• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

What should I add/ change according to my mutations?

renerdrat

Every teardrop is a waterfall
Messages
46
Location
Temecula
Sorry if this post is all over the place. I've actually been taking for.. like a good year + methylfolate. I didn't notice a significant difference though and when I would add things like b12 I had weird reactions. Anyway so recently I started taking significant very large doses of b12 2500mcg, methylb9 10mg, b6 200mg as well as b complex and find that I am feeling better than I have in a long time. But still have some issues with I think dopamine, also definitely still having food sensitivities and just feeling generally itchy.

I'm thinking maybe adding in betaine TMG would help? And taking out high sulfur foods. What else should I be doing?

So first I'm heterozygous for A1298C which I think most people already know what that means..



Also I am homozygous cbs
In these patients, it's common to see low levels of cystathionine and homocysteine since there is a rapid conversion to taurine. This leads to high levels of taurine and ammonia. The CBS upregulation has been clinically observed to result in sulfur intolerance in some patients. Other mutations, such as MTHFR A1298C, Chronic bacterial infections, and aluminum can also lead to low BH4 levels. Lack of BH4 can lead to mast cell degranulation and possibly mast cell activation disorder (MCAD).

Homozygus MTR A2756G helps recycle B12. The combination of MTR and MTRR mutations can deplete methyl B12.is not very common (<1% of CEU population). Some studies have demonstrated that people with a combination of MTHFR C677T and MTR A2756G have persistently high homocysteine levels unless they are treated with both B12 and folate.

homozygous
MAO-A R297R
MAO-A (Monoamine oxidase A) is a critical enzyme involved in breaking down important neurotransmitters such as serotonin, norepinephrine, and dopamine. Males only have one allele since the gene is inherited through from their mother since it is located on the X chromosome. (kinda confused about this one because it seemed to not be as important unless combined with a comt mutation which I have none.

THen I'm also:
Heterozygus for
  • VDR Bsm VDR seem to affect dopamine and vitamin d levels
  • VDR Taq
  • BHMT-02 seems to affect conversion of homocystein to methionine
  • BHMT-08
 
Messages
15,786
Also I am homozygous cbs
In these patients, it's common to see low levels of cystathionine and homocysteine since there is a rapid conversion to taurine. This leads to high levels of taurine and ammonia. The CBS upregulation has been clinically observed to result in sulfur intolerance in some patients.
I wish Yasko would at least learn the basics of what specific genes do before she spouts her nonsense and tries to sell the cure for it to everyone :bang-head:

1) CBS converts homocysteine into cystathionine. Yes, this might result in slightly lower levels of homocysteine, but it's completely irrational to suggest it results in lower levels of cystathionine.

2) Any research into CBS C699T (the only one on her list which has any effect on the CBS gene at all) shows that the upregulation is mild and beneficial.

3) There are no proven health risks associated with low or low-normal homocysteine. Just Yasko's ridiculous speculations. The only known pathogenic SNPs on CBS are serious down-regulations which result in raised homocysteine.

4) Clinical observations are not reliable. There seems to be a connection in "some patients" because a large majority of human beings have those SNPs. Bring in someone with sulfur issues, or any other random and obviously unrelated problem, and odds are a lot of them will have those SNPs. Because nearly everyone has those SNPs.
 

renerdrat

Every teardrop is a waterfall
Messages
46
Location
Temecula
I wish Yasko would at least learn the basics of what specific genes do before she spouts her nonsense and tries to sell the cure for it to everyone :bang-head:

1) CBS converts homocysteine into cystathionine. Yes, this might result in slightly lower levels of homocysteine, but it's completely irrational to suggest it results in lower levels of cystathionine.

2) Any research into CBS C699T (the only one on her list which has any effect on the CBS gene at all) shows that the upregulation is mild and beneficial.

3) There are no proven health risks associated with low or low-normal homocysteine. Just Yasko's ridiculous speculations. The only known pathogenic SNPs on CBS are serious down-regulations which result in raised homocysteine.

4) Clinical observations are not reliable. There seems to be a connection in "some patients" because a large majority of human beings have those SNPs. Bring in someone with sulfur issues, or any other random and obviously unrelated problem, and odds are a lot of them will have those SNPs. Because nearly everyone has those SNPs.


So do you think I shouldn't bother avoiding high sulfur foods? I think? I sometimes have negative reactions to sulfur foods but could be me just trying to relate my symptoms to something. Thanks for replying
 

alicec

Senior Member
Messages
1,572
Location
Australia
So first I'm heterozygous for A1298C which I think most people already know what that means..

Actually it means very little. I suggest you read this thread. I noticed that you recently posted on the thread but it doesn't sound as if you read it in its entirety if you still think the SNP is significant.

homozygous
MAO-A R297R
MAO-A (Monoamine oxidase A) is a critical enzyme involved in breaking down important neurotransmitters such as serotonin, norepinephrine, and dopamine. Males only have one allele since the gene is inherited through from their mother since it is located on the X chromosome. (kinda confused about this one because it seemed to not be as important unless combined with a comt mutation which I have none.

This is more Yasko nonsense. This SNP does nothing at all. Here is a post about it and also COMT. There is a lot of info in the entire thread which you may find helpful.

The VDR and BHMT SNPs you mention also do little to nothing.
 

renerdrat

Every teardrop is a waterfall
Messages
46
Location
Temecula
Actually it means very little. I suggest you read this thread. I noticed that you recently posted on the thread but it doesn't sound as if you read it in its entirety if you still think the SNP is significant.



This is more Yasko nonsense. This SNP does nothing at all. Here is a post about it and also COMT. There is a lot of info in the entire thread which you may find helpful.

The VDR and BHMT SNPs you mention also do little to nothing.

No I did see what you wrote but I don't agree with it. By your thoughts mthfr doesn't affect much of your health but that's your opinion.. I'm confused as to why you are even bothering frequenting the SNPs as it doesn't seem like you agree that they have anything to do with our health disorders?

Yes I do know that it is just a slowing of the gene but that's a big deal if you've lived a life with lots of stress and other negative genetic and environmental predispositions
 

barbc56

Senior Member
Messages
3,657
s mthfr doesn't affect much of your health but that's your opinion
Actually it's not opinion but a science based fact.

https://health.clevelandclinic.org/2013/09/a-genetic-test-you-dont-need/

From the above article.
There is a genetic test for MTHFR variations. But there’s also a cheaper and more accurate way to test for whether MTHFRvariations are causing disease. We simply check the levels of homocysteine in the blood. If levels are high, we can react appropriately. If homocysteine levels are normal — even if there is an MTHFR variation — then nothing needs to be done clinically.

In other words, the homocysteine levels determine our actions, not the MTHFR test results.
 
Messages
15,786
So do you think I shouldn't bother avoiding high sulfur foods? I think? I sometimes have negative reactions to sulfur foods but could be me just trying to relate my symptoms to something.
If avoiding "high sulfur" foods makes you feel better, then go for it. But CBS variants are not a reason to avoid those foods.

By your thoughts mthfr doesn't affect much of your health but that's your opinion.
Some rare MTHFR variants, which bring the enzyme activity down to nearly or at 0%, are properly pathogenic. Those ones cause disease, and people absolutely require supplementation to deal with them, preferably starting at birth.

The common MTHFR SNPs, like A1298C and C677T, are not pathogenic but can contribute to raised homocysteine and associated birth defects in the children of affected mothers. But A1298C is a pretty mild variant by itself, even more so when it's heterozygous.

Basically it means your MTHFR enzyme is 17% less effective than the optimal version. But since the A1298C and C677T are so very common, the average healthy person has MTHFR enzyme activity which is 30% less effective than the optimal version. So only having MTHFR A1298C +/- means you're doing quite a bit better than average.

Basically, inefficiency in some enzymes is not a big deal. Often it's not relevant at all unless enzyme activity gets seriously low. But even when someone has MTHFR C677T +/+ or compound heterozygous C677T and A1298C, and enzyme activity drops by 65-70%, there is still no disease resulting - just the increased risk of birth defects in offspring. And even that elevated risk completely disappears if the affected mother eats a diet with a good amount of vegetables or takes a normal supplement with folic acid.

I'm confused as to why you are even bothering frequenting the SNPs as it doesn't seem like you agree that they have anything to do with our health disorders?
I can't speak for @alicec but she, like me, seems to have a genuine interest in SNPs and the science behind them. Some SNPs obviously do have an impact, but the majority do not. And most of those SNPs which have an impact are not causing health disorders.

As someone who is very enthusiastic about genetics, I feel that it's important to correct claims which are contradicted by quality research, or otherwise obviously unfounded. No one is helped with overhyped or completely inaccurate claims, and it creates distrust of genetics in general when patients and even practitioners make ridiculous claims.

And if your underlying argument is that only people who agree with Yasko should be able to post about Yasko's claims, you're on the wrong forum. Her own forum does have such a policy, however, so if you're looking for a place where people will regurgitate complicated and expensive protocols to "treat" SNPs which are completely incapable of having any impact, that would be the place to go. But on this forum, we are most certainly allowed and even encouraged to politely debate such claims.

Yes I do know that it is just a slowing of the gene but that's a big deal if you've lived a life with lots of stress and other negative genetic and environmental predispositions
No, it isn't. You and Yasko and whoever else can make random guesses about interactions with mysterious unknown factors, but it's completely baseless. At the end of the day, if you think MTHFR A1298C +/- is somehow having a profound effect on you which has never appeared in the research, have your doctor test your homocysteine. This is an extremely common test in the US, often done at yearly preventative physical exams, and is quite cheap as well.
 

alicec

Senior Member
Messages
1,572
Location
Australia
By your thoughts mthfr doesn't affect much of your health but that's your opinion..

It's nothing to do with my opinion or my personal health. As has been pointed out by others, studies of A1298C show that it has a very small effect on enzyme activity which doesn't result in disease.

I'm confused as to why you are even bothering frequenting the SNPs as it doesn't seem like you agree that they have anything to do with our health disorders?

If I thought SNPs were irrelevant, I wouldn't have bothered to do a 23andme test nor spent considerable amounts of time understanding at least some of my SNPs.

But we need to place them in a proper context and look to properly conducted scientific research to understand their consequence. Yasko's half-baked theories and myths and her serious misunderstanding of the scientific research she does cite means that she is not a reliable source.

Some SNPs do nothing at all (probably most), a few seem to have very significant effects (usually because they completely disable a critical enzyme) and some have a small effect.

This latter group includes most of the SNPs that get discussed over and over again on PR. The internet discussion of SNPs has completely distorted the significance of these small effects and convinced people that they have serious mutations that directly cause their health problems. There have been many scientific studies of many SNPs and they simply don't support this idea.

Well done association studies (not the early ones with small sample groups and inadequate statistics) do show a degree of association of some SNP combinations with various disease states, but the genetic contribution is small.

I see knowledge of SNPs as something of an insurance policy - ie it is knowledge of potential weak points.
In healthy people who are eating well, they probably don't matter much. But we are not healthy and many of us are forced into very restricted diets because of food intolerances. Both of these circumstances (and especially the widespread metabolic derangements which seem to be associated with this disease) place our systems under strain and here weak points might manifest themselves. So if there is anything I can do to bolster the weak points I will do it.

I don't attribute symptoms and sensitivities to particular SNPs, I don't single out some SNP as being the cause of some problem, particularly when there is no evidence for it and plenty of evidence to the contrary. Instead I recognise that the endpoints that we perceive as symptoms have complex inputs, only one of which might be a small genetic contribution from various SNPs.

Where there is good reason to think that my combinations of SNPs might be contributing to slowing of an important metabolic pathway, and particularly when this is backed by functional data from an OAT, then I might decide to supplement cofactors for the affected enzymes and/or end products of the pathways, to help my struggling system.