Suspected Overmethylation and Inflammation - How to fix?

[hb8847]

After taking a methyl-B12 & methylfolate supplement (Cytoplan's Methyl Factors - contents: 1000 methyl-B12, 800 Methylfolate, TMG & B6) for 3 months straight I think I am chronically overmethylating.

I stopped it over 2 months ago now and am still dealing with all the side effects you hear about - anxiety, insomnia, bloating, diarrhoea, aching joints, headaches, muscle spasms, depression, and a weird sort of tingling sensation running through my body. I suspect some of this might also be caused by inflammation.

I have read most of Ben Lynch's site and have tried all the usual supplements to calm this down.

Niacinamide seems to do very little - even at high doses of up to 2000mg - as do electrolytes. Glutathione seems to worsen things, as does glycine. Vegetables seem to do the same, in particular they worsen the bloating and insomnia. Meat ups my inflammation and anxiety. Due to food intolerances I can't even consider grains or gluten. Curcurmin capsules haven't helped with inflammation. And my histamine intolerance rules out most fruit and nuts (the latter of which is also high in methyl-donors folate and methionine).

One thing that does seem to settle things down somewhat is if I stop eating entirely for 2 or 3 days, but this isn't a permanent solution and once I start eating again all the symptoms begin to fire up.

I have a theory as to what's going on. If you think any of the following is likely/unlikely please do comment.

The bloating in particular makes me think I've got a huge excess of Methylfolate in my system. I suspect I didn't require as much of that as I did of B12. (In fact, I have taken B12 on its own before and didn't experience nearly as bad inflammation symptoms, the fact I didn't do so this time around was probably a mistake and for reasons I explain below).

Vegetables contain lots of folate, and if they're causing me to bloat it would appear to me to be because I already have a large excess of it? I suspect the issue with meat is that it contains methionine which further spurs on overmethylation. Meat is also directly inflammatory.

Unfortunately that doesn't leave me with much in the way of dietary solutions, so I'm hoping that someone here might have experienced something similar and knows how I might be able to get over this hurdle.

Like I said nothing so far apart from a complete 48hr food fast seems to calm this down. The past few weeks I've been on vegetables alone, and things don't seem to be getting much better. Veg is anti-inflammatory, so to me it seems the only way it could be prolonging things is if I were still overmethylating and the veg is contributing to it.

There are some things I'm considering, like starting the B12 again on it's own in the hope that it "soaks up" some of the excess folate - is this viable? Or sensible? The last thing I want to do is worsen the methylation & inflammation and so I'm pretty wary about this option, hence why I'm bringing it up here first.

Any help or advice with any of this would be amazing, frankly I'm at a bit of a loss. Also feel free to ask any questions. I know this is a long post, but I've added some of my backstory below for clarity.

Bit of backstory:

Prior to supplementing with B12 & Folate I had a severe problem with food intolerances (as well as CFS and cognitive symptoms - see my introductory post for more). It got to the point where I couldn't eat anything at all without getting intense brain fog.

Eventually I found a doctor who suspected this might be an autoimmune problem related to B12. I began taking the aforementioned Cytoplan Methyl Factors supplement on his advice and this immediately changed everything - it was like a switch was flicked inside me and from ingesting the first capsule suddenly the reactions to foods was gone, most significantly the brain fog.

This made me (and the doctor) think the B12 was very significant in my health issues. I've since taken a 23andme genetic test which confirms this.

The problem was, in spite of the Cytoplan supplement I wasn't getting entirely better. I still had bad underlying CFS and the supplement seemed to be worsening my aches and pains, as well as cognitive symptoms such as despondency. But all of this was preferable to the food intolerance and brain fog, so I persisted.

Then suddenly after about a month of this I drastically improved. I went from being practically bed-bound to having much more energy, I was singing, I was motivated. Considering the state I'd been in the previous week (and preceding 5 years) this change was CRAZY, and my family were all shocked.

This lasted about 5 days.

Gradually I began to notice other problems - very rapid thoughts, like my brain was firing uncontrolled, and a growing anxiety to the verge of panic. I was also beginning to bloat significantly, to the point where my stomach was like a balloon ready to pop. This culminated at the end of the week in a severe panic attack with numbness and tingling through my extremities.

I urgently got in touch with the doctor who suggested I was "overmethylating". I immediately came off the Methyl Factors supplement and over the course of about 3 weeks these symptoms slowly died down.

The state I was then left in, while not completely cured from my CFS and cognitive symptoms, was SIGNIFICANTLY better than I had been before. Not just the food tolerance, but I was focused, more active. Something significant had clearly occurred. But I was also wary of the Methyl Factors supplement - occasionally I would try it again in very small doses and the bloating and anxiety would come rushing back. So - perhaps foolishly - I stopped it for good.

After about a month of feeling better, I then gradually started to decline again. My food intolerances slowly returned, as did my cognitive and physical symptoms. For some reason I didn't put two and two together with the Methyl Factors supplement - initially I had a fever and thought it might have been that.

Eventually it became too significant to ignore and I decided to repeat everything I'd previously done that had helped - that meant getting back on the Methyl Factors. Again it immediately fixed the brain fog and food intolerances, although again it caused side effects like bloating, despondency and anxiety. This time though I was so concerned about a relapse I just continued to take it regardless, relentlessly, for about 3 months non stop.

Eventually again the side effects became too significant to ignore. This was early May of this year. I wasn't getting brain fog or food intolerances, but I was despondent, depressed, highly fatigued, aching in my joints, dizzy, anxious, and had a mixture of diarrhoea and stomach pain.

Since then I've been in largely the same state. Nothing I do seems to be able to calm these symptoms down, safe for a complete food fast. I have considered that I might be back to undermethylating, although seeing as I'm not getting the brain fog (and I'm getting all the usual stuff like bloating, anxiety, insomnia) I tend to think I'm more likely to be over- rather than under-.

Again, any questions or comments on this or my wider health issues I'm more than happy to answer. Thanks so much for reading.

Hugo.

 

[hb8847]

I've since read elsewhere on the site that SIBO can cause a simultaneous B12 deficiency and a Folate surplus! This might explain a thing or two as I definitely have SIBO...

For the record, today I experimented with just B12 on its own, and eating just meat and vegetables. The bloating and inflammation seems to have died down significantly so I'm hopeful this is something I can work with for the time being. In the meantime if anyone has any insight to this I'm all ears.

Thanks,
Hugo

 

[Learner1]

Niacin should reduce overmethylation.

You might be misding other cofactors... you might wish to investigate your levels of B1, B6, B2, magnesium, potassium, molybdenum, methionine, cysteine, and glycine. Any of these might affect what's going on.

You might also want to look into MCAS meds.

 

[JES]

I think you need to be very careful with interpreting your reactions as over- or undermethylation. It is common for ME/CFS patients to "temporarily" respond to a supplement and to then have it stop working. People report this can happen anywhere from a few days to months, for me it's usually less than a week, at most a couple of weeks. I have responded like this to a countless number of supplements. I made the big mistake thinking it was some ingredient in the supplement I was missing, when it was most likely not the case. If the supplement was truly beneficial and your body was missing it, it would proably cause a gradual improvement that wouldn't be followed by setbacks.

From the excellent and detailed description you gave about how your condition has changed, it makes me think over/undermethylation has little to do with it. One good rule is to go by "Occam's razor" when the cause of a disease is unclear, that is, go with the expalanation that requires the least assumptions, as it is most often times correct. I think your doctor is catching at straws thinking your issues are related to B12, as there is very little if any credible research linking B12 to ME/CFS.

I can only see the connection to B12 making sense if you measured low on a lab test. 23andme will only give you SNPs and most attempts at explaining a disease from one or two SNPs have been pseudoscience. For example, the MTHFR mutations are extremely common, something like 40% of the population test for heterozygous MTHFR and 10% for homozygous. All this really tells us is that you may have a slightly higher need for folate and in particular the active form, methylfolate (folic acid should be avoided). But it's not like the 10 or 40% of population with MTHFR walk around with bloating, ME/CFS and chronic inflammation. The amount of folate you get from vegetables is insignificant compared to the dosages used in methylation protocols, so almost certainly the issues you get from vegetables aren't due to excessive folate.

Going by Occam's razor and what proper ME/CFS research has found, I think your bloating is more likely due to SIBO and gut inflammation. Gut inflammation and microbiome changes have been found in plenty of studies and while they may not necessarily be the ground cause of ME/CFS, they surely contribute to SIBO and bloating. High-quality research have already detected a plethora of gut issues in ME/CFS, for instance with MAIT cells and a shift in microbiome. All of these are much more likely explanations for the gut issues than B12.

Sorry if this wasn't of much help, but I think you should not to experiment with high doses of supplements if there is no good reason to. I started developing bloating and stomach issues few years ago and for me I'd say the only things that have ever helped are a) diet and b) drugs that speed up gut motility c) certain herbs that kill the bacteria causing SIBO, but even this isn't a cure as such.

 

[hb8847]

I think you need to be very careful with interpreting your reactions as over- or undermethylation. It is common for ME/CFS patients to "temporarily" respond to a supplement and to then have it stop working. People report this can happen anywhere from a few days to months, for me it's usually less than a week, at most a couple of weeks. I have responded like this to a countless number of supplements. I made the big mistake thinking it was some ingredient in the supplement I was missing, when it was most likely not the case. If the supplement was truly beneficial and your body was missing it, it would proably cause a gradual improvement that wouldn't be followed by setbacks.

From the excellent and detailed description you gave about how your condition has changed, it makes me think over/undermethylation has little to do with it. One good rule is to go by "Occam's razor" when the cause of a disease is unclear, that is, go with the expalanation that requires the least assumptions, as it is most often times correct. I think your doctor is catching at straws thinking your issues are related to B12, as there is very little if any credible research linking B12 to ME/CFS.

I can only see the connection to B12 making sense if you measured low on a lab test. 23andme will only give you SNPs and most attempts at explaining a disease from one or two SNPs have been pseudoscience. For example, the MTHFR mutations are extremely common, something like 40% of the population test for heterozygous MTHFR and 10% for homozygous. All this really tells us is that you may have a slightly higher need for folate and in particular the active form, methylfolate (folic acid should be avoided). But it's not like the 10 or 40% of population with MTHFR walk around with bloating, ME/CFS and chronic inflammation. The amount of folate you get from vegetables is insignificant compared to the dosages used in methylation protocols, so almost certainly the issues you get from vegetables aren't due to excessive folate.

Going by Occam's razor and what proper ME/CFS research has found, I think your bloating is more likely due to SIBO and gut inflammation. Gut inflammation and microbiome changes have been found in plenty of studies and while they may not necessarily be the ground cause of ME/CFS, they surely contribute to SIBO and bloating. High-quality research have already detected a plethora of gut issues in ME/CFS, for instance with MAIT cells and a shift in microbiome. All of these are much more likely explanations for the gut issues than B12.

Sorry if this wasn't of much help, but I think you should not to experiment with high doses of supplements if there is no good reason to. I started developing bloating and stomach issues few years ago and for me I'd say the only things that have ever helped are a) diet and b) drugs that speed up gut motility c) certain herbs that kill the bacteria causing SIBO, but even this isn't a cure as such.

Hi JES, thanks for this reply, and I'll definitely consider lots of stuff you've mentioned.

As for the B12, all I can really go on is what I've experienced. Prior to supplementing with B12 (in particular, the aforementioned Methyl Factors supplement) I was experiencing - amongst other symptoms - severe reactions to food. It began with more toxic foods such as gluten, progressed to grains, and eventually got to the point where I was literally unable to put anything into my gut without experiencing an array of - sometimes horrendous - symptoms. I'm talking organic vegetables, medications, supplements, fish, probiotics - anything you absorb into the blood would cause me issues almost immediately.

These symptoms ranged from intense stomach pain and agony in my joints, to sudden and severe depression and brain fog. To manage this, or until I found a 'cure', I would generally go around 48 hours without eating anything before trying a new food. There is a list of around 60 individual vegetables, grains, nuts, animal products, supplements and medications in my diary that I tried individually, listing the specific symptoms from each. I was losing a lot of weight and it's safe to say the situation was getting pretty urgent.

Then from the first time I tried the Methyl Factors supplement these symptoms went away. I was able to eat most of those foods without any brain fog or symptoms whatsoever. My underlying CFS didn't get better immediately, but it also did start to gradually improve. It's clear to me something extremely significant happened here that was too important to ignore.

Now, I'm not a doctor. But it's also not like there isn't a plausible explanation for what could be going on here. I know following a CDSA I have extensive gut dysbiosis that I've been attempting to resolve for the past few years. SIBO and the ensuing damage to the gut lining can severely limit your body's ability to absorb B12. And a deficiency in B12 is a direct cause of autoimmune conditions such as pernicious anaemia, as well as food intolerances.

I agree with you that the MTHFR gene variant is unlikely to be to be the only cause for any of this, as otherwise half the population would probably be in bed with CFS. I am though homozygous for MTHFR, and this is at best unlikely to be helping the above situation.

As for the bloating - in spite of the dysbiosis this is again something I never experienced prior to supplementing with the Methyl Factors. I also don't appear to get it from pure B12 supplementation on its own, purely from Methylfolate and TMG.

As I mentioned in my earlier post, I've since read about how SIBO can reduce one's ability to absorb B12 and increase the quantity of folate. I know I have SIBO, so this could provide another explanation as to what I'm dealing with.

My reason for explaining this all is that there just seems to me to be too much evidence pointing at B12 for me to ignore it and move onto other things. And there is some sort of plausible narrative as to how it might be contributing to my issues. That said, I do appreciate your advice and will definitely look into it, and I agree that the long term solution to this will likely be found in the gut.

Hugo.

 

[Hip]

I have read most of Ben Lynch's site and have tried all the usual supplements to calm this down.

The Ben Lynch website tends to present every medical problem in terms of methylation. The maxim relevant here is "if the only tool in your toolbox is a hammer, then everything look like a nail". There are tens of thousands of metabolic pathways in the body, and any drug or supplement you take, and any health conditions you have, will impact many of these pathways.

So in trying to understand why a medication has improved or worsened your health condition, you have consider all the possibilities. That might take 10 years of study, but that's the way it goes!


Just to throw in a random bit of biochemistry: methyl donor supplements increase the alpha interferon response. Ref: here. So perhaps (this is pure speculation) if you have ongoing viral infections, these supplements may increase interferon and thus the immune attack on these viruses.

Methyl donor supplements also help restore the myelin sheath on nerves. I don't know if you have been following the craniocervical instability (CCI) excitement on this forum, but after surgical correction of CCI, ME/CFS patients with CCI not only experienced full remission from their ME/CFS and POTS, but also from their MCAS food and chemical sensitivities.

One of the things that CCI surgery appears to do is to restore the autonomic nervous system (ANS), which becomes compromised due to the mechanical nerve and brainstem compression caused by CCI. A lot of new research suggests that the ANS plays a major role in the immune response. In the opinion of Dr Ross Hauser, compression of the vagus nerve can cause symptoms such as POTS, MCAS, anxiety and leaky gut. See this video at 2:24.

Thus (and again this is pure speculation) if you had some compromised vagus / autonomic nerves due to poor myelination of the nerve, the methyl donors might have corrected this, leading to improved autonomic functioning and thus improved immune function.

 

[Learner1]

There are some interesting clues above. I have MCAS and my naturopathic doctors greatly reduced my MCAS/allergy symptoms by optimizing methylation.

Have you looked into MCAS testing? Definitely seems you have gut issues to resolve and that B12 deficiency can be a symptom of gut issues as 3 separate processes must work in the gut to assimilate B12.

there is very little if any credible research linking B12 to ME/CFS.

This is untrue. The Naviaux metabolomics paper identifies this.

The Ben Lynch website tends to present every medical problem in terms of methylation.

I know Ben Lynch and have been to his conferences. He originally began looking into MTHFR, but then found methylation was more tgan just MTHFR, and know he's into an entire functional medicine approach. He is thoughtful and investigates huge amounts of research in to a body of knowledge that can be used by clinicians and patients.

Methylation is critically important as it goes on in every cell in our bodies and it's a key to DNA copying, running the immune system, mobilizing and eliminate toxins and waste products, and many other important tasks. A biochemistry professor friend gave me a large poster showing all the biochrmical pathways and folate is a large circle near the middle with a bunch of arrows interscting with it - its important.

I agree with @JES - figuring out of you are over or undermethylating is tricky

 

[Sophiedw]

After taking a methyl-B12 & methylfolate supplement (Cytoplan's Methyl Factors - contents: 1000 methyl-B12, 800 Methylfolate, TMG & B6) for 3 months straight I think I am chronically overmethylating.

I stopped it over 2 months ago now and am still dealing with all the side effects you hear about - anxiety, insomnia, bloating, diarrhoea, aching joints, headaches, muscle spasms, depression, and a weird sort of tingling sensation running through my body. I suspect some of this might also be caused by inflammation.

I have read most of Ben Lynch's site and have tried all the usual supplements to calm this down.

Niacinamide seems to do very little - even at high doses of up to 2000mg - as do electrolytes. Glutathione seems to worsen things, as does glycine. Vegetables seem to do the same, in particular they worsen the bloating and insomnia. Meat ups my inflammation and anxiety. Due to food intolerances I can't even consider grains or gluten. Curcurmin capsules haven't helped with inflammation. And my histamine intolerance rules out most fruit and nuts (the latter of which is also high in methyl-donors folate and methionine).

One thing that does seem to settle things down somewhat is if I stop eating entirely for 2 or 3 days, but this isn't a permanent solution and once I start eating again all the symptoms begin to fire up.

I have a theory as to what's going on. If you think any of the following is likely/unlikely please do comment.

The bloating in particular makes me think I've got a huge excess of Methylfolate in my system. I suspect I didn't require as much of that as I did of B12. (In fact, I have taken B12 on its own before and didn't experience nearly as bad inflammation symptoms, the fact I didn't do so this time around was probably a mistake and for reasons I explain below).

Vegetables contain lots of folate, and if they're causing me to bloat it would appear to me to be because I already have a large excess of it? I suspect the issue with meat is that it contains methionine which further spurs on overmethylation. Meat is also directly inflammatory.

Unfortunately that doesn't leave me with much in the way of dietary solutions, so I'm hoping that someone here might have experienced something similar and knows how I might be able to get over this hurdle.

Like I said nothing so far apart from a complete 48hr food fast seems to calm this down. The past few weeks I've been on vegetables alone, and things don't seem to be getting much better. Veg is anti-inflammatory, so to me it seems the only way it could be prolonging things is if I were still overmethylating and the veg is contributing to it.

There are some things I'm considering, like starting the B12 again on it's own in the hope that it "soaks up" some of the excess folate - is this viable? Or sensible? The last thing I want to do is worsen the methylation & inflammation and so I'm pretty wary about this option, hence why I'm bringing it up here first.

Any help or advice with any of this would be amazing, frankly I'm at a bit of a loss. Also feel free to ask any questions. I know this is a long post, but I've added some of my backstory below for clarity.

Bit of backstory:

Prior to supplementing with B12 & Folate I had a severe problem with food intolerances (as well as CFS and cognitive symptoms - see my introductory post for more). It got to the point where I couldn't eat anything at all without getting intense brain fog.

Eventually I found a doctor who suspected this might be an autoimmune problem related to B12. I began taking the aforementioned Cytoplan Methyl Factors supplement on his advice and this immediately changed everything - it was like a switch was flicked inside me and from ingesting the first capsule suddenly the reactions to foods was gone, most significantly the brain fog.

This made me (and the doctor) think the B12 was very significant in my health issues. I've since taken a 23andme genetic test which confirms this.

The problem was, in spite of the Cytoplan supplement I wasn't getting entirely better. I still had bad underlying CFS and the supplement seemed to be worsening my aches and pains, as well as cognitive symptoms such as despondency. But all of this was preferable to the food intolerance and brain fog, so I persisted.

Then suddenly after about a month of this I drastically improved. I went from being practically bed-bound to having much more energy, I was singing, I was motivated. Considering the state I'd been in the previous week (and preceding 5 years) this change was CRAZY, and my family were all shocked.

This lasted about 5 days.

Gradually I began to notice other problems - very rapid thoughts, like my brain was firing uncontrolled, and a growing anxiety to the verge of panic. I was also beginning to bloat significantly, to the point where my stomach was like a balloon ready to pop. This culminated at the end of the week in a severe panic attack with numbness and tingling through my extremities.

I urgently got in touch with the doctor who suggested I was "overmethylating". I immediately came off the Methyl Factors supplement and over the course of about 3 weeks these symptoms slowly died down.

The state I was then left in, while not completely cured from my CFS and cognitive symptoms, was SIGNIFICANTLY better than I had been before. Not just the food tolerance, but I was focused, more active. Something significant had clearly occurred. But I was also wary of the Methyl Factors supplement - occasionally I would try it again in very small doses and the bloating and anxiety would come rushing back. So - perhaps foolishly - I stopped it for good.

After about a month of feeling better, I then gradually started to decline again. My food intolerances slowly returned, as did my cognitive and physical symptoms. For some reason I didn't put two and two together with the Methyl Factors supplement - initially I had a fever and thought it might have been that.

Eventually it became too significant to ignore and I decided to repeat everything I'd previously done that had helped - that meant getting back on the Methyl Factors. Again it immediately fixed the brain fog and food intolerances, although again it caused side effects like bloating, despondency and anxiety. This time though I was so concerned about a relapse I just continued to take it regardless, relentlessly, for about 3 months non stop.

Eventually again the side effects became too significant to ignore. This was early May of this year. I wasn't getting brain fog or food intolerances, but I was despondent, depressed, highly fatigued, aching in my joints, dizzy, anxious, and had a mixture of diarrhoea and stomach pain.

Since then I've been in largely the same state. Nothing I do seems to be able to calm these symptoms down, safe for a complete food fast. I have considered that I might be back to undermethylating, although seeing as I'm not getting the brain fog (and I'm getting all the usual stuff like bloating, anxiety, insomnia) I tend to think I'm more likely to be over- rather than under-.

Again, any questions or comments on this or my wider health issues I'm more than happy to answer. Thanks so much for reading.

Hugo.

Hey Hugo,
Did you ever find any other supplements that corrected this response to methylation supplements? All the best

 

[hb8847]

Hi @Sophiedw ,

This was quite a while ago now but if essentially I think I was going down the wrong path with the methylation stuff. After having some success with B12 I assumed everything was methylation related and so went down that route for a while, some things working, some things not, but I basically kept pushing at it cos I was so keen for it to work.

In retrospect most of the symptoms I had were probably not to do with overmethylation but likely manifestations of other issues in my body and the issues the supplements were causing could have been due to any number of issues.

I've since refocused my efforts on fixing the gut. The best solutions I've found to date for calming down negative reactions to things have been either fasting or an Elemental diet, but I'm still a long way from recovery. Hope that helps and best of luck.

 

[Victronix]

Just FYI, taking a B-multi (or other Bs) along with B-12 is necessary to keep from feeling overly anxious. I couldn't take certain Bs (B6, methylfolate) so I take each of the others separately. It does sound like B-12 made a difference for you. The "start-up" effect for me is just like you described - singing, basically! - but wears off after a few days.

The gut is the hardest part. Even if you get significant improvement, one change elsewhere can then change the gut all over again. I have yet to "fix" mine. I had my gallbladder removed last year and that's taken at least a year to adjust to, now have to take ox bile.

Please post if you find solutions!

 

[Sophiedw]

Will do! Thanks for the reply both x

 

[Sophiedw]

I agree sounds like interplay of methylation and gut issues or whatever but you are the scholar of your own experience as we all bloody have to be. Strength in your continuing search. Glad you found some improvement with b12 etc. or at least a shift I think that’s positive that you could tolerate supplements and such so when you’ve cleared the gut stuff maybe you could return on that front as well. Lots to juggle always but we persevere.

 

[Guwop2]

Would someone kindly summarise what methylation is and why I might want to try it?

 

[Nanni]

Just FYI, taking a B-multi (or other Bs) along with B-12 is necessary to keep from feeling overly anxious. I couldn't take certain Bs (B6, methylfolate) so I take each of the others separately. It does sound like B-12 made a difference for you. The "start-up" effect for me is just like you described - singing, basically! - but wears off after a few days.

The gut is the hardest part. Even if you get significant improvement, one change elsewhere can then change the gut all over again. I have yet to "fix" mine. I had my gallbladder removed last year and that's taken at least a year to adjust to, now have to take ox bile.

Please post if you find solutions!

Do you know why that yahoo effect from methyl b wears off. Those few days were the best. I still have gut stuff to fix as well. I had my gallbladder out as well. What is the best ox bile?