. If they’re attacked not as much vasodilation and thus less oxygen. Not that I want an autoimmune condition but at least there might be a treatment. Keep hoping!
Yes, beta adrenergic and muscarinic receptors.
Could the difference in blood flow response be caused by deconditioning rather than CFS?
Too many studies compare CFS patients with healthy controls. We need to keep in mind that most CFS patients are severely deconditioned.
van Campen CMC, Visser FC (2018) The Abnormal Cardiac Index and Stroke Volume Index
Changes During a Normal Tilt Table Test in ME/CFS Patients Compared to Healthy Volunteers,
are Not Related to Deconditioning. J Thrombo Cir: JTC -107. DOI: 10.29011/ JTC -107. 000007
Thanks, that’s a good info. I’ll read through that when I have more energy.
Actually, I was highly functional for the first 20 years with both CFS and Fibromyalgia.
MY CFS/ME/FMA Came on in the middle of the night in Oct 1987 & a
HORRIFIC SHOCK & THE REALISATION THAT THERE WAS NOTHING I COULD DO
ABOUT THE SITUATION THE OTHER PERSON HAD DONE TO ME!!… – I’m
VERY VERY TIRED & I FEEL AS IF I’VE JUST BEEN IN A CAR CRASH,etc,etc here in
Hull,UK!!… 🙁
All very interesting stuff. I had blood tests some 20yrs ago, taken by a CFS/ME medical research team in New Zealand, showed I had a high number of flat blood cells which also indicates lack of oxygen in the blood. So this is nothing new to me. Just more confirmation of what this is saying and hopefully finding a cure.
What are your thoughts on this possible mechanism: epinephrine is released by the adrenal gland in response to adrenergic receptor signaling. The autoantibodies to the adrenergic receptors in ME/CFS patients reduce the amount of epinephrine that’s released from the adrenal gland during the stressor of upright positioning. Administration of phenylephrine during the tilt table test compensated for the reduced epinephrine.
I’m trying to reconcile these findings with my previous experience as ME/CFS-only patient. (I now have POTS but it developed years after my initial ME onset, in response to a ME relapse that led to severe deconditioning.)
If reduced brain blood flow occurs almost immediately in orthostasis, then one would think that symptoms would be most severe during upright exercise. But in my case, I usually felt pretty good during and immediately after mild-moderate exercise. This especially applied to brain fog: I could think most clearly during and immediately after exercise. The symptoms tended to flare only once the delayed PEM had begun.
Even now, with both moderate ME and mild POTS, I tend to feel okay during mild-moderate exercise. Sometimes the severe symptoms take up to 48 hours to appear.
So I guess my questions is, why might my symptoms be most mild in the middle of exercise? And why is PEM so delayed? Is there something about exercise, as opposed inactive standing, which temporarily compensates for the brain blood flow issue?
” Is there something about exercise, as opposed inactive standing, which temporarily compensates for the brain blood flow issue?”
Yes: using your leg muscles acts as a supplementary pump for blood, preventing blood to pool that much in the legs when standing up making more available for the rest of the body. Tilt table test don’t “activate” the leg muscles.
Unfortunately, exercising with the leg muscles over time causes PEM too, just like standing upright without exercising. Details may be different, but both affect us.
Thanks dejurgen, Exercise involving legs is exactly the sort I was talking about, so that makes sense.
That makes sense to me too because the times when I have felt as though I was going to faint were when I was standing still. Usually standing and talking – I wouldn’t normally just stand for that long otherwise.
I was a bit susceptible to fainting as a child too and after feeling faint on numerous occasions when queuing at airports, I called it airportitis.
One of the cues that someone has orthostatic intolerance is that when standing they shift around a lot. They are unconsciously using their muscle pump to stop the blood from pooling in their legs. 🙂
I think it has more to do with narrowing and relaxing the vascular system. The control system is not working properly. Why? Damage or autoimmunity. This has been sufficiently proven. A critical note. The thicker blood and less well-formed (shape) red blood cells can also cause this problem.
I experience this too. I can generally exercise to some extent OK. Not as good as I used to but my main symptoms show up later. Nancy Klimas has found a burst of inflammation occurs early in exercise in ME/CFS. As time goes on other problems in other systems show up.
I think we are built to be able to exercise no matter what. We have had to be able to create energy quickly in order to survive – our body will do whatever it can – no matter how destructive it might be – to carry out that imperative.
After all, even in healthy people there can be a delayed reaction to exercise – showing up with aching muscles a day or so later.
Does anyone have hyperhomocystienemia? I was diagnosed in 2011. I have not been diagnosed with Me/Cfs, but am 98% sure I have it after a bad flu/bronchitis in 2017. Have not been able to get out of bed since. Dizzy, nautious, all the symtoms of POTS. Was tested in 2018 and it was negative. It’s getting harder for me to stand for longer than 15-20 minutes. No Drs in my area of TN treat me/cfs that I know of.
Just wondering if their could be a relation to hyperhomocystienemia and post viral me/cfs?
Hi –
I’ve been working on this model/theory:
I think it is possible that a number of us have some form of homocystinuria/methylation/remethylation disorder.
Have you ever been properly investigated for any of these,
given that you have high levels of homocysteine?
Events like sickness are known to bring about a metabolic crisis in inherited metabolic disorders
Think of diabetics when their glucose shoots up and affects their whole system.
All the organs, etc. So insulin is administered to bring glucose back down to normal levels. Each inherited metabolic disorder has its protocol to restore the body from crisis.
I do sometimes wonder if ME/CFS being triggered by sickness is pretty much a metabolic crisis. They just haven’t figured out what is needed to bring you out of it.
With hyperhomocystenemia, there is a higher risk of blood clots and thrombosis. Thicker blood? That could lead to development of POTS?
Are you doing treatment for it to bring levels down?
I have heard form some people that their doctors did not further referred them to specialists, and instead were prescribed B6/methylfolate.
This is not good – as some do not respond to B6 and that leads to more problems.
It’s important to figure out why it is high, as treatment differs depending on the genetic defect, if you have it.
You could also do the NASA lean test at home to figure out if you can be diagnosed with POTS. Cort just recently posted on this, you can find links there for how to do it.
You can check out the Homocystinuria Network for guidance.
https://hcunetworkamerica.org
or
http://www.e-hod.org
I love the cardiologist “pumping out” lots of studies. Nice one Cort! I heart that!
Ha! I made a funny without even realizing it 🙂
I have wondered why I feel a bit woozy just standing. I do tend to shift around and try to find something to lean against and breathe more. I have never been tested for OI but maybe I should. I always fear a test that might make me worse. Is there any treatment for OI? sorry to post again, this article just makes so much sense!
Thank you as ever Cort. You are heaven sent. But how long before treatment. Or is this a permant disability. It’s a rough haul.
Great question. I wish I knew. I do feel we are getting closer though. When different study results start to support each other – that’s a good sign. Time will tell.
I know this is an old question, but there are a few treatments for OI, ranging from compression leggings to volume expansion to medications to increase vasoconstriction. All depends on the individual person’s overall medical situation, but there should be a couple that are applicable to just about everyone.
Oh…and it’s refreshing…literally!
I’m glad they have discovered that blood flow is the key problem with having OI symptoms. I’m glad they have found a good way of testing for OI symptoms in CFS/ME. I had a tilt table test years ago. I was not diagnosed with POTS in spite of having OI symptoms. I was, however, severely impaired after the tilt table test. I could not move without hanging on to something; very dizzy and unstable. It took over an hour before the symptoms went away.
I wonder how those of us with hypertension fit into this? Or, is it possible that in some of us the body has constricted blood vessels in an attempt to get more blood to the brain? Although my BP is well controlled on average, when I get flares it spikes for the duration of the flare.
Dr Peter Novak has identified high blood pressure in a subset of his patients with OCHOS. (And he has diagnosed several people with ME/CFS with OCHOS.)
So that could be a potential direction to investigate.
The original research article is easier to understand than your article. Your article obfuscates the research, rather than elucidating it.
This is really not helpful. In some corners it’s what is called a “dump”. A dump is when you basically crap on something and walk away – leaving everything smelly. Suggestions on how to improve the blogs are always welcome but your comment provides no opportunity to do that. I have no idea what you’re upset about or how to fix it – so it’s not helpful and obviously leaves me in an upset state.
Since you did it here – you might consider whether you’re doing it elsewhere as well – and are leaving a stream of upset people in your wake.
On the brighter side – we accept well-written (:)) guest blogs and if you can do better we would love to have them. I could learn some things and you could help get the word out.
Thank you, Cort, for this article and all the others I’ve read in about the 6 months I’ve been on Health Rising. It’s so helpful that you synthesize all the complicated data for us!! I’m always trying to figure out why I cannot think (pain and major fog and exhaustion) sitting up or standing (though walking is ok). (Many neurologist and neurosurgeons and surgery have not helped this issue). I have EDS, have been fused for major CCI and have CSF leaks and get patches for them. But also an MRI reported tortuous Carotoid (sp?) arteries. And I have dysautonomia. This blog on blood flow confirms just how complex and varied our issues are. I feel for all of us and appreciate the work you are doing. It is hopeful as are all the studies on Long COVID. I’m going to participate in your fund drive. Keep up your amazing work. I so appreciate your dedication to CSF/ME. This blog helps me realize what I am feeling is real. Thanks also to all those who comment. Hope we see some breakthroughs in 2022.
Thanks Paige! So glad the blogs are validating and helpful. I look forward to getting into EDS more as time goes on. Good luck with everything!
How to get phenylepiphrine? It’s not an OTC medicine..
Was there ever a follow-up trial of treating patients with phenylephrine?
Interesting reading this and thinking back over the last 20 years of the issues I have had, especially having such difficulties getting comfortable sleeping and feeling disconnected or losing connection to my body over night because of sleeping postural issues, also years and years of chronic head/jaw/shoulder pressure clearly restricting blood flow along with restricting mental/physical flow/functioning as well. And this is also why I have been able to make such progress with years of postural disciple, breath work and cold exposure, it all links into vascular, muscular, facia, vagal stimulation and conditioning, getting the body back to a place where everything is flowing and signalling more naturally and efficiently. Spent years on and off in parks and in nature simply lying flat, a lot of the time on a slight incline, to support the posture/circulation as well and recover conditioning and strength. To this day I still have to be quite careful, too much time spent sitting and it can quickly start creating poor patterns which can quickly start to disrupt the system and even ruin a whole nights sleep, for me it really tends to disrupt and put out of place my vagal/trigeminal nerves.
Why did those who tested negative for O.I., i.e. did not have POTS or OH, still have abnormally low blood flow?
I feel a bit silly for suggesting the obvious, but here goes…
The 30-minute test is not going to pick up all the people with NMH. In Peter Rowe’s 2014 Information Brochure, he says that the diagnosis of NMH requires at least 45 minutes of upright posture. In his 2019 webinar, he says that the median time for the detection of NMH is 29 minutes.
In 2018, I tested myself for O.I., using the method and criteria in oiresource.com., and aiming for 45 minutes standing. I gave up at 30 minutes. My blood pressure and pulse were close to the diagnostic values. More impressive was that I was exhausted and blue to the knees. After 2 hours of lying down, I was 70% recovered.
It is due to low blood flows to the brain – the reason for that is unclear but may be due to overly constricted blood vessels leading to the brain.
If I read rightly, they didn’t test negative for OI, they tested negative for certain types of OI that show up in blood pressure changes, heart rate changes, or both.
Dr Peter Novak has named one type that only shows up when cerebral blood flow is measured:
https://www.brighamhealthonamission.org/2019/06/03/expanded-autonomic-testing-helps-to-pinpoint-causes-of-orthostatic-intolerance/
Sure. My point is that the standard 30min tilt test for O.I. might be a convenient benchmark for some research, but it seriously underestimates the number that “really” have O.I., like about half of those with NMH.
Trying to explain my brain fog and understand low blood flow getting to the brain brought back memories from my living in Bolivia. When a person is not used to the high altitude, where there is less oxygen, a sort of headache/dizziness occurs. This phenomenon is called soroche in Spanish. Very similar to brain fog. Apparently, our system adapts by producing more red blood cells. It takes about two weeks for the tourists to acclimate to this condition and not suffer from soroche. I can’t help thinking that there’s a clue in this adaptation, that maybe ME/CSF patients are not able to do.
Hyperventilation has been used in traumatic brain injury to quickly reduce intracranial pressure.
So many of these studies return connections to ICP while never looking directly at it.
In addition, the brainstem may be affected by high intracranial pressure (pressure directly applied) or longterm low intracranial pressure (leading to brain sag pressure).
The brain connects to every aspect of this illness. Gut function, sleep cycles, immune reaction, autonomic function—it all happens there—along with cranial nerves. I’d love to see a study focused on ICP in ME/CFS by some means other than lumbar puncture.
Is the extracranial doppler available for purchase by non-medical people? Forgive me if someone already asked this above, I’m too symptomatic to read all of the questions/replies.
No, it’s a medical device for purchase by hospitals or labs only. However a company in the US is making an in-ear device that measures blood flow to the brain. Cort wrote a recent post about it. Note that this new wearable is classified as a wellness device, not a medical device.
If you are diagnosed with OCHOS, your doctor can try you on calcium channel blockers or ACE inhibitors.
That is what Dr Novak has been trying with his OCHOS patients, with some responding well.
Ask your specialist to have a look at Dr Novak’s journal articles and his textbook:
https://academic.oup.com/book/24760/chapter-abstract/188284693?redirectedFrom=fulltext
(Excerpt only; your specialist should be able to access the full content through their institution’s library)
A letter to the editor of the journal Clinical Autonomic Research has called for Doppler ultrasound to be used more fequently in the diagnosis of syndromes of orthostatic intolerance.
It is behind a paywall, but you can read the first page here:
https://www.deepdyve.com/lp/springer-journal/is-it-time-to-move-beyond-blood-pressure-and-heart-rate-during-head-up-A27wOQkjUg?key=springer
And a summary on a forum here:
https://www.s4me.info/threads/is-it-time-to-move-beyond-blood-pressure-and-heart-rate-during-head-up-tilt-testing-2024-mitchell.38582/#post-533165