ApoE4.Info

Meta-analysis shows it increases risk of AD. And one that we can tackle with appropriate supplements.

Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism and Alzheimer Disease Risk: a Meta-Analysis.

MTHFR C677T polymorphism had a significant association with susceptibility to AD in all genetic models (for T vs C OR = 1.29, 95 % CI = 1.07-1.56, p = 0.003; for TT + CT vs CC OR = 1.29, 95 % CI = 1.19-1.40, p = 0.0004; for TT vs CC OR = 1.31, 95 % CI = 1.16-1.48, p = 0.001; for CT vs CC OR = 1.24, 95 % CI = 1.13-1.35, p < 0.004; and for TT vs CT + CC OR = 1.13, 95 % CI = 1.00-1.28, p = 0.02). Results of present meta-analysis supported that the MTHFR C677T polymorphism was associated with an increased risk of AD.

http://www.ncbi.nlm.nih.gov/pubmed/26820674

I know, I know, I need to get some general info about methylation out on the wiki. Promise I'll work on synthesizing my research in the next couple of weeks. In the meantime, you can go to Ben Lynch's blog to learn more. http://mthfr.net

wow.. I am so clueless about what this is .. that I thought it was an abbreviation for a couple of curse words! lol

Schnooks I must confess I'm pretty clueless about this too.
In my brain it goes something like....methylation....something...homocysteine....something....b vitamins....something....complicated....something.....um....umm...

We can feel lost together!!!

This is the C->T mutation at rs1801133

If you've got one T, then you're somewhat less efficient at processing folic acid. If you've got two of them then you're very inefficient at that. Do not go vegan, and eat your meat and fish (and greens, although they won't help) if you don't want AD, cvd, bone fractures, and various other conditions.

ApropoE4 wrote:This is the C->T mutation at rs1801133

If you've got one T, then you're somewhat less efficient at processing folic acid. If you've got two of them then you're very inefficient at that. Do not go vegan, and eat your meat and fish (and greens, although they won't help) if you don't want AD, cvd, bone fractures, and various other conditions.

From what I understand, the C->T mutation reduces the production of the methylene tetrahydrofolate reductase enzyme which helps to convert 5,10-CH2-THF to 5-methyl-THF for lowering homocysteine (elevated via methionine intake.) It seems like eating meat + fish would increase methionine intake without doing much for improving the levels of the MTHFR enzyme. On the MTHFR.net site, it's recommended to limit high methionine-containing foods (particularly meat + seafood), and limit protein intake to approximately 0.7g/kg -- for a 140lb individual, this seems fairly compatible with a low-protein vegetarian / vegan diet (who likely eat more protein than 0.7g/kg.) http://mthfr.net/mthfr-c677t-mutation-basic-protocol

I would think a simple B-vitamin supplement and vegetables (containing folate) would be useful. 1-2 copies of MTHFR limits enzyme production by 30-70% -- it seems relatively easy to increase folate intake by 333%+ over the average western intake (I likely eat more folate-rich plants per meal than my family eats over the course of a day combined.)

I can only offer an agenda free, medical-advice based opinion (meaning I asked a medical professional about it). I don't know what agenda that site is promoting, but there was nothing ambivalent about the response I got.

Apropo, I know Lynch is associate with Seeking Health which sells vitamins. I do find he has condensed a lot of research into more understandable bits for those of us without PhDs. In fact his advice is to go low and slow when adding methylated supplements, and he says he does not personally take B vitamins daily for his methylation variants. So, I put him the category of maybe being pretty pragmatic about the whole vitamin thing.

When I first found out I was homozygote for C677T (and had variants on other methylation-related genes), my doctor focused on supplementing methylated B vitamins. He started testing for homocysteine, still does. I'd say my doctor is definitely agenda free (he doesn't make money on vitamins). And I do now restrict my animal protein somewhat to keep homocysteine in check, because I'm still adjusting amounts to find the right levels of the B vitamins to avoid side effects. It's a balancing act to find the right mix.

So, I found out the hard way that changing my diet from mainly plant protein and carbs (legumes and grains) to increasing my animal protein (to work on IBS problems) without supplementing methylated folate raised my homocysteine.

If you want to know why homocysteine is bad, check out the article below.

That said, apod correctly points out that the lack of C677T enzymatic activity gets one in "trouble" because the dietary folate from greens do not get converted as completely to the active form, and eventually homocysteine builds up because those co-factors are missing. Using methylated folate will bypass the underperforming enzymatic dietary folate conversion and supply the necessary active versions to convert homocysteine back to methionine. Without supplying the right amount of methyl folate, eating an excess of animal protein will lead to high homocysteine. What's an excess? This is an N=1 and I track my homocysteine levels pretty closely to know.

Here's an image from DNA methylation, a hand behind neurodegenerative diseases
http://journal.frontiersin.org/article/ ... 00085/full
ps. Bear with me on the methylation info - this image isn't as complete as I'd like, so I'm still working on finding a good one that has the gene names and co-factors from a reputable source but still understandable...and yes I know about heartfixer and Yasko's stuff. No need to post them because they are not what I'm looking for.

So does this mean that for someone who is CC (or GG as 23andme reports ) for this rs1801133 such as myself, the money I'm spending on the methylated folate is a waste?

Perhaps.

There are other genes that sit on the pathway between dietary folates (or folic acid) and MTHFR, including FOLR2, DHFR, and MTHFD1. If any of those aren't working as well, you might have the same need. I don't have those snps at the moment, it's part of what I still need to research.

Probably be worth trying folic acid and seeing if it still works for lowering your homocysteine. If it does, you're good to go.

DUH . No surprise that this polymorphism which leads to higher homocysteine is associated with Alzheimer's. I completely agree with Susan that ALL of the snips leading to elevated homocysteine should be addressed to best avoid AD pathology.

ApropoE4, thanks for the info. Would you mind sharing the medical professional's name?