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23andMe Results - How Best To Interpret?

Messages
10
Hi all

I posted here once before re some methylation queries and a few people were kind enough to help - I was advised to get 23andMe testing which I've now done and have my results courtesy of Genetic Genie. I've read a LOT of posts on here and the web generally (and my head now hurts) and just wondered if anyone could point me in the right direction or advise to help get properly to the bottom of things! I am UK-based and I don't think there are any specialist doctors coming up who specialise in this stuff at present. My results were as follows:
Homozygous:
MAO A R297R

Heterozygous:
COMT V158M
COMT H62H
VDR Bsm
VDR Taq
MTHFR A1298C
MTRR A66G
CBS C699T

I knew about the MTHFR before from a separate test, and have been on a MethylB12, Methylfolate (Quatrefolic) and Biocare B-Plex (inc B6/P5P but no folic acid) supplement regime for a few months. Where I get confused is the interplay between the mutations and what’s actually agreed should be done. I also note that 23andme doesn’t cover SUOX or NOS but am running out of funds for any extra tests.

CBS stuff seems really contentious – lots of stuff seems to cite Amy Yasko saying this is a massive deal (not sure if quite so much for heterozygous) and demands a low-protein diet and limited sulphur. But then I’ve seen various very well-reasoned arguments against this saying that it’s not nearly so significant and that’s NOT what should be done. Is there any conclusion on this – and is it co-dependent on other mutations? The Heartfixer site is pretty amazing but seems based on Yasko principles so I wondered if anyone had any differing views to point at.

As far as I can see, my MTHFR and CBS stuff means I’ll have lots of ammonia kicking around, so I need molybdenum, carnitine and manganese and work on ‘BH4’. I can’t work out how the other stuff comes into play though – Heartfixer seems to suggest COMT mutations actually could be a good thing if you have BH4 problems I think.

I have had previous issues with adrenals, anxiety, high histamine and tiredness which have all been enormously improved since taking the methylation supps and 2-3g of vitamin C per day (have been on vit C for several years). Any help very much appreciated indeed if anyone has any idea of the interplay/seriousness of the above, what to do or where else to look.


Thanks again.
 
Messages
15,786
I also note that 23andme doesn’t cover SUOX or NOS but am running out of funds for any extra tests.
23andMe probably tests a lot of SNPs on those genes - but you need to look through your raw data by hand to see if any are problematic, pending a free program to do it for you.

CBS stuff seems really contentious – lots of stuff seems to cite Amy Yasko saying this is a massive deal (not sure if quite so much for heterozygous) and demands a low-protein diet and limited sulphur. But then I’ve seen various very well-reasoned arguments against this saying that it’s not nearly so significant and that’s NOT what should be done. Is there any conclusion on this – and is it co-dependent on other mutations? The Heartfixer site is pretty amazing but seems based on Yasko principles so I wondered if anyone had any differing views to point at.

There's no research showing the faster versions of CBS are ever harmful. And quite a bit of research showing that the slower versions are the more harmful. Hence I think that if Yasko wants to contradict all of the published research, she probably needs to publish a scientific paper showing otherwise. Otherwise it's just her word (subjective experience) versus a lot of research (objective evidence). If respecting scientific principles at all, the objective evidence wins.

As far as I can see, my MTHFR and CBS stuff means I’ll have lots of ammonia kicking around, so I need molybdenum, carnitine and manganese and work on ‘BH4’. I can’t work out how the other stuff comes into play though – Heartfixer seems to suggest COMT mutations actually could be a good thing if you have BH4 problems I think.
Are you lab yeast with half of your entire CBS gene removed? Because that's the only case where it's been suggested that CBS might be capable of producing excess ammonia. There may be some other cause of elevated ammonia, but there's little to no chance that your CBS gene would be at all involved. Hence I'd be extremely skeptical of any ammonia treatments being advocated on the basis of "curing CBS".
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Homozygous:
MAO A R297R

Heterozygous:
COMT V158M
COMT H62H
VDR Bsm
VDR Taq
MTHFR A1298C
MTRR A66G
CBS C699T
Kernel,
Congrats! You have one of the best (least problematic) sets of SNPs I've seen on here. Trade you?
I have the same MTHFR and CBS and had my ammonia tested - and it was very low. I also have thyroid and adrenal low function and histamine intolerance. So, you can't conclude you have ammonia issues. I wouldn't treat for ammonia unless you test high for it or if you or another can smell it on yourself.
I think the methylation supps you're doing are probably really good for you - it makes sense from your SNPs and your symptom improvement. If you find that methylB12 increases your anxiety, you might try hydroxyB12.
I guess my question is whether any of your symptoms remain. If you're doing well, I'd say just keep doing what you're doing. Have you checked your Vitamin D?
 
Messages
10
Many thanks guys, really appreciate it

My Vitamin D was checked a fair while ago and was very low - about 20something. I was put on a supplement and it went rocketing up quickly and was fine on subsequent tests with the supplement used every now and again but yes, was very low initially despite very good exposure to sun. Is it the VDR that causes low vit D? I think I'll still supplement through winter etc.

My CBS is 'AG' allele apparently, not quite sure what that means. I've never been tested for ammonia so was simply going on what I'd read.

My Genova MAP test suggested I had a high need for manganese and especially B6. I'm slightly confused re the B6/P5P as to whether I should or shouldn't be taking this (as part of my B-complex it includes 50mg made up of pyridoxine and P5P) due to the CBS side of things. When I first started taking 50mg P5P in isolation (before the MB12 and methylfolate) it made me incredibly tired, yet unable to sleep. Initially methylfolate made me have insomnia too, but that now seems ok after I take a balanced formula. So the MAP test says I need lots of B6 but consensus on here seems to be that B6 is bad for CBS and causes sulfur issues. Not quite sure what to do. When I first started taking B complex I felt some small sharp pains in my arms/hands but that's died down now after a few weeks.

My main 'symptoms' were/are fatigue/adrenals, poor circulation, sub-fertility (my wife has had 3 miscarriages and I have relatively poor fertility stats), high histamine, sporadic palpitations, sinus issues, poor digestion and low alcohol tolerance. This all despite lots of exercise, no smoking, good diet and low alcohol. Vitamin C and potassium have helped things so will keep plugging away.

Thanks for the advice and support - everyone on this site is very helpful and knowledgeable about a science that blows my mind!
 
Messages
15,786
Is it the VDR that causes low vit D? I think I'll still supplement through winter etc.
VDR doesn't cause low vitamin D, but slow VDR activity can be boosted by increasing vitamin D levels. Basically the active form of vitamin D hooks up with VDR (Vitamin D Receptors) to trigger a lot of important things to happen.

I think the theory is that even when there's less VDR around, that VDR can do its job more efficiently if it's running into vitamin D all the time, versus the VDR encountering the vitamin D less frequently.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Many thanks guys, really appreciate it

My Vitamin D was checked a fair while ago and was very low - about 20something. I was put on a supplement and it went rocketing up quickly and was fine on subsequent tests with the supplement used every now and again but yes, was very low initially despite very good exposure to sun. Is it the VDR that causes low vit D? I think I'll still supplement through winter etc.

My CBS is 'AG' allele apparently, not quite sure what that means. I've never been tested for ammonia so was simply going on what I'd read.

My Genova MAP test suggested I had a high need for manganese and especially B6. I'm slightly confused re the B6/P5P as to whether I should or shouldn't be taking this (as part of my B-complex it includes 50mg made up of pyridoxine and P5P) due to the CBS side of things. When I first started taking 50mg P5P in isolation (before the MB12 and methylfolate) it made me incredibly tired, yet unable to sleep. Initially methylfolate made me have insomnia too, but that now seems ok after I take a balanced formula. So the MAP test says I need lots of B6 but consensus on here seems to be that B6 is bad for CBS and causes sulfur issues. Not quite sure what to do. When I first started taking B complex I felt some small sharp pains in my arms/hands but that's died down now after a few weeks.

My main 'symptoms' were/are fatigue/adrenals, poor circulation, sub-fertility (my wife has had 3 miscarriages and I have relatively poor fertility stats), high histamine, sporadic palpitations, sinus issues, poor digestion and low alcohol tolerance. This all despite lots of exercise, no smoking, good diet and low alcohol. Vitamin C and potassium have helped things so will keep plugging away.

Thanks for the advice and support - everyone on this site is very helpful and knowledgeable about a science that blows my mind!

Wow, you sound so much like me... Are you ME or CFS too? I'm not. The 'main symptoms' could be taken out of my appointment notes, just add muscle wasting, low thyroid/temps, body hair loss, altered sweat patterns, and there I am.

To me this means that testing is important, because no matter what the picture, I keep having just the opposite test results as expected. You might too, and if you are opposite of what you'd expect and you treat for something you don't have, you can really mess things up.

I really don't think your CBS could be causing any sulfur or ammonia issues, but some people still have sulfur or ammonia issues. I would look for evidence before you treat for it. The simplest would be to go on a low sulfur diet for a week - no animal protein (nothing with eyes), no dairy, no soy, no eggs; limit grains to quinoa, buckwheat, amaranth; limit veggies to green beans, summer squash, carrots, celery; no peanuts or Brazil nuts; most fruits are good...you can look up a good plan, but these are the main ideas. In a week you'll know whether you feel a whole lot better or not. If you do, you may want to add things back in slowly - it could be sulfur or it could be other dietary, but if you don't feel better, you eliminate a whole lot of possibilities. Or you could buy the urine test strips for sulfite and sulfate. Or have a serum test for ammonia.

I have read (but can't back it up) that P5P is better than pyridoxine hydrochloride B6 when it comes to fixing the methyl/sulfur cycles. I apparently was B6 deficient taking 100 mg of pyridoxine hydrochloride per day. I switched to P5P and the deficiency was reduced (or eliminated, I'm not sure). So, I don't know why, but I must have had trouble converting/activating it. To me, it just makes sense to take the active form, especially if you don't know whether you can activate it. If you're going to take it, that is.
 
Messages
10
Thanks for the further advice guys, much appreciated as ever.

Thankfully, and with full sympathy to everyone on here that does, I don't have ME or CFS either. I certainly had adrenal issues and still get the 'tired and wired' feelings, but the tiredness is definitely improving with methylation supplements. Whilst I'm quite a calm and placid person for the most part, I do find it difficult to relax and switch off - I am constantly 'braced' despite not being stressed most of the time. This always confused me as I couldn't work out why I wasn't able to just switch off but now I assume genes have something to do with it.

I did actually have the body hair loss (well, on legs anyway) thing when adrenals were down but it's grown back in spades on the methyl stuff. For this and fertility (to try to improve my swimmers - my testosterone levels are fine) I take:

Vit C
B-50 complex (no folic)
Methylfolate 400mcg
MB12
L-carnitine
Co-Q10
Royal Jelly
Pcynogenol
L-Arginine
Zinc (plus some copper, but 2x zinc)
Kelp
Trace Minerals (manganese, molybdenum)
Potassium
Mangesium (citrate pm, malate am)

Costs a fortune! Hopefully this is right to drive my BH4 up.

I'll speak to my naturopath about ammonia and sulfur tests and will experiment with the diet change. Looks like my recent 'paleo' (sort of, in moderation) diet of high protein, low carb may need to change a bit.

Thanks for the P5P/B6 advice. I'd read previous stuff (I think some it may have actually been from Valentijn) about B6 affecting sulfur and affecting CBS, so wasn't sure if I should or shouldn't be on it with my +/- CBS. Map test says yes, but I don't know my SUOX results . B vitamins generally seem to help now - they used to make me agitated but seem much better of late, perhaps since I removed the folic acid and got on the B12 first. P5P on its own made me very, very tired but seems ok as part of a B-complex (but the ratio of P5P to Pyridoxine is low).

I need to try to work out how to extract NOS and SUOX from my 23andme results - I simply can't understand what all the raw data means as there are numerous lines of text for each gene.

Thanks again for the help and advice. This is a genuinely helpful site - I wish I could do more to help others on here but don't feel too qualified to dispense advice. The only thing I can advise is that magnesium really, really helped me with my oesophageal spasm condition and vitamin C is essential for sinuses. Without it I have a permanently blocked nose! With it, I'm mostly fine. I'm sure it does a million things but those two seem to be the supps I can't do without.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Thanks for the further advice guys, much appreciated as ever.

Thankfully, and with full sympathy to everyone on here that does, I don't have ME or CFS either. I certainly had adrenal issues and still get the 'tired and wired' feelings, but the tiredness is definitely improving with methylation supplements. Whilst I'm quite a calm and placid person for the most part, I do find it difficult to relax and switch off - I am constantly 'braced' despite not being stressed most of the time. This always confused me as I couldn't work out why I wasn't able to just switch off but now I assume genes have something to do with it.

I did actually have the body hair loss (well, on legs anyway) thing when adrenals were down but it's grown back in spades on the methyl stuff. For this and fertility (to try to improve my swimmers - my testosterone levels are fine) I take:

Vit C
B-50 complex (no folic)
Methylfolate 400mcg
MB12
L-carnitine
Co-Q10
Royal Jelly
Pcynogenol
L-Arginine
Zinc (plus some copper, but 2x zinc)
Kelp
Trace Minerals (manganese, molybdenum)
Potassium
Mangesium (citrate pm, malate am)

Costs a fortune! Hopefully this is right to drive my BH4 up.

I'll speak to my naturopath about ammonia and sulfur tests and will experiment with the diet change. Looks like my recent 'paleo' (sort of, in moderation) diet of high protein, low carb may need to change a bit.

Thanks for the P5P/B6 advice. I'd read previous stuff (I think some it may have actually been from Valentijn) about B6 affecting sulfur and affecting CBS, so wasn't sure if I should or shouldn't be on it with my +/- CBS. Map test says yes, but I don't know my SUOX results . B vitamins generally seem to help now - they used to make me agitated but seem much better of late, perhaps since I removed the folic acid and got on the B12 first. P5P on its own made me very, very tired but seems ok as part of a B-complex (but the ratio of P5P to Pyridoxine is low).

I need to try to work out how to extract NOS and SUOX from my 23andme results - I simply can't understand what all the raw data means as there are numerous lines of text for each gene.

Thanks again for the help and advice. This is a genuinely helpful site - I wish I could do more to help others on here but don't feel too qualified to dispense advice. The only thing I can advise is that magnesium really, really helped me with my oesophageal spasm condition and vitamin C is essential for sinuses. Without it I have a permanently blocked nose! With it, I'm mostly fine. I'm sure it does a million things but those two seem to be the supps I can't do without.
Thank you, Kernel,

"Braced" is a good word to describe how I often am. I'll use that!

You can do the sulfur tests yourself with urine test strips bought on Amazon, about $70 plus shipping. Or maybe your doc will have them and it will cost less.

SUOX you can get from 23 and me with the following:

rs11171718 (A = 4%)
rs705703 (T = 2%, TT = 0)
i5000977 (A is normal)
i5000976 (A is normal)

There are a couple of NOS genes, but Yasko tests on that I don't think is on 23andme,T is risk allele:
NOS D298E rs1799983 T
It's possible that if you looked this up on dbSNP that you could find the position on the gene and then find that position in 23and me, but there are other NOS SNPs you can check. I got the following off the CDC website

NOS2A rs1800482 Minor allele:C
NOS2A rs9282799 Minor allele:T

NOS3 rs1799983 (no SNP on my 23andme)
NOS3 rs2070744 Minor allele:C

My notes on NOS2A are:
This gene encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines.

and on NOS3 rs2070744:
Variations in this gene are associated with susceptibility to coronary spasm. Multiple transcript variants encoding different isoforms have been found for this gene.

You say you're not too qualified to dispense advice, but I think that it's a good thing not to dispense advice here. I tend to get offended by people who say 'do this, stop doing that'. If there is one thing I've come to realize, it's that we are each unique to a far greater degree than I'd ever imagined. I think that the best use of this site is to help each other further our understanding, craft good questions to ask our health care practitioners, learn to do research into our own condition, to be scientific about how we observe the effects of supplements and medications on ourselves, and to take responsibility for what we do and don't accept or use as treatment. That said, I think that you will surprise yourself sometime when you read what someone writes and have something constructive to say, either from your own experience or your own research.

Oh, you do know, don't you, that BH4 can be purchased online. Other say that you should get to the point where everything else seems to be working well before you try this experiment. It's really expensive, though.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
This is what I was looking for re: NOS

Gene....rsID...........risk allele (per Sterling of the MTHFR Support page on Facebook)


NOS1 rs3782206 T
NOS2 rs2297518 A
NOS2 rs2274894 T
NOS2 rs2248814 A
NOS3 rs1800783 A
NOS3 rs1800779 G
NOS3 rs3918188 A
NOS3 G10T rs7830 T
NOS3 T786C rs2070744 C
 
Messages
10
Thank you so much - and really sorry for delayed acknowledgement, haven't been able to get online for a couple of days to reply. I need to study how to interpret the raw data as it's a bit complicated for me without genetic genie! Will get working on it, this is really, really helpful data.

Thanks again and take care!
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Thank you so much - and really sorry for delayed acknowledgement, haven't been able to get online for a couple of days to reply. I need to study how to interpret the raw data as it's a bit complicated for me without genetic genie! Will get working on it, this is really, really helpful data.

Thanks again and take care!
Kernel,
If you find someone with the genetic genie results (there are plenty posted here), copy out the rs numbers. Then in 23andme, go to the settings and browse raw data. There will be two search bars. I find it most convenient to copy the rs numbers one at a time into the search bar on the right. It will give you your results for that rs number. Every time I find a post like that, I copy it out into an excel spreadsheet, even with the person's results. That way, I can be sure that if I am identifying the right risk SNPs, i.e., if they are CC and +/+, I'm + for each C I have.