methyl sensitivity

[Bdeep86]

I have COMT and I just started introducing methylfolate after building b12's. I seem to be very sensitive to methyl's, getting very irritable feeling very unwell. So I am going very slow, I'm at 200mcg and holding. Do people usually adjust at some point to the methyls so that I can build. I'm in a catch 22 because I am getting really bad folate deficiency symptoms, but I really can't tolerate more methylfolate due to the methyls. Anyone been in this situation?

 

[stridor]

FWIW - I do not have significant COMT problems but I have come across a couple of things along the way. http://www.socialanxietysupport.com...-i-have-low-dopamine-high-comt-enzyme-182919/
Thought that this post was interesting. I heard that magnesium is important for those with COMT. I also heard that you have to increase very slowly.

 

[Marlène]

I cannot tolerate methyl at all when I'm close to or having my period I'm a danger to myself and others. Unfortunately I tend to forget every time till it's too late.

 

[rawcreamqueen]

i also have issues tolerating methyls. had huge fatigue issues and mood swings - depression and anger- and brain fog. it was debilitating. i have restarted re-introducing the b12s again just this past week with 1/8 th lozenge adb b12 and methyl b12 (125mcg)- i am ok this week and going every other day with the b12s on top of daily base of 1.125 grains of natural dessicated thyroid, 1ml of LDN, 1 tab of the neurological health formula, 1 tab thorne trace minerals, 1 x now 1500mg sunflower lecithin, 1/4 cap (will build to half a cap, ie 2.5mg) lithium oratate, 500-600 mg of mag citrate through the day, 250mg lipocare vit c, 1 x biocare b plex (no b12 and no folic acid) and i am learning to add 25mg nicotinic acid when i need it (see articles and comments under these links - useful guide to those of us who experience difficulties with methylation) http://mthfr.net/?s=niacin

going through the dr ben lynch links and dr rich's protocol and posts again here on this forum have really helped . i have have a break in brain fog this week so that has helped with retention! also re-reading dr yasko's autism: pathways to recovery (chapters 4 - 6 particularly) http://www.dramyyasko.com/wp-content/files_flutter/1327512160_9_1_1_8_pdf_02_file.pdf

i am hetero for 3 comp snps but homo for VDR TAQ which means i should be able to tolerate some methyls.but i have a bunch of other mutations which show i might have processing 'issues' with b12 amongst other things. i have added back the small bit of methyl b12 and made sure i am not taking any methyl donors (i had been taking nadh). soon i will add back a small bit of folinic acid. and then revisit my b12 and add to that. i had to remind myself that there are no hard and fast rules when it comes to this methylation protocol. we are all different with different SNPs interactions. i have read of some staying on low amounts of active b12s and folinic/5mthfr going forward. some that started with pinhead amounts of 5mthfr etc and building up very slowly. i hope this helps

 

[stridor]

Would you mind expanding on the other SNPs related to B12 metabolism? brad

 

[rawcreamqueen]

Besides COMT homozygous or heterozygous, in this post http://forums.phoenixrising.me/inde...-snps-methylation-protocol-supplements.25090/ Crux points out my FUT2, TCN1 and MTRR mutations impacting B12 transport and absorption . I am normal for MTR snps but if one has MTR mutations this can also mean that B12 is not recycled well and used insufficiently.

 

[stridor]

I have one hetero FUT2 and 2 MTRR ++ as well as TCN2 ++ .....so I guess we are in the same boat. I am on daily injections and after starting the huge B12 thread, I ordered dibencozide. I tried 2 injections one day and did not gain much.

 

[rawcreamqueen]

I don't have access to shots. Am based in UK. Basically I am self treating with help from others. I have self treated my thyroid too as once I was given the CFS dx years ago there was nothing anyone could do apparently. I was told to get used to being I'll during winter and hopefully less ill in summer. So been on a journey ever since!!! An illuminating one!!

I found with the restart on 125mcg MeB12 every other day I was still getting depressed/feelings of hopelessness/anger running into the next day too. 50mg of nicotinic acid really helped 'normalise' me!

I am now trialling OH (hydroxy) B12 - an 1/8th of the 2000mcg sublingual along with the Adb B12 (c.1/8 of the sublingual lozenge). I am taking a teeny bit of folinic acid now too. Yesterday I was good mood wise so I shall see how I go.

I have 4 homozygous GAD1 snps and also 2 hetero GAD1 plus homozygous MAO A. So I have been using pharma GABA (only 1/8th of a lozenge and time release 5htp (again only a 1/4 of 100mg pill)- I have found that one doesn't really help without the other and more 5htp is not helpful for me. My moods had been really bouyant once I got my NDT dose right for my thyroid but I never got beyond 70% better (unable to be consistent with even mild exercise) so hence choosing to use 23andme to find out more for myself. I had suffered bouts of depression and anxiety from my 20s but could never tolerate any meds for that- leaving docs baffled but 23andme results showed me why! So I am not surprised that depression/mood issues have raised their ugly heads now on the simplified methylation protocol.

 

[stridor]

I have 4 homozygous GAD1 snps and also 2 hetero GAD1 plus homozygous MAO A. So I have been using pharma GABA (only 1/8th of a lozenge and time release 5htp (again only a 1/4 of 100mg pill)- I have found that one doesn't really help without the other and more 5htp is not helpful for me. My moods had been really bouyant once I got my NDT dose right for my thyroid but I never got beyond 70% better (unable to be consistent with even mild exercise) so hence choosing to use 23andme to find out more for myself. I had suffered bouts of depression and anxiety from my 20s but could never tolerate any meds for that- leaving docs baffled but 23andme results showed me why! So I am not surprised that depression/mood issues have raised their ugly heads now on the simplified methylation protocol.[/quote]

Sounds like you don't really need injectable with the doses you tolerate (?) MAO A....is that for the breakdown of serotonin? I can't remember SNPs that I don't have. I have 7 hetero GAD1. When I was at my worst with ME/CFS, I started using nicotine patches and they helped some. Not a miracle, but better. High glutamate can kill neurons and nicotine is protective (at least for rats....and me). I had the dx of Bipolar but have also had anxiety attacks, agoraphobia, every flavour of depression - a pile of other psych symptoms.
My protocol has removed all psych symptoms. The best guess on Bipolar is that the symptoms are related to high oxidation, less inherent antioxidants (glutathione) or both. I am a bit nervous about starting dibencozide as it gets to the heart of the matter. I have never been able to tolerate anything that is purported to increase energy output of mitochondria.
Never-the-less I have to try. It is on its way.

 

[aaron_c]

Hey bdeep and rawcreamqueen, any updates on how the methylB12 has gone?

I have similar issues with COMT and , and am curious about the same thing. My COMT and VDR is supposed to behave like COMT ++ according to heartfixer. And I'm definitely methyl sensitive. Plus, niacin gives me diarrhea... Anyhow, I just want to know if yall have had any luck.

Thanks!

 

[rawcreamqueen]

i don't take the methyl b12 nor methyl folate -i am doing much better on folinic acid and adb b12 (1/4 tab of source naturals dibencozide sublingual). i add in a small amount of hydroxy b12 2 to 3x a week. i limit my methyl donors as i overmethylate really easily. but i like the niacin! have you tried small (er) amounts of the niacin to see if that helps without giving you diarrhea or see what the minimal amount you can take is and then maybe build up very slowly over time to 50mg?

 

[aaron_c]

Wow, so you don't take any methyl groups at all? No Betaine, even?

What happens when you take 50 mg of niacin? Is that enough to make you sleepy? I ask, because I am actually taking about 50 mg with each meal, and I haven't noticed that much of an effect.

Thanks Queen

 

[rawcreamqueen]

sorry i have not answered this!! i meant to and then forgot….please excuse the delay.

i tend to not supplement with methyl groups per se as i eat well and my gut and digestion is good for the past year - worked on that! - bar the 1 tab of holistic health's (dr amy yasko's multi vit) neurological health formula (the serving size is 6 tabs - i only take 1) that has some methyl groups/donors in it like tmg (betaine), choline, curcumin. i do eat several egg yolks a week (which are really rich in choline and betaine) and offal like local grass fed lambs' liver /kidney's once a week, plus local lamb/beef a couple times a week and a lot of green veg (i stay away from high oxalate veggies like spinach, kale as i have oxalate issues) every day so i am getting the methyls in my diet.

i found this re tmg and choline and saved it a while ago- it was posted by fredd back in 2010 on this forum(i hope the quote box comes up as i have never used such before…!!):

[
"TMG supplies about 30 times as many donatable methyl groups mg per mg as methylb12. So, one might think that 0.033mg of TMG has the same methylating power as 1mg of methylb12. If a person takes 500mg of TMG then they are taking as many methyl groups as if they took 15,000 mg (15 grams, not mcg) of methylb12.

SAM-e supplies 3 times as many methyl groups mg per mg. So a typical dose of 400mg of SAM-e supplies as many methyl groups as 1200mg (NOT mcg, 1.2 grams) of mb12. This would be equivalent to the methyl groups found in 1200 1mg injections of mb12 of of 1200 5mg sublinguals each held for about 90 minutes all at once.

A typical egg with the 113 mgs of choline it contains, has about 5000 times the methyl groups of 1mg of mb12 into serum.

So if the the startup effects of 1mg of mb12 are attributed to it's meager methyl content than an egg or 1mg of SAM-e (not the 200-600mg of a typical dose) or 33mcg of TMG or choline ought to put a person on the roof.


Telling somebody to avoid methylb12 because of it's meager quantity of methyl groups in light of the quantities of methyl groups from other sources, it ought to be clear the startup effects of mb12 are about all sorts of other things but very little attributable to the methyl groups it brings into the body per se. Mb12 isn't magic. It's donatable methyl groups are not magically 1000 times more powerful than the methyl groups from other sources. Since it clearly isn't based on the quantity of methyl groups brought into the body by mb12 it has to be the qualities of the complete methylcobalamin itself, and there are several forms of mb12 with somewhat different effects and effectiveness that has nothing whatsoever to do with the methyl group itself "
]

i do take 25mg of niacin about 4 to 5 days a week - occasionally 50mg. the 50mg niacin may give me a warmth that is all no redness to my flushing. i do not have stomach issues like some do from the niacin and sometimes i get a calm feeling from it but not sleepy. if i do supplement with 5mthlf or me b12 even at small amounts i will get low energy first/tired, then if i continue by the 3rd day (even if i am skipping days in between doses…i have experimented!) my mood will go downhill..if i continue i am getting brain fog, really bad depression/suicidal thoughts, sleep gets totally disrupted. generally a very miserable time.

 

[Freddd]

I have COMT and I just started introducing methylfolate after building b12's. I seem to be very sensitive to methyl's, getting very irritable feeling very unwell. So I am going very slow, I'm at 200mcg and holding. Do people usually adjust at some point to the methyls so that I can build. I'm in a catch 22 because I am getting really bad folate deficiency symptoms, but I really can't tolerate more methylfolate due to the methyls. Anyone been in this situation?

Hi Bdeep,

What brands and types of b12s are you taking and how are you taking them. Does the irritability go to anxiety or anything else or does it stay as straight irritability It can be a balance problem in some cases Also, irritability can be a sign of neurological healing as it can be caused by activating inflamed or irritated nerves. Don't be too quick to avoid what may be healing. So maybe you can tell me what all supplements you are taking and we can think this through. I had quite a bit of irritability during neurological healing. It was harder on my family than on me.

 

[Freddd]

sorry i have not answered this!! i meant to and then forgot….please excuse the delay.

i tend to not supplement with methyl groups per se as i eat well and my gut and digestion is good for the past year - worked on that! - bar the 1 tab of holistic health's (dr amy yasko's multi vit) neurological health formula (the serving size is 6 tabs - i only take 1) that has some methyl groups/donors in it like tmg (betaine), choline, curcumin. i do eat several egg yolks a week (which are really rich in choline and betaine) and offal like local grass fed lambs' liver /kidney's once a week, plus local lamb/beef a couple times a week and a lot of green veg (i stay away from high oxalate veggies like spinach, kale as i have oxalate issues) every day so i am getting the methyls in my diet.

i found this re tmg and choline and saved it a while ago- it was posted by fredd back in 2010 on this forum(i hope the quote box comes up as i have never used such before…!!):

[
"TMG supplies about 30 times as many donatable methyl groups mg per mg as methylb12. So, one might think that 0.033mg of TMG has the same methylating power as 1mg of methylb12. If a person takes 500mg of TMG then they are taking as many methyl groups as if they took 15,000 mg (15 grams, not mcg) of methylb12.

SAM-e supplies 3 times as many methyl groups mg per mg. So a typical dose of 400mg of SAM-e supplies as many methyl groups as 1200mg (NOT mcg, 1.2 grams) of mb12. This would be equivalent to the methyl groups found in 1200 1mg injections of mb12 of of 1200 5mg sublinguals each held for about 90 minutes all at once.

A typical egg with the 113 mgs of choline it contains, has about 5000 times the methyl groups of 1mg of mb12 into serum.

So if the the startup effects of 1mg of mb12 are attributed to it's meager methyl content than an egg or 1mg of SAM-e (not the 200-600mg of a typical dose) or 33mcg of TMG or choline ought to put a person on the roof.


Telling somebody to avoid methylb12 because of it's meager quantity of methyl groups in light of the quantities of methyl groups from other sources, it ought to be clear the startup effects of mb12 are about all sorts of other things but very little attributable to the methyl groups it brings into the body per se. Mb12 isn't magic. It's donatable methyl groups are not magically 1000 times more powerful than the methyl groups from other sources. Since it clearly isn't based on the quantity of methyl groups brought into the body by mb12 it has to be the qualities of the complete methylcobalamin itself, and there are several forms of mb12 with somewhat different effects and effectiveness that has nothing whatsoever to do with the methyl group itself "
]

i do take 25mg of niacin about 4 to 5 days a week - occasionally 50mg. the 50mg niacin may give me a warmth that is all no redness to my flushing. i do not have stomach issues like some do from the niacin and sometimes i get a calm feeling from it but not sleepy. if i do supplement with 5mthlf or me b12 even at small amounts i will get low energy first/tired, then if i continue by the 3rd day (even if i am skipping days in between doses…i have experimented!) my mood will go downhill..if i continue i am getting brain fog, really bad depression/suicidal thoughts, sleep gets totally disrupted. generally a very miserable time.

I would like to add to what you said. As MeCbl is almost always excreted as MeCbl it isn't even a net methyl donor. What MeCbl does is take methyl groups from bulk donors and passes them on and then has the methyl group replaced. MeCbl acts more like a catalyst than anything else. It is used over and over and at the end of the cycle is unchanged.

 

[rawcreamqueen]

thank you Fredd. i am really trying to get my head around all this stuff!! also i don't even know how to put a quote into the post let alone comprehend the complexities of methylation, detox etc! so can this (your post above i mean) explain why i seem to be fine on folates and b12 that come from the food that i ingest but that taking supplements of 5mthf and meCbl (even small amounts) seem to push me over a nasty edge? what do you mean by "then has the methyl group replaced" and also your last sentence? thank you, caroline

 

[Freddd]

thank you Fredd. i am really trying to get my head around all this stuff!! also i don't even know how to put a quote into the post let alone comprehend the complexities of methylation, detox etc! so can this (your post above i mean) explain why i seem to be fine on folates and b12 that come from the food that i ingest but that taking supplements of 5mthf and meCbl (even small amounts) seem to push me over a nasty edge? what do you mean by "then has the methyl group replaced" and also your last sentence? thank you, caroline

Hi Caroline,

To quote me press the reply that is on my post and it will quote. Then eliminate what you don't want included.

The nasty edge most people experience with MeCbl and l-methylfolate is to induce low potassium and/or induced donut hole methylfolate deficiency. See the lists of symptoms below. About 95% of what people call "detox" is actually low potassium and/or low folate. So Glutathione and NAC "detox" are both methyltrap situations causing paradoxical folate deficiency symptoms. When methylation starts, cells start getting made and low potassium results as healing begins. Again though it is usually called "detox" it is low potassium. Also, a little bit of folate starts a lot more healing than it can maintain. That induced low folate is also called "detox". Perhaps 20 different things are called "detox". Most of it is low potassium and/or low folate. To ignore low potassium by calling it "detox" is dangerous and can end up in the hospital or morgue as well as being just plain miserable.

People keep blaming MeCbl for being a source of methyl groups (CH4). It isn't. 99% of MeCbl is excreted as MeCbl within 48 hours according to research. A catalyst participates in a reaction and is the same at the end as it was at the beginning. MeCbl facilitates the passing of a CH4 to other things, along with methylfolate. These things are measured in micrograms. The bulk methyl-donors, like TMG and Choline are measured in mgs, 1 mg = 1000 mcg. Also, MeCbl has a total molecular mass of 1335 or so (several versions). A CH4 group has a molecular mass of 16, 1.3% of the total.

The reason you have no reaction to the food b12 and folate can be manifold. That you have a reaction so large to the supplements says to me that you are VERY DEFICIENT. The food can't possibly contain enough for you to get out of the hole of deficiency in your lifetime most likely. Pick out all the symptoms you get from the list below and any others that are not on the list below and let's talk about them. They will tell the story.




Version 1.2 12/08/2013

Group 1 – Hypokalemia onset. Symptoms may appear with serum potassium as high as 4.3. May become dangerous if ignored. Considered “rare” with CyCbl (cyanocobalamin) it is very common with MeCbl (methylcobalamin) and AdoCbl (adenosylcobalamin) and less so with HyCbl (Hydroxycobalamin).

There does not appear to be a clear order of onset. The order of onset varies widely from person to person but many appear consistent for each episode for any given person. There tend to be more and more intense symptoms as it gets worse. Some people have ended up in the ER because of not recognizing the symptoms.

IBS – Steady constipation, Nausea, Vomiting, Paralyzed Ileum,

Hard knots of muscle, Sudden muscle spasms when relaxed, Sudden muscle spasms when stretching , Sudden muscle spasms when kneeling, Sudden muscle spasms when reaching , Sudden muscle spasms when turning upper body to side, Tightening of muscles, spasms and excruciating pain in neck muscles, waking up screaming in pain from muscle spasms in legs. Muscle weakness

Abnormal heart rhythms (dysrhythmias), increased pulse rate, increased blood pressure

Emotional changes and/or instability, dermal or sub-dermal Itching, and if not treated potentially paralysis and death.


Group 2a - Both

IBS – Diarrhea alternating with constipation, IBS – Normal alternating with constipation


Group 2b – Either or both

Headache, Increased malaise, Fatigue



Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency

These symptoms appear in 2 forms generally, the milder symptoms that start with partial methylation block and the more severe symptoms that come on as partial methylation block gets worse or very quickly with methyltrap onset.

Edema - An additional thing I would like to mention. I would never have found it without 5 years of watching the onset of paradoxical folate insufficiency and trying to catch it earlier and earlier and to figure out what was causing it and to reverse it. For me the onset order goes back to the day of onset now with edema and a sudden increase of weight. I noticed that within 2 hours of taking sufficient Metafolin I would have an increase in urine output.


Old symptoms returning

Edema

Angular Cheilitis, Canker sores,

Skin rashes, increased acne, Skin peeling around fingernails, Skin cracking and peeling at fingertips,

Increased hypersensitive responses, Runny nose, Increased allergies, Increased Multiple Chemical Sensitivities, Increased asthma, rapidly increasing Generalized inflammation in body, Increased Inflammation pain in muscles, Increased Inflammation pain in joints, Achy muscles, Flu like symptoms

IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Stomach ache, Uneasy digestive tract,

Coated tongue, Depression, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Increase irritability, Heart palpitations,


Longer term, very serious

Loss of reflexes, Fevers, Forgetfulness, Confusion, Difficulty walking, Behavioral disorders, Dementia, Reduced sense of taste, bleeding easily




Group 4 - HyCbl onset, degraded MeCbl onset, MeCbl after photolytic breakdown onset.

Itchy bumps generally on scalp or face that develops to acne like lesions in a few days from start.

 

[rawcreamqueen]

hi fredd,

this listing is very comprehensive and helpful!

i had symptoms from group 2a, group 2b and group 3…i def have never had high bp. i tend to be 100/60 no matter what..i still suffer from oedema at times but have done since def moving towards menopause more. am trying to get consistent good energy and sleep. my moods have been pretty good for last few months.

i am on thyroid meds for the last few years- and had been on hc and t3 for a few years and now on natural desiccated thyroid for the last 18 months. i am 50 and perimenopausal and basically dx'ed with ME 6 years ago following 2 years of ill health after getting MRSA and septicaemia. i cannot supplement oestrogen and have difficulties with progesterone and other steroid hormones (like hc) even when labs showed i was low. i also have bad reactions to drugs and always had that- i was put on rifampicin for 3 months post hospital following my month hospital stay for the MRSA and septicaemia. the 23andme showed i am homoz for cypb1, cyp3a, cyp2a6 and hetero for cyp2d6. i am hetero for a1298c - so all this difficulty handling/processing drugs and supplementing hormones is backed up by these polymorphisms.

over the summer when i was on the simplified methylation protocol with the methyl b12 and 5mthf, i got to the point where my dyslexia returned - after about a 5/6 weeks ( i was badly dyslexic as a child but had severe head injuries following a car running into me when i was 8 - i was in a coma for about 3 weeks and had a series surgeries to my head over a course of a year- i was not dyslexic after the injury, and only mildly dyslexic under stress - i.e. exams, work deadlines). the fatigue, achiness and depression progressed as well over that summer leading to being bed bound with suicidal thoughts. i was not on high amounts of supplements as i was following dr rich van k's protocol. as stopped the protocol for a few weeks completely and restarted very low and very slow and kept to folinic acid and adb12 (with occasional hydroxy b12). the

since reading your post yesterday, i thought in for a penny, in for a pound…so i threw in some 5 mthfr (200mcg to add to the 200mcg of folinic i take). i was taking predominantly adb12 c2000mcg (1/4 of the source natural sublingual) but last 2 days i now take 1/8th of the source naturals sublingual and 1/8th of the hydroxy perque sublingual.…

caroline