8 replies to this topic

[j87]

Did 23andme test.

Have MTHFR A1298C double mutation (can't convert folic acid), and MTR/MTRR single mutations that deal with b12 being converted.

I started taking quatrefolic, methyl b12. Was feeling amazing for several weeks, then for unknown reason had an allergic reaction. Became very itchy and ringing in ears. I stopped everything until it went away, I have tried to take methylfolate again twice, and each time had the same reaction. Itching is finally gone but I still have ringing in the ears. Depression/anxiety/brainfog are back in full force since stopping.

 

Was I being overmethylated? What could have caused this? Any advice much appreciated. 

[Mr Matsubayashi]

I'm hetero for 1298 and 677 but i'm also hetero for VDR, MTR/MTRR and homo for all COMT genes. On one hand supplementation of Methyl B12 and Methyl Folate are meant to be helpful but on the other hand excess methyl groups don't play well with my other mutations.

 

Right now i'm experimenting with supplementing niacin to remove excess methyl groups while supplementing the above.

 

Characteristically i'm an overmethylator but through niacin experiments i'm also high in histamine which is contradictory to all the homeopathy talk out there so I have to be careful not to give myself flushes haha.

 

If I ever settle for a stack i'll get a compound pharmacy to compound me a batch so I stop looking like Ray Kurzweil at breakfast.

 

I think the science on over/under methylation is very vague, some people have had success but from what I've read treatments based on the science are firmly in the realm of homeopathy. This isn't to say there isn't anything behind it but rather that the field is just young.

 

I realise i've just been talking about myself here but hopefully some of it is helpful.

Edited by Mr Matsubayashi, 07 January 2015 - 11:52 AM.

[caruga]

Quatrefolic is dosed very highly, perhaps your b12/folate ratio is off.  How are you administering the b12?  I've taken too much folate in the past and become 'switched off', despite delivering vast amounts of b12 directly into the bloodstream, but then came back to life after taking 1 mere 5mg methyl-b12 orally.  I'm guessing it reacts directly with the bile folates and that somehow has a cascade reaction across the rest of the body.

 

I don't know if there's science out there to back me up but my personal experience is that being 'water-soluble' doesn't automatically mean that the body will happily excrete the excess, as some people like to think.  Folate needs to be treated with respect when dosing.  It is one of a very few vitamins to get enterohepatically cycled and it is polyglutamylated to hold it inside the cell.  I don't know how long it stays in the body, but I suspect quite a while.

 

Also try taking zinc, histidine and tri-methyl-glycine.  Zinc and histidine are structural components of many of the folate-converting enzymes.  Histidine catabolism and tmg degradation are two pathways to converting tetrahydrofolate (the by-product of methyl-folate and b12 recycling homocysteine to methionine) to other folates.

Edited by caruga, 08 January 2015 - 01:46 AM.

[cinnabar]

You probably have elevated histamine when you go over a threshold of folic acid cycle throughput, e.g. the same might happen with higher doses of mb12 or p5p, if you care to test this theory. According to Walsh, this reflects a lack of ability to produce SAM-e and the treatment is to cut back on methylfolate/mb12/etc and the main thing is to use SAM-e or methionine. Specifically, his claim is that taking folic acid factors interacts with DNA in the nucleus but for whatever reason does not increase methyl-doner (SAM-e) throughput where its actually needed in the cell (cytoplasm? He is not clear on this).

 

In any case, i have developed histamine intolerance and it is made worse by anything that increases the folic acid cycle and many other supplements that I am already deficient in (5mthf, mb12, p5p, Fe, Cu, Mn, D3, fish oil, lecithin, almost all foods with some notable exceptions). However since starting methionine a week ago, I'm actually seeing some changes for the better. I'll know in a few weeks because its still too early for me to be definite, but I am seeing evidence of more SAM-e production with minor improvement in histamine levels. I'm quite relieved that methionine hasn't spiked my histamine so that in itself is significant.

 

Walsh has written somewhere that he sees improvement taking 6 months in those with excessive histamine and are folate intolerant but at doses of 2-3g/day of methionine. I've been taking 1g/day for a week. Walsh calls them undermethylators, i.e. low SAM-e throughput, which is distinct from what lynch/yasko/etc call undermethylators because they assume that taking mb12/methylfolate automatically increases SAM-e production accordingly. This is simply not the case for the few who have histamine issues from mb12/methylfolate and feel improvement from increased or exogenous SAM-e. It probably explains why people who become more histamine intolerant with mthf/mb12 on those forums (e.g. pheonix rising, mthfr, ch3nutrogenomics, chris kessler) never get a useful response.

 

Another source for information about this topic is this seminar

 

[j87]

You probably have elevated histamine when you go over a threshold of folic acid cycle throughput, e.g. the same might happen with higher doses of mb12 or p5p, if you care to test this theory. According to Walsh, this reflects a lack of ability to produce SAM-e and the treatment is to cut back on methylfolate/mb12/etc and the main thing is to use SAM-e or methionine. Specifically, his claim is that taking folic acid factors interacts with DNA in the nucleus but for whatever reason does not increase methyl-doner (SAM-e) throughput where its actually needed in the cell (cytoplasm? He is not clear on this).

 

In any case, i have developed histamine intolerance and it is made worse by anything that increases the folic acid cycle and many other supplements that I am already deficient in (5mthf, mb12, p5p, Fe, Cu, Mn, D3, fish oil, lecithin, almost all foods with some notable exceptions). However since starting methionine a week ago, I'm actually seeing some changes for the better. I'll know in a few weeks because its still too early for me to be definite, but I am seeing evidence of more SAM-e production with minor improvement in histamine levels. I'm quite relieved that methionine hasn't spiked my histamine so that in itself is significant.

 

Walsh has written somewhere that he sees improvement taking 6 months in those with excessive histamine and are folate intolerant but at doses of 2-3g/day of methionine. I've been taking 1g/day for a week. Walsh calls them undermethylators, i.e. low SAM-e throughput, which is distinct from what lynch/yasko/etc call undermethylators because they assume that taking mb12/methylfolate automatically increases SAM-e production accordingly. This is simply not the case for the few who have histamine issues from mb12/methylfolate and feel improvement from increased or exogenous SAM-e. It probably explains why people who become more histamine intolerant with mthf/mb12 on those forums (e.g. pheonix rising, mthfr, ch3nutrogenomics, chris kessler) never get a useful response.

 

 

 

Thanks for the info. Why did you choose to take methionine over SAM-E, is it safer?

Is TMG helpful also?

 

I took some zinc and ringing in ears is now mostly gone. I suspect I had too much copper.

[cinnabar]

 

You probably have elevated histamine when you go over a threshold of folic acid cycle throughput, e.g. the same might happen with higher doses of mb12 or p5p, if you care to test this theory. According to Walsh, this reflects a lack of ability to produce SAM-e and the treatment is to cut back on methylfolate/mb12/etc and the main thing is to use SAM-e or methionine. Specifically, his claim is that taking folic acid factors interacts with DNA in the nucleus but for whatever reason does not increase methyl-doner (SAM-e) throughput where its actually needed in the cell (cytoplasm? He is not clear on this).

 

In any case, i have developed histamine intolerance and it is made worse by anything that increases the folic acid cycle and many other supplements that I am already deficient in (5mthf, mb12, p5p, Fe, Cu, Mn, D3, fish oil, lecithin, almost all foods with some notable exceptions). However since starting methionine a week ago, I'm actually seeing some changes for the better. I'll know in a few weeks because its still too early for me to be definite, but I am seeing evidence of more SAM-e production with minor improvement in histamine levels. I'm quite relieved that methionine hasn't spiked my histamine so that in itself is significant.

 

Walsh has written somewhere that he sees improvement taking 6 months in those with excessive histamine and are folate intolerant but at doses of 2-3g/day of methionine. I've been taking 1g/day for a week. Walsh calls them undermethylators, i.e. low SAM-e throughput, which is distinct from what lynch/yasko/etc call undermethylators because they assume that taking mb12/methylfolate automatically increases SAM-e production accordingly. This is simply not the case for the few who have histamine issues from mb12/methylfolate and feel improvement from increased or exogenous SAM-e. It probably explains why people who become more histamine intolerant with mthf/mb12 on those forums (e.g. pheonix rising, mthfr, ch3nutrogenomics, chris kessler) never get a useful response.

 

 

 

Thanks for the info. Why did you choose to take methionine over SAM-E, is it safer?

Is TMG helpful also?

 

I took some zinc and ringing in ears is now mostly gone. I suspect I had too much copper.

 

 

 

Methionine is cheaper, and SAM-E always comes with fillers like mannitol that I don't want to ingest.

 

I've tried it with and without TMG, I don't know if its useful or not.

 

It's been about two months since starting methionine, and my life has improved a great deal. I do not have histamine issues like before. I have been able to tolerate P5P, D3, Iron, and lecithin without any histamine issues. I have also been able to eat chicken and beef again. Manganese still gives me histamine issues if the dose is too high. MB12 gives me histamine issues if I take it more often than once every week or two, but it does not last long. I haven't taken any folates recently.

 

However, nothing happened for the first few weeks of methionine before my histamine levels started to improve. Walsh was right about that.

I personally have copper deficiency issues, and I've found my histamine issues come back again without sufficient copper.

 

 

[timar]

Methionine is cheaper, and SAM-E always comes with fillers like mannitol that I don't want to ingest.

 

You happily ingest large doses of supplemental copper and methionine - of both which an excess has been associated with increased inflammation, mTOR activation and shortened lifespan - and are affraid of a tiny bit of mannitol, a completely benign sugar alcohol present in many fruits?
 

 

It's been about two months since starting methionine, and my life has improved a great deal. I do not have histamine issues like before. I have been able to tolerate P5P, D3, Iron, and lecithin without any histamine issues. I have also been able to eat chicken and beef again. Manganese still gives me histamine issues if the dose is too high. MB12 gives me histamine issues if I take it more often than once every week or two, but it does not last long. I haven't taken any folates recently.

 

I don't want to ridicule your observations but I really don't think they make much sense, biochemically. Neither manganese nor B12 should give anyone histamine issues, nor vitamin D kidney and back pain (or hypercalcemia for that matter, which has never been observed with doses up to 10,000 IU a day).

 

Honestly, I think some people simply have a great deal of imagination when it come to relate observations about how they feel to the supplements they take and forgetting about the complexity and contingency at work.

 

The problem with basing your supplementation on such random observations and obscure theories is that you may well end up with a regime that in the short term may cause a favorable (placebo?) response, but harm you in the long term, as it seems likely in your case (copper, manganese and methionine).

 

Edited by timar, 05 March 2015 - 08:34 AM.

[cinnabar]

 

Methionine is cheaper, and SAM-E always comes with fillers like mannitol that I don't want to ingest.

 

You happily ingest large doses of supplemental copper and methionine - of both which an excess has been associated with increased inflammation, mTOR activation and shortened lifespan - and are affraid of a tiny bit of mannitol, a completely benign sugar alcohol present in many fruits?
 

 

It's been about two months since starting methionine, and my life has improved a great deal. I do not have histamine issues like before. I have been able to tolerate P5P, D3, Iron, and lecithin without any histamine issues. I have also been able to eat chicken and beef again. Manganese still gives me histamine issues if the dose is too high. MB12 gives me histamine issues if I take it more often than once every week or two, but it does not last long. I haven't taken any folates recently.

 

I don't want to ridicule your observations but I really don't think they make much sense, biochemically. Neither manganese nor B12 should give anyone histamine issues, nor vitamin D kidney and back pain (or hypercalcemia for that matter, which has never been observed with doses up to 10,000 IU a day).

 

Honestly, I think some people simply have a great deal of imagination when it come to relate observations about how they feel to the supplements they take and forgetting about the complexity and contingency at work.

 

The problem with basing your supplementation on such random observations and obscure theories is that you may well end up with a regime that in the short term may cause a favorable (placebo?) response, but harm you in the long term, as it seems likely in your case (copper, manganese and methionine).

 

 

I'm not sure why you would respond with something that's so ill-conceived.

 

What shouldn't happen does occasionally happen to individuals who have metabolic differences that vary significantly from the norm. This forum and the internet in general is full of people who have idiosyncratic reactions.

 

I'm deficient in copper. It's not unheard of.

 

I've observed hypercalcemia from D3 at 5K IU/day when copper deficient. A simple search of the literature would show that this is certainly possible in suscetible individuals. The vast majority of people would not report this kind of reaction to begin with.

 

[j87]

Copper was bad news for me personally. SAM-E helped. For some reason, l-methionine as well as certain foods will cause temporary tinnitus now. I'm not sure why, sulfur sensitivity? 

 

The biggest thing that helped was instead of just taking b12+folate, I take a b complex with all proper forms. I suspect I was deficient in certain b vitamins.