Newbie: Pots, Mast Cell Disease And Lots Of Pain.

[Science girl]

I'm quite new to this site though I've been reading a lot here all year. Thank you for all the things you all share that have helped me understand my illness better. I have called myself science girl as I have had to become the expert to get any help. I haven't practiced as a molecular biologist for 13 years now and find it funny that this part of me has been reawakened to find an answer to my own health.

I have had a positive tilt test for pots and am on mast cell stabilizers as I have a clinical diagnosis of mast cell disease. I live in Belgium and there are no tests for MC activation here expect tryptase which is not raised for me. I did react well to the ketotifen I have been on but still get lots of break through symptoms especially the more active I become putting me back at square one - flat one my back!

Since being on the stablizer I have found I have heaps of pain and immobility in my pelvis and knees. In fact the better I feel (with regard to the fatigue, muscle weakness, flushing and POTS) on the meds the worse my pelvis gets. This is really hard and disheartening. Is this normal for anyone else? If I aggregate my pelvis the next day all my mast cell symptoms are back then the POTS sets in. They say I have pelvis instability and I need to do physio exercises but the exercises cause this reaction too. I know many of you have EDS, is cyclic a problem for you too and how do you overcome it?

I have seen a internalist, endocrologist and bone specialist, physioclinic, cardiologist and allergist. Of which no one can really help me with all my symptoms. Who would you recommend seeing? Would a neurologist help? I get nerve pain in my legs and arms and experience tingling, burning pains and when lying down after prolonged time with my heart raise while upright i get this tingling, buzzing feeling through my body like im surging with electricity and as i recover i have whole body twitches/convulsions (like when people are shocked in the ER). Just recently I have started having random muscle contract involuntarily so much you can see the muscle bending in. This has only happen 2 times but doesn't hurt.

Is there anyone here who lives in Europe or England and knows of a POTS or mast cell specialist?

I feeling really alone and misunderstood. I not sure if I should keep looking for help or just try and get by on what I know now and experiment with the mast cell drugs for relief.

Really happy to be on this site. It's amazing to know there are others out there who understand your world.

Thanks Karen

[DoozlyGirl]

Karen,

Welcome! Glad you felt comfortable enough to begin posting. You will find everyone here very informative and helpful. I also have MCAS and likely VEDS, in addition to orthostatic hypotension and autonomic neuropathy, so understand how frustrating all this is.

There is some discussion in the academic world that mast cells could be responsible for the whole mess. But I am finding in my case that I have issues stemming from my inability to process/breakdown/inactvate various items, such as sulfur/thiol based meds and food, sulfite preservatives and food dyes, all related to single nucleotide polymorphisms (SNPs) along my methylation cycle. My CBS SNPs lead to ammonia toxicity and exasperates brain fog. I also have SNPs related to diminished capacity to deactivate and catabolize histamine, norepinepherine, epinepherine, dopamine, and estrogen, all which correspond directly to my specific symptoms. Once you get your feet wet around here, this methylation stuff may fascinate the molecular biologist in you. Here is a link to get you started. http://www.drmyhill.co.uk/wiki/CFS_-_The_Methylation_Cycle. You may want to check out Dr Amy Yasko's work.

I have attached a link to The Mastocytosis Society, the US based organization dedicted to mast cell disorders. There are two well published mast cell experts on the TMS Medical Advisory Board, both whom from what I've read, actively diagnose and treat masto and MCAS. Dr Escribano authored the REMA Mast Cell Emergency Protocol, but Dr Valent, I believe, is closer to you.

Best wishes,

Lyn

http://www.tmsforacure.org/medical_board.php

Luis Escribano, M.D., Ph.D

Director, Centro de Estudios de Mastocitosis de Castilla la Mancha (CLMast)
Hospital Virgen del Valle
Carretera de Cobisa s/n
Toledo E-45071 Spain
E-mail: lescribanom@sescam.jccm.es OR luisescribanomora@hotmail.com

Peter Valent, M.D.

Department of Internal Medicine
Division of Hematology and Hemostaseology
Medical University of Vienna,
Waehringer Guertel 18-20
A-1090 Vienna, Austria
Email: peter.valent@meduniwien.ac.at
Phone: +43-1 40400 -5488 or -6086
Fax:: +43 1 40400 4030Phone: +34-925269335

[Science girl]

Wow thanks for this information and you might be right about it tickling my molecular biologist bone! I have wondered if clearance issues (through methylation) may be an issue instead of activation of the mast cells. But I have found as far as I tolerances go it is mast cell activators that I react to. How did you get tested?

Looking forward to looking through the info. Thanks again.

[DoozlyGirl]

Wow thanks for this information and you might be right about it tickling my molecular biologist bone! I have wondered if clearance issues (through methylation) may be an issue instead of activation of the mast cells. But I have found as far as I tolerances go it is mast cell activators that I react to. How did you get tested?

Looking forward to looking through the info. Thanks again.

Karen,

I'd love to hear your thoughts on methylation and all this. From my reading, i believe that methylation issues AND activation of mast cells are both involved in my case. Since methylation is responsible for deactivating histamine, and histamine is broken down by DAO (extracellular) and HNMT (intracellular), My DAO and HNMT SNPs point to issues here. Mast cells can be triggered by inflammation, digestion, stressors (such as chemicals, stress, hormones, weather, meds, allergens, etc) and set up further cascade through degranulation, leading to anaphylaxis. I face cardiovascular anaphylaxis when exposed to chemicals, such as aspartate, MSG, sulfites, Yellow # 5/6 food dye, and others. Now that I know those ingredients are excitotoxins, and what they do to the nervous system, this fits in my case.

I've found that once I removed as many stressors as I could identify, my mast cells calmed right down. They still trigger, but not nearly as much as several months ago. I eat things that limit inflammation (goal is to eat gluten and casein free), low sulfur/thiols and low animal proten (due to CBS issues and lead to high ammonia). I rotate and moderately eat histamine foods, based off my previous reactions, but admitedly don't have issues with histamine, oxalates, or salicylates in my foods. Meds were a HUGE trigger for me. Once I learned of my SNPs through 23andMe, a personal genome service, I was able to chase down the meds and supplements and foods that set me off.

After reading up on my CYP 450 SNPs, I have learned that Tagamet is a DAO inhibitor as well as Zantac, ALA, milk thistle, contains sulfur so is contraindicated until clearing my CBS status. My reactions to sulfur/sulfites/sulfa and are screaming that I have issues with CBS and SUOX, and 23andMe confirmed my CBS and MTRR hetero SNPs. From a dysautonomia perspective, my homo COMT, VDR, MAO A and MAO B SNPS all deal with tolerance to accept methyl donors, and point to issues breaking down dopamine, nor epi, epi, serotonin, and melatonin.

I have stopped looking for the magic pill and one size fits all solution. I am now using my own biochemistry to guide my personalized treatment. In this light, I am looking to it all: methylation issues, leaky gut, inflammation, underlying co-infections, heavy metal toxicity, mast cell degranulation, nutritional deficiencies, malabsorption, and the list goes on.

When you get to the point of wanting to persue this, there are tons of solid resources out there, FB pages, webinars, satelite radio shows, etc.

Would love to hear your perspective on methylation and hear how you are able to connect the dots in your own journey. Thanks.

Lyn

[issie]

I'm along with you guys on this line of thought. I have HyperPOTS, MCAS and EDS and recently DX'd with a protozoa and co-infection. I also have autoimmune issues going on too. Interestingly, I have many of the mutations in the methylation pathway that Lyn has. I'm also trying to understand this and learn how it works and what to do to reset the pathways and make them function better. Interestingly, the diet that I was put on for the protozoa issue ---addresses a lot of the mutations in the mehtylation pathways that I have.

Eager to learn more on this subject.

Issie

[Science girl]

I enjoyed reading the first site you posted by the doctor in Wales. If help me understand more about what might be happening with my body pain. I found his take on fibromyalgia refreshing. It was very validating. I get the sense from many doctor that they see this as a result of people being stressed and therefore tensing their muscles. I find this offensive and so oversimplified. My own doctor told me to not mention fibro as most doctors will stop taking you serious! But the reality is that my muscles, joints, nerves and bones all hurt and we need to try and understand why. His explanation of lack of oxygen to produce ATP makes heaps of sense with POTS due to the circulation problems. I get lactic acid fatigue in my arms and legs for hours. Though I didn't quite follow the negative glucose relationship he explains, as normal aerobic energy production uses glucose and oxygen. Also his advice on exercise was very helpful.

Wow doozlygirl it will take a bit to digest your mail. You have certainly done your research. I'm not sure of all the acronyms tho. If you read the other thread of this question you will find my story. It was the immune clinic in London that told me to get tested for mast cell activation disease. I had written to them about my reaction to h1 and h2 blockers. Basically they cause the symptoms of the other receptor which lead me to believe I had high histamine levels ie block one makes it more likely for the histamine to bind to the other. I found this clinic as I was looking to see if the DAO and HNMT. Many of my family have histamine related issues so I started to look up medical articles about histamine clearance and mutations and discovered links and wanted to know if the tests had made it out of the science lab into a clinical setting. At this stage I hadn't heard of MCAD. Since being positive for POTS MCAD seemed a more logical link and I haven't pursued having the genetic tests but this clinic could also do the N methyl histamine and prostagladin d2 test for MCAD too. I asked the allergist to write me a letter for my insurance to say I could get the tests done in Belgium and recommend going to england but be wouldn't do it as this clinic is not a university hospital but he did not know any hospital who does them either! I may just pay to go to England.

I also rang a genetic lab who does the testing to find out if these polymorphism where actually mutations but they couldn't help me. You see we can find polymorphism in many genes but they have no clinical significance as they don't change the molecular structure of the product ie enzyme, proteins, receptor...whatever the gene is a blueprint for. Therefore it is not possible for a functional change to occur in the molecule either. My concern was that many of these tests are done by clinics that are alternative or nutritional. There advice has obvious bias to what is good and bad food ie all should avoid milk, acholol, coffee, sugar...whether it is related to your disorder or not. It is easy to test for polymorphism that have no evidence of causing functional disruption and with these other obvious other bias I was reluctant to trust the testing also. Not that conventional medicine is unbiased - not by a long shot!

How did you get tested for you genetic findings?

Blessings and thanks again for the mind simulation!

[DoozlyGirl]

Karen,

Sorry about all the acronyms. Not sure what you know, so I'll go through and share a bit on the acronyms I used. CYP 450 enzymes are part of Liver Phase I Detoxification and are companions to Liver Phase II Detoxification where methylation SNPs fall under.

SNPs= Single Nucleotide Polymorphisms, transcription errors tested by companies like 23andMe, where I got part of my genome tested during a research protocol testing mast cell disorders as part of myeloproliferative disorders. Now, the price of the genome testing using saliva costs USD $99 through them or a higher with other testing companies using blood. The real value of this testing is in the raw data, and there are several avenues to help with looking up the rs ID numbers, comparing to the risk alleles, and identifying hetero or homozygous status for the important SNPs.

There is a growing interest in epigenetics and nutrigenomics, especially with overriding MTHFR SNPs, and now SNPs along the mehtylation pathways. Dr Amy Yasko has numerous resources, including her Pathways to Recovery book that goes into some detail about the individual functions of various genes along those detoxification pathways. Her book and work is foccussed on autism, but has been expanded to include neurological and immune disorders. She also has a molecular biology, medical research and ND background. I have found that my symptoms correlate spot on with my SNPs, and have given me insight in sorting out other issues.

Yeah, H1s and H2s may help, but there is emerging thought that this causes competition for the remaining receptors, H3 and H4. I'm now confident it is better to tame the immune responses and get to the root cause of this metabolic imbalance. Some antihistamines contain additives, dyes, preservatives, etc that trigger mast cell degranualtion. Do you list somewhere which antihistamines you actually took? Depending upon your SNPs, some can cause more issues than may be helpful.

Back to the acronyms. ALA - alpha lipoic acid, a common supplement to help neuropathy. CBS and SUOX, two genes/enzymes along transulfonation pathway in the methionine cycle. MTRR is in part responsible for recylcling Vit B 12.

The rest are part of the BH4 cycle. COMT is responsible for breaking down dopamine, epi, nor epi, estrogen. VDR is the Vit D receptor and in combination with COMT determines ones ability to accept methyl groups. MAO A is involved in breaking down serotonin and involved in melatonin. MAO B is inovolved in breaking down nor epi and epi from dopamine.

Hope you can now better digest my previous post. Take care,

Lyn

[ramakentesh]

While some doctors suggest that many or most pots patients ave an underlying mcad disorder triggering their autonomic problems, the main research bodies and autonomic centres suggest mcad is relatively rare in pots and when present may be the result of sympathetic overstimulation - in other words caused or associated with pots.

as for the methylation clearance theory in not sure many realize this is a theory created by a patient who admits there is very little peer reviewed science that supports it as an etiological factor that has been adopted by a few cfs mds.

[Science girl]

Thanks doozlygirl for the explanation. Even though i did genetics i am not familiar with the genes you where referring too. So do you have a doctor or did you get your own genetic results and interpret them with these sites and book? I find it incredible that you can get such testing without a doctors request. I am unaware of it in Belgium or New Zealand.

[issie]

While some doctors suggest that many or most pots patients ave an underlying mcad disorder triggering their autonomic problems, the main research bodies and autonomic centres suggest mcad is relatively rare in pots and when present may be the result of sympathetic overstimulation - in other words caused or associated with pots. as for the methylation clearance theory in not sure many realize this is a theory created by a patient who admits there is very little peer reviewed science that supports it as an etiological factor that has been adopted by a few cfs mds.

While this may be true - the symptoms for those who have MCAS are pretty undeniable. It's pretty easy to spot it - once you know what to look for. And if treatment makes a difference --then Yayyyyy!

Most medical DX's start with a theory. If the ideas of that theory when placed into action - make a difference - and it is a proven difference, over time, with many claiming success with the results ---then HEY ---however the theory got here and got sorted out ----if it fixes something and makes things better. Who cares who came up with the idea. It takes those willing to be the subjects and test out the theories to have anything become a proven DX and no longer a theory. Then we get the peer reviewed articles written up and then there is less questioning of the ideas. Although, I think, there will always be those few skeptics in the crowd.

Issie

[Science girl]

Ramakentesh. Your input is great. This is the question I have been asking is the autonomic dysfunction causing the mast cell reaction or the other way around? When dealing with such complex systems that interlink finding a cause is a bit like trying to find a needle in a haystack! I asked my allergist and he just shrugged his shoulders and said yes it's a problem. My mast cells may are not the source of my problems but are definitely helping to spin the cycle and treatment helps at least with aome symptoms. There is a benefit in genome testing as the system could fall down at any point. But how beneficial for treatment depends on what research has been done.

I definitely think that patient directed research could be helpful for illnesses on the edge of being fully understood. This can be threatening for the medical profession. As a scientist I tried to speak to patients and find out as much as I could from them. They hold some of the keys to unlocking what is happening to their bodies. I believe that more respect on by sides is vital. In saying that I don't support fades. Many people believe supplements and health foods etc are natural and not harmful so you can experiment with them without side effects. This is a dangerous approach.

There are many dogmas in medicine and science in general. A dogma is a commonly held view that has not or cannot be actually proven. A lot of our understanding of our bodies normal functioning is dogma. Ie someone proposed at theory based on limited evidence and that theory got quoted here there and everywhere and soon it is written in medical text books and taught to med students as fact. I found this extensively when writting my thesis on early menopause. Many 'facts' about the normal development of the female reproductive system are in fact dogma. This comes from the lack of funding for 'pure' science in human biology. Ie science that is trying to understand our world not treat or cure disease. Investors often, even if they will not profit from the research, don't see this as a 'good cause'. They want their money meaning something in the lives of suffering patients. Unfortunately it is difficult to do accurate research without a good understanding of normal. Therefore we compare to what we think are 'normal' patients and often understand the body more because of disease. This approach does however have limitations.

So why tell you this? Well just to point out we are all learning. Just because something is peer reviewed it doesn't make it good research. I used to write for a medical publishing firm critiquing and reviewing research. And some research is just plain bias or doesn't have good controls, or too many factors to be accurate to the claims being made. And just because something is not peer review it doesn't make it not good research. And vice versa. And both fields are just as likely to rely on dogmas of science as the other. There are also prejudices on both sides. Like any natural is lacking research or anything pharmaceutical is toxic. This are bias the researches in both fields often bring.

I choose to keep an open mind but tread with caution. Turn over every rock to understand more but start any treatment with as much certainly as is possible.

[issie]

Thank You Science girl ----I'm always saying that anything that is written in any medical paper or really anything for that matter - is written to reflect the ideas of the writer. Even a review of something can be written to reflect what the intended conclusion will be from the reader.

I think with me, POTS came first and then mast cell. (My mom has mast cell issues too.) I think that it is a PART of the picture and not the whole picture. I'm not sure that any of us will know for sure what "caused" our POTS. Was it a vaccine, a virus, a protozoa, EDS, MCAS or faulty genes ---it could be a combination of all of those and something that created the perfect storm. Ultimately, the goal is to find what gives us the most quality of life and hopefully with time and experiments - some of those things will correct themselves - via either the right med combination, herbals, lifestyle changes (diet), or just time.

I'm with you on keeping an open mind. I never dismiss something suggested to me and try to consider whether or not it might apply and if it possibly could, what would be the correct action to take to determine if it is valid for me. I think there is still way too much unknown and we may find that what we think today or what treatments are being given today ---will be found in the future to be totally wrong. (Everyone that knows me ---knows I question some of the treatments being used.)

As for herbals ---they are medicine. You need to be real knowledgeable about what you are doing. Just because you don't have to have a script for them ---you can mess yourself up royally if you combine them wrong or take something that is wrong for something else going on in your body. Many meds are the product of extracts from herbs - just more concentrated. That's one reason why health stores are not supposed to suggest things to people - because if there is something that is not being told (high blood pressure, high blood sugar, etc.) some of these herbals can cause issues with those things. This is also true of vitamins and minerals and even amino acids. Our bodies are made up of these things ---but, if there are problems with metabolising them and the ratios get out of balance --you can have some serious problems.

Issie

[DoozlyGirl]

While some doctors suggest that many or most pots patients ave an underlying mcad disorder triggering their autonomic problems, the main research bodies and autonomic centres suggest mcad is relatively rare in pots and when present may be the result of sympathetic overstimulation - in other words caused or associated with pots. as for the methylation clearance theory in not sure many realize this is a theory created by a patient who admits there is very little peer reviewed science that supports it as an etiological factor that has been adopted by a few cfs mds.

Rama,

May I ask who you are referring to as the author of the original methylation clearance theory? I am reading the works of several PhDs and MDs, and not seeing a reference to the patient you are referring to. I've been able to track the theory of impaired detoxification pathways back to a PhD, and then expounded upon by several PhDs and MDs, taking this concept in various tracks from the central concept. The Autism, CFS, EDS, and Lyme infection communities are actively discussing these concepts and connecting the dots in conjunction with the these disorders, but I am not familier with the patient at the center of this theory concept. Thanks for sharing.

Lyn

[DoozlyGirl]

I find this conversation intriguing. My own experiences and reading have pointed to my immune system as setting off my mast cell reactions leding to cardiovacular anaphylaxis. I even had such an episode in the office of my autonomic neurologist, who recognized my massive flushing as histamine related. This then set me down the path of chronic mast cell activation that triggers my plummeting BP. But I do also have other autonomic symptoms that have been classified as autonomic neuropathy of the sympathetic and parasympathetic systems.

Upon looking at this from various angles, I have found that there are gaping holes in the published research and clinical data particularly where these systems interact. In my experience and reading, many specialists just haven't considered data outside of their areas of conventional expertise. I know my endo had a hard time wrapping her head around my fluctuating BP and HR and it wasn't until I kept pushing her in the direction of autonomic, did she even consider it. I miserably failed my TTT a few weeks later. In fact, I've been able to find little published data about autonomic neuropathy, as most of the data is on POTS, so I've had to carve out and piece together resources to connect some dots myself. Same thing with the cardiovascular side of my anaphylactic reactions. But looking back, we can go back to my vitals during reactions and now the puzzle pieces begin to fall into piece.

For folks who hold published medical data and medications as gold standard, they may be waiting for a long time to get well from complicated and complex chronic illnesses. I've spent 15 years down the conventional testing, pills and surgery route and only got sicker with every procedure, pill and surgery. Learning about mast cell degranulators has allowed me to identify things I can't tolerate, and the vast majority are synthetic dyes, flavorings, sweetners, and other additives in my meds, food, personal care and home goods. Using conventional approaches to allergies and sensitivites and avoiding these things have helped me tremendously. But several big ticket items are at the crux of my current ongoing issues.

After getting a free 23andMe kit as part of a study offered to the mast cell community, I quickly learned of methylation and liver detoxifying enzymatic pathways, but couldn't connect my dots to any of it. After running out of options in either the dyautonomia and mast cell worlds, I turned to this methylation stuff, which is actually the wrong term to call it, as there is so MUCH more to all this than mehtylation.

At first glance, methylation looks benign, but after six months of intensive study, I am absolutely convinced that there is plenty of science, anectdotal information, and medical guidance out there for me to finally be able to unravel my own metaboic fubar. Using my polymorphisms found in my 23andMe data, I have been able to connect my remaining symptoms to the SNPs. Funny thing is that I don't have any additional SNPs than what is already linked to my symptoms. Hope this gets me to the next level.

I have yet to take a methylation supplement, but have used my own genetic information to guide dietary changes. This all has lifted quite a load off my immune system, therefore limiting my autonomic dysfunction. My overall visable inflammation is down. I dropped a size and a half shoe size in the past few weeks. This tells me I am doing something right.

I don't need a published paper to tell me what my own body is telling me. I'm able to read my body better, and developed strategies to limit and accomodate my symptoms. This is what I have been looking for all long. And none of it came in the form of a pill, procedure, surgery or medical journal. I had to do the work of sorting it all out myself.

Karen, your approach will fit in nicely here. I look forward to hearing more from you.

Lyn

[ramakentesh]

Interesting comments. Please dont be offended by my response - its not meant to be emotive, just an alternative view:

* Issie - sure thing Im not saying and have never said that new theories arent welcome or that they have no merit, more that some do not have adequate peer-reviewed research to support their contentions or to explain observations or data.

* Sciencegirl - I dont agree that patients-based research is important in investigating illnesses other than in terms of treatment. This is because often patients misinterpret subjective experiences, are unable to test their contentions due to lack of understanding of physiology, dont have access to a cohort of patients, dont have access to proper medical equipment to gather viable data, and dont have their research peer-reviewed. Often patients arent objective with their research and try to apply something they read to a misinterpretation of a subjective experience. Often patients dont subject their contentions to rigour and be their theories worst enemy. Often patients attach to one specific theory that makes sense to them (based on their level of understanding of physiology) and refuse to consider alternatives or even anything that casts doubt on their theory.

When there arent answers the void is often filled. In history there are many examples. People were convinced that vapours caused the plague and refused to believe that the fleas of rats could be the transmitting factor.

The key is applying all theories to basic tests: does this seem physiologically plausible? Does it explaint the basics of the illness such as 4 / 1 ratio of females v males and sudden onset, etc. Are there doctors that disagree or have alternative hypothesis? Which have the most peer-reviewed research backing them up? Im not suggesting that what your saying is a load of ballony, more that I tend to lean towards the direction of the research coming out of the best and most qualified people involved.

If you talking from a CFS perspective then sure there are myriad of theories. But from the perspective of POTS/NCS/NMH several research facilities have published compelling research often involving highly qualified researchers using proper medical equipment, testing protocols and data analysis. The picture is slowly emerging and finally there is some consensus among the main research bodies - there is compelling evidence of neuropathy in some POTS patients demonstrated by failed QSART tests and reduced vasoconstriction; there is compelling evidence of unusual aldosterone responses in some patients, compelling evidence of abnormal norepinephrine reuptake and activity in some POTS patients. There is evidence of abnormal vasodilatory responses in some POTS patients; abnormal peptide profiles and elaboration of autoantibodies in some patients. Cerebral autoregulation is often found abnormal in POTS. And we are talking about published data in journals like the New England, Circulation, etc.

THis doesnt mean that anything you have said in your post is incorrect. Im just weighing up the research basis of a variety of different postulated etiological mechanisms and in doing so I have to conclude that the main research groups (vandebilt, NY, Mayo and a few others) are all heading in a similar direction.

Sure there is poor research published all the time and all sorts of problems like you've outlined but some peer-reviewed research is better than none. And when we are talking about peer-review we are talking about highly reputable journals as mentioned above at least in relation to POTS. But as a person with a background in science you are respectfully basically advocating for theories that have much less science behind them than others.

I know for a fact that one of the main peer reviewers for one of the major journals that publishes on it is very sceptical of many things and very demanding on researchers attempting to publish. His review is very objective and does not allow any assumptions.

* Doozygirl - the methylation theory was first described by Rich Van Konynenburg, Ph.d ( who sadly passed away recently). Rich was a great and smart individual and his theory is widely followed by many CFS patients. However Rich was an independent researcher and not an autonomic specialist and I believe was not a medical researcher.

Ive spoken to Rich myself before he passed away and he acknowledged that the whole thing was purely a theory and at that time had very little published research to support it. Doesnt mean its wrong or a load of ballony and Im not saying that. He often posted a long with a few others on a major forum and what I used to find entertaining was that when new research came out each of the proponents of the various theories would try and fit this new finding into their paradigm: 'this makes sense in the low b12 theory because of blah blah; this makes sense in the hydrogen sulfide theory because of blah blah' - but this is the opposite of what good science does - good science continually casts doubt on a theory and tries to poke holes in it to test it, not try and use every opportunity to try and bolster its claim to the extent that some large assumptions have to be made for that bolstering to prove true.

That being said Rich was one of the better ones on this forum and he NEVER claimed this theory was proven or gospel and that is what I liked about his approach. But even he must have been bemused by the amount of patients that took this theory/framework as proven gospel and went about self-treating as if this was 100% proven to be THE etiological mechanism behind CFS in all cases.

I always go back to the whole XMRV fiasco; a situation where an unemployed medical researcher is working in a restaurant, sees a story on CFS and decides on the spot that its a retrovirus causing the illness. She applies for a job at a new patients-sponsored research facility and then finds the FIRST retrovirus she tests for in 97% of CFS patients! Then so many patients instantly got on the bandwagon with statements like 'when i test positive for XMRV and I WILL test positive.' Or how the methylation protocol fits into the replication of XMRV etc. But it was all a mistake and all wrong. And when you look back the signs of it being wrong were written in the very likelihood of the circumstances of it arising in the first place. For that to actually happen - for an umemployed researcher to guess the correct retro virus in one go after making the assumption that it was a retrovirus in the first place is just so unlikely that it surprises me that so many didnt see the obvious flaws from the start.

Most of the paid and qualified researchers in CFS do not currently believe that the methylation theory is part of the primary etiological picture. They could all be wrong and I know Rich was a VERY smart guy and could be very right but the burden of proof has not been satisfied in relation to the methylation idea and until it has we have to be honest about the evidentiary support for that view.

* and in general - We have to be very careful about making statements like suggesting that medical researchers are 'threatened' by alternative theories as is really kinda doing a discredit to these highly qualified people. Unlike patients and armchair theorists, doctors have to comply with ethical restrictions, research protocols, wrestle for funding and a myriad of unforseen issues that arise during their research, then they have to publish and re-write their copy to get it peer-reviewed and accepted to a journal.

Research in CFS pays very poorly. Its VERY hard to get funding for any type of research on such a nebulus and ambigious entity as CFS. that is why POTS and autonomic research is so much better funded. But NO doctor involved in CFS research is in it for the money or for their ego because there is very little - if they wanted money they would be going for grants on diabetes Type II or hypertension were there is good coin and access to top medical facilities. They are in it for the patients and trying to find the answer for the many long suffering people they see every day. CFS is an area that is often scorned by the established medical profession - researching in CFS is seen as damaging to the career of some researchers. CFS docs often have to use substandard equipment because no one will give them proper funding.

Think about if from the perspective of a doctor. A doctor I know of worked long hours for months rigouressly testing a finding in CFS that was eventually successfully published in a journal. However EVERY patient involved in the test told the doctor with 100% convinction that their CFS was caused by what ever theory they had attached to and none were even interested in hearing his team's finding or result because they were already convinced of their own. What a thankless task. Problem was many of the theories didnt even make basic sense from a physiological perspective.

* In relation to autism, my wife works as a researcher in this area (just completed masters) and I know a lot about autism. I can definately say that none of the research in this area is suggesting that the methylation cycle theory has etiological significance in this disorder.

As for reading your own body. Sure all patients have to do this because there arent any firm answers yet, just clues with varying levels of evidence behind them. But often people need to be careful of misinterpreting subjective observations.

[Kellysavedbygrace]

This reminds me of a discussion I had with Dr. Afrin about MCAS and Dysautonomia. And although he suspects a connection between the two conditions he is very quick to say it is simply a guess, not fact. He the proceeded to explain there is need for further research and then he shared:

"Neil Degrasse Tyson has a great quote in this vein: "The good thing about science is that it's true whether or not you believe in it." In other words, quality research will reveal the truth regardless of what I or any other physician "believe" based on our individual sets of experiences."

[issie]

I think that some need to believe in something - even if the science may not be there in it's entirety. If a portion of it makes sense to them and the treatment for it can not damage them in any way ---and in fact, may make things better. Then until things are proven otherwise ---there is no harm in allowing people their ideas, beliefs etc.

Even with some of the things that some were so dogmatic about 3 years ago ---those have had to change their views and platforms on those things --because science has proven otherwise. And some things that were thought would never be accepted by the medical field ---now have been. So, for me, I try to keep an open mind and realize that it all may have some validity and time will sort it all out. But, for now, we need something to focus on and that "purple band-aid" to give us the best quality of life --until the complete answer is found.

Issie

[DoozlyGirl]

Interesting comments. Please dont be offended by my response - its not meant to be emotive, just an alternative view:

* Doozygirl - the methylation theory was first described by Rich Van Konynenburg, Ph.d ( who sadly passed away recently). Rich was a great and smart individual and his theory is widely followed by many CFS patients. However Rich was an independent researcher and not an autonomic specialist and I believe was not a medical researcher.

Ive spoken to Rich myself before he passed away and he acknowledged that the whole thing was purely a theory and at that time had very little published research to support it. Doesnt mean its wrong or a load of ballony and Im not saying that. He often posted a long with a few others on a major forum and what I used to find entertaining was that when new research came out each of the proponents of the various theories would try and fit this new finding into their paradigm: 'this makes sense in the low b12 theory because of blah blah; this makes sense in the hydrogen sulfide theory because of blah blah' - but this is the opposite of what good science does - good science continually casts doubt on a theory and tries to poke holes in it to test it, not try and use every opportunity to try and bolster its claim to the extent that some large assumptions have to be made for that bolstering to prove true.

That being said Rich was one of the better ones on this forum and he NEVER claimed this theory was proven or gospel and that is what I liked about his approach. But even he must have been bemused by the amount of patients that took this theory/framework as proven gospel and went about self-treating as if this was 100% proven to be THE etiological mechanism behind CFS in all cases.

I always go back to the whole XMRV fiasco; a situation where an unemployed medical researcher is working in a restaurant, sees a story on CFS and decides on the spot that its a retrovirus causing the illness. She applies for a job at a new patients-sponsored research facility and then finds the FIRST retrovirus she tests for in 97% of CFS patients! Then so many patients instantly got on the bandwagon with statements like 'when i test positive for XMRV and I WILL test positive.' Or how the methylation protocol fits into the replication of XMRV etc. But it was all a mistake and all wrong. And when you look back the signs of it being wrong were written in the very likelihood of the circumstances of it arising in the first place. For that to actually happen - for an umemployed researcher to guess the correct retro virus in one go after making the assumption that it was a retrovirus in the first place is just so unlikely that it surprises me that so many didnt see the obvious flaws from the start.

Most of the paid and qualified researchers in CFS do not currently believe that the methylation theory is part of the primary etiological picture. They could all be wrong and I know Rich was a VERY smart guy and could be very right but the burden of proof has not been satisfied in relation to the methylation idea and until it has we have to be honest about the evidentiary support for that view.

* and in general - We have to be very careful about making statements like suggesting that medical researchers are 'threatened' by alternative theories as is really kinda doing a discredit to these highly qualified people. Unlike patients and armchair theorists, doctors have to comply with ethical restrictions, research protocols, wrestle for funding and a myriad of unforseen issues that arise during their research, then they have to publish and re-write their copy to get it peer-reviewed and accepted to a journal.

Research in CFS pays very poorly. Its VERY hard to get funding for any type of research on such a nebulus and ambigious entity as CFS. that is why POTS and autonomic research is so much better funded. But NO doctor involved in CFS research is in it for the money or for their ego because there is very little - if they wanted money they would be going for grants on diabetes Type II or hypertension were there is good coin and access to top medical facilities. They are in it for the patients and trying to find the answer for the many long suffering people they see every day. CFS is an area that is often scorned by the established medical profession - researching in CFS is seen as damaging to the career of some researchers. CFS docs often have to use substandard equipment because no one will give them proper funding.

Think about if from the perspective of a doctor. A doctor I know of worked long hours for months rigouressly testing a finding in CFS that was eventually successfully published in a journal. However EVERY patient involved in the test told the doctor with 100% convinction that their CFS was caused by what ever theory they had attached to and none were even interested in hearing his team's finding or result because they were already convinced of their own. What a thankless task. Problem was many of the theories didnt even make basic sense from a physiological perspective.

* In relation to autism, my wife works as a researcher in this area (just completed masters) and I know a lot about autism. I can definately say that none of the research in this area is suggesting that the methylation cycle theory has etiological significance in this disorder.

As for reading your own body. Sure all patients have to do this because there arent any firm answers yet, just clues with varying levels of evidence behind them. But often people need to be careful of misinterpreting subjective observations.

Rama,

I agree that the XMRV fiasco must be avoided in the future. What a terrible blow to anyone in the chronic illness world.

While the work of Rick Van K has been remarkable and his presence is missed greatly in the CFS world, he is not the originator of the methylation concept in chronic illness. Rich got interested in CFS to help out a friend and used his research skills and experience at Lawrence Livermore National Laboratories to help his friend find relief from debilitating symptoms of CFS. From what I've read on Phoenix Rising, he learned of Dr Paul Cheneys thoughts on glutathione deficiency, found Dr S Jill James work on methionine cycle blockage, then stumbled upon the work of Dr Amy Yasko using these theories to treat autism, prompting him to create several versions of his simplified protocol for CFS based off the Dr Yasko's intensive and SNP driven protocol for autism. His simplified protocol was derived off generalities of what is likely happening in PWCs, and is not patient specific, in the way that Dr Yasko's protocol is. As far as I know, Rich's simplified protocol and theory did not have published clinical study data yet to back it, but there are dozens of people of several CFS sites that state they have found relief, and that efforts are underway to study his theories. His obit mentioned "Rich suggested that an existing treatment for autism might be used in the treatment of ME-CFS".

Rich's Obit

http://www.legacy.com/obituaries/modestobee/obituary.aspx?pid=160243735

In his own words, he talks about the journey he took in connecting these dots, Rich wrote. "I want to emphasize that I did not develop the Glutathione Depletion–Methylation Cycle Block Hypothesis out of thin air. The autism researchers had already provided a convincing basis for this model in that disorder. S. Jill James and coworkers did much of the clinical work that underlies it. Richard Deth and his coworkers had worked out much of the theory of the methylation cycle block and had applied it to autism. Professors James and Deth had been presenting talks on their work at autism conferences. The physicians in the DAN! project

(as well as Dr. Amy Yasko, though I had not yet learned of her work when I began to understand the importance of the methylation cycle block) had already been treating autism cases by measures intended to lift the methylation cycle block. What I did was to apply the results of their work to CFS, and to present a detailed biochemical and symptomological case to support the proposition that this model also applies to CFS."

Rich's Journey in Creating his Simplified Methylation Protocol

http://phoenixrising.me/treating-cfs-chronic-fatigue-syndrome-me/treating-chronic-fatigue-syndrome-mecfs-glutathione-and-the-methylation-cycle/a-simplified-treatment-approach-based-on-the-glutathione-depletion-methylation-cycle-block-pathogenesis-hypothesis-for-chronic-fatigue-syndrome-cfs-by-rich-van-konynenburg-ph-d

Dr James has 130 published articles on various aspects of methionine cycle dysfunction. Below is her shortened bio, and link to her current employer. From what I could find she had published in MTHFR, a methylation blockage as early as 1999. Much of her early work focussed on Down's syndrome and MTHFR/folate metabolism errors.

Dr S Jill James

http://media.mindinstitute.org/video/graphics/dls/2010/james_bioabstract.pdf

http://www.ncbi.nlm.nih.gov/pubmed/?term=S+Jill+james

http://achri.archildrens.org/researchers/jamesj.htm

Dr Yasko is a molecular biologist, medical researcher, and naturapathic physician, who is often credited in linking together several adjacent cycles and looking at methylation as a whole in the methionine cycle (including transulfuration pathway), folate cycle, BH4 cycle and Urea cycle. She has also identified critical genes along these pathways to include in nutrigenomic testing. She also uses biochemical testing to evaulate if those SNPs currently contribute to enzymatic blockages. Her approach is to systematically open up critical pathways in a specific order using various testing methods to determine which steps to take, then after confirming that the SNPs correspond to specific biochemical testing indicating decreased enzymatic efficiency, she recommends various cofactors, vitamins and other molecules to open up those blocked pathways to ultimately resore functioning of these 4 cycles, restore natural inate detoxification capabilities, and produce ample glutathionine. There is so much more to it than this. I've been actively studying this for 6 months and am intrigued that I finally found tools to help me sort out my messed up biochemistry.

Dr Amy Yasko

http://www.dramyyasko.com/our-unique-approach/methylation-cycle/

Rama, I'd love for you and your wife to really spend some time reading up on Dr Yasko's protocol, and then share your thoughts, once you get a handle on her approach. I don't necessarily believe it is going to take all those supplements to get me well, but am finding great value in her line of thinking to help me make better choices and avoid things that trigger my mast cells to degranulate.

If you are interested in more information, there are several 200 plus page ebooks available free of charge online that shares the bulk of her protocol. I'm currently reading this one, called Autism: Pathways to Recovery, with a link below. Her website contains all of her references. This book is meant for parents and patients to describe her approach. There are tons of her presentations available on her site with full references.

http://www.dramyyasko.com/wp-content/files_flutter/1327512160_9_1_1_8_pdf_02_file.pdf

I may not be a PhD medical resarcher, but there are dozens of MDs, NDs, DO's and PhDs that are all taking note of this approach to sorting out chronic illness. I didn't know this world even existed until 6 months ago, and everyday I learn something new. It is underground for the most part, but PENN state, University of Arizona and UC Davis have opened nutrigenomic programs, so I expect this concept will continue to grow.

Lyn

[Science girl]

Ramakentesh: I think you may have miss understood. I said 'patient directed', not patient based. I by no means intended to suggested patients become the researchers any more the children become teachers in student directed learning. The term was simply an attempt to say that researchers need to listen carefully to patients symptoms and experiences and use this information to help guide research.

This is a cry for the medical profession to treat patients with the respect of being the person who holds a lot of information about what is happening to them. It is the job of the doctor to help the patient decode these experiences and hopefully be able to manage their illness better. It is not helpful for dr to say things like 'well you shouldn't have that symptom' especially of a poorly understood disorders.

Please understand no disrespect was intend.

[issie]

I think there is something to the methylation angle. With the little bit that I've done so far with my mutations ---I'm finding that it is helping a good bit. I still have an awful lot to learn ---but, trying to correct the dysfunction that I have and staying off foods that contribute to the problems has been a big help with me. And, when I mess up and don't follow this correctly ----I can really tell a difference.

Rama, since your wife is so interested in Autism ---I hope she will read Dr. Yasko's work and give us feedback. (Lyn, I sent this to him awhile back.)

Thanks for all the info on the origination of this "theory", Lyn.

Issie

[ramakentesh]

I agree with Dr Afrin.