Friday, April 11, 2014

The Methylation Cycle: Central to ME/CFS

I sat down to write a post about vitamin B12 supplements for people with ME/CFS and how much they have helped my son and I. I soon realized, however, that I couldn’t explain the importance of B12 without first explaining what the methylation cycle is and why it is so critical to those of us with ME/CFS (and similar illnesses). I’m no expert, but here is what I have learned:

What Does Methylation Do?
I already knew in a vague way that methylation was an important process in the body, but now I understand it is absolutely critical to multiple bodily systems. Before delving into exactly what methylation is, let’s look at its role in the body. Here are some of the vital functions of the methylation process:
  • Critical to the manufacture of DNA and RNA, the body’s basic genetic material;
  • Essential for several important neurological processes;
  • Required for the manufacture of adrenal hormones, which affect all sorts of bodily functions, including sleep, energy, temperature regulation, and neurological functions;
  • Responsible for several detoxification pathways, allowing your body to get rid of toxins, including excess medications, supplements, dead viruses or bacteria, as well as environmental toxins. 
Almost everyone with ME/CFS (and many people with other similar illnesses) has a dysfunctional methylation process. It’s hard to tease out cause and effect because every one of our dysfunctional systems (immune, endocrine, nervous, etc.) causes further dysfunction in other systems. Put simply, ME/CFS is a very complex knot of vicious cycles where each problem worsens all the other problems. So, it is likely that the longer you have been sick, the worse off your methylation cycle is.

In addition, the more health problems you have, the worse the methylation process gets (more vicious cycles), so someone like my son who has ME/CFS and also Lyme disease plus two other tick infections just keeps getting worse and worse – which is what we saw with him a few years ago and again this past year. Same goes for anyone with any kind of underlying infections behind their ME/CFS (which is probably most of us).  

What Happens When Methylation Isn’t Working Properly?
So, if people with ME/CFS have messed up methylation cycles, what exactly does that mean? When the methylation process isn’t working properly, the following problems result:
  • Detoxification doesn’t work well (as explained above) so toxins build up in your body;
  • Less serotonin, dopamine, and melatonin (all directly linked to sleep dysfunction as well as depression) are produced, as well as less of other neurotransmitters;
  • Decreased production of adrenal hormones; Elevated levels of homocysteine, which can lead to cardiac problems; 
  • Decreased cellular energy production aka mitochondrial dysfunction, leading directly to fatigue and post-exertional malaise; 
  • Possibly also an underlying mechanism for depression (see note on serotonin and dopamine above).

Take a look at that list again – notice anything familiar? It’s pretty much a list of most of the symptoms and dysfunctions that define ME/CFS! So, now you begin to see how important methylation is to each and every ME/CFS patient.

Detoxification, one of the processes affected by methylation, becomes supremely important if you have underlying infections (as the majority of ME/CFS patients do) and especially if you are treating those infections. In that case, you need an efficient detox process even more, in order to remove toxins like dead viruses and bacteria and excess medications and supplements from the body.

Those with Lyme or those being treated with antivirals are familiar with Herx reactions, where symptoms worsen (often severely) with treatment because the body is being flooded with dead bugs and extra medication that it can not properly get rid of, causing the immune system to react against the increased presence of viruses or bacteria in the bloodstream.

When methylation is not working well (as in most with ME/CFS) and therefore detoxification pathways aren’t working well, the herx reaction can get worse and worse, until the patient is stuck in crisis mode – totally incapacitated by herx symptoms, even when the medication (antibiotics or antivirals) are severely reduced. That’s where our son was twice – first, at the end of high school a few years ago and again, this past year (sophomore year of college).

This is where it gets somewhat complicated, but even a basic understanding of the methylation process will help you understand what kinds of treatments might help. Methylation is a biochemical process in the body that uses certain raw materials (foods, vitamins, supplements) to convert molecules into other molecules. When the process is working well, all those things listed above happen as they should: DNA, RNA, and crucial neurological components are manufactured; critical hormones (for sleep, mood, healthy adrenal function, and more) are made; and the body detoxes effectively, getting rid of those things that might be harmful to you.

I find the best way to understand the methylation process is to look at it visually:

(NOTE: Diagram is from an excellent article on B12 at ProHealth. Click on diagram to enlarge)

You may not recognize or understand all of the components, but this diagram shows how each step leads to another step and how interrelated the 3 different cycles shown here are to create the full methylation process. You can also see some of the important inputs to the process: proteins, amino acids, vitamin B12, folate and folic acid. And I think it is quite clear that if any one part of this process breaks down – for instance, there isn’t enough B12 or folate – then the entire process will fail, leading to the kinds of problems listed above.

Several methylation experts have emerged who understand the critical importance of the methylation cycle in people with ME/CFS and related illnesses and have made it their life’s work to try to help. Each of the experts has his or her own protocol, so there are some choices; however, they all rely on the critical components of the methylation cycle: vitamin B12 and folate (in various forms).

Dr. Amy Yasko is perhaps best known for pioneering a methylation protocol, designed to help repair dysfunctional methylation processes (and thereby improve the patient’s symptoms in a number of different areas). Interestingly, the focus of her work is in autism in children but it is equally applicable to ME/CFS (not the first time links between ME/CFS and autism have shown up). She has her own explanation of the methylation cycle, if you want to learn more, along with additional diagrams (more complicated than what I included here). Dr. Yasko advocates first getting some genetic testing done and then customizing the methylation protocol based on your results (more on that below).

With our son, we started with Dr. Rich van Konyenburg’s simplified methylation protocol, which I have written about here before. My son was in such terrible shape to start with that we had some difficulties, so I e-mailed Rich directly, and he was kind of enough to respond personally and help us through some of those challenges. Unfortunately, Rich died unexpectedly last year, leaving a big gap in our small world of expert ME/CFS resources. The last version of his simplified methylation protocol is available here, with an excellent Q&A on methylation written by one of Rich's colleagues here.

Typically, any methylation protocol begins with a good quality multi-vitamin, vitamin B12 (more on that in the next post), and 5-MTHF, a form of folate. However – and this is critically important – anyone with ME/CFS should start very slowly with tiny doses and only gradually increase, as tolerated. Any of these supplements can cause their own sort of “herx” reaction, as they get the methylation process working again, suddenly getting detoxification working again and flooding the bloodstream with toxins. As with most things in ME/CFS, low and slow is the rule. For instance, our son started with just a quarter of an 800 mcg 5-MTHF tablet every other day, very slowly working up to 400mcg per day. (Update: As of January 10, 2018, he now takes 20 mg of 5-MTHF a day).

Our son improved a bit on Rich’s protocol, but he was scheduled to start college in a month or so and was still too sick to manage it (as I mentioned earlier, his case is even more complex than most because of the 3 tick infections he is fighting along with his ME/CFS). Our Lyme doctor recommended a consultant who is a registered dietician and has an MS in biochemistry. She is brilliant and not only understands this complicated methylation process but also how that fits in with all the other complicated biochemical processes that are dysfunctional in ME/CFS and Lyme patients.

In the methylation arena, she ran a methylation panel for our son and made recommendations specifically based on his results. She also recommended dietary changes, in part because gluten, casein (the protein found in milk), and gliadin (another protein in wheat and also oats) can all block part of the methylation process. Also foods high in oxalates aren't good for people with ME/CFS (I don't fully understand why yet - still working on that one!).

With her help (and some other changes as well), our son recovered enough to start his freshman year of college alongside his peers, living on campus and taking 3 classes with enough energy left over for a social life. It felt like an absolute miracle to us, and treating methylation problems was definitely a big part of that.

We discovered, however, that you have to be diligent to stay ahead of all the complex problems in ME/CFS and Lyme. After two months, our son gave up on the restricted diet (he was feeling pretty good by then). He kept up the folate and B12 supplements, and continued with his Lyme treatment and all of the treatments for ME/CFS. Eventually, he began gradually declining again, until he was back in crisis mode and completely incapacitated during this winter break (note: this was more than methylation problems but we could tell that was part of the picture). We got back in touch with our dietician, got him back on an even stricter diet (he was so sick, he was willing to try anything). He is again recovering, back in school living on campus, and able to enjoy a social life with his friends, too. Part of his recovery is due to treating yeast overgrowth caused by his Lyme treatment, and part of it is due to getting back on track with the methylation process.

(Update: As of March 16, 2017, he continues to experience ups and downs. He knows how important diet is, but he's 22 and on his own, so it's sometimes tough for him to stick with it. He has learned, though, how important methylation is, and he knows he feels much better when he keeps up with his meds and supplements and remembers his B12 injections every other day.)

To help with methylation and associated processes, he (and I) take the following supplements (links below), remembering that we added these very gradually and slowly:
  • 5-MethylTetraHydroFolate (5-MTHF) We started at 200 mcg every other day and slowly worked up to 400 mcg every day. [3/17 Update: Now, four years later, we have gradually increased to 20 mg daily for both of us.] Links at the end of this post include several options at different doses, as you work up.
  •  Xymogen ActivNutrients multivitamin with no Iron or Copper (rec by our dietican - apparently, it is important to leave out Iron and Copper when you have infections). We order Xymogen products at cost through our specialist's office or online (link is to WholeScripts site, which now sells Xymogen products), using a code we got from our Lyme doctor. 
  • Xymogen ALAMax and Resveratin to assist in mitochondrial energy support [3/17 update: my son is currently off ALA because it can contribute to yeast overgrowth]
  • Calcium D-glucarate for detox support 
  • S-Acetyl Glutathione for detox support and energy (studies have shown people with ME/CFS to have low glutathione levels) - see also my post on glutathione for more information - we have seen big improvements in energy and immune function with glutathione injections.
  • N-Acetyl Cysteine (NAC) - Critical to detox and liver support in ME/CFS and a precursor to glutathione Note that NAC is no longer sold through Amazon and will be switching to prescription in the U.S. but companies are allowed to sell their supplement stock. You can find more brands available at eVitamins and at iHerb.
  • Milk Thistle - brand varies, taken throughout day and helps with detox - critical for liver support and a precursor to glutathione. 
  • Vitamin B12 (more info at the link) - I started with a sublingual tablet combo product, until my son told me to stop being a baby! ha ha He and I both now do subcutaneous (under the skin) self-injections every other day, alternating hydroxy- and methyl- B12. The needles are tiny and he was right - I barely feel it - and our injections are also tiny because we use a high concentration (25 mg/ml). Injections are known to be far more effective in getting the B12 to where it is needed. Sublingual pills (that melt under your tongue) are next in effectiveness, and B12 pills that you swallow or chew are very poorly absorbed. You need a prescription for injectable B12 and get it from a compounding pharmacy - it is inexpensive.

More recently, my son and I both had genetic testing done through 23andme (maybe I need another post on that!) and ran our results through Genetic Genie to find out what genetic defects we each have relative to methylation. A couple of problem areas showed up for each of us, so our next step was to work with our dietician to understand what the genetic results mean and how to adjust the methylation protocol accordingly (as Yasko recommends, too).

This post turned out much longer than I had planned, but it is a complicated and important subject. Next up is a post on the use of B12, including importance, uses, dosing, types, etc. From what I’ve read, it seems that everyone with ME/CFS can benefit from vitamin B12 supplementation, but it has to be done right in order to be effective. That one is already half-written, so I hope to post it here within the next week. [3/17 Update: you can find the B12 post here.]

Please share your own experiences with treating methylation and/or questions in the comments area. I am still learning about this critical part of ME/CFS, and I’m sure others would benefit from comments and questions also.

NOTE: Someone reminded me that I didn't mention SAMe in this summary. if you look at the diagram above, you can see that SAMe is a part of the methylation cycle; however, it is not recommended that all people with ME/CFS supplement with SAMe. My son tried it and got worse. Here's the way that Rich Van Konyenburg explained it to me:
"This was initially included in the protocol I proposed, but so many people could not tolerate it that I took it out.  SAMe will come up automatically if the partial block of methionine synthase is lifted by the methylation protocol.  I think that some people have difficulty dealing with all the sulfur if given NAC and SAMe.  The sulfur must all pass through the sulfite oxidase reaction, and if it can't handle it, sulfite builds up and gives headaches, difficulty in breathing, and/or rashes.  It also further lowers glutathione."
One of the common genetic defects related to methylation causes an inability to metabolize sulfur compounds, and this is relatively common in people with ME/CFS (both my son and I both have this defect and have reacted badly to sulfa antibiotics), so perhaps this is part of the reason why supplementing with SAMe sometimes makes ME/CFS patients worse. So if you do try it in spite of Rich's warning, watch for negative reactions which may worsen over time.

NOTE: FolaPro is the 5-MTHF supplement that Rich recommends in his Simplified Methylation Protocol, linked to above. It is a low dose and comes in tablets that can be halved or quartered, so we started with that at a very low dose, as described above. As we increased the dose, we switched to other brands shown below.

Note: This post contains affiliate links. Purchases from these links provide a small commission to me, to help offset the time I spend writing for this blog, at no extra cost to you.

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Karen said...

people, who have sensitive stomachs might want to try the following, It's a cream that has worked for me, I couldn't tolerate the 5MTHF, Awesome post, Sue, way to explain methylation!

Shelli said...

Thank you so much for another excellent, informative post! I have excellent supplements for mitochondrial support and multivitamin, but I'm wondering what to do for B12. I'm looking forward to your B12 blog post, because I'm curious to know if you *have* to have injections, or if you can find a good supplement that would help.

Sue Jackson said...

Great suggestion, Karen I will include the link also in the B12 post. I wish we had known about this back when Jamie was so sick and couldn't tolerate much!

Sue Jackson said...

I'll give you a sneak preview, Shelli ;) The experts now say sublingual is absorbed as well as injections, though the type is important - that gets complicated, so I will try to explain it in the post.

Unknown said...

Thank you, dear Sue.
Maybe this video will be useful to you.

I found it when I was searching for some explanation for my severe neurological decline after my knee replacement surgery. I discovered that the Nitrous oxide, (commonly used for anaesthesia) irreversibly oxidizes the cobalt atom of vitamin B12 and thereby suppresses the activity of B12-dependent enzymes such as methionine and thymidylate synthetases. Animal and human studies have demonstrated that the haematological, immune, neurological and reproductive systems are each affected.

Cyanocobalamine injections were the “must «for me: 3 weeks every day and then twice a week. I’m better now.

I'm French-Canadian Lymie.

Sue Jackson said...

Thank you, Nina - I will definitely watch this. Nitrous oxide is a big no-no for people with ME/CFS (and FM and many with Lyme) for another reason, too - it is a very strong vaso-dilator which makes OI get much worse, thereby causing a severe post-op crash. We made sure to avoid it for both of our sons' surgeries. I hadn't heard about its other negative effects before - so glad we talked to our surgeons and anesthiologists before each surgery!

Thanks -


Anonymous said...

Thanks Sue, this is really interesting. I will have to look into this :)

Unknown said...

Hi Sue:
Thanks for sharing this VERY informative post. I am currently being treated for a dysfunctional methylation process along with Lyme, Babesiosis, Bartonella, EBV, and multiple autoimmune diseases. No fun. I am sorry to hear that you guys have been dealing with this as well. I can't imagine how hard this would be to be a college student and to be dealing with all of this. My thoughts are with you guys. Thanks for sharing this post on Small Victories Sunday!

Sue Jackson said...

Hi, Amy -

Nice to "meet" you - it's always amazing to me how many people are struggling with similar medical issues behind the scenes - we are all over!

Glad to hear you are already being treated for methylations problems - it's so critical with the tick infections. Sounds like you are in the same boat as my son. I did have Lyme for a few years but now am back to "just" CFS (an immune disorder).

Glad you found the post helpful - I will try to come by your blog and visit!


Unknown said...

This is very interesting info.. I've been unwell since the middle of the year after taking metranidazole antibiotic .. Gave me heart palpitations and terrible acid reflux. Earlier blood tests showed low ferritin and low b12 (ignored by my dr) I went to a natruopath and used b12 spray and got my levels back up as well as a diet to increase stomach acid. I'm taking a lot of supplements but have been suffering terrible fatigue and brain fog. Now reading it sounds a bit like it could be a methylation problem! Also battling candida in my digestive tract.
Dr now wants to diagnose CFS as its dragged on for months. I just wanna feel better!!!

Sue Jackson said...

Thanks for sharing your story, Debbie. Sorry you have been through so much! Definitely try treating methylation.

Candida/yeast overgrowth alone can make you feel TERRIBLE! That alone could easily lead to a misdiagnosis of CFS - for me, it causes flu-like aches and complete exhaustion. I, too, struggle with chronic yeast overgrowth, and I feel so much better when it is under control. I highly recommend you focus heavily on that first. Here is some of what has helped my son and I....but when it's bad (as it has been lately, after antibiotics this fall for bronchitis), strong antifungal medications are a MUST. I have been on 200 mg of Diflucan a day for 6 months now, and I feel so much better. A strict diet is also critical:

Good luck!

NQ said...

Hi Sue
I am new to your blog and have been reading through it feverishly - so informative! I’ve had CFS for 5 years.
I am currently in a severe crash post abdominal surgery. My OI has never been this bad, I can’t tolerate anything other than being flat on my back.
After reading this, I am wondering if Nitrous Oxide maybe the big culprit here. If yes, what can I do to ease the symptoms?

Thank you for sharing your journey with all of us. It certainly makes me feel less isolated.

Sue Jackson said...

Sorry for the delay in responding - I was away for the holiday week.

Yes, yes, yes! Your crash is due to the anesthetic used in surgery. All anesthesias dilate the blood vessels, worsening Orthostatic Intolerance, an integral part of ME/CFS...and NO is the worst culprit among them! The best approach with surgery (in case you go through it again someday) is to talk to the surgeon and anesthesiologist ahead of time, request the least vaso-dilating anesthetics (though they all are to some extent), and - most importantly - request 2-12 hours of IV fluids after your surgery to get your blood volume up.

Unfortunately, this is a problem best prevented - there's not a lot you can do after the fact except lots of rest and LOTS of salt and fluids, again to try to get your blood volume up to ease the OI symptoms. Compression garments may help, too.

My son had 4 knee surgeries. With the first 2, he crashed for a full month after, even though his ME/CFS was usually mild. With the last 2, he got 12 hours of IV fluids after surgery and was feeling great (other than knee pain) within a couple of days - huge difference.

Here's more info on OI- there are many, many ways to treat it and treating OI usually dramatically improves ALL symptoms. This will not only help you recover from your surgery but will help to improve your overall quality of life & ability to function without crashing so easily:

Good luck!


Lois said...

Wow! This all makes total sense! I took the ME/CFS test on another site and it's me!! I am going to see my Lyme doc on the 30th, he's a DO, and am going to bring this up to him. I have Lyme and at least 2 confections, Candida, CFS, adrenal fatigue syndrome.....I wonder, do you also suffer from your eyes not focusing for hours after reading? Thank you so very much for doing all this!!

Sue Jackson said...

So glad you found this post helpful! The vision problems are due to Lyme disease - a very common symptom. Kepp treating your Lyme and co-infections, and hopefully, the problems will reverse.

Methylation is SO important for anyone undergoing treatment for tick infections - we went through that with my son - his methylation was so poor that he could barely tolerate any treatments - he didn't start improving until we addressed methylation - it's a huge part of the detox process, which is necessary in order to progress with tick infections.

Have you seen my post on candida? Another integral part of treating tick infections, unfortunately. This post links to several that you might find helpful in getting that yeast under control:

And here is another post on Herx reactions that you might find helpful:

Good luck! These are complex illnesses to deal with - let me know how it goes.


Dawn said...

Is it possible to let me know if your son has any endocrine abnormalities? For example Thyroid hormones, testosterone and growth hormone?

Sue Jackson said...

Hi, Dawn -

Endocrine abnormalities are an integral part of ME/CFS, so we both have had some at various points in the illness (low cortisol, for instance, is extremely common). Neither of us, however, has had any primary endocrine disorders, like hypo- or hyper- thyroidism, Hashimoto's, Addison's, or the problems you listed.

Primary disorders like those I listed need to be addressed directly by your doctor; however general abnormalities in the endocrine system will often normalize as you treat various aspects of ME/CFS - like methylation, immune dysfunction, OI, and correcting sleep dysfunction. Each of those approaches will naturally help to bring the endocrine system back to normal - ours is a very complex illness and all of these pieces are interconnected. Hope that helps! If had a more specific question, please let me know.


Angie Y. said...

Dear Sue,
i am overwhelmed to tears to suddenly find out so much practical information on cfs after 4 years with it!!! I am an American living in Berlin, Germany and was diagnosed at the Charite hospital here (a hospital that everyone thinks is so advanced) and then just given a piece of paper with a list of supplements and instructions to pace and that was that.
i have mostly been trying to improve my health by looking into my childhood patterns and meditating, etc. I have greatly improved but i haven't been able to cross the threshold into being able to do yoga again or to fully live my life really....and last year, to my dismay, i was diagnosed with Graves disease on top of it.
I just can't believe what i have been through without knowing any of the approaches you have suggested!! Tears are pouring down my face! I have seen so many doctors and health practitioners!!
Anyway, my question is that i don't know where to start - Do you know any cfs experts in Germany or Europe?
I have short acting beta blockers for the Graves disease since the hyperthyroidism makes my heart race at times. I see you recommend long acting ones so i will try to get them from my endocrinologist. i will also order a heart monitor right away and try to stay below my AT. But for the LDN and Immunovir and perhaps the nasal Glutathione, i will need a prescription. If i manage to get it from my family doctor (who has been useless), should i not start them all at once? If not, which one would you recommend starting with?
And about the salt, do you know if there are salt supplements without the iodine since i shouldn't have that with Graves disease?
Also, if you happened to know a website where i might buy GlutaQuick in Europe, that would be wonderful.
Pardon all my emotions and questions! I am extremely grateful for your writings.
Thank you so much, all my best wishes, Angie

Sue Jackson said...

Dear NB -

Welcome! I'm so glad you found your way here - better late than never :)

Yes, long-acting beta blockers taken at bedtime are a great start. They will help to treat OI (which you definitely have) and will thus improve your exercise tolerance. Then starting a regimen to wear the HRM, stay below your AT, and begin - VERY slowly - to do some exercises while lying on the floor (just 5 min at a time always staying below your AT) and beginning to walk - again, very gradually and with the HRM.

You are on the right track - I would definitely try to tackle immune dysfunction next since it is at the heart of the illness. Here, inosine is sold as a supplement and doesn't require a prescription. Is that not true in Germany? I usually recommend starting inosine first, for that reason and also because it often has the most dramatic effects. You can also begin to increase glutathione on your own, with all the precursors available as supplements while waiting to get the glutathione nasal spray. Sorry I don't know where to get GlutaQuick. Definitely start one treatment at a time so you can see how you react, what causes side effects, what helps, etc.

Oh, and salt... only table salt contains iodine and it is added to it. Naturally occurring salt NaCl does not contain iodine. So, use sea salt or Himalayan Pink Salt on your foods, and salt supplements like Salt Stick or Thermotabs should be iodine free also.

Have you sen this page on my blog? It acts as a roadmap to all the treatments, with links to more info.

Nice to meet you! Let me know how it goes and if you have any other questions!


Angie Y. said...

Dear Sue,

You are so kind to take the time to help me! Thank you so much for the information.
Yes, now i see that i can order inosine here without a prescription! That's great. Right now from Source Naturals, only the Ultra-Inosine is available - i am guessing that i should wait until they restock the normal inosine?
That's also great to know about the salt, thanks.
And now i see the roadmap to all treatments, oh my, it's so much information - I will go through that slowly! I did check out the doctors recommended in Europe. Even Dr. Schiebenbogen is included there from Charite but as i said, i didn't find it helpful there. That's a shame because according to your notes, her interest lies in EBV and i have had a test by a functional medicine doctor that shows that i have antibodies to it...
And unfortunately, the clinic in Sweden has closed down and the link to the Belgian doctor is not functioning.....but perhaps i can go to the UK one day.
In the meantime, i will slowly start with what i can, one thing at a time.
Thanks again, take care,

Sue Jackson said...

Angie -

Yes, that's the right approach - one thing at a time :) Sorry to hear the Sweden clinic closed! Thanks for letting me know - I will update the list. And a quick search shows that Dr. Kenny De Meirleir is now working here in the US at the Whittemore Peterson Institute (still on ME/CFS). That doesn't leave many European options, does it?? I will ask around.

I looked up Ultra Inosine, and I would stick with the regular to start with. The Ultra has loads of extra ingredients, and there's no telling what might help and what might cause a side effect. The Source Naturals brand is our favorite, but it has been back-ordered for a while now. I found some on iHerb last week - not sure if they ship internationally. Might just try a general search online and see which other providers come up. Sometimes Amazon has some brands of inosine available, so check there (we get 95% of our supplements from Amazon!).

Once you get some, be sure to follow the dosing instructions carefully - always take weekends off and alternate "high" and "low" dose weeks. Start VERY low to see how you react, with just 1 pill Mon thru Fri morning, then a week off OR if you get the source naturals (which can be cut), cut them in half and alternate weeks with 1 pill and a half pill (always weekends off). After a couple of weeks, leave the "low week" low but try increasing the high dose week a bit. Very slow and very gradual.

Good luck!


Angie Y. said...

Dear Sue,
Yes please do let me know if you find any experts in Europe! Interestingly, when i was getting diagnosed at Charite, the doctor i saw admitted to me that in Germany they are behind the UK and the US in treating this disease...
I found the regular Source Naturals Inosine on - i had to do some digging - it didn't come up straight away in the search but i found it. i think it is older packaging but it looks right!
And thank you for the detailed instructions! i think i won't even start it until i have gotten used to long acting beta blockers first.

Yikes, bedtime for me now! Have a peaceful election day!
all the best,

Sue Jackson said...

Angie -

Glad you found it! Yes, trying one thing at a time makes good sense, so you can separate cause and effect and know what helps or what causes side effects.

Behind the UK?? Wow, that would be REALLY behind, since the UK's NHS does not offer ANY real medical treatments - only therapy and exercise (which of course makes us worse), though the UK is currently working to update their treatment guidelines. Here in the US, it is only the top ME/CFS specialists on that list who really know how to treat the complexities of ME/CFS - most family doctors don't even understand it's an immune disorder. Those top experts may seem like a lot, but we are a huge country, and there are no specialists near the middle of the country - they are mostly on the coasts. So, we are mostly in the same boat - having to educate our doctors and ask for the treatments we want.

Anyway, good luck with long-acting beta blockers and with inosine - let me know how things go!