Help! 5 red / 9 yellow. Where to start?

[MMe]

I finally got my results! But I'm not sure if I should be happy with them...
I think they explain a lot of my complaints: anxiety, depression, racing thoughts which go on and off...

+/+
COMT V158M
COMT H62H
VDR Bsm (VDR Taq -/-)
MAO A R297R
BHMT - 08

+/-
ACAT1 -02

CBS C699T

MTHFR C677T (MTHFR A1298C -/-)

MTRR A66G
MTRR A664A

(BHMT-01 not found)
BHMT-02
BHMT-04

AHCY-01
AHCY-02
AHCY-19

No call for CBS A360A, SHMT1 (I don't know what 'no call' means...)

Urine:
Dopamine: 288 (137 - 338)
Homovanilline acid: 3 (2 - 4,9)
MHPG: 1,4 (1,4 - 5,10)
VMA: 2,6 (2 - 4)
Serotonin: 70,9 (41 - 120)
Noradrenalin: 40 (17 - 40)
Adrenalin: 4,19 (1,7 - 6,6)
Metanefrine: 121,9 (41 - 91)
Normetanefrine: 145,8 (103 - 230)

Blood:
B12: 567 ng/L
Folic acid in rbc: 205 microgr/L (140 - 628)
Homocysteine: 6,8 micromol/L (bloodtest march 2013)
5,1 micromol/L (bloodtest august 2012)
MMA (methyl malon acid): 2,9 mg/g creatinine (0 - 3,8)
Gluthation peroxydase: 57 U/g Hb

Please can some of you, bright spirits, shine a light on these results?

I've read already a lot on this forum, but I don't know how to choose the right supplements for this different genetic defects...
Where do I have to start?

Thanks!!!!

 

[caledonia]

No call means there wasn't enough data in your results to make a determination.

So you would work on your SNPs in this order - First do the First Priority Mutations ACAT, then CBS. Then do the Second Priority Mutations - MTHFR, MTRR, BHMT, MAO A, VDR.

The supplementation for ACAT is extensive. Yasko makes an all in one supplement for ACAT and BHMT that combines everything you need into one pill. It sounds expensive, but I think it's cost effective.

The AHCY could make determining if CBS is expressed tricky. Here is what Heartfixer says:

AHCY S-Adenosylhomocysteine HydrolaseS-Adenosyl Methionine (SAMe), the key methyl donor generated from methionine, is metabolized in to S-Adenosyl Methionine, and then on to homocysteine by AHCY. Individuals (+) for both AHCY and CBS often have low baseline urine sulfate levels, which then rise and fall in response to treatment. Early on the levels rise, as the “bottle neck” abnormal AHCY enzyme has been “limiting the supply” of homocysteine. Once the cycle starts to spin, homocysteine is made available to CBS, and urine sulfate will rise. Later, in response to a low animal protein/low sulfur diet, urine sulfate levels will fall. Defects in AHCY are addressed by measures designed to improve overall Methyl Cycle function, such as Methyl support RNA 1/8th dropper per day.

I personally wouldn't bother with the RNAs unless other measures aren't working.

Your COMT/VDR Taq combination is unfortunately the worst one, which will be most sensitive to B12 supplementation. Yasko says to stick mostly to hydroxycobalamin. You can have mood swings if you overdo, so take it easy - start low and go slow. Especially in your case, it would be good to have some niacin in the form of nicotinic acid on hand before you start any supplements. If you get overmethylated, take 50mg. This will stop methylation and relieve symptoms quickly.

Work on everything in the order listed above, work on one thing at a time. Start each new supplement one at a time and give your body time to adjust. Start with very low doses and work your way up gradually.

It's a marathon, not a sprint. Like the fable of the tortoise and the hare - slow and steady wins the race. Good luck!

 

[MMe]

Thanks Caledonia!
I know I have to go slowly, but ooooh, I wish I could go FAST!

How do I know if ACAT is expressed? I don't have a high MMA or problems with cholesterol...

About CBS: I've tried charcoal flushes and molybdenum. But: no difference.

Does a ACAT/CBS +/- mean you always have to adress these ones first? (I know, I know, probably I want to go too fast... )

 

[Valentijn]

How do I know if ACAT is expressed? I don't have a high MMA or problems with cholesterol...

The ACAT SNP tested is meaningless - there's no research anywhere suggesting that it has any effect on ACAT function. The heterozygous genotype is also very common.

 

[MMe]

Valentijn, you said yesterday in another thread:

The MAO interpretation is also largely baseless. While TT is associated with some increased risk factors, GG is associated with other increased risk factors. All variants are equally common. GG is the more active form, but that very well might mean that TT is the "normal" form and GG is over-active.

What does this say about my MAO TT +/+?

The heterozygous CBS is very common - about 40% of the population has it. There's no indication that it's meaningful.

So I don't have to adress my CBS AG +/- first?
Perhaps the combination of AHCY-01 CT +/- and AHCY AG +/-, AHCY-19 CT +/- with CBS c699T AG +/- indicates that CBS upregulation might be an issue anyway?

MTRR A664A has no indication that it's associated with any dysfunction, and GG is the more common genotype (well over half the population) so no idea why that is flagged as abnormal.

I do have MTRR A664A AG +/-. So no problem either??

COMT V158M does result in a mutation, reducing the activity of the COMT gene. The heterozygous version probably does indicate some dysfunction, such as with increased homocysteine, but pretty mild compared to homozygous AA. And even AA only elevates homocysteine by 10%. But there probably is a bit of a slow down in breaking down neurotransmitters. It also sounds like AA increases immunoreactivity compared to GG, with AG being in the middle.

I think this one is my major 'problem', being COMT V158M AA +/+ (with VDR Taq GG -/-).

BHMT-08 actually does indicate a problem. It looks like a bit of a down-regulation in converting homocysteine into methionine.

And this one too. I'm BHMT-08 TT +/+.

I'm just trying to understand what's going on. And where I have to start. Which supplements should I take first?

Thank you very much for your input!

 

[Valentijn]

What does this say about my MAO TT +/+?

It says that you have the slower version. But I haven't seen any research that this creates problems. Theoretically it might result in raised neurotransmitters and/or reduced need/tolerance for methyl groups.

So I don't have to adress my CBS AG +/- first?

The other comment I made was regarding a different SNP on the CBS gene. According to the research, GG is the riskier combination for C699T, though AG also seems likely to be problematic too.

Perhaps the combination of AHCY-01 CT +/- and AHCY AG +/-, AHCY-19 CT +/- with CBS c699T AG +/- indicates that CBS upregulation might be an issue anyway?

The AHCY SNPs in the panel are completely meaningless, and should be ignored until there's research showing that they have any impact on the functionality of the AHCY gene or peoples' health.

I do have MTRR A664A AG +/-. So no problem either??

Yup! Well, there might be a problem, but not because of that

I think this one is my major 'problem', being COMT V158M AA +/+ (with VDR Taq GG -/-).

And this one too. I'm BHMT-08 TT +/+.

Yup

I'm just trying to understand what's going on. And where I have to start. Which supplements should I take first?

Thank you very much for your input!

I really don't know where you should start - I haven't looked at all of your stuff together. What I'm trying to do currently is put together a methylation panel based on 23andMe SNPs which are shown to be relevant in published research. This requires reading a lot of research papers for hundreds of genes. In the process, I'm making notes when I come across info regarding Yasko-tested genes, so I can rain on everyone's parade when the bad ones come up But I'm not looking for the Yasko ones specifically, so it might take me a while to get to them.

 

[greenshots]

The ACAT SNP tested is meaningless - there's no research anywhere suggesting that it has any effect on ACAT function. The heterozygous genotype is also very common.

In my old 30 member biomed group, the people with SHMT and ACAT were consistently harder to treat then the rest of us. I have to say I think Yasko's right about this. Acat is at an important spot for mitochrondrial energy so it makes sense. My doc has a short list of acat sups but even then its still sorts long. D ribose, CoQ, Lcarnitine fumarate, ox bile salts, digestive enzymes, adenosyl b12 and sometimes Vit E and K. You can see these have some crossover for other cofactors and biochem needs so its not like they're wasted. But Caledonia's right that when you have acat and bhmt the combo sup is really inclusive. Trouble is, unless you tolerate alotta stuff, I haven't seen anyone take this right off the bat and do well. It could be better for down the road or something. Especially with the comt ++

acat doesn't just increase chol since other genes make a difference there. And if your aminos are low, the MMA isn't usually correct anyway. Rich talked about this in the past.

I think Caledonia nailed it so I guess now its about streamlining the sups down to start.

 

[Valentijn]

In my old 30 member biomed group, the people with SHMT and ACAT were consistently harder to treat then the rest of us. I have to say I think Yasko's right about this. Acat is at an important spot for mitochrondrial energy so it makes sense.

I don't disagree that ACAT is relevant ... but if the SNP which is being tested is relevant, then it's blind luck. There's no research anywhere showing that any variation of rs3741049 affects how the ACAT gene functions.

 

[MMe]

Thanks Valentijn, you're input is always very appreciated.
Greenshots, thank you for replying. Somewhere I read you recovered pretty well, and that's something very important to me. Just some hope, a glimp of a future...
I'm glad I finally got my 23andme results, but at the same time I feel like I'm drawning. My case seems rather complicated and I really really don't know where to start. And reading on this forum is not a walk in the park!

In my old 30 member biomed group, the people with SHMT and ACAT were consistently harder to treat then the rest of us. I have to say I think Yasko's right about this. Acat is at an important spot for mitochrondrial energy so it makes sense. My doc has a short list of acat sups but even then its still sorts long. D ribose, CoQ, Lcarnitine fumarate, ox bile salts, digestive enzymes, adenosyl b12 and sometimes Vit E and K.

I'm 'only' +/- for ACAT, so I hope I'm not a difficult case when it comes to that...
About the energy: mine is 'low normal'. The anxiety and depressed feelings are much worse...
I'll read more about the supplements you suggest. Did your doc give you also a dosage for each of them? Or is it just trial and error?

That one supplement that makes me feel like my old, smiling, optimistic self, I would give a million for it!

 

[Sea]

I don't disagree that ACAT is relevant ... but if the SNP which is being tested is relevant, then it's blind luck. There's no research anywhere showing that any variation of rs3741049 affects how the ACAT gene functions.

So does anyone know how Yasko came up with the idea of which SNPs to test for and her reasoning behind those choices?

 

[greenshots]

I don't disagree that ACAT is relevant ... but if the SNP which is being tested is relevant, then it's blind luck. There's no research anywhere showing that any variation of rs3741049 affects how the ACAT gene functions.

From one of her lectures, I think it was blind luck. She had three kids who were the sickest & had huge mito issues including a 4 year old girl who reverted to crawling and their panels weren't that bad so she went looking and this popped up. As I know it, they all had full allopathic workups for mito disease that were neg. Then she started random testing & then regular testing and compared the groups biochem tests and symptoms. Then treatment began and lo & behold, the kids with ACAT and mito based support got better. Then she added it to her panel and began to track it and the same theme emerged. I think this is the fun part of science, the accidental finds like penicillin and a zillion other wonders. Some of it is curiosity, some great intellect, and some just lucky finds. As for some of the others, she based this on research like drs. Richard Deth, Jill James, and other PhDs who studied methylation and diseases like cancer, ADD, Down's, Autism. and more.

ACAT & SUOX doesn't appear to be +/+ or at least she says she's never seen it. Whenever they say that, it can mean that a +/+ isn't survivable so a +/- is important.

 

[greenshots]

Thanks Valentijn, you're input is always very appreciated.
Greenshots, thank you for replying. Somewhere I read you recovered pretty well, and that's something very important to me. Just some hope, a glimp of a future...
I'm glad I finally got my 23andme results, but at the same time I feel like I'm drawning. My case seems rather complicated and I really really don't know where to start. And reading on this forum is not a walk in the park!



I'm 'only' +/- for ACAT, so I hope I'm not a difficult case when it comes to that...
About the energy: mine is 'low normal'. The anxiety and depressed feelings are much worse...
I'll read more about the supplements you suggest. Did your doc give you also a dosage for each of them? Or is it just trial and error?

That one supplement that makes me feel like my old, smiling, optimistic self, I would give a million for it!

I don't think you'll ever find one medicine or supplement that will do that but the others are based on how you tolerate them. If you rush in to treat one gene without having some basic stuff on board it may be a big problem. When your ready to go after that you'd probably be wise to start little doses in sprinkles since the body doesn't always do so well with higher doses right off the bat.

 

[Valentijn]

ACAT & SUOX doesn't appear to be +/+ or at least she says she's never seen it. Whenever they say that, it can mean that a +/+ isn't survivable so a +/- is important.

Plenty of researchers have seen all varieties of ACAT1-02 many times. None are rare, much less nonexistant.

And the SUOX S370S seems to be a mystery SNP which no one else knows about. It doesn't even have an RS ID.

 

[greenshots]

Plenty of researchers have seen all varieties of ACAT1-02 many times. None are rare, much less nonexistant.

And the SUOX S370S seems to be a mystery SNP which no one else knows about. It doesn't even have an RS ID.

I hadn't heard that about the ACAT so if you come acrossed a study that mentions a full block I'd love to have it. I have two friends with this defect and they are big about the science behind it.

 

[Valentijn]

I hadn't heard that about the ACAT so if you come acrossed a study that mentions a full block I'd love to have it. I have two friends with this defect and they are big about the science behind it.

Many groups have genotyped it at http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs3741049 . There's no research into how it functions.

But the Yasko homozygous "risk" version is present in 20% of asians, 0% of africans, and somewhere in between for europeans. There's no indication anywhere that the different genotypes of ACAT1-02 influence function of the ACAT1 gene, and based upon how common it is in some groups (heterozygous in 40% of asians) it seems unlikely that it's harmful.

But most of the Yasko panel looks the same - looking at SNPs where there's no indication that they impact the gene at all. And a couple results where the risk is reported backwards, which is a bit annoying if you're looking for methylation problems, not cancer risks.

So far the only useful results I can see on her panel are for SHMT1, NOS3, CBS C99T (but results are backwards - GG is the risk), BHMT-08, MTRR K350A, MTRRH595Y, MTR (but results are backwards - AA is the risk), MTHFR A1298C, and MTHFR C677T. I still have 9 left to look into (COMT, VDR, MAO, MTHFR 03, MTRR A66G).

But it's pretty shocking how badly supported the inclusion of most of the SNPs is. I can't believe someone would charge $500 for testing and then create a treatment protocol based on what seems to be 75% guess work.

 

[greenshots]

Please understand that this is said in the true spirit of debate and not hostility of any sort. Since this is one of my biggest pet peeves, I feel I must clear something up. I'm gonna assume the best here, that your not an armchair quarter back who scours the "scientific" literature without having any clinical background at all (anyone whose participated in actual studies knows double blind placebo controlled studies, meta analyses, and the like are the purest form of BS ever created to suit big business and big pharma's purpose). I'll assume you have real life experience in these fields as a clinical geneticist and know exactly how all of those play out despite Yasko's decade of clinical and scientific experience? That you understood from her lectures what I explained above about consistently running into specific clinical presentations and test results that led Yasko to test for some snps and not others. Because of course one cannot accurately discount a theory without being fully informed of the rationale used on BOTH sides. After all, you cannot possibly find something your not looking for. If so, I wish I had your professional background. Because that would have saved me years of researching everything. Except I'd still be sick because what appears to be a 100% certainty one decade, unfolds differently in the complexity of the human body. I feel one of my old rants coming on.

But I still have to wonder about some of her findings being accurate in these areas because I followed many, but not all, of the treatments for the main snps and most of my family and biomed group did too and despite these being completely pulled out of thin air as you've implied, we've gotten well and more are in the process of getting better and better. I'm not sure if you've done any of the protocol but I'm guessing you've done some and it hasn't helped you since you consistently have negative things to say about it. But strangely, just about everyone whose working clinically in this field are basing their programs on things like Yasko's work with MTHFR+CBS+SHMT+others and yet you continue to chime in on the methylation forum and criticize someone's clinical work that you cannot possibly know. Even worse, most of the detractors haven't seen the majority of her talks where she lays out the groundwork for her research. This confuses me. Because when I don't believe in something, I'm not gonna spend much time on a forum opposing the main theories, it seems like a big waste of time. Especially when its just negative comments without purpose. Why not stick to an area you find more palatable? I mean, I'm all for problem solving stuff together, having disagreement to stimulate more thought, and questioning a hypothesis when it doesn't pan out for you in reality but if you don't think the majority of its worthwhile, why bother?

Everyone is entitled to their own opinion and I know not every program works for everyone and maybe me and all the people I know are just a complete coincidence. Hard for me to believe though. I sure don't agree with everything Yasko says, thats for sure, but I've seen it work wonders so many times its hard for me to deny it all. But nothing works for everything. And this is going to be completely antagonizing to some but I think the real problem is its way too complicated and its easier to just say its all BS and doesn't work so people won't have to put the time, money, and effort into something they have doubts about. I can't say I blame them either. If I hadn't been forced to do it for my kids I'm pretty sure I wouldn't have taken it on to recover myself. It was honest to God murder and I was just fried out.

But to suffer with CFS/ME where most specialists and scientists think its just in our heads and then still hold onto the old dogma of "standard scientific inquiry" being the one true way and somehow clinical outcomes are not that relevant? Well, I don't get it but would really like to understand your point of view somehow.

Many groups have genotyped it at http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs3741049 . There's no research into how it functions.

But the Yasko homozygous "risk" version is present in 20% of asians, 0% of africans, and somewhere in between for europeans. There's no indication anywhere that the different genotypes of ACAT1-02 influence function of the ACAT1 gene, and based upon how common it is in some groups (heterozygous in 40% of asians) it seems unlikely that it's harmful.

But most of the Yasko panel looks the same - looking at SNPs where there's no indication that they impact the gene at all. And a couple results where the risk is reported backwards, which is a bit annoying if you're looking for methylation problems, not cancer risks.

So far the only useful results I can see on her panel are for SHMT1, NOS3, CBS C99T (but results are backwards - GG is the risk), BHMT-08, MTRR K350A, MTRRH595Y, MTR (but results are backwards - AA is the risk), MTHFR A1298C, and MTHFR C677T. I still have 9 left to look into (COMT, VDR, MAO, MTHFR 03, MTRR A66G).

But it's pretty shocking how badly supported the inclusion of most of the SNPs is. I can't believe someone would charge $500 for testing and then create a treatment protocol based on what seems to be 75% guess work.

 

[Sea]

But the Yasko homozygous "risk" version is present in 20% of asians, 0% of africans, and somewhere in between for europeans. There's no indication anywhere that the different genotypes of ACAT1-02 influence function of the ACAT1 gene, and based upon how common it is in some groups (heterozygous in 40% of asians) it seems unlikely that it's harmful.

I don't think you can decide whether something is harmful simply based on how common it is. For instance I think in celiac disease the figures are something like 30% with predisposing genetics but only about 1% who have celiac disease (over 95% of celiacs have predisposing genetics)

 

[Sea]

But most of the Yasko panel looks the same - looking at SNPs where there's no indication that they impact the gene at all. And a couple results where the risk is reported backwards, which is a bit annoying if you're looking for methylation problems, not cancer risks.

So far the only useful results I can see on her panel are for SHMT1, NOS3, CBS C99T (but results are backwards - GG is the risk), BHMT-08, MTRR K350A, MTRRH595Y, MTR (but results are backwards - AA is the risk)

How are you determining that the risk factors are backwards Valentijn? Where is such information available? I look mostly at SNPedia and then follow up any referenced published articles, but many of the SNPs have so little information.

 

[Valentijn]

How are you determining that the risk factors are backwards Valentijn? Where is such information available? I look mostly at SNPedia and then follow up any referenced published articles, but many of the SNPs have so little information.

http://scholar.google.com/ is an excellent source, and http://www.ncbi.nlm.nih.gov/projects/SNP will also bring up links to a lot of free full text articles on specific SNPs you're looking at.

The problem with methylation is that what's "good" for an ME patient is "bad" for a cancer patient - that is, we want folate, but folate also feeds cancer. So you have to be careful not just assume that because something is associated with higher cancer risk/mortality, it's "bad". Yet that seems to have happened for at least a couple of the SNPs Yasko tests for - though maybe that's a problem with geneticgenie.

 

[Valentijn]

I don't think you can decide whether something is harmful simply based on how common it is. For instance I think in celiac disease the figures are something like 30% with predisposing genetics but only about 1% who have celiac disease (over 95% of celiacs have predisposing genetics)

Yes, that's why it's essential to look at research too. Yasko doesn't cite any that I've seen. I can see why someone might be interested in a rare genotype even when there's no research indicating it's harmful, but it seems quite random to say a common genotype is significant when there's also no research indicating any problems with it.