MTHFR

Peata

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I don't know if I have the mutation, or whether I have pyroluria for certain (I have *many* of the symptoms) but I do know since taking the B vitamins I'm almost a different person as far as much more steady moods, less anger and flying off the handle.. things that used to bother me just aren't that big of a deal anymore, less anxiety and depression, more motivation. I take B1, B3, B6 + P5P and most days I take half of another B spectrum supplement. Also zinc, magnesium and others.

When I went off them for a week or two I saw an increase in the old symptoms, which again started to subside after a week or two back on the supps.

Off and on over the years I've taken a B complex and/or multi and still hadn't noticed anything from it like I do now from taking these individual supps. Maybe the Peat foods help my body use them better, I don't know. Anyway, that's just my experience.
 

BingDing

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My lab work says I have two C677T mutations. I think RP wrote something like "it's a minor inconvenience that can be addressed with nutrients". I'm not gonna worry about it much; how my new doctor approaches it will tell me a lot about whether he's worth keeping.

I found this page with some studies about niacin/niacinimide and methyl donors. One person on the thread concluded that niacinimide does reduce methyl donors.

I was using 500mg of niacinimide/day for quite a while, and my lab work also said my serum homocysteine was high. I suspect they are related, I have to read everything again (or six more times) and I might be able to figure it out.
 

Mastemah

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An easy way to understand the MTHFR thing is this: all of the things that people are sold expensive version of are things people would benefit from anyway and are commonly low in the modern diet. When people say that have this or that gene issue, its because someone with a vested interest in that outcome has been sold the idea that we know a lot of about genes. Sequencing the genes doesnt mean we understand them. You can know the names of all of the notes, that doesnt mean you can write songs. Dont worry :)
 

Blossom

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There is a Peat quote in the ' need to try dairy-free peat???' thread from his January 2014 newsletter that is perfectly in line with mastemah's reply. Peat mentions that people who lack this gene seem to have a reduced rate of cancer. Most people eating common foods on a Peat inspired approach will get plenty of the b vitamins. My personal takeaway is to not mess with methylation. I did take deplin myself many years ago along with fancy methyl b's and now I regret it.
 

BingDing

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Thanks Mastemah and Blossom. One thing I saw on blogs was how little people understand the chemistry of the body, making them so vulnerable to panic and snake oil salesmen.

I have a pretty good handle on this now so I want to share it. This page has several diagrams and he writes in a style that I can understand.

The whole point of it all is to produce S−Adenosyl Methionine (SAMe), which is the main methyl donor in the body and is used in lots of important pathways. Norepinephrine -> epinephrine uses SAMe, for example.

Methionine is the rate limiting substrate in the production of SAMe. The only other factor is ATP and if you're running low on that you have much bigger problems than this.

When SAMe gives up its methyl group to some other compound it becomes SAH and when an adenosine molecule is taken off the H is homocysteine. If that was the end of it the only way to make more SAMe would be to eat more methionine.

So there are two parallel pathways from homocysteine -> methionine, both of which simply add a methyl group to homocysteine. One uses methylfolate and the other uses betaine (trimethyl glycine). It is easy to speculate that having two ways of doing the same thing shows how important it is to produce more methionine without having to eat it.

The enzyme the 677 gene codes for just changes one form of methylfolate to another form of methylfolate, 5,10 MTHF -> 5 MTHF.

This page has a bunch of info about names and isomers, and says about 70% of the folate in food is in the final usable form, so the enzyme isn't needed at all.

There are other odds and ends but I'll quit. There is a lot of chatter about high homocysteine and CVD, etc but it seems to me the important issue is low SAMe if the methylation cycle is sub par for any reason.

Edit: my statement that methionine is the rate limiting substrate in the production of SAMe was incomplete. There is an enzyme involved in addition to ATP, which may be rate limiting.
 

Poppyseed13

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Hello.

I am heterozygous for MTHFR C677T and MTHFR A1298C (among other snps). I used 23andme to obtain the raw data and GeneticGenie to filter it in a recognizable/readable format.

I took these tests after a year and a half of Peating, and although I made great improvements with the diet changes and Thiroyd supplementation, I was still feeling tired ---and I felt there was more to the picture.

In response to the test results I began supplementing with Methylb12--and had a fantastic surge in energy---I had been taking cyanocobalamin for years in a B-complex. I slowly added each b-vitamin in tiny amounts---and when I started taking the Methylfolate, I had serious headaches, nauseau---I quit for 8 months, and continued with the rest of the bs. Recently, I tried Methylfolate again --microdose/sliver of a tablet---and felt quite wonderful
 

Poppyseed13

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oops! The Methylfolate gave me more energy --but I think it is critical to have enough b12 in your system when taking methylfolate. I also use niacinamide to help with the minor side-effects (it's supposed to "mop up" the extra methyl groups). It does make the methylfolate-induced headaches go away. And in the last week, I haven't needed any extra niacinamide.... my body seems to be getting used to the methylfolate.

I will gradually increase the methylfolate to about 400 mcg and see how it sits.

I don't think the science is definitive about these SNPs and how they affect us. It's in its infancy, and the studies are not clear....

I will continue to take all the active bs---they clearly help me---more energy, clear thinking, feeling good about life.

I feel sad that most doctors dismiss much of what we discuss here at RPF --they are not terribly interested in helping patients be optimally healthy---nor do they like patients who want to experiment on themselves. But it doesn't matter, I will continue to take leaps and risks--

Cheers,
Poppyseed13
 

BingDing

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Nice posts, poppyseed. I know what you mean about feeling there is more to the picture. I am going on two years with this and I've never been stable, or feeling the same day after day. Magnesium, pregnenalone and adequate protein were big boosts for me and I'm better off for it. But I still struggle, I feel like I've been swimming upstream forever.

I started using betaine anhydrous at first and immediately felt stronger and better. I had good b12 after all that milk but got some more methylb12 and that was good. Methylfolate gave me tinnitus problems so I started using small amounts, too, so far so good.

Using 2g/day of creatine monohydrate was a huge boost, I am so glad I figured that out. It is critically important for normal muscle function and supplementing it spares SAMe for more important uses like making Co-Q10 and lipoic acid in the mitochondria.

My biggest takeaway from this, though, is how great it is to have Ray Peat in my corner. And having the people on this forum in my corner! Working through all the steps to understand Ray's research and conclusions has given me a great deal of confidence in what I am doing to get healthy.

Getting a handle on the methylation cycle and the minor effects of the MTHFR mutation in a few weeks and without much angst has actually been very rewarding.
 

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