A research team at Stanford gave an update yesterday on some of the breakthroughs its team has made in understanding the metabolic cycles that are not working properly in people with ME/CFS that might be at the heart of the disease.
Ronald W. Davis, PhD, made the announcement via YouTube. Davis directs the CFS Research Center team at the Stanford Genome Technology Center (SGTC).
Problems with metabolic cycles
The team’s metabolomics tests on severely-ill patients revealed problems with the citric acid cycle. Participants’ blood work showed that some of the chemicals involved in the citric acid cycle are very low, making it difficult for the patient to generate the chemicals we use for energy. Several chemicals were found to be two standard deviations away from those of healthy controls, which is serious, according to Davis. The problems found in the citric acid cycle of ME/CFS patients does not look like the result of a typical genetic defect in the mitochondrial metabolism, Davis noted.
Recent research by Fluge and Mella has also suggested that pyruvate dehydrogenase, the enzyme that helps glycolysis transition into the citric acid cycle, may be blocked.
“We have not investigated that, but it is consistent with glycolysis being shut down,” Davis said. “We also think that pyruvate kinase might be shut down. Those are not inconsistent and it is possible there are blocks in both of them.”
The problem with NIH
Davis and his team applied for federal funding from the National Institute of Health (NIH) for the research that led to the data showing the dysfunctional citric acid cycle in people with ME/CFS. The NIH turned down both of his grants “because we were trying to do discovery, and they wanted us to only do hypothesis testing,” Davis said.
“I said to them: the scientific method is first observation, then hypothesis. And if you have virtually no observations you can’t generate a good hypothesis. I think one of the big problems we have is that we do not know enough at the molecular level to generate hypotheses.”
Technology to screen drugs without using patients
Davis also announced a device that the Stanford team has developed to test metabolic functions, which will enable them to do mass screenings of drugs without the time and cost restraints of using patients.
The device is about the size of a computer chip. It has a small channel in it to accommodate a tenth-of-a-drop of blood, all that is needed for this assay. It has 2500 electrodes in it, and each electrode is sampled 200 times a second. This generates a massive amount of data.
Davis explains how the device works:
“What we have noticed from this device is that if we put bacterial population into this, we will get a certain electrical impedance signal. If we then add an antibiotic that kills the bacteria, the electrical impedance will rapidly increase. If the bacteria are resistant to the antibiotic, we see no change.
“So, if we put healthy cells and their serum into the device, it is pretty stable and does not change. If we put in ME/CFS cells and their serum, it doesn’t change. However, if we put a demand on the cells, we require them to consume energy, and that demand is seen in this graph where there is a slight dip in the healthy controls – but they handle that demand quite well and don’t change after that – however the cells from the ME/CFS patient shows a rapid increase in impedance. And that has been shown for every patient we have looked at, and also every healthy control is the same.”
Most importantly, the device provides a way for Davis and his team to test drugs on ME/CFS cells and serum to see the effect.
Davis noted that the rapid rise in impedance is caused by the serum, not the cell, which means that there is something being released into the serum that may be causing or contributing to symptoms.
“If it is in the serum, we probably can find it,” Davis said. “And that is what we’re trying to do now, which is find the component or components – most likely plural – that is causing this effect… Now this a good hypothesis, and we are now testing it.”
Davis said that the next step is to use the device to test the effects of various drugs on the cells and serum of ME/CFS patients. For example, Davis’ team found that adding ATP to unhealthy ME/CFS cells and serum made the cells respond normally. The team also plans to test drugs that many ME/CFS patients have reported helpful using this device, such as Valcyte and Rituximab.
If the device turns out to be a good diagnostic test for ME/CFS, Davis said his team will disseminate information to doctors’ offices.
This device may be applicable to other diseases as well, including Lyme and Fibromyalgia.
The magnetic levitation device
Davis and his team have also developed a magnetic levitation device which separates cells based on their magnetic properties. The device is small and can fit onto an iPhone. This device can be used to separate and examine cells with differing properties, which has broad applications, including examining specific cell types in ME/CFS patients. The magnetic levitation device costs 5 cents per assay.
“We’re accumulating a list of things that we are trying with this device,” Davis said.
“One of our focuses is on developing engineered biosensors and devices. We also have a synthetic biology core that is used to develop new ways to do production of drugs and test drugs… So we have a heavy focus on how to reduce cost of tests and simplicity of those tests and portability,” Davis said.
Listen to Davis speak about the team’s research here, or read the full transcript.
The Open Medicine Foundation (OMF) is helping fund the work of Dr. Davis’ CFS Research Center team at SGTC. So far, their breakthroughs have been achieved by doing one experiment at a time, week-by-week. At this point, the team is ready to ramp up the project in order to carry out multiple parallel investigations to get answers as fast as possible. However, substantially more funding is needed for this to happen. Please donate to OMF here.
Some edits were made to this article by Jaime Seltzer.
48 thoughts on “Stanford team announces update on ME/CFS research”
Thank you for describing what’s in the video and for posting the transcript. I can’t watch videos over my dial-up internet connection.]
I am very hopeful that this research will be available to physicians.Here is a bit of background about me. I’m a 64 year old white female who lives in a very small rural town in Wyoming. I go to doctors out of town, as there are not the right specialists to deal with my health issues. I got active EBV 10 years ago which attacked my liver and thusly had hepatitis. After that I was diagnosed with CFS and was sent to a rheumatologist who did pressure point testing and diagnosed fibromyalgia. I soon developed neuropathy and was referred to a neurologist. He did skin punch biopsies in my legs. They were sent to a lab in New York. They diagnosed small fiber neuropathy that has gotten worse and worse over the years. I had to retire from teaching. My balance has also been affected, and I have to use a cane or walker. My stomach developed gastroparesis which was very bad. Doctors said it was from vagus nerve damage. I was on a feeding tube directly into my intestines, using a electrical pump for two years. I am now able to eat a special diet and take domperidone high I get from Canada as it isn’t FDA approved. Basically I’m a changed person who has become very introverted after spending my adult life very extroverted. I have developed recently urinary tract problems which include chronic infections. I see a urologist regularly. He has me on a daily small dose of antibiotics. I have had a dilation done which was helpful initially. I have severe chronic dry eye and poor production of saliva which is causing dental problems. I also developed a tumor in my gall bladder and the whole gland was removed. I naturally have depression and difficulty with sleep even though I get very “foggy” frequently during the day. I spend most of my time in bed. I make small goals of doing activity away from home that don’t involve seeing doctors. I would love to be considered for research. Thank you!
Thank you Ron Davis!!! This is very exciting. I’m hopeful for all of us.
I’m an RN who was bicycling 200 miles weekly and working full-time until ME dropped me dead in my tracks after getting the flu on 12/24/09. I just want to add my thanks as well! Praying for that day I will be able to tolerate being up again!
Thank you Ron Davis and your whole team at OMF! There is HOPE for those of us ill with me/cfs. And thank you to Adriane to sharing this information with us.
This does not seam to correlate with the Australian theory that people with me/CFCs may have an aberrant cell or gene that is part of the immune system and could be causing the condition.
It may be part of the reason why some people get it and others dont, and may have a role in explaining the long-term continuance of the illness. Ron Davis mentions Valcyte [sp] and Rituximab as possible treatments. The latter works on the immune system, the whole disease feels like PTSD for the immune system. My own experience tells me that Mg is involved, and Ca and Mg are usually paired in cellular processes. Its all so very exciting, I just have to have a lie down…
I believe there is more correlation than might be evident initially. Immune dysfunction is consistent with a hypometabolic state. We are not reliably producing sufficient energy to properly run our immune (and a number of other) system(s). Hence, immune dysfunction.
This research is suggesting that cells are not producing energy properly because of a signal/toxin/whatever in the blood. That is consistent with the idea of aberrant cells that you mentioned.
Or, from another perspective, the Australian group is suggesting “something” (cell, gene) is disrupting the immune system. That “something” could be whatever is running around in our blood that is disrupting energy production in immune cells (along with many other cell types).
Finally, we don’t know what is the origin of this substance in our blood that is shutting down or disturbing some of our metabolic cycles. It’s possible there is a genetic factor, so genes could be involved.
IIRC, Davis et al said earlier that this hypometabolic state hypothesis can easily explain most of our abnormalities — immune, hormonal, cognitive, GI.
Thanks for that helpful summary JJ. I just wish the research teams in Australia, USA and the U.K could get together – they are all doing similar types of research and I’m sure would make more progress working together than in their respective silos. Researchers in UK have developed a test that measures energy production and expenditure in blood cells, measures the effect of magnesium on the energy production cycle (citric cycle) and determines whether any DNA adducts are there – and if so, they can identify which chromosone the adduct is on and what chemicals they are caused by. Treatment can then be directed at improving the nutrient deficiencies and detoxing the liver to eliminate the DNA adducts. Sadly, there is only one lab who will test patients blood and only certain practitioners who the Acumen lab will work with so not easily accessible even for those willing to pay the cost of the tests.
I would also recommend the book by Dr Sarah Myhill that Tom Wood mentions in a post below. She has been involved in this research and has published a few papers with Prof Tom Booth and Dr McLaren from Acumen labs. What they have been doing complements and extends Davis research and whatsmore, her approach is proven to work – it does lead to recovery.
It all stems from the health of our gut! When I was told that 20 years ago I laughed and didn’t believe. Now I not only believe, but understand why our gut is so intricately linked to our immune system and health.
My immune system is over active after an infection the same as Auto Immune so I do not know where you get that from
It would be totally consistent with that. Both Davis’s team and Fluge and Mella’s team found that whatever is causing the problems with the cellular process that generates ATP (the energy currency of the body) is found in the blood. This could plausibly be immune factors (though other things are possible as well).
It’s early days, though, and more research is needed with more participants before we can be sure of anything. To that end, more funding is needed. And having several labs looking at different aspects should be helpful.
All the best.
If an aberrant immune system cell is responsible for producing whatever is in the serum that causes metabolic malfunction, then the two research channels will likely merge into a river of knowledge.
If you’re not able to donate directly to the Open Medicine Foundation for whatever reason, you can do what I do: when you shop on Amazon go to Smile.Amazon.com instead and choose OMF as your recipient – then every time you purchase something a portion of your purchase will be sent to them at no extra charge to you!
As someone with severe ME, I am happy I can contribute in some way to the amazing work Ron Davis and everyone else is doing over there… Mahalo nui for your diligence and dedication and to the team at MEAction.
What a great idea, Donia!
As someone with ME/CFS for many years, I am heartened by the news of these innovative approaches to hopefully treat this illness. Thank you ME action, and to the Stanford researchers, for your encouraging efforts.
If you’d like to save lots of time and donated money, stop trying to reinvent the wheel. Buy and Read “Diagnosis and Treatment of Chronic Fatigue Syndrome and Myalgic Encephalitis – It’s mitochondria, not hypochondria” (New – Second Edition) by Dr. Sarah Myhill, the well-known UK Doctor who has been working of ME/CFS. I’ve had ME/CFS for years and had learned that our problem is largely a problem with dysfunction or our cellular mitochondria – the essential step to move energy from the Blood Stream to Muscles (i.e., From Blood Energy to Muscle Energy). I ordered the new 2nd edition and received in on Feb 9, 2017. I’m not cured, but I’m getting better all the time. If you want to help people, please educate yourselves first – Read This Book.
I have read that book, though not the new edition. It sounds a bit premature to claim that this is the answer as it is early days for you. I have also written to Dr Myhill about Mg [which worked brilliantly for a year and now doesn’t work at all] and she could throw no light on my experiences. Not that I would expect help there, but its hard to find researchers to discuss it with. I found her advice in the book not helpful to me, but will now re-read it. My experiences tell me that we have a faulty battery, in all cells. Good luck, I hope the improvement continues. Do let us know how it goes.
Beatriz, I understand that Dr Myhill had an accident and broke her spine so has not been taking or dealing with patients. My recovery was supported by the nutritionist at Optimum Health Clinic in London who use similar protocols as Dr Myhill and functional tests to determine the next steps for each individual. I think her book is very helpful but confusing for many people and some of her recommendations unnecessary. I believe all who have this condition, have one or more underlying issues and until these are detected one by one, then full recovery is impossible. For some people the underlying issue is mitochondrial dysfunction alone but for others myself included, it was also adrenal fatigue and when recovery stalled again, another functional test revealed undetected parasites in the gut. I would urge you to explore the help available at the OHC which is a charitable foundation started more than a decade ago by someone who had recovered from ME and is determined to help others too. Good luck on your journey.
I agree. Much of what is now being deemed ‘new’ research has already been done by the brilliant biochemist Dr John McLaren Howard in the Uk along with Dr Myhill. Suggest everyone reads her book Chronic fatigue syndrome It’s Mitochondria not Hypochondria.
Many thanks and hopefully one day this sickness will become a past! Difficult to believe considering the damage level and severity of the sickness, but there is always a HOPE!
You are giving us all hope, Dr Davis. My daughter is very ill with this terrible disease, and I pray for you and your team to come forward with at least a viable treatment to relieve the pain and suffering that this insidious disease.
“Cannot utilize glucose”
Diagnosed with diabetes two years ago precisely when my fatigue began.
I believe there is a mistake in your text, when you mention “Some research participants showed accumulations of specific chemicals within the cycle, implying the presence of a block” from the video, And the transcript from one patient, Dr Davis mentions accumulation of specific substrates in the Citric Acid Cycle in mitochondrial disease.
Here is the transcript passage:
” You can also see an awful lot more blue than red, which suggests it is a hypo-metabolic disease. That is what I could see in the first 15 seconds. So you can look into all the metabolic cycles and learn a lot of detail about a particular patient, but a particular interest is looking at a citric acid cycle, which generates all of the energy for a person. And if you look at that you realise there is an awful lot of blue, that means the citric acid cycle intermediates are all very, very low. That suggests that this patient cannot generate energy or ATP very well.
If we look at a patient that has a mitochondrial defect, you see it all in red. That means that it accumulates the citric acid cycle, because it can’t burn them. So that is a case in which a person cannot burn the glucose that they are getting. The fact that the citric acid cycle intermediates are somehow shutdown, and if we look at that we say that probably glycolysis is actually shutdown [in ME patients].”
i would appreciate knowing whether you are providing new unpublished data or this is simply an error.
Thank you for your comment. We’ve made a few changes to the paragraph that address your concerns.
HI while we are waiting on whats really happening to be worked out, is citric acid to be avoided ?
Well it certainly appears to be a basis for carrying out more research on and there is definitely a pattern for which ME/CFS sufferers are following here!
Helpful and Challenging- our own much smaller study is consistent with Ron’s results and future possibilities
I’d like to donate but I don’t see a secure connection or a Paypal option.
Here’s the link to donate to Ron Davis work via the Open Medicine Foundation, which supports his lab: http://www.openmedicinefoundation.org/donate-to-the-end-mecfs-project/
If you’d like to donate to #MEAction, here is our link:
Thankyou for your dedication to researching this terrrible illness. I have suffered/battled with it for 29 years. And became frustrated little investigation was being done. It has cost me 250,000 over this time in alternative treatments & supplements to keep going. For me when I crash it is very connected to the symptoms of complex migraines.
I actually feel a ‘block’ in my physicial and neurological functioning.
I wonder if and research as been done to draw connections between migraines and CFS. I also have had low lymph readings .5 to .8 for years as the only blood test marker. (Possible viral cause?) Once i managed to get my lymph up to 1.5 nirmal is 1-4 and i felt very different my exercise intolerance dissappeared completely. Unfortunately i couldnt keep the levels there. Thanks again for yr work.
Thank you for posting this amazing and inspiring talk by Dr Davis.
One minor question I had after watching this is, if pyruvate has an effect like he found, why isn’t it going to be useful for treatment?
We patients are extremely fortunate to have Dr Davis working to find a cure; the work that he and his colleagues are doing is, I believe, going to be what solves this puzzle.
Please everybody, support the OMF in any way you can, so they can find an answer and stop the suffering.
I am failing to see that this is a breakthrough when Dr Sarah Myhill and the brilliant medical biochemist Dr John McLaren Howard have been working on this basis for a very long time in the UK. Could someone explain the difference between what they are doing and this ‘new’ research. Thank you
Dr Myhill has always maintained that the blockage is WITHIN the mitochondria (caused by heavy metals blocking ion pumps, for exmple). This new research is pointing towards a substance (perhaps autoantibodies?) in the serum, not within the cell. The knock on effect is that citric acid cycle and electron transfer chain go slow. Research is also pointing towards genetic mutations playing a role in this – aka making individuals susceptible in the first place. Also, if this is true, then it is unlikely that detoxification and supplementing mitochondrial cofactors will be enough for some/most ME patients…I think that’s the difference. Its a more complicated picture.
I have to say that I’ve followed Dr Myhill’s advice and regimens diligently for nine years (because i was convinced she was on to something and I had nothing else to offer me any hope besides), and I have a lot of respect for her. She’s a star! – But I have certainly not been cured. I haven’t gotten worse, but I have made very little progress, if any.
Thankyou Rachel for this email …I can really relate my story is very similiar I too have followed Dr Myhill’s program and have not got much worse but not better either..thx
Thank you for your hard work and dedication on behalf of so many sufferers.
Grateful thanks from someone who has lost 30 years to this awful illness.
I have read where Dr. Myhill in the UK suggested that 1000mg of Acetyl L Cartinine has the potential ability to help the affected cells to begin metabolizing as they should, as well as giving increased energy as a result. Have you done a test using this supplement? I have CF, fibromyalgia, myofascial pain syndrome, advanced degenerative disc disease and osteoarthritis, needless to say, my quality of life
is not good. I have just ordered a bottle of the above supplement to see if it helps me.
I hv been in contact with sr myhill 8 yrs ago i hv had cfs fibro ibs complex migraines for 28 yrs I take 2000 acetyl cartine 200 coq 10 Dribroise 15 grams Magnesium glycenate **600 -800mg Epsom salt baths All these are from Dr myhill then i also take
Ala r 200mg Nac 500mg Zinc 50mg Vit c ascorbic acid 5000 mg 5 tbs coconut oil Sea salt minerals in my water 6 cups a day &
4 cups liqouirce tea
These hv helped me enormously Along with gluten free diet And no nitrates or preservatives mo margarines No white sugar.
Best of luck dr myhill is a leader in the field imo and her book and website hv been a tremendous help
Thanks Dan, helpful information. I too follow a gluten free/dairy free diet and this was my first line of attack for inflammation.
Yr welcome Pam best of luck wit this very challengimg condition
Please can someone update the UK M.E. Association with this if you have not already done so. Dr Charles Shephard needs to know about this to get it into the next Membership Newsletter. This is so exciting, what a lovely man you are, and the emotion is evident when you discuss it with your son as a sufferer. I am an M.E. Sufferer and I am upbeat most of the time. But this is the most useful thing I have seen or read for such a long time and I have been researching Cell Biology myself for a while as a type of hobby because it is where the problem lies I have been certain about that for so, so long. I am so incredibly hopeful now but we must get this news out to as many people as poosible through all the organisations and charities all over the world before they try to supress it. Because they are trying to supress it.
My daughter who is 24 has had me CFS since birth I believe. She is close to bedridden now. The supplements mentioned above we have tried with no real Improvement we have tried removing gluten and sugar and she actually got worse. Sugar and simple carbs seem to be essential or she has no ability to even get out of bed. She relies on caffeine to have some mental Clarity but of course that tends to make the energy worse. It is such a balancing act between enough sugar and too much. I read that me CFS is very hard on the pancreas. Do you have any thoughts advice regarding the pancreas and should there be pancreatic testing. I read that recently that cardiac testing is important. Testing that shows the amount of blood that’s flowing through the heart not typical EEG type of testing. I will be asking our doctor for that next time. I wish there were specialists in this. Our family doctor does not seem know anything or to care very much. Charlotte was depressed for years before meCFS was finally diagnosed I still think he thinks that she is a hypochondriac. She is far from that she is never a complainer. Amazingly no longer suffers from depression incredibly given how sick she is. Thank you so much for your work. The the family and Friends and sufferers the world over thanks you. I pray every day for cure but we will also try the drugs mentioned because I didn’t know about those. While writing my comment I saw that there is a way to get on your email list for others reading the comments may like to know that.
Believe this is HIGHLY relevant!!!
Metabolic features of chronic fatigue syndrome
Robert K. Naviauxa,b,c,d,1, Jane C. Naviauxa,e, Kefeng Lia,b, A. Taylor Brighta,b, William A. Alaynicka,b, Lin Wanga,b, Asha Baxterf, Neil Nathanf,2, Wayne Andersonf, and Eric Gordonf
aThe Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine, San Diego, CA 92103-8467;
bDepartment of Medicine, University of California, San Diego School of Medicine, San Diego, CA 92103-8467;
cDepartment of Pediatrics, University of California, San Diego School of Medicine, San Diego, CA 92103-8467;
dDepartment of Pathology, University of California, San Diego School of Medicine, San Diego, CA 92103-8467;
eDepartment of Neurosciences, University of California, San Diego School of Medicine, San Diego, CA 92103-8467;
fGordon Medical Associates, Santa Rosa, CA 95403
Edited by Ronald W. Davis, Stanford University School of Medicine, Stanford, CA, and approved July 13, 2016 (received for review May 11, 2016)
Dear Dr. Davis,
When you described the results of the serum swap, you could have knocked me down with a feather — and not just because I, too, have ME/CFS. The metabolic graphing data were also impressive, showing widespread effect and not just a single locus or worse, no site of effect at all. I look forward to more. Thank you and everyone in your lab for their hard work. Thanks also to your son, as he perhaps inspired you. May he and all of us return to full health, someday soon, because of your efforts.
Thank you so much Doctor Davis. I have had ME/CFS for thirty years. God bless you for your work . J
Thank you to the team doing research for possibility of some off getting our lives back. God Bless your efforts to success.
Please add me to the list to receive your newsletter.
Thank you; we will.
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