“Our Raman spectroscopic approach has great potential as a diagnostic technique for diseases like ME/CFS” the authors
A blood test for ME/CFS is like the holy grail. This research team thinks they may be onto something.
A blood test – it’s like the holy grail for chronic fatigue syndrome (ME/CFS). Not only would it legitimize the disease, and make it easier to diagnose the disease, but it should also give us clues as to what’s causing it and perhaps even provide the long-sought biomarker drugs companies could use to assess the effectiveness of their drugs.
Of course, the question persists whether finding a single biomarker is even possible in such an apparently heterogeneous disease. If one was found, though, one would think given the disease’s apparent heterogeneity, it would be getting at its core elements.
Factors have been proposed before, but none has yet stuck. The “Developing a Blood Cell-Based Diagnostic Test for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Peripheral Blood Mononuclear Cell” study employed a different testing regimen (using Raman spectroscopy) and artificial intelligence (AI) to analyze the results. The authors believe that an AI-led approach is going to crack ME/CFS and similar diseases. (A blog on the potential role AI could play in ME/CFS is coming up.)
The mostly Oxford-led study also included researchers from the London School of Tropical Medicine, Poland, and the US. Led by long-time mitochondrial researcher Karl Morten of Oxford and Raman specialist Jiabao Xu, it was funded by the ME Association, with help from the Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences (!).
Raman Spectroscopy Takes Center Stage
The single cell Raman spectroscopy (SCRS) uses a laser to get a fingerprint of all biomolecules in a cell. Its ability to chart all the major building blocks – proteins, amino acids, lipids and phospholipids, and carbohydrates – makes it possible to assess the metabolic and physiological status of each cell.
The study – a follow-up to an earlier pilot study – combined “single-cell Raman” with artificial intelligence (machine learning) to come up with some intriguing findings. The pilot study (5 patients and 5 healthy controls) was able to differentiate the patients from controls astoundingly well (98%) and fingered high phenylalanine levels as a possible differentiating factor. That finding suggested that ME/CFS patients’ cells were – as other studies have concluded – turning to the less capable amino acids for fuel instead of relying on better substrates such as glucose and fatty acids.
Encouraged by the positive results, the investigators expanded their study to almost 100 individuals, including 61 ME/CFS patients, 16 healthy controls, and in an indication that they were pretty serious about the biomarker stuff – 21 multiple sclerosis patients. (Biomarkers must be tested against other diseases as well as healthy controls). They used the Raman approach to assess immune cells called peripheral blood mononuclear cells (PBMCs).
Results
The rates of mitochondrial respiration using thawed-out frozen cells were similar in all groups. (While other studies have found problems with the little energy centers of our cells, this measure of them has failed in two out of three studies and the authors discarded it as a possible biomarker.)
A supervised linear discriminant analysis (LDA) of the Raman spectroscopy findings, however, clearly differentiated the ME/CFS, MS, and healthy controls from each other. We’re used to seeing considerable overlaps between ME/CFS and controls, but in this case the groups were very well differentiated (D and E) – suggesting these researchers were really onto something. They were even able to capture differences between mild, moderate, and severe ME/CFS patients (group F).
Check out the separation between the healthy controls (green), ME/CFS (red), and MS patients (green) in Figures D and E, and the healthy controls (green), mild (tan), and moderate/severe ME/CFS patients (red) in Figure B (!).
Adding to the pluses, the researchers found little indication of any possible confounding factors (sex, body mass index (BMI), age, disease duration, types, and total counts of medications and supplements, as well as the freezing duration and processing time for each sample). The fact that gender – which has complicated other results – did not in this case was encouraging.
A universal increase in tryptophan and tyrosine in cellular PBMCs was found in both ME/CFS and MS. With the nice separations, it was a little surprising to see some muddy findings. The phenylalanine picture, for instance, got more complicated with moderate and severe patients showing reduced levels and mild ME/CFS (and MS patients) showing increased levels. Similarly, elevated unsaturated fatty acid levels also left mild ME/CFS patients looking more like MS patients than moderate to severe ME/CFS patients, who had reduced unsaturated fatty acid levels. Why such a physiological break between mild and moderate and severe patients might be present is not clear.
Reduced glycogen levels in the mild and severe ME cohort (but not the moderate cohort?), as well as in the MS group, presented another complication as well. Glucose quantification – the amount of glucose present – on the other hand, was decreased in all ME subgroups – plus, the MS cohort had the lowest glucose levels.
All in all, the authors reported that the findings agreed with the altered utilization of amino acids (tryptophan, tyrosine, and phenylalanine) in patients with ME/CFS. Interestingly, the same general process of amino acid dysregulation was found in the MS group.
Note the similarities seen between ME/CFS and MS thus far. Increased tryptophan, tyrosine, reduced glycogen levels and glucose quantification were common to both diseases (in some subsets). Plus, the elevated unsaturated fatty acid levels and reduced phenylalanine levels were similar to mild ME/CFS.
A Focus on Tryptophan
The tryptophan-kynurenine pathway has been an object of discussion for some years but has been showing up more, recently. Just how versatile this pathway is can be seen in the two opposing hypotheses that have popped up about it.
THE GIST
- A blood test – it’s like the holy grail for chronic fatigue syndrome (ME/CFS). Not only would it legitimize the disease, and make it easier to diagnose the disease, but it should also give us clues as to what’s causing it.
- This team of Oxford, London School of Tropical Medicine, Polish, and U.S. researchers, used a technique called Raman spectroscopy which has the ability to chart all the major building blocks – proteins, amino acids, lipids, and phospholipids, and carbohydrates – in a cell, making it possible to assess the metabolic and physiological status of each cell.
- Encouraged by the positive results of an earlier pilot study, the investigators expanded their study to include almost 100 individuals, including 61 ME/CFS patients, 16 healthy controls, and, in an indication that they were pretty serious about finding a biomarker – 21 multiple sclerosis patients.
- The artificial intelligence-driven Raman spectroscopy findings were able to- to a remarkable degree – differentiate the ME/CFS, MS, and healthy controls from each other. We’re used to seeing considerable overlaps between ME/CFS and controls, but not in this case (see image in blog). The Raman Spectra analysis was able to differentiate ME/CFS, MS, and healthy controls with remarkable accuracy (91% specificity; 93% sensitivity for ME/CFS).
- Lauding the ease of the test, the small amount of blood it requires, its ability to be done on “fixed material”, and the fact that it can be frozen without deterioration the authors stated:
- an “objective, sensitive, and straightforward diagnostic tool can therefore resolve the controversy concerning the nature of ME/CFS and…has the potential to make drastic impacts on patients’ quality of life….(When used in combination) “with sophisticated machine learning algorithms, our Raman spectroscopic approach has great potential as a diagnostic technique for diseases like ME/CFS”.
- A universal increase in tryptophan and tyrosine and reduced glucose levels were found in the mild moderate and severe ME/CFS patients.
- There were some oddities, though. Moderate and severe patients showed reduced phenylalanine levels while mild ME/CFS (and MS patients) showed increased levels. Similarly, elevated unsaturated fatty acid levels were found in mild ME/CFS patients while moderate to severe patients had reduced levels. Reduced glycogen levels were found in the mild and severe ME cohort (but not the moderate cohort (?).
- Increased tryptophan, tyrosine, reduced glycogen levels, and glucose quantification were found in both ME/CFS and MS patients (in some subsets). Plus, the elevated unsaturated fatty acid levels and reduced phenylalanine levels were similar to mild ME/CFS.
- The increased tryptophan levels found in both the ME/CFS and MS groups jive with Robert Phair’s metabolic trap hypothesis for ME/CFS, which proposes that genetic mutations in an enzyme are inhibiting the metabolism of tryptophan to kynurenine and could result in high serotonin levels. The authors asserted that it “is crucial to acknowledge the potential dysfunctional effects of tryptophan and serotonin in the context of ME/CFS“.
- The findings also suggested – once again – that ME/CFS patients’ cells are turning to “dirty fuel” – amino acids – for energy instead of using the cleaner burning glucose and fatty acids. Evidence of altered fatty acid and lipid metabolism – two hot research topics right now in ME/CFS – were also found.
- The authors looked beyond ME/CFS, stating that in chronic, complex, unexplained conditions like it, including fibromyalgia, chronic Lyme disease, and long COVID, they believe that complex data and machine learning approaches such as those used in this study are going to lead the way.
The authors proposed that the high tryptophan levels in the immune cells they measured could, by sequestering abnormal amounts of tryptophan in them, result in reduced brain tryptophan levels – a situation known to cause central or brain-induced fatigue. Or, as both Phair and Cortene propose, high levels of tryptophan in the blood could produce the symptoms of ME/CFS by producing high levels of serotonin in the brain.
Regardless of the specific mechanisms involved, the authors asserted that it “is crucial to acknowledge the potential dysfunctional effects of tryptophan and serotonin in the context of ME/CFS“.
The authors reported their results also fit with broad-spectrum metabolite analyses which found reduced levels of serum amino acids and disturbances in pyruvate dehydrogenase, sphingolipid, and phospholipid metabolism. The cells of both ME/CFS and MS patients appeared to be having trouble utilizing glucose – a preferred fuel source – and were turning to amino acids instead.
The low glycogen levels found were reminiscent of what’s seen after continuous exercise – which clearly wasn’t happening in ME/CFS. Instead, the authors believe they may reflect the increased use of amino acid stores to power their cells. Evidence of altered fatty acid and lipid metabolism – two hot research topics right now in ME/CFS – were also found.
Budding Diagnostic Tool?
While some similarities were found between ME/CFS and MS, the AI-driven Raman Spectra analysis was able to differentiate ME/CFS, MS, and healthy controls with remarkable accuracy (91% specificity; 93% sensitivity for ME/CFS).
The authors, clearly encouraged by the results, lauded the ease of the test, the small amount of blood it requires, its ability to be done on “fixed material”, and the fact that it can be frozen without deterioration. All in all, it appears to present an easy diagnostic – with the proviso that Raman microscopes – not apparently in great supply – need to be used. They stated:
an “objective, sensitive, and straightforward diagnostic tool can therefore resolve the controversy concerning the nature of ME/CFS and…has the potential to make drastic impacts on patients’ quality of life….(When used in combination) “with sophisticated machine learning algorithms, our Raman spectroscopic approach has great potential as a diagnostic technique for diseases like ME/CFS”.
They looked beyond ME/CFS, stating that in chronic, complex, unexplained conditions like it, including fibromyalgia, chronic Lyme disease, and long COVID, they believe that complex data and machine learning approaches are going to lead the way. As diagnostic algorithms get more precise, treatments will be identified and developed for the subtly differing disease states found in ME/CFS and other diseases.
In fact, they expect that as the biological footprints of these diseases become increasingly uncovered, subtle tests will be able to pick up their signs before major symptoms have shown themselves. Predictive analytics that employ machine learning algorithms are already being used to ferret out disease states before they become evident.
Conclusion
Using a new technique called Raman spectroscopy, in combination with machine learning, this British-Polish and US research group were able to distinguish ME/CFS from healthy controls and multiple sclerosis with an unusually high degree of accuracy.
Could a new technique produce a blood test for ME/CFS? Time will tell.
The reduced glucose levels and increased tryptophan and tyrosine levels across the mild, moderate, and severe ME/CFS groups made sense, given what we know, and put a spotlight on energy metabolism, tryptophan, and serotonin. With regard to those last two, the authors went so far as to assert that it’s “crucial to acknowledge the potential dysfunctional effects of tryptophan and serotonin” in ME/CFS.
The findings also suggested – once again – that ME/CFS patients’ cells are turning to “dirty fuel” – amino acids – for energy instead of using the cleaner burning glucose and fatty acids.
Some of the findings were curious. The phenylalanine and unsaturated fatty acids findings were complicated with mild patients showing opposite results from moderate and severe patients. With low glycogen levels in the mild and severe ME/CFS patients – but not in the moderate patients (?). Perhaps not so surprising for a fatiguing disease, multiple sclerosis showed some clear similarities (and differences) to ME/CFS.
In the end, in its broad scope, the study validated problems with energy metabolism, demonstrated amino acid abnormalities, and highlighted tryptophan issues,
Could a long wished-for, (prayed for), biomarker for ME/CFS be next? Time will tell. The authors were certainly excited, stating, “Our Raman spectroscopic approach has great potential as a diagnostic technique for diseases like ME/CFS”. A biomarker would require larger studies that include more disease groups that are similar to ME/CFS, such as fibromyalgia.
Larger, more comprehensive studies that incorporate the Raman spectroscope with metabolomics and proteomics and use more disease controls appear to either be underway or are planned for. We shall see!
However, this turns out it’s good to see ME/CFS researchers and their funders turning to the new technologies to solve ME/CFS. It comes as no surprise that the massive capabilities of artificial intelligence may be particularly helpful for complex diseases like ME/CFS. More on that later.
For more from Professor Morten on the mitochondria and ME/CFS check out his presentation below.
Do these findings Re anomalous metabolism suggest particular foods would be helpful? Low or high tryptophan, for example? (To eat turkey or not…)?
I don’t know. In general, my experience is that when you get into these cellular tests that the remedy or even the potential treatments often go far beyond diet. Maybe someone will know better though.
It could also be that there is a backlog of these because the rate limiting step (hydroxylase) is suppressed by cytokines causing them to build up and their conversion to neurotransmitters suppressed. Thus boosting hydroxylase rather than suppressing these substrates might be better.
I think I remember Bob Phair being asked the question of diet modification for the tryptophan serotonin problem. And he did think it would make a difference. Also the theory has not been proven.
In 2019 researchers at Ohio State University developed a blood test using spectroscopy for fibromyalgia. https://news.osu.edu/experimental-blood-test-accurately-spots-fibromyalgia/
I’m a complete layman and have no idea if that test has anything to do with the one in this post. I just saw the word spectroscopy in both. OSU signed a contract with a company called Exagen to commercializ it. It would be available in 2024 at the earliest and that’s if it turns out to be successful at all.
Nice! I think it is a different form of spectroscopy – there are many different kind – https://www.wikiwand.com/en/Spectroscopy – but how intriguing, huh? Thanks for the link 🙂
The fibro study also used Raman spectroscopy, and mid-infrared spectroscopy. So yes somewhat the same technique as this study! They also did other mass spec analyses but yeah this paper had a lot of the same ideas as the ME/CFS paper (but in 2019 in fibro). https://www.jbc.org/article/S0021-9258(20)40006-7/fulltext#seccestitle20
41 year veteran of ME/CFS and found many answers in my DNA. I have 3 homozygous mutations that affect my detoxification and methylation cycles. My folate/thiamine functions 75%.
This has been a hell of a ride but through DNA testing, I have much more understanding. I think Fatigue Disorder Spectrum describes my symptoms more fully, but it’s just a label. Take care everyone.
What type of testing did you use for your diagnosis? Was it a type of genetic testing you can order yourself or did you go through your physician?
Gina and Tera, I was just listening to Peter Attia interviewing a geneticist and they thought Ancestry and 23and Me were good for certain things but one of Peter’s favorites is Self Decode, one reason being they help interpret the info and what to do with it. There’s another he likes but forget the name. If you search PeterAttia best genetic companies it’s there, plus pros and cons of many others. Sounds like what Judy did worked fine too. 🙂
Thanks for the information
Did you do the 23&ME testing? Or was it something different? I’ve been considering something like this also and wasn’t sure which to try out. Thanks
I initially did 23andme and then Ancestry. I then ran the DNA link through Genetic Genie and Promethease – free. I then ran my DNA through Chris Masterson web site. You need to follow through to get your genetic variants.
It’s all been very enlightening for me.
I got my data from Ancestry and ran it through StrateGene and also Found My Fitness DNA report. It took a couple of years going through all the data to self educate and decipher my results but they were every enlightening and helped to guide my treatment.
I have very low conversion of vitamin D from sunlight so have to supplement to keep levels in range. I also have very low COMT activity (associated with fibro) which makes me very sensitive to stress and stimulants. I’ve had to adjust my lifestyle to suit and avoid some common supplements which would add to this problem.
daphne-krantz.com offers genetic coaching if you’re not up for the task of self-educating.
“I have very low conversion of vit D from sunlight”.
did you ever have the biologically active form of vit D (1,25idihydroxycholecalciferol) tested in your blood?
I have very low vit D and high 1,25 vit D levels ; FM
I requested that test a few years ago but it was not available through the Australian Medicare system. We don’t have many independent labs here so I just forgot about tbh. But thanks for reminding me!
Thanks for the information
Hi Judy. Nice to hear from another veteran (30 years for me). Have you gotten much relief from changes you made resulting from DNA testing?
Implementing some of them. My biggest eye opener was my thiamine (folate) gene only functioning 75%. I trialled TTFD (B1) for a week and life was wonderful! Body pain reduced, more energy, more stamina – magical 🪄
But, had to abandon after first week as my eyes felt as though they were gassed. I am working through a protocol (Elliott Overton) and need to add in lots more Bs. Yesterday I started using a B1 patch for next 12 days to see if it helps. The TTFD (water based) took me to an almost unremembered past. Take care
Thanks Judy
Judy, I did some similar genetic things that you did, and it found issues with folate metabolism, and all Bs. But when I take them, they make me wired and weaker, and keep me from sleeping, even at a low dose, so I don’t take them. So many variables.
Judy, do you recommend Elliott? Thanks
Judy, do you recommend Elliott? Thanks
I recommend that people do their own research. For me, his information has been valuable and I am finding my way through. Taking TTFD for 1 week gave me a week that I haven’t experienced in years. I’ve been doing a lot of tweaking and experimenting and am using a B1 patch for 12 days and my body pain has lessened. I’ll keep on down the “B” road as my body is desperate for these vitamins.
Judy, how much B1 did you take? I just bought an Ecological Formulas B1 that is the same form you mentioned, in 50 mg capsules. The comments on Amazon from other buyers specifically said it reduced muscle pain. Some people also said you have to take Magnesium when you take B1. I don’t know if that is part of the regimen you tried.
Cameron, I took Allithiamine 1 daily and a B1 from EO that I think has changed formula. I also take magnesium and potassium. There are FB and YouTube info readily available. Cheers
Thanks, Judy! I’ll look into the YouTube info. (I don’t do Facebook). Don’t know what EO is, but I’ll ask my vitamin guy. I did notice, after taking the Allithiamine just once, a very unpleasant but short-lived after effect. I generally don’t tolerate garlic, so that could be the problem. If you’re happier on the other B1, I’ll look for it.
I’m so glad it helped you, even a little!
Interesting: “The findings also suggested – once again – that ME/CFS patients’ cells are turning to “dirty fuel” – amino acids – for energy instead of using the cleaner burning glucose and fatty acids.”
I minimize carbs deliberately, because I feel better and am less dysfunctional when I stay away from them. Is that possibly because I deliberately load up on amino acids from protein?
It is not a large effect, but it IS noticeable: carbs lead to soggy days for me.
Alicia have you ever tried only meat, nothing else. Some folks say it cured their autoimmune diseases. Can’t imagine it’s healthy but we’re all a different chemistry set.
Hope the third book of your trilogy is coming along. 🙂
I have done a PSMF – eating only protein for about a month – earlier this year, as that’s the only way I ever lose weight. I didn’t notice much change in my usual ME/CFS symptoms.
I lost a few pounds, but had pretty constant gastric problems (but no hunger), and gave it up after a month or so because I couldn’t manage the gastric problems any longer.
I have no documented autoimmune disease – unless that’s what ME/CFS turns out to be. No doctor has ever found anything (when they actually looked, which isn’t often), and the symptoms don’t suggest anything in particular.
It’s healthy enough – if you hydrate and take a multivitamin and extra potassium – but it’s a little drastic. I used to be able to tolerate it every couple of years – didn’t this time. I’m getting old.
Sweet of you to ask. LIMBO is coming along as fast as I can manage with the brain fog and lack of energy – and that’s the best I can do. I think getting over the final organizing of the plot – which lets me go back to working on a scene at a time until it’s finished – will help immensely, as it has for the previous two books.
Due to some other stresses, I haven’t quite reached that point yet. No problems, but I write realistic fiction, and all the dates and timings have to be right – and it’s not there yet. Close (I hope) but no cigar. I’m really champing at the bit – can’t wait to do the final writing. But I’m an extreme plotter – and structure comes first. If you want to know when it’s ready, sign up to Follow at prideschildren dt com.
Too bad about the gastric problems. I may give it a try for a couple weeks although whole food plant based seems healthiest to me, at least for the general population.
I do follow along with your book and see great reviews. 🙂 What an accomplishment especially considering your ME/CFS.
I’d like to give you a recipe that finished with my gastric problems: “bay leaves tea”. I drank during 3 months, 3 cups/day. Sometimes, i used to drink for 1 or 2 days. It was fantastic for me!!
Only a suggestion!!! Good luck!!
Alicia, I eat an only meat diet (with some cooked carrots sprinkled in), and have done for years. It makes a difference in how I feel, but it certainly was not a cure.
When you say that you minimize carbs………….what foods specifically are you referring to? Most all foods contain carbs.
Interesting! Wondering what criteria were used to determine mild, moderate, and severe ME/CFS – clinical criteria, questionnaires? Maybe we don’t have a good method of distinguishing?
I was only diagnosed with FM by a physical Medicine Specialist, but always felt that I also had CFS. This research has confirmed my suspicions.
Abut 10 years ago, My Naturopath Doctor had me tested for my AMINO ACID status. Most of my essential amino acids were rock bottom. Included with the lab results, was my exact prescription needs, witch my ND. sent to a compounding pharmacy to be filled.
Amino acid therapy has been “a God sent for me” It has been the most beneficial treatment I received in my 29 years of health struggles. Though I’m not cured, I’m a functional human again! My FM symptoms are being well managed by my MD & ND.
My Amino Acid test was a 24 hour urine collection, sent overnight to DR’S DATA LAB IN THE USA. They have other labs in some countries and I’m sure there are other labs doing this testing.
The results included the specific amounts of the amino acids I need.
My ND. sent the information to a compounding pharmacy.
The amino acids came in a powder form and I take a heaping teaspoon morning & evening.
I also want to mention the following book which my MD. & ND. found really helpful in the treatment of both CFS & FM. I bought & gave it to them.
FROM FATIGUE TO FANTASTIC, 4th edition
Dr. Jacob Teitelbaum
He also was diagnosed with CFS/FM. In this 4th edition, he shares all the medical & natural therapies he has used in his years of practice, plus a guide for diagnosing our difficult illnesses.
thanks for the tip! hope they have aminoaciid test here to…
may i ask where you bedridden to in darkened room, etc? on wich level where you if i may ask? I do not know how to get so bedridden an aminoacid test. i ordered wheyproteine with al kinds of aminoaccids but that is as you describe not the good way..is it? thanks!
Wow…..interesting.I got the results of my Organic Acids test (OAT) yesterday. My amino acids are all VERY low !!!!!!
was the test in blood or 24 urine collection? by an alternative docter or at home through gp please? does it say how much amino acids you must take every day of each of them? thanks!
It was not a 24 hour test….just a sample of first morning void. It was ordered by my ND. It does not provide recommendations. I will be discussing it with my doc in a couple of weeks. The company was Mosiacdx.
thanks, i live in Belgium. who/what is ND and void please? good luch with it! hope it makes you better!!!
ND is a naturopathic doctor…..also called functional medicine doctors. Void is another term for urination !
thanks!!! i am to bedridden (99%) to go to see a nathuropath docter sadly enough. And they do no homevisits. i wish you good luck!!! and improvement!!!!
So sorry to hear that. I am housebound but my doc does video visits. I’ve been with him for 3 years but have never met him in person ! I hope something breaks for you in a positive way soon. This is all so difficult…
thank you, that is a sweet wish! here only gp of witch i may not decline or be put away, still only cfs, get, cbt, etc so no good thing…
ment good luck ofcorce…!!!
Edith please could you tell us which amino acids were the lowest for you.
It’s difficult for me to describe the graph showing the results of my test, but I am giving you my prescription replacement ordered. Please do not use my prescription as it’s specific for me and could cause more of an imbalance in someone else’s health.
These are L-configured Amino Acids.
Tryptophan 215 mgs
Arginine 830 mgs
Histidine 1205mgs
Isoleucine 1045 mgs
Leucine1485 mgs
Lysine 1385 mgs
Methionine 550 mgs
Phenylalanine 920mgs
Threonine 755mgs
Valine 930 mgs
Pyridoxal-5-phosphate (B6) 30mgs
Alpha-ketoglutarate 650 mgs
My biggest problem is malabsorption of food. Essential Amino Acids must come from the food we eat. My Naturopath Dr. also put me on superior digestive enzymes. Panplex-2-phase by Integrative Therapeutics. I also find that New Roots digestive enzymes with betaine and ox bile works great for me as well.
Thank you very much for your reply Edith. I’m not sure if I would be able to get my Amino Acids tested in the U.K. I promise I would not try to get your prescription for myself, I may just try a very low dose BCAA supplement for a short time to see if it would help. Thank you also for the information about digestive enzymes. I hope that you continue to improve.
First theory / pathological mechanism I feel has fit the basic physiology of CFS for a while.
My personal theory has always been inflammatory suppression of tyrosine and tryptophan hydroxylase which manifests as increased glutamate transduction and reduced central norepinephrine and dopamine transduction.
Interesting. So taking medication that boosts dopamine and norepinephrine should help?
In theory and Im not advocating medication for anyone else.
But they definately do for me personally (the best med Ive ever found was Pseudoephedrine and I was expecting to make my heart explode) but it appears others under the CFS rubic respond poorly to these. I did however wonder whether that low dose neuroleptic that helped some did so by boosting tonic dopamine transduction even as it lowered larger bursts. Pramipexole helps fatigue in Fibromyalgia as an example.
I hope so much that this test would be it, but honoustly-I find it strange that there is no sex difference. Many more women have ME/cfs then men. Also the NIH was talking about different tests for ME/cfs. But I cross my fingers that this will be it and that they go fast!
Interesting because a lot of people are talking about this in long COVID too and one treatment involves using niacinimide to get energy back.
AMINO ACID testing required my doctor to arrange for the test kit with Drs Data.
After a year on my Amino Acid prescription, my ND. wanted me retested. I had to be off the AAs for a month. Within 2 days, I was back in bed full time because I could not function brain wise. It was a hellish and long month. Back on my AAs, it took about 5 days to fully recover again.
I was taken off my AAs again 5 years later for testing, but this time, I stayed well. Was I happy!!!
This article proves how important Amino Acids are for energy recovery and I can vouch for brain function recovery as well.
I’ve always wondered why I couldn’t take tryptophan and nearly everyone else I know just thinks it’s The Answer to Insomnia.
Anybody else can’t take tryptophan? Now we know why.
Some years ago, I heard that Ron Davis from Stanford was perfecting a test for ME/CFS. What ever came of that effort?
Ron Davis has been working with Robert Phair (mentioned above) on the metabolic trap hypothesis.
I heard there were funding issues – they needed a grant that was not forthcoming and then an important researcher was lost to other projects outside of ME.
The grant was denied because the assessor wanted us to know ‘why’ the test may work and thought that was more important than ‘if’ it worked. But often we find out the ‘why’ later on. Early medics did not need to know about insulin and the pancreas to know that sweet urine meant diabetes…
(Referring to Ron Davis’ nanoneedle diagnostic test, not the metabolic trap/kynurenine areas, btw)
Would probably add to a better understanding if they also looked at samples drawn during PEM and on “normal days” separately. From all we know now (e.g. from Maureen Hanson´s work) PEM and non-PEM are pathobiologically distinct states. And most likely, the key to understanding ME/CFS is to be found in this gap.
for me no more..got ill in ’94, could do a bit, crashed a week, but now 99% bedridden. how do you measure for the bedridden oned the “good” days? it is a continu torture, every day, every hour, evere second, every year, every decade… And we are with 25% home and/or bedbound.
In 2016, VA researchers found the following:
“Based on a study of 85 Gulf War Veterans, VA researchers in Minneapolis have developed a tentative panel of blood markers they say can verify a diagnosis of Gulf War Illness with 90 percent accuracy.
The method now needs validation in larger groups of patients, say the researchers.”
Gulf War Syndrome affects as many as 300,000 veterans who served in the first Gulf War and has symptoms like ME/CFS. In fact, ME/CFS is 100% service connected in Gulf War veterans.
As far as I have been able to find out, the VA blood marker study was never repeated.
what a scandal…I hoped there was more money for GWI. I allways thought, serve you country with your life and get that in place and no one cares… so sorry!!!
Hi Konijn,
I apologize that my email was confusing. The Gulf War veterans diagnosed with CFS were 100% compensated. That means they received the highest level of compensation the VA provides. They also are approved for Social Security Disability.
There must be something about tryptophan (serotonin) level. I noticed that after eating food rich in tryptophan I feel much worse. I learned to avoid it.
This is all very interesting. I get lost in the finer details but I can relate to the production of ‘dirty energy’ from glucose. Last year I discovered through gut testing that I wasn’t metabolising fat (so assume that was pushing my body to use amino’s). Once I added a digestive enzyme my energy improved rapidly and has been stable for over 12 months (I still take the enzymes with every meal)
I also started supplementing with tyrosine last year (in addition to 5-HTP which I’d been on for a while). My psychiatrist diagnosed a dopamine deficiency and prescribed me dexamphetamine (which I thought was crazy given my very slow COMT). My integrative doctor suggested tyrosine instead. My depression cleared up rapidly and I have not had a day of low mood in over 12 months (after 15 years of rapid cycling mood changes).
It’s hard to know if it was the amino’s or other gut therapies (probiotics and strict dietary elimination alongside the enzymes) that worked wonders but I’ve gone from 20 years of fibro pain and moderate CFS to being symptom free for 12 months.
GforGeorgie, can you tell me which digestive enzyme you took and the dosage? Also the type and dose of tyrosine? Thanks very much for sharing your wonderful health news.
I use Thorne Bio-Gest (AKA Advanced Digestive Enzymes), 1 at the beginning of each main meal.
I take 1/4tsp of pure tyrosine powder daily.
Please note that both of these were recommended to me by highly qualified medical professionals who continue to monitor my overall health and supplements regime. These recommendation were based on long term observation and functional testing. They may not be suitable for everyone.
Thanks so much, GforGeorgie! I’m ready to try something in addition to my usual regimen. I’m not afraid to experiment once again. Your experience is very valuable, as is this amazing HeathRising site. Cort keeps us all going in the direction of the best health we can have. I’m grateful.
Oh my! I’m almost 79 and have had ME/CFS (1997) and Fibromyalgia (1988) since forever. All this information, though quite interesting, sometimes makes me feel like my brain will explode!
Regarding the serotonin, I have been on one antidepressant or another for years. I am currently on Pristiq, a SNRI. If too much serotonin is entering the brain, or causing dysfunction, I wonder if taking a SNRI may worsen things. But being off of them is rather bad, too. 🤔
I do have methylation problems. I have not investigated this issue further, however. I had just mentioned to the telemedicine doctor who prescribed my LDN in the past that when I take more than 1000 IU of Vit D, the arthritis in my hands worsens. She said “that sounds like a methylation issue.”
Maybe I will still be alive to see some of this ongoing research come to fruition. 🤞
Hi, Judith, I’ve been taking Rich VanKonynenburg’s 5-supplement protocol for my genetic methylation problem for years now. Here’s a link if you’d like to check it out:
https://www.healthrising.org/treating-chronic-fatigue-syndrome/treatment-protocols/methylation-treatment-plan-chronic-fatigue-syndrome-me-cfs-konynenburg-ph-d-ii/
Thank you very much, Sarah. I did read that on Cort’s site some time ago, but didn’t follow up on it.
You likely already knew this. Rich Van Konynenburg passed away from a heart attack in 2012. I do not have any physician among my physicians who would support me in such a protocol here in NY. Being on Medicare supplemental, no medical provider would probably try and guide me through this. There are things in the protocol that I have had bad reactions to, and all the meds I take would need to be evaluated. I am so glad it has apparently helped you for years, Sarah.
Don’t know where to put this in the comments, but re:- energy Health Rising ,2021 or 04/11/2022?, Mitochondrial Enhancers part 4 or 6 ? Niacinamide, NMN nicotinamide mono nucleotide, nicotinamide riboside…. from Comments section, Colm Smith:- ME/CFS/Long COVID
R ALA, (R alpha lipoic acid) IS KEY TO GETTING NIACIN INTO CELLS ( into mitochondria through gated ion channels? )
Protocol from epidemiologist studying Alzheimer’s & dementia
High dose niacin,500mg, r alpha lipoic acid 500mg
methionine
B vits
Theory involves
Leaky Gut
Lack of Butyrate producing bacteria
Low melatonin
Low NAD
Papers on Niacin effects on T cells, immune system, & inflammation
R-ALA IS KEY , gets niacin into cells, otherwise there is lots in the blood -> flushing
Reactivated EBV & Herpes virus’
Links to refs
Also Dimitry Kats PhD MPH ME/CFS/LCOVID PROTOCOL
Join community on Telegram HOM3OSTASIS
I was already taking R ALA & niacin 2x daily but separately, put them together et voila no more flushing & more energy, but it quickly runs out.
Taking lots of Bs including B1 ( does makes for blurry short vision, but just put on reading specs) B3, B2 , B5 , B multi, methyl B12. plus many other supplements,
I know the authors are probably tired, but what are they doing next?!? Can’t wait to see where this goes.