Need SAMe, but cannot take methyl donors?

I have many heterozygous conditions for numerous genes in COMT and homozygous for MAO-A. There are 24 versions of MAO-A genes that I can see from 23andme test results, which I think can vary based on the version of 23andme test. I am homozygous for many of them, but there has not been much research on specific gene within MAO-A. Two specific genes that result in downregulation of MAO-A activity are rs6323 and rs1137070 while rs2072743 results in upregulation of MAO-A activity according to this thread, which also coincides with what Nutrahacker result says. FYI, I think Nutrahacker has a lot of conflicting information and their report is not thorough at all.

As pointed out by many members on the forum, genetic defects work in combination, which is why each individual responds so differently to various treatments and protocols. Having homozygous MAO-A could be compensated by other SNP's, and it's the combination of SNP's that matters at the end. Unfortunately, my genetic profile is full of defective genes that slows down breakdown and conversion of neurotransmitters. For instance, the lab results showed that I am high in glutamate level and low in GABA level, even though I have not been supplementing with any glutamate or gluatmine recently. The fact that my GABA level is low explains why I could never fall asleep or have deep sleep for the past decade.

Because of slow breakdown and conversion of neurotransmitters, my body reacts very negatively to methyl donor supplements. I have only tried mb12 (horrible body rashes everywhere, insomnia, restless syndrome) as a methyl donor, but the side effects I have gotten from it were so extreme that I am hesitant to try other methyl donor supplements. The negative reaction is somewhat countered when I take high doses of B2 or activated B2 in the form of FMN. This is because FMN can be converted to FAD, which increases MAO-A activity.

Also, the combination of my MAT1 genes is defective as well, revealed by low SAM-e level. Defective MAT1 combination makes my body unable to convert methionine properly into SAM-e. So in addition to high sensitivity to methyl groups, I have an innate block in the methylation cycle. I would love to increase my SAM-e level as it is an important factor in many biosynthesis and conversion processes like creatine conversion process.

I feel a bit overwhelmed to have such strange combination of genes . Should I bite my tongue and try SAM-e at a low dose? Please share your thoughts and suggestion. Thank you so much.

 

@Changexpert

One thing I've noticed is that when someone has a slowed-down gene and can't take the product of that gene (SAMe), that they are sometimes told to take the reagent (Me), so that whenever the enzyme is free, there is a some reagent it can find and make the conversion. It happens more slowly (of course, since the enzyme is slow) than if you took the product. The first time I saw this I thought "What??? They are taking the two reagents for the gene that doesn't work!?!?!?" but then it made sense - a trickle of what they need to avoid the kaboom of a bolus dose. Not sure if it would help you to take Me (methionine), but it's a thought. What is the other reagent that makes SAMe?

Another thought - you haven't listed a lot of homo and hetero SNPs. Is it possible that when you took MB12 that you were depleting methylfolate? And that your reaction was from that instead of from the B12? MTHFR C677T would be the probably culprit there, with maybe an SHMT to go with it.

Crit

 

Crit, Thanks for some ideas. To my surprise, all my MTHFR genes are good, but I do have other defects related to methylfolate conversion. For instance, I am homozygous for FOLR2, which is responsible for conversion of folic acid into DHF (starting point). Similarly, I am heterozygous for FOLR1, which is responsible for conversion of folate into DHF. 23andme results did not include SHMT genes, but I am homozygous for one of MTHFS genes (conversion of folinic acid into 5-10 methynyl THF). So this poses another dilemma for me where I cannot take folic acid, folate, or folinic acid because they will not be converted to THF easily. I was on heavy folate diet (leafy greens) and took folic acid when I took mb12, but never took methylfolate because I did not know about methylation back then. So it is very possible that the point you brought may have caused all the side effects I got from mb12.

I cannot take methionine as they contain sulfur and my body has never been able to utilize sulfur efficiently. For instance, when I eat foods that are high in protein (amino acids), my urine becomes both foamy and smelly. This may have to do with excessive sulfate reducing bacteria in the large intestine.

@Critterina , have you tried SAM-e personally? If so, did you get histamine reaction from it? I would sincerely appreciate your response.

 

@Changexpert , Yes, I tried SAMe. The question is when: had I identified my histamine issues at that time? I took a look at my protocols and see when I was taking it, but apparently it was between doctor visits, so I couldn't tell you.

My amino acid panels have showed low methionine (which is not too surprising with my MTRR and BHMT SNPs), so I was supplementing that for a while, and tried SAMe as an alternate. I don't remember it making any difference, but that could have been because I was really sick already and didn't know to avoid histamine foods. Probably, though, it was after my elimination diet, and before I knew about histamines, so I was mostly well, and would have noticed.

 

@Changexpert FWIW, I had the same issues with SAMe as with other sulfur-based sups: excitoxicity.

 

So many useful information in one post.
I am homo COMT on both 158 and 62. I have a very hard time tolerating methyldonors.
MTHFRSupport tells me this:
MAT1A C1131T ++
MAT1A C15656T ++
MAT1A T*1297C --
MAT2B A7755681G +-
FOLR1 G-20A --
FOLR2 G-1316A +-
FOLR3 A3771G --
MTHFS - ST20 MTHFS G39646A ++
MTHFS - ST20 MTHFS G56057A --
So I probably also have problems converting methionine into SAMe. I've taken SAMe in the past and it would give me great benefit. But, the effect long term were very similar to taking methylB12 long term High irritability and mood swings. I really hate COMT genes.
This was all before even knowing about methylation. I've also never taken a functional methylation test, so I'm actually curious about my SAMe levels.
I also have one MTHFS mutation, so I guess that I have to avoid foods that contain folic acid.
You also mention rashes. I'm experiencing rashes right now. Only minor though.

I'm gonna take some SAMe tomorrow to see if it makes a difference.

Edit: Yesterday I only slept 4 hours and I was kind of hyper that day. I've taken some niacinamide in the evening to slow myself down. I slept very well.
Today, I've been in a somewhat lower mood, after taking SAMe my mood got reversed and I'm in the 'up' zone at the moment. I'm very awake and not depressed at all. Maybe this is what 'normal' people experience. I don't have any form of ADD or anxiety yet.
I'll continue to update my progress.

Edit: I've taken hydroxyB12 + methylfolate + TMG + SAMe which seems to be too much. If I drop out the methylfolate, there doesn't seem to be a problem. I only have one FOLR mutation. HydroxyB12 + TMG + SAMe is the best combination so far. I'll update this post when I've found a better combination.