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"Overmethylation" / TMG supplements and irritability?

tmg methylation irritability

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#1 brosci

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Posted 16 October 2016 - 10:04 PM


I recently ramped up my B-Complex to the Seeking Health HomocysteX Plus supplement to target lower HCy and address polymorphisms like C677T:

 

25mg of R5P (1,471% DV)

15mg of P5P (750% DV)

800mcg of Methyl-Folate (200% DV)

1,000mcg of Methyl-B12 + Adenosyl-B12 (16,667% DV)

700mg of Trimethylglycine

 

I was reading that TMG might improve mood + productivity, but I'm actually noticing irritability through the day and less focus, and I'm not generally an irritable person.

 

Does it take time to acclimate to a sort of high-dose methyl donor B-complex, or should I scale back and maybe drop the TMG (or get these as separate supplements to space out over the day / week) ?  Would it make sense to add on alpha-GPC or Theanine to try to reclaim some focus, or is that throwing more fuel on the fire?

 

I would be curious to hear if others have experienced an uptick in aggressiveness / irritability following this sort of methylation support stack.


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#2 OneScrewLoose

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Posted 17 October 2016 - 02:26 PM

First of all, why are you trying to lower homocysteine? Have you had your blood tested for HCy? Have you been tested for the two common mutations of the MTHFR gene? Is this just a hunch?

Second, why are you paying so much for a supplement, when you can get its components individually much cheaper, combined?



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#3 Heisok

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Posted 17 October 2016 - 06:45 PM

Hi brosci, you mentioned C667T. Are you heterozygous (1 copy?) If you are heterozygous, Dr. Lynch indicates that those individuals might not need to go beyond the more basic methylation levels.

 

If you have 2 copies, or simply want to go with the more advanced supplement levels; once you have gone through a process of slowly increasing methylation support, then start a process of adding HomecysteX Plus at 1 pill a day in the morning for a week. If at any time you feel worse, simply stop. Go back to a level of Methylation which worked.

 

 

"Methylfolate Side Effects
These are common despite what physicians may inform you.

Common undesirable side effects of methylfolate must be identified.

  • headache
  • migraine
  • rashes
  • irritability
  • anxiety
  • joint pain
  • muscle pain
  • insomnia
  • depression

If side effects occur, then the amount of methylfolate you are taking needs to be taken under consideration and likely reduced. Talk with your physician before altering any protocol or supplement/pharmaceutical.

Many times one is not yet ready to take methylfolate.

There are other steps that must be taken prior to supplementing with methylfolate if these side effects occur.

If side effects occur, taking Niacin helps bind the excessive methyl groups which are likely causing the issue. Consider taking 100 mg or 1/5th tablet of Niacin if these symptoms occur. It is a good idea to have a bottle of Niacin on hand in case these symptoms occur from taking too much methylfolate. Be sure to swallow the 1/5th tablet of niacin – not chew or place sublingually."

 

It is far more complicated to state what is likely obvious to you as you have done the research into what you are doing.

Just in case you might have missed something, I am including links to some of his information. This issue is at the top of my mind, and why am commenting is because I heard him interviewed yesterday. I first heard him about 18 months ago. Good luck. I do not use his products, and long before hearing him speak, I was following a comprehensive methylation supplement combination. I ran into one issue of taking too much Methylcobalamin B12. It seems to have helped simply cutting out my added 5000 mcg.

 

These are from 2012. Some of his specific recommendations might have changed some, but the general idea is here:

 

http://mthfr.net/mth...col/2012/02/24/

 

http://mthfr.net/mth...col/2012/02/24/

 

 


Edited by Heisok, 17 October 2016 - 06:51 PM.


#4 brosci

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Posted 18 October 2016 - 06:11 AM

I have the ++ MTHFR C677T gene (homozygous), the ++ MTRR A66G gene (homozygous), the ++ MTRR A664A gene (homozygous), and I’m +- on all of the BHMT-02, BHMT-04, and BHMT-08 genes (heterozygous).  In theory, I believe this means I should see some benefit from methylated forms of the B-Vitamins and possibly with TMG.  Rounding out the last of the polymorphisms, I'm also ++ on CBS A360A (homozygous) and ++ on VDR Taq (homozygous).
 
I've only measured HCy once while taking Methyl-Folate + Methyl-B12 + alpha-GPC while I was eating much less protein (nearly vegan -- protein from vegetables, fruits, nuts, legumes) a few days into a fast.  This read 7.5 umol/L, well within my target range, although there was little methionine in my diet -- on cronometer, it looks like the bounds on my methionine intake were around 0.9-1.4g/d at the time, where I'm now up around 2-3g/d... occasionally 3.5g.  I haven't checked HCy since adding more meat / protein into my diet (particularly on hypercaloric resistance training days) or with the new b-complex stack.  I tolerate the Seeking Health "Active B12 + B9" lozenge well -- it might as well be a sugar pill, vs this one is noticeably energetic.  I'm not quite sure if I should wait this out and see if it calms down, or find something closer to the middle.  I have read that some target just under 7 umol/L for longevity / cardiovascular goals (eg. LEF.)
 
The price doesn't really bug me, thinking about the convenience : price ratio -- I'm not trying to source out R5P and P5P from a lab and measure them with a milligram accurate scale into a capping machine along with microgram-active methylated forms of these chemicals, nor am I wanting to really take a handful of caps from cheaper spots on the internet which ends up providing higher cumulative doses of fillers & excipients (although, I suppose multiple separate supplements instead of the complex is an option for dividing this out over the day / week.)  It was ~$30 bucks for 60 days.  If I skipped a couple days a week, that'll last me 84 days.  Or, if I just take half, I'm good for 120 days.  I often spend more than that going to watch 1 movie or eating one meal, or make more than that with 20-30m of work.
 
Thorne sells a "Methyl-Guard Plus" version at ~$47 for a 90d regimen (they actually recommend 30d on the site.)  I'm happy to support the Seeking Health company, as they seem to provide a decent product line that meets cGMP standards.  The Thorne version lacks adenosyl-b12 (not a deal-breaker.)  I wouldn't mind tacking on some B1 + B5 as additional separate B-Vitamin supplements.
 
Adding niacin on top does seem a bit like putting the gas and brakes on at the same time, in terms of what I'm trying to get out of this supplement (where perhaps a lower dose might be a better way to accomplish that lower level of methyl groups.)  I wonder if nicotinamide riboside would provide a similar methyl-group mopping action as niacin.

Edited by brosci, 18 October 2016 - 07:10 AM.


#5 OneScrewLoose

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Posted 18 October 2016 - 08:11 AM

You should get familiar with this:

 

http://jn.nutrition....53/F1.large.jpg

 

And perhaps know everything on it by heart within 2-3 months.

 

I'll try to help you out, but I haven't looked at the Folate cycle in 8 years, when I was trying to decipher if I had a MTHFR mutation. I went with yes (they later came out with a blood test and it turned out I was right). Your case is way more complicated than you realize and could be problematic for your health down the line. I'll try to get back to you in a few days to a week when I can wrap my head around all of this at once.

 

Your supplements a good start. I would recommend L-Serine to further lower HCy levels. Have you had your vitamin D levels checked due to that VDR Taq mutation? Also, Alpha-GPC and L-Theanine are neither here nor there in your case. If you're having methylation problem, SAM-E is the end product of methylation, the final methyl donor that methylated a plethora of neurotransmitters. If you lack energy, given all the mutations, it could very well be that you're not making enough of that, and supplement SAM-E may well be worth a try. 


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#6 IWS

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Posted 18 October 2016 - 08:29 AM

IMO the amount of the folate/B12 you take is too high also causing an imbalance which leads to irritability, each body reacts differently but this is pretty common.

Try to take a more balanced B-complex formula including all the B family plus Choline and Inositol.

From time to time I cycle up to 3 gr of daily TMG (NOT for homocysteine issue) and never felt any irritability. What I can say after trying a lot of B-complex brands is that the calming and relaxing effects of Bs greatly vary depending on the brand.


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#7 OneScrewLoose

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Posted 18 October 2016 - 10:10 AM

IMO the amount of the folate/B12 you take is too high also causing an imbalance which leads to irritability, each body reacts differently but this is pretty common.

Try to take a more balanced B-complex formula including all the B family plus Choline and Inositol.

From time to time I cycle up to 3 gr of daily TMG (NOT for homocysteine issue) and never felt any irritability. What I can say after trying a lot of B-complex brands is that the calming and relaxing effects of Bs greatly vary depending on the brand.

 

You are very much going to have to cite a source, as in a research paper and not some blog, that too high of an intake of folate (except for folic acid, which causes cancer and not an imbalance), or B12 can cause any sort of imbalance. I'm not saying you're wrong. I'm just saying you're very likely wrong.

 

Choline and Inositol are not part of the B family. Sticking them in their as such have been marketing ploys to increase sales.

 

The effects of B vitamins do not depend at all on the brand, as long as the label accurately describes what's in the bottle and there are no adulterants (i.e. the company isn't bullshitting you).


Edited by OneScrewLoose, 18 October 2016 - 10:10 AM.


#8 Heisok

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Posted 18 October 2016 - 01:40 PM

OneScrewLoose, It is great they you are going to be able to give specific advice. As you imply, my understanding is that each individual is different.

 

brosci, Sorry for the misunderstanding. The recommendation for Niacin by Dr. Lynch was only to put the brakes on if you found yourself needing that on a given day due to acute side effects.


Edited by Heisok, 18 October 2016 - 01:54 PM.


#9 brosci

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Posted 01 April 2017 - 08:59 PM

I'm re-investigating my TMG supplementation, thinking that it might be the R5P + P5P that I'm not tolerating well, or simply the full stack being taken all at once.

 

Looking at TMG, I found these articles:

 

"Betaine enhances metabolic reactions in the methionine cycle, but inhibits cystathionine synthesis and cysteine uptake, leading to a decrease in supply of cysteine for glutathione synthesis."
 
"However, the hepatic levels of cysteine or glutathione are not affected, most probably due to the depression of taurine generation from cysteine."
 
I'm curious if this might warrant taurine, glutathione, or NAC supplementation?  I often do a ketogenic diet, which I've read can decrease hepatic glutathione and lower glutathione synthesis, and I'm thinking about adding back in Beta-Alanine, which I've read can deplete taurine stores.  What are your thoughts?

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#10 PeaceAndProsperity

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Posted 01 April 2017 - 11:44 PM

Jesus Christ people have some freaking common sense. You're taking COENZYME B vitamins that produce monoamine neurotransmitters and you're talking about methylation. You think you may have missed the most obvious, such as increased serotonergic, dopaminergic, adrenergic activity? p5p causes irritability in many.


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#11 ta5

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Posted 02 April 2017 - 12:11 AM

p5p causes irritability in many.

 

Maybe you should lower your dose.  :-)


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