Methylation completely stopped working...Can’t find the missing cofactor.

Learner1

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Without RCT, how do you suggest that we gather evidence for the efficacy of a treatment?
Through clinical observation. Most of the treatments I've had have been prescribed off-label. In fact, most drugs typically prescribed by doctors are prescribed off-label, because it costs too much for the drug companies to do RCTs for every possible indication for their drugs.

It is prudent to read case studies, results of clinical trials, etc. But at best, ANYTHING is just a guess by the clinician.
If a drug company develops a new drug to treat disease X, and wants to test how effective that drug is, how are you going to do that without performing a RCT?
We are not discussing marketing a new drug for disease X and getting an FDA approval. There are dozens of treatments out there doctors prescribe to patients with ME/CFS, based on their clinical experience, and the copious literature already available on a given drug, a given condition, and interactions with other factors.
What replacement for RCTs would you suggest that works better?
I don't know how old you are, but I simply don't have 20 or 30 years to wait around for perfect RCTs to be done on all the genetic and environmental variables in subsets of patients with ME/CFS.

It just seems to me that this is a false way to go about this.

The 21st Century Medicine White Paper I provided (did you happen to read it??) points out the fallacies of RCTs and suggests a different way of finding solutions for patients. That is to take a careful inventory of all the symptoms, the health history, and to do testing to identify treatable problems that work toward "normalizing" the body.

This can be a far more successful approach than the "cookbook medicine" approach common to conventional medicine, where we look for what pill treats what disease. As I've pointed out, you can give someone the "correct" pill for a certain disease, but they can be damaged due to their basket of genetics and environmental factors that make them different than the widget patients that the clinical trial was done on for that drug. (Or maybe they match up with patients in the clinical trial group who had the bad side effects.)
And other question: without drug treatment efficacy data from RCTs, how would functional doctors know which treatments to try?
I have 4 doctors who use a functional medicine approach, but also have training in conventional medicine. They take the time to understand my history, they sequenced my genome and are aware of some of the "gotchas" involved (like heriditary hemochromatosis, Factor II, COMT, CYP1B1), and most importantly, they are excellent at ordering and interpreting tests that we base our decisionmaking on. I provide ME/CFS research articles that relate and my doctors and I discuss the points pertinent to my labs, my symptoms, and my genetics. Then, they put together a coordinated and comprehensive treatment plan that has included these elements, with dosing based on the labs:
  1. Immune system - IVIG, antivirals, antibiotics, LDN, zinc, vitamins A, C, and D, HBOT
  2. Dysautonomia - beta blockers, cholinergic substances (Huperzine A, neostigmine)
  3. Mast cells - cromolyn, ketotifen, ranitidine, quercetin, diphenhydramine, ondansetron
  4. Hormones - T3, T4, hydrocortisone, pregnenolone, DHEA, testosterone, estrogen, progesterone
  5. Blood - phlebotomies, bromelain
  6. Mitochondria - mitochondrial cocktail, phospholipids, oxidative and nitrosative stress reduction, BCAAs, FAD, NAD+, methylation support
  7. Metabolism - amino acids, B5, trace minerals
  8. Gut - probiotics, prebiotics, and mast cell meds above.
This has thoughtfully been coordinated over time, with participation from doctors with different expertise. This is why I find it odd to be limited to one treatment in isolation - the items in this plan work in synergy.
Conventional medicine treats multiple illnesses with multiple treatments. Nothing unusual about doing that. If you are a diabetic with high blood pressure and depression, you will be treated for all three illnesses at the same time.
And that is exactly the same here. I have found that ICD codes G93.3 or R53.82 merit no treatment or tests. However, the other 16 ICD10 codes that apply are far more useful in getting everyone's attention applied to problem solving. If you read through the document with all of the ICD10 codes, you'll find many that apply to many of us with ME/CFS. The 2015 IOM/NAS document clearly stated this is no longer a diagnosis of exclusion and that all comorbidities should be treated.

And, while we wait for the scientists to tease out a perfect solution, this is the only path I know of to get better, and so far, though it's been tedious and expensive, it has been working for me, and I know of other ME/CFS patients who are quietly approaching this the same way with their doctors with a similar slow but positive path to success.
Many treatments have serious side effects, and going to a functional doctor (or ecological doctor as they are called in the UK) will not give you some indemnity against them. IVIG for example can sometimes cause serious side effects like meningitis; a functional doctor cannot protect you from these risks.
Agreed. But I sure feel safer having people who have gone to years of medical school prescribing them vs. ordering bulk powders from large Asian countries and experimenting on my own at home. I also make sure to keep my doctors apprised of what the others are suggesting, and actively solicit risks and concerns, and work to mitigate them. I have also been able to talk directly to researchers at conferences, which has offered helpful insights. And, though I have excellent help, no one on earth knows all there is to know about this disease, and both doctors and clinicians have freely admitted that they don't have all the answers and we are on the bleeding edge of science. So, there will be some pitfalls, and I find that working with a team gives me more treatment options and more knowledge and more hope.
 

Learner1

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IVIG for example can sometimes cause serious side effects like meningitis; a functional doctor cannot protect you from these risks.
Just wanted to add, after I ended up in the emergency room with aseptic meningitis after my second IVIG treatment, my functionsl medicine doctor prescribed curcumin and boswellia to reduce brain inflammation, as well as CBD oil to reduce headache pain and nausea. I also do take dexamethasone and Benadryl, but the botanicals reduce the dosage and need of the steroid.

My functional medicine doctors have also been able to mitigate other risks brought on my conventional pharmaceuticals. For example, I was prescribed n-acetyl-cysteine which reversed paclitaxel-induced peripheral neuropathy.
 

Learner1

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@Hip Another big problem with RCTs:

https://www.nature.com/articles/d41586-019-01851-x

The authors conducted in vitro tests to assess the ability of 76 bacterial strains from the human gut, representing 68 species from the main bacterial taxonomic groupings, to metabolize 271 drugs (Fig. 1). These drugs were chosen to provide a diverse group in terms of factors such as molecular structure or effect on the body.

Zimmermann and colleagues report that 176 of the drugs tested underwent a substantial metabolic change, caused by least one bacterial strain, that resulted in a reduction in the level of the active drug molecule in bacteria.

Each bacterial strain tested metabolized some of the drugs, with the numbers ranging from 11 to 95 drugs per strain. Given that the authors tested a broadly representative panel of drugs, the scale of these results is remarkable because it raises the possibility that most drugs are modified by the microbiota.
 
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One author explains it like this: "a lack of methionine synthase activity resulting from vitamin B12 deficiency
leads to reduced synthesis of methionine and THF and accumulation of homocysteine and 5-methyl-THF."

It is underpinned by (1) poor function in methioinine synthase for whatever reason but usually B12 deficiency and (2) the irreversible direction of the pathway from methylene-THF to methyl-THF in the folate cycle. Methylfolate accumulates and causes a blockage on its pathway which, in turn, backs up and limits various preceding reactions in the folate cycle.

Another author explains it as "Because the formation of 5-methyl THF is irreversible, a vitamin B12 deficiency traps body folate in the 5-methyl form, in what is known as the methyl-folate trap hypothesis."

It was proposed in 1962 and has proven elusive because not all researchers can account for it from their results. There are a couple of slight variations on what occurs - such as the role of dietary methioinine. Nevertheless, the general conclusion is that there is a series of highly dysfunctional biochemical outcomes from (1) and (2) above and which may need dealing with when overcoming a B12 deficiency.

It has been very widely discussed in this forum, although sometimes under names like "donut hole deficiency" or "paradoxical folate deficiency". It is often said that the high levels of accumulating folate gets dumped out of the cell into a non-functional compartment leading to a functional deficiency of folate.

We started this by you posting that methyl-THF can convert to methylene-THF but I have never come across that.
Do not get me wrong. I support the hypothesis that the reaction is reversible (partially). I respect your idea but you can't convince me. Even the dogma of biology was a dogma and seemed unidirectional, and instead it is two-way :D
 
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Do not get me wrong. I support the hypothesis that the reaction is reversible (partially). I respect your idea but you can't convince me.

Even the dogma of biology was a dogma and seemed unidirectional, and instead it is two-way :D
I don't really understand what you have written.

Do you have any examples or research studies which might illustrate how methyl-THF can convert to methylene-THF ?
 
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Not sure about all his recommendations, but this is an interesting article on MTHFR/riboflavin:
https://chrismasterjohnphd.com/blog/2019/02/26/mthfr-just-riboflavin-deficiency/
That's it. Please do not damage your antioxidant system. I cannot give advice or prescriptions, but I can say my humble opinion. And this is that a healthy methylation protocol (beyond a MTHFR mutation or a chronic fatigue syndrome) should include lower doses of b12 and adequate doses of riboflavin (this is not a prescription but what I would on myself :D) . Using an excess of b12 and little or nothing riboflavin can only do long-term damage. The article you posted is absolutely worthy of consideration .. thanks for putting it here.

My only purpose here is to avoid damage related to a wrong methylation protocol. You say that only 3% of forum members have had benefits .. there will be a reason perhaps. Maybe something should be revised. And, if riboflavin is a cofactor of MTHFR, how is it possible to think of being able to make it over-work without FAD?
 
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So, how can you measure if this folate trap is happening?
Sorry, yesterday I couldn't reply due to lack of time.. I have a complicated life..

For me the evidence of folate trapping is clinical, and the presence of headache, muscle weakness, paraesthesia in the extremities, nausea, apathy, lethargy and drowsiness could indicate it. Be careful because a folate deficiency (absolute or relative) obviously manifests itself with the same symptoms, although more pronounced.

If one is overdosing b12, always in my opinion, folate trapping doesn't depend on mb12 dosage, and shouldn't be addressed with even more b12, and preferably it should not be treated with niacin every 2-3 hours as some do, because niacin "breaks down" all the methyl groups in the body " (not in biochemical terms, because niacin is methylated itself and you pee out its methylated metabolites, but I think it's not advisable taking a lot of niacin that it is not needed in a system already overloaded with b12, exhausted, and FAD depleted )

I think it's better instead reduce folate taking for a while, and hydrate yourself until the symptoms subside.

Always bearing in mind that (in my opinion) it should necessary not to overload the system with b12, ensure adequate dosages of riboflavin in a system FAD depleted, and the correct doses of cofactors.

In short, a gentler and milder methylation protocol. I suppose the main reason the current protocol doesn't works well (or works well just in the beginning) is
1) b12 overload and
2) FAD depletion.

I repeat, this is my opinion, and it should not be considered as a medical prescription but only as a suggestion.

Love and Joy..

Davide.
 
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Measurement of methionine synthetase activity can give functional assessment of DNA metabolism, primarily in vitamin B12 deficiency… a real " 5-methyl-THF trap" , is only related to a vitamin B12 deficiency, or very high chronic folate intake. It's my opinion (maybe right, maybe wrong.. who knows? :nerd:) that those exposed to chronic high b12 doses (more than 5-10 mg/day for months-years) can only have a "iatrogenic transient folate trap, in a in a framework of suboptimal folate status", and, if I have to answer your question, I think the best, cheapest and most simple way of defining it, is s a folate dosage, with a ratio b12/folate. But I think this is more didactic than practical, because these individuals (who have taken megadoses of b12 for years) are more prone to develop a folate deficiency than a transient folate trap, and I would be more worried about that.
Have a nice day 👋
 

Learner1

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I've been on a pretty stable protocol for methylation for about 4 years. No unpleasant symptoms. It's like this:
  • 5.5 5-MTHF
  • 10mg MB12 daily + 5mg HB12 2x a week
  • 395mg P5P
  • 340mg R5P
  • 2mg TMG
  • 450mg magnesium glycinate
  • 750mg benfotiamine
  • 2mg molybdenum
However, I've been having trouble managing my T3/T4 dosing for Hashimotos and my hydrocortisone dose for adrenal insufficiency. I have been improving over the past year, and found I was gaining weight. My FT3 was just over the high end of range and my cortisol was low from wake-up to 4pm when it was high, before dropping to normal low at night.

Responding to the labs, I tried lowering both the T3 dose and hydrocortisone, and crashed, dizzy and limp without them. 5-MTHF was suggested, and my brain felt energized in minutes after taking 1mg 5-MTHF without taking additional hydrocortisone or thyroid,

After playing with this a few days taking 1-3 extra mg 5-MTHF, I was able to cut bsck om the HC (I'd started 3 years ago at 20-25mg, then have been at 15-20 recently, and now am at 10-12.) If I can stay there, then I want to try to reduce T3 and T4 (I do take iodine and selenium.)

I think what's happened is my methionine cycle was the worst of my problem, so a lot of attention went there. Then I had a tendency to emit sulfur, solved by the B1 and moly. Then my homocysteine was 3-5, so I needed methionine.

I haven't noticed any trapping, and am pretty aware of where the symptoms come from if methylation is off, but I am currently discussing with my doctor on how to measure folate status, as it definitely seems short.

I think the low hanging fruit is an RBC folate test, with a Genova Diagnostics NutrEval, or an HDRI methylation panel.

What do you think here? I know you'll think I'm on a lot of methylation support, but I had stage 3 cancer thsn chelated platinum, as well as arsenic, lead, cadmium, and mercury. My glutathione and vitamin C were always depleted until I went to 3 doses of 3mg Vitamin C a day and 450mg total of liposomal and Thorne glutathione SR.
 
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I've been on a pretty stable protocol for methylation for about 4 years. No unpleasant symptoms. It's like this:
  • 5.5 5-MTHF
  • 10mg MB12 daily + 5mg HB12 2x a week
  • 395mg P5P
  • 340mg R5P
  • 2mg TMG
  • 450mg magnesium glycinate
  • 750mg benfotiamine
  • 2mg molybdenum
However, I've been having trouble managing my T3/T4 dosing for Hashimotos and my hydrocortisone dose for adrenal insufficiency. I have been improving over the past year, and found I was gaining weight. My FT3 was just over the high end of range and my cortisol was low from wake-up to 4pm when it was high, before dropping to normal low at night.

Responding to the labs, I tried lowering both the T3 dose and hydrocortisone, and crashed, dizzy and limp without them. 5-MTHF was suggested, and my brain felt energized in minutes after taking 1mg 5-MTHF without taking additional hydrocortisone or thyroid,

After playing with this a few days taking 1-3 extra mg 5-MTHF, I was able to cut bsck om the HC (I'd started 3 years ago at 20-25mg, then have been at 15-20 recently, and now am at 10-12.) If I can stay there, then I want to try to reduce T3 and T4 (I do take iodine and selenium.)

I think what's happened is my methionine cycle was the worst of my problem, so a lot of attention went there. Then I had a tendency to emit sulfur, solved by the B1 and moly. Then my homocysteine was 3-5, so I needed methionine.

I haven't noticed any trapping, and am pretty aware of where the symptoms come from if methylation is off, but I am currently discussing with my doctor on how to measure folate status, as it definitely seems short.

I think the low hanging fruit is an RBC folate test, with a Genova Diagnostics NutrEval, or an HDRI methylation panel.

What do you think here? I know you'll think I'm on a lot of methylation support, but I had stage 3 cancer thsn chelated platinum, as well as arsenic, lead, cadmium, and mercury. My glutathione and vitamin C were always depleted until I went to 3 doses of 3mg Vitamin C a day and 450mg total of liposomal and Thorne glutathione SR.
hello .. I replied via private message :) ...
 

Hip

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Through clinical observation.
Isn't clinical observation just an informal version of a clinical trial (a clinical trial which may be questionnaire based)?

You say that treatment efficacy questionnaires are ludicrous, but clinical observation is in essence the same thing, but just not written down on paper. The doctor observes what works in his patients, and remember it. Though clinical observation may be less accurate, as it relies on the doctor's memory, which may be a selective memory, ie, he may remember the successes more than the failures.



The 21st Century Medicine White Paper I provided (did you happen to read it??) points out the fallacies of RCTs and suggests a different way of finding solutions for patients.
Much as I would like to read it, long documents like that are beyond my cognitive capabilities. Not so much because of brain fog, but due to the brain damage I sustained from a viral brain infection in 2005, which affected my reading skills (by causing severe ADHD). I used to read one book a week, but since the brain infection have not read a single book. Brain fog makes things worse, but it's the ADHD which is the main issue.

I've tried many things to try repair the brain. The only thing that seems to have helped with repair is daily breathing oxygen from an oxygen concentrator. That seems to have improved the ADHD in a permanently way, though only to a certain degree. I'd like to try HBOT, but last time I enquired at my local multiple sclerosis HBOT clinic, which does very cheap HBOT at £25 per session, they told me they could not accept ME/CFS patients, only MS patients.
 

Learner1

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Isn't clinical observation just an informal version of a clinical trial (a clinical trial which may be questionnaire based)?
No, they are not the same. Many docs observe patients and then publish case studies, like the one attached. Two of my doctors saw this case study and gave it to me and said they felt it might be helpful in my case.
You say that treatment efficacy questionnaires are ludicrous,
I don't believe I said questionnaires are ludicrous. I just don't find them effective at providing actionable information.

Look at the 2 notable patients who had effective spinal surgeries - do we all run off and do that too? I'm not sure that treatment would be equally effective for all of us, do you? (Though, as a patient, I asked my doctor of PT to evaluate me for the problems described by the other patients, to find its not a fit for me.)

I just find that the scale you repeatedly trot out and judge treatments one by one against to not be very useful.

An overall disease scoring system doesn't make much sense, when ME/CFS us such a heterogeneous phenomenon at present and the impact of categories of symptoms on functionality, quality of life, and ability to work, think, talk, or exercise varies so widely. You only seem to value a particular treatment if by itself, unrelated to any other treatment or variable or preexisting condition or genetic or environmental factor, it moves a significant percentage of the population of ME/CFS patients up one notch on this rather arbitrary scale.

As a patient, my goal is to improve my function and quality of life. There is NO single treatment that has moved me anywhere near one notch on your 4 item scale, and its a rare phenomenon for others.

What has worked is looking at the body as a system of interrelated systems with genetic predispositions and environmental influences and carefully selecting groups of treatments that improve the function of each system, how they relate with other systems and work synergistically to reduce symptims and improve overall function and quality of life.

In the world you describe, its something like "what made this student get from early education to A levels to an Oxford degree? Was it learning the alphabet, learning the history of the Boer War, learning to divide fractions, or to learn Latin?"

Or was it the synergistic components of a thoughtfully designed program?
but clinical observation is in essence the same thing, but just not written down on paper. The doctor observes what works in his patients, and remember it. Though clinical observation may be less accurate, as it relies on the doctor's memory, which may be a selective memory, ie, he may remember the successes more than the failures.
Maybe things are done differently in the UK, but here in the US, doctors are expected to keep records of patient symptoms, patient labs, hralth history, patient treatments and patient progress. Depending on the doctor's employer, business relationships, need to be paid, and personal goals, how this documentation is created and whether it is kept private or made public varies widely.
Much as I would like to read it, long documents like that are beyond my cognitive capabilities. Not so much because of brain fog, but due to the brain damage I sustained from a viral brain infection in 2005, which affected my reading skills (by causing severe ADHD). I used to read one book a week, but since the brain infection have not read a single book. Brain fog makes things worse, but it's the ADHD which is the main issue.
Given the copious reading material you provide to all of us, and the questions you are asking me which are covered by experts in the paper I shared, this seems somewhat disingenuous. It's an easy to read paper, divided into 6 chapters, covering 94 pages.

I truly believe that if you can be generating so many questions, providing so many references of your own that you expect us all to read every page of, that you might be able to tackle a 94 page book, over a reasonsble amount of time, even if you could only absorb it a page or even a paragraph at a time. The reading level is much simpler than the voluminous reading you have mastered enough to provide to us. It might be quite helpful to you and lead you down some new avenues.
I've tried many things to try repair the brain. The only thing that seems to have helped with repair is daily breathing oxygen from an oxygen concentrator. That seems to have improved the ADHD in a permanently way, though only to a certain degree. I'd like to try HBOT, but last time I enquired at my local multiple sclerosis HBOT clinic, which does very cheap HBOT at £25 per session, they told me they could not accept ME/CFS patients, only MS patients.
Functional Medicine provides a number of helpful tools which can greatly and positively impact brain function.

I have had my own cognitive issues, and immediate family members with stroke, Parkinson's, ADHD, Aspergers, and bipolar2, and have seen the limits of conventional psychiatry and neurology after visiting 23 psychiatrists and 11 neurologists with family members or on my own, and witnessing the effects and side effects of numerous brain-altering drugs.

It was at the point of seeing the dangers of psychiatry and psychiatric and neurologic drugs that I first learned about functional medicine and about effective testing patients to identify and treat biochemical imbalances through coordinated supplement plans, selective use of pharmaceuticals, and additional and effective treatments like HBOT, PEMF, cranial sacral therapy, mindfulness, deep brain stimulation to heal the brain.

This is a long way from what I call "cookbook medicine" where doctors match symptoms to ICD10 code and then to a pill, and send patients on their way. It is overly optimistic to think that for a disease as heterogeneous snd complex as ME/CFS that one intervention will make someone one giant step better. At best, if it works, someone got really lucky.

But, having seen the wide variety of research findings showing abnormalities across many complex organ systems, it seems that at best, it will take multiple synergistic interventions to gain traction.

Of course, I'd be as excited as anyone if someone found a magic pill tomorrow.

But right now, reading all the literature, seeing what's working in case studies or by anecdote and making educated guesses based on adequate laboratoryand other tests, symptoms and unique health histories seems to offer the most promise.
 

Hip

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I just find that the scale you repeatedly trot out and judge treatments one by one against to not be very useful.
Maybe you just don't like the scientific method, because a major part of science is measuring and quantifying. Without empirical measurement, science would become unsubstantiated nonsense.

If I were to buy a car, I'd like to know how fast it goes, what mpg it attains, what crash safety rating it has. I will use this to make the critical decision of which car I buy; I am not just going to be swept over by the salesman's patter.

I like functional medicine, and I use its approach myself; but it's important to be aware that functional medicine often lacks evidence. Some of functional medicine / ecological medicine is just salesman's patter.

It's important to differentiate between things that are proven, and statements that are sales talk. I have had a personal history of interest in ecological medicine: the first ecological medicine doctor I sought out and has an appointment with was back in 1991, so I know a bit about it. I agree with the functional approach, but that does not mean I believe everything a functional doctor might tell me.

Because it lacks evidence, functional medicine often throws everything but the kitchen sink at an illness, in the hope that something will work. But if you do improve, it then becomes hard to work out which elements were helpful, and which had no effect. If money is no object, and if you don't mind throwing dozens of medicines down your throat daily, without knowing which of them is helping, then there no problem with the functional approach. But personally I like to drill down to the empirical facts of what's helping and what's not.

For example, earlier you stated that LDN was part of the protocol that helped you. But I expect that you've no real idea whether LDN contributed to your health improvements.

Do you feel comfortable with taking a drug when you don't know whether it's working or not? Obviously you do. But I prefer to carefully test a drug on myself to see if it works for me or not. Dr John Chia has stated that LDN only works for around 10 to 20% of patients. That's his clinical observation.

So in fact, my approach is a personalized medicine. A functional doctor throws everything but the kitchen sink at a patient, whereas I like to carefully determine which drugs or supplements are right for me, by trial and error, and sharp self observation. I appreciate that not everyone has sharp self observation and the ability to accurately introspect (which is important when examining the effects of treatment on mental symptoms).



In the world you describe, its something like "what made this student get from early education to A levels to an Oxford degree? Was it learning the alphabet, learning the history of the Boer War, learning to divide fractions, or to learn Latin?"

Or was it the synergistic components of a thoughtfully designed program?
I understand what you are saying, and I understand that the whole may be more than just the sum of the parts. But working out the complex causal interplay of hundreds of components generally beyond human calculational abilities. Anyone who tells you they can calculate the effects of hundreds of components is just pulling your leg.



Maybe things are done differently in the UK, but here in the US, doctors are expected to keep records of patient symptoms, patient labs, hralth history, patient treatments and patient progress.
I don't think anyone would deny that primary care physicians in the US are much more attentive to patients than those in Europe. In part, I expect that's to do with the fact that the US spends nearly twice the amount on healthcare in terms of annal GDP than European countries. If I remember correctly, the US spends 17% of GDP on healthcare, whereas the UK spends just 9%. Thus you get what you pay for.

I don't know any NHS primary care doctor in the UK who would provide the attention to detail that US doctors give. I wish we spent more money on healthcare here, so that patients could have more attention. Although I don't think this attention to detail necessarily translates into better outcomes or better healthcare quality.



It was at the point of seeing the dangers of psychiatry and psychiatric and neurologic drugs that I first learned about functional medicine and about effective testing patients to identify and treat biochemical imbalances through coordinated supplement plans, selective use of pharmaceuticals, and additional and effective treatments like HBOT, PEMF, cranial sacral therapy, mindfulness, deep brain stimulation to heal the brain.
As I mentioned, I like the functional approach, and agree with this approach and use this approach in my own treatment.

When I try to work out the efficacy of a treatment, when I try to find out what works for me and what does not, it does not mean I am negating functional medicine.

If I say that the methylation protocol usually does not make major improvements in ME/CFS patients according to a poll, that does not negate the methylation protocol, and does not imply that patients should not try it. It's just giving some realistic appraisal of what benefits an ME/CFS patient is likely to get from methylation.



Given the copious reading material you provide to all of us, and the questions you are asking me which are covered by experts in the paper I shared, this seems somewhat disingenuous. It's an easy to read paper, divided into 6 chapters, covering 94 pages.
Disingenuous? For me, not being able to read anymore is the most tragic effect of my viral infection and ME/CFS. I loved reading, and I had a very wide range of interests in all sorts of subjects. Now I read nothing for pleasure, and only read what I think is medically absolutely essential. All the subjects I loved I had to abandon.

If a new study comes out, and I think it has great importance to ME/CFS or to my own health situation, I will try my very best to read it. Although I am not able to read in a linear way, from beginning to end. My brain is to fried for that.

Even trying to read your lengthy reply above has been difficult, as I am not able to read linearly, my brain is too scattered for that, so I am not sure if I have seen everything that you wrote. Believe me, it's horrible, and my reading impediment is little to do with brain fog, more do with brain damage. I've spent 1 hours 40 minutes trying to read your above comment, and trying to reply to it.

If you have any suggestions for good brain repair treatments, I am interested. But I've spent years looking at brain repair therapies, and nothing has helped.
 

Learner1

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Thank you for your thoughtful reply @Hip.

First, to be clear, i am not a fan of doctors selling snake oil. I look for the research or scientific articles that support any treatment that my functional medicine doctors (or my conventional doctors) suggest.

Here, for example is an article on LDN by my a well-regarded ME/CFS researcher. It doesn't guarantee it'll work on a patient like me, but gives a rationale for why it might be worth a try:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962576/

As for improving brain function, these are some places worth looking, though this might be worth a new thread:
  • reduction of inflammation/calming microglial cells
  • reduction of oxidative and nitrosative stress
  • repair of cell and mitochondrial membranes damaged by oxidative and nitrosative stress
  • support of ATP production by improving mitochondrial function
  • nutrient support for biochemical pathways, like methylation and neurotransmitter production
  • removal of ammonia, mycotoxins, heavy metals, lipopolysaccharides
  • treating infections
  • Improving the microbiome
  • Improving vagal nerve function
  • reducing hypoxia
The above ideas are in my own words, collected from things I have explored and that have helped me and others I know. (I have had immediate family members with Parkinson's, stroke, and serious mental illnesses, and it seems that there are some foundational things that support proper brain function.)

Though I have worked with many of these treatments and can self-adjust to a degree, I find it extremely helpful to use testing figure out what's actually going on, rather than relying on how I feel to determine if a treatment is working. Many times, what had expected was happening was not, and the testing led to new insights that leapfrogged improvenent. And, when trying multiple interventions, it's important to see what the overall effect is. Progress can happen much faster tban one intervention at a time.

And you're right, you do get what you pay for. It's unfortunate, but in fighting this disease, acquiring accurate data and using robust treatments offers more chance of success. Very frustrating that governments and insurance companies have little appetite for spending money to find treatable problems and treat them.
 

Hip

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Thanks for those suggestions, @Learner1. These are all things I have tried over the years, but unfortunately they have not made much difference to my ADHD and the difficulty reading that ensures from it. In the first few years after my brain infection, when the ADHD was really bad, and I often could not read even a 3 sentence email, strangely enough, the only thing that helped the ADHD was a really long hot bath. I've never been able to figure out why, but it worked without fail.