Mthfr help and recommendations according to my mutations please!!

[mthfr_lifter]

Hello everyone,

I've been reading on this forum frequently as of late and see the amount of help members provide here. I've been a member of many forums and have not seen this level of effort in helping one another..renews my faith in humanity!

Anyway, I recently did a 23andme test and ran my results through Nutrahacker, promethease, genetic gene, foundmyfitness, livewello, and a few other platforms; Needless to say, I am VERY overwhelmed. I am new to MTHFR mutations and constantly reading threads and I'm reading Nutrient Power: Heal Your Biochemistry and Heal Your Brain by William J. Walsh and I now realize I should of started with MTHFR Basics by Benjamin Lynch first..

MY question is this.. I'd really REALLY appreciate some knowledgeable members aim me in the right direction. Mainly because most of the stuff I read contradicts my findings or my individual results ( I.e If something I find on promethease contradicts something on nutrahacker (which I trust less). I've attached my results of mthfr results. IF you would please please please help me with which methylated vitamins you feel would be fit for me or steer me in the right direction... I would be eternally grateful!



As of right now I'm taking the following supplements:


I took sam-e first (400mg) and felt great for two days and on the third I felt extremely anxious and anti-social.
I lowered the dose to 200mg and felt great for a couple of days and the same thing happened. I'm assuming build up? I ceased using it and started the below.


B-right by Jarrow (400mcg of methylfolate)
Kirkland methylcobalamin (5000mcg) subliminally
Vitamin D 5000 ui (due to VDR mutation)
Biovite multi (contains multiple methylated B vitamins, I know this is not recommended as it might be harder to gauge results.)

I want to add in magnesium, zinc, and a couple of other vitamins but I want to wait till I "figure out" this mthfr mutations.

I was wondering if I should switch to hydroxocobalamin as my source of b12 or would I be able to stack it with methylcobalamin? I've heard of methylcobalamin and adenosylcobalamin working well together.

I've attached my nutrahacker and genetic gene.


SORRY FOR THE ESSAY! Thank you very much in advance

 

[mthfr_lifter]

Bump

 

[alicec]

till I "figure out" this mthfr mutations

It's not quite clear from your post what it is that is puzzling you. The MTHFR variant that is discussed so vigorously on the internet is MTHFR C677T. The homozygous (+/+) variant does significantly slow the enzyme and in some circumstances at least this may have some consequences, but the variant is not uncommon. Millions of people have it and they are not all sick.

In a healthy person, simply ensuring they obtain plenty of folate from vegetables may be enough, or possibly some modest supplementation with methylfolate would be a good precaution. During pregnancy or if homocysteine is elevated, suggesting that the methylation cycle is not working well, other measures may be warranted.

You are +/-, so nothing particularly to be concerned about.

Here is a thread discussing this and other MTHFR variants.

I suspect you are referring to the interlinked methylation and folate cycles. Again internet discussion has distorted the significance of the various associated SNPs. Again most of them are relatively common and are not likely to be the cause of people's health problems.



Of the methylation-related SNPs which Genetic Genie reports on, the ones that do something are

COMT V158M +/- would have a modest slowing effect on the enzyme. Supplementation with its cofactor magnesium may help to stimulate the enzyme.

It is a myth the COMT SNPs mean sensitivity to methyl groups. Some people are sensitive but it has nothing to do with COMT.

There are other COMT SNPs of significance and often combinations can be important. Here is a thread which discusses them.

As already mentioned, MTHFR C677T +/- would have a modest slowing effect on the enzyme. Supplementation with its cofactor B2 and with the end point of the reaction, methylfolate, may be helpful.

MTR A2756G +/- and MTRR A66G +/- would have a modest slowing effect on the enzyme complex. Supplementation with methylB12 may be helpful. Zinc is also important for the MTR enzyme. SAMe is used as a cofactor by MTRR - whether you would need to supplement this in addition to B12 is hard to say - best determined empirically I think.

Your experience with SAMe alone suggests that other things were not in place to sustain the reaction.

Here and here are threads which discussed those genes.

CBS C699T +/+ might be a small upregulation which would be protective. Here is a thread on that gene.

None of the other SNPs amount to anything.

As for what you should do about these SNPs, it depends entirely on what you are trying to achieve - do you have specific health problems that you think may be related to these SNPs, are you one of the worried well?

Many people on this forum have found that supplementation with active folate and B12 has been helpful. This is not necessarily because they have SNPs which affect these metabolic pathways, though some might, it is more that these pathways often seem to go wrong in our population and supplementation does help many people to feel a bit better - no cure though - and not everyone is helped.

There has been much discussion about how best to approach this supplementation. These active vitamins can be very potent and many of us can be sensitive to them. Here is a recent post I made on the subject.

Maybe after looking at these links you might want to come back with more specific questions.

PS I agree, Nutrahacker is not reliable. Here is another thread which discusses resources which may be helpful in analysing 23 and me results.

 

[mthfr_lifter]

Thank you very much @alicec! I'm reading through all the links now! Thank you so so much! This was extremely helpful.

It's not quite clear from your post what it is that is puzzling you.

I totally understand what you mean and it kind of segways perfectly into the core of my issue. I have been experiencing pretty bad brain fog which has made learning this whole mthfr thing much harder than it needs to be. At the risk of sounding self-aggrandizing, I consider myself a fairly intelligent individual; however, for the last couple of months my memory has been extremely foggy and relatively simple concepts take twice as long to comprehend and even then my understanding and fluidity of thought is not nearly as acute as it once was. I get tongue tied and frustrated very easy with overwhelming anxiety (not to the point of a panic attack). Even normal tasks that I used to complete easily now come as a chore and is monumentally more cumbersome for no real reason. My healthy habits (water consumption, eating healthy, work ethic,etc) and overall habitual tendencies that I've spent years cultivating are now extremely difficult). That is to say that motivation has dropped to a near minimum and the only thing keeping me going is sheer will. Needless to say, my life has gone down-hill and I have been very unhappy, to the point of hopeless depression, due to my mental state; put simply, I feel dumb and unmotivated. This spurred the 23andme testing, in hopes to find hints into what the heck is going on with me and why I am so scatterbrained.

I seemed to react well to Alpha-gpc (a choline source) which I understand is a methyl-donor and lowers homocysteine from my understanding.

I feel it's noteworthy to add that I used to take that regularly but have sense stopped due to benefits seemly decreasing overtime. For a couple of years I have been taking a standard b-vitamin with no notable side effects and this was back when I was not experiencing these symptoms.

Here are some other questions I had:

What are your thoughts on hydroxocobalamin? Since I believe I react better to cyanocobalamin and find methylcobalamin a tad too stimulating and since hydroxocobalamin has similar efficacy as cyanocobalamin? Should I just take less methylcobalamin? or switch forms? or add niacin to sponge up the extra methyl?

Does my mutations mean I should avoid folic acid all together? Or just that due to only being able to process with 70% efficiency that I should limit intake?

My nutrahacker said to stay away from methyl's and folate.. does this have any real merit? I mean avoiding folates would mean to avoid greens, correct? Also, it said to avoid Folinic acid?


I truly appreciate all your help and cannot express my gratitude enough for your help!

Thank you very much

 

[alicec]

memory has been extremely foggy and relatively simple concepts take twice as long to comprehend and even then my understanding and fluidity of thought is not nearly as acute as it once was.

Sounds like most of us on PR unfortunately. There are a number of thread on brain fog discussing things people have found helpful.

I seemed to react well to Alpha-gpc (a choline source) which I understand is a methyl-donor and lowers homocysteine from my understanding.

It is important not to view everything entirely through the methylation lens (notwithstanding internet chatter). This product also stimulates acetylcholine production so has a direct effect on the parasympathetic nervous system. Or there might be other more indirect reasons for changes in your response to the supplement.

What are your thoughts on hydroxocobalamin? Since I believe I react better to cyanocobalamin and find methylcobalamin a tad too stimulating and since hydroxocobalamin has similar efficacy as cyanocobalamin? Should I just take less methylcobalamin? or switch forms? or add niacin to sponge up the extra methyl?

The reason that hydroxyl and cyanocobalamin forms cause less trouble is likely to be because they do very little (high dose injected hydroxyl is a different situation). Personally I think they are a waste of time and for some people at least can be problematic. Often the cyano form is processed very slowly and accumulates in blood where it may compete for uptake with active forms.

If you are sensitive to methylB12 then you need to start very low and increase slowly.

Does my mutations mean I should avoid folic acid all together?

Folic acid is processed very slowly by everyone - it is not a natural substrate after all. For healthy people this may not matter much but for others there is a definite build-up of folic acid in blood which may compete with active forms for uptake.

Internet chatter has linked this to MTHFR variants but I don't think there is any evidence for this. I'm not sure it has been studied very well. In any case it seems more likely to be related to the enzyme which processes folic acid, dihydrofolate reductase.

I think everyone should avoid folic acid.

My nutrahacker said to stay away from methyl's and folate.. does this have any real merit?

I imagine the recommendation about folate (probably mean methylfolate here) and methylB12 is based on COMT. You can check this in your report - ie which SNP the recommendation is listed against.

There is no evidence for this idea (one of Yasko's theories) and plenty of people on PR have put it to the test and found the claim wanting. There's no reason to take this seriously.

I mean avoiding folates would mean to avoid greens, correct? Also, it said to avoid Folinic acid?

Nutrahacker plagiarises stuff from PR so some of that could be due to a few people here who have reported problems with too much vegetable folate apparently competing with methylfolate and reducing its effect. The mechanism is unknown and it certainly can't be attributed to some particular SNP.

Folinic acid is a different case. It is a storage form of folate and some people do react to it adversely. I don't think the reason is really known though presumably it has something to do with problems with the two enzymes which act directly on folinic - viz MTHFS and SHMT. Unprocessed folinic may accumulate and inhibit other folate pathways.

The only way to determine this is empirically. Again it can't be attributed to some SNP.

You could experiment with folinic later if you wanted to but the foundation is really methylfolate, methyl and adenosyl B12 and some would say carnitine, along with a raft of other nutrients which are used in the metabolic pathways linked to these vitamins. Others put the emphasis on the two active B12s plus making sufficient active B2, plus a small amount of methylfolate. I canvas that in one of the links I gave you.