anxiety, food intolerances, cbs and sulfation

[racerbiker39]

@alicec Thanks for the info and the links. Yes, I have been reading based on what I saw on the internet. In my case the connection between MTHFR A1298C, BH4 and NOS made sense based on my symptoms. When you are desperate to get well you would like to believe any hypothesis that seems like a cause and a potential cure. I also have homozygous COMT H62H mutations which could aggravate my anxiety.

I still need help in understanding why Sulphates or Thiols (Magnesium Sulphate cream), NAC, Phenols, Turmeric etc..cause me anxiety. I have seen that P5P (10mg) and Molybdenum (500 mcg) help to a good extent. I am going to try and up the dose to see if it helps.

If we were to ignore the CBS and the sulfation connection for a while, is it reasonable to say that BHMT (hetero 2,4,8) , Low BH4 and NOS hetro can cause sulfation issues? I am exploring other aspects like Estrogen dominance, Low Testosterone, High Phenylalinine as a cause.

 

[Learner1]

@racerbiker39 You haven't mentioned taking anything that would help the methylation cycle.

B6 is used in methylation and in the transsulfuration pathway and in heme production and in sphingolipid production. Being low in it is not good.

Taurine helps with bile acid conjugation in the gall bladder, which is essential for getting toxins out of you. Low taurine can be caused by low B6.

You might find this an interesting read:

http://www.beyondmthfr.com/side-high-oxalates-problems-sulfate-b6-gut-methylation/

The genetics can have an impact, but environmental factors can alter how they express themselves, so you won't have a good picture of what supplements you need without a test like a Genova Diagnostics NutrEval. Your SNPs suggest you may need more 5-MTHF and methylB12 than some people, and you may also need TMG, B2, magnesium, potassium, and glutamine.

Getting your gall bladder working better and methylation balanced should take care of your anxiety.

 

[alicec]

COMT H62H mutations which could aggravate my anxiety.

That SNP has no effect. The product of the variant gene is identical to that of the wildtype gene.

Sulphates or Thiols (Magnesium Sulphate cream), NAC, Phenols, Turmeric etc..cause me anxiety.

Many people report sensitivity to those things and there are likely to be a number of reasons for this. Often the reason is not clear.

People have reported a number of things that may be helpful and you will find various threads on PR discussing this.

I am simply saying you should not be mislead by false claims that certain SNPs are the reason. They are not.

is it reasonable to say that BHMT (hetero 2,4,8) , Low BH4 and NOS hetro can cause sulfation issues?

No.

BHMT 2 and 4 have no effect. 8 has a very slight effect which is protective since it reduces homocysteine.

I've given you links which explain that the MTHFR SNP you are concerned about has nothing to do with BH4.

The NOS3 SNP does change the enzyme but this does not appear to have much consequence. It is classified as benign in ClinVar. There are a few old association studies of poor quality which suggest the SNP may be associated with increased risk in a few conditions but these don't appear to hold up with further scrutiny.

 

[Learner1]

@alice What do you think of Pall's theory of peroxynitrites? Particularly the BH4 component of it?

 

[Learner1]

@alicec I asked as I have very high nitrotyrosine and mitochondria that seem to be damaged from peroxynitrite production, and SNPs that seem to lead to low BH4, low folate, low B12, and low SOD production.

Today's Health Rising blog refers to this situation:

Some genetic findings may be simply waiting to be discovered. Dr. Martin Pall’s small study (consisting of 17 ME/CFS patients and 111 healthy controls) revealed increased levels of 3-Nitrotyrosine, a byproduct of nitrating agents that reflect how much peroxynitrite, a potent oxidant that can do much damage to cell tissues and energy enzymatic processes is present. The study suggested that peroxynitrite levels are on average 5.43 times higher in patients with ME/CFS.

In fact, the patients in the study with the lowest amount of 3-Nitrotyrosine still had 2.25 times higher levels of peroxynitrite than the healthy controls. Dr. Pall noted that such a dramatic disparity is rare in medicine. His hypothesis proposes that vicious cycles in both ME/CFS and fibromyalgia converge to form high amounts of peroxynitrite.

Individuals who are genetically handicapped with SNPs that affect their body’s ability to recycle a substance called BH4 may be vulnerable to forming peroxynitrite in various tissues of the body, including the central nervous system due to a well-researched phenomenon called “uncoupling” in the formation of nitric oxide.

I've found I also have other SNPs affectung my health like COMT, HFE and prothrombin.

Though we have many genes that may be interacting with environmental factors and with each other, I have repeatedly found that various genes are working together to make me sick, and it's looking more and more like the researchers are, too. And working to make genes behave better can offer the opportunity for better outcomes.

Therefore, it's wise to suggest that people get tested to confirm or deny vsrious theories, rather than offering studies that supposedly disprove the link, when there are many studies that say just the opposite. Those folks in the studies have millions of different gene combinations and environmental factors that could be confounding the results.

 

[alicec]

What do you think of Pall's theory of peroxynitrites? Particularly the BH4 component of it?

I seriously doubt the notion that the NO/ONOO- vicious cycle is causative of ME/CFS and the other conditions Pall discusses but I can certainly see that it could be a perpetuating factor.

A high BH4/BH2 ratio is critical to keeping NOS properly coupled and thus producing NO and not superoxide and peroxynitrite. Chronic oxidative stress can deplete BH4 and increase BH2, leading to uncoupling and the vicious cycle that Pall describes.

Anyone who suspects this might be going on would be wise to try the things that Pall recommends. They may well help considerably.

Individuals who are genetically handicapped with SNPs that affect their body’s ability to recycle a substance called BH4 may be vulnerable to forming peroxynitrite.

I've found I also have other SNPs affectung my health like COMT, HFE and prothrombin.

I have repeatedly found that various genes are working together to make me sick, and it's looking more and more like the researchers are, too. And working to make genes behave better can offer the opportunity for better outcomes.

Therefore, it's wise to suggest that people get tested to confirm or deny vsrious theories, rather than offering studies that supposedly disprove the link, when there are many studies that say just the opposite.

I agree that genetics can make a contribution to various illnesses, including ME/CFS, and that if such genetic variants can be identified, action to counter the effects would be worth pursuing.

I think it is definitely worth getting 23andme or complete exome analysis and working hard to try to identify variants that might be relevant.

For any individual, important variants might be identified, but I am not aware of any robust studies identifying particular SNPs that might be relevant to ME/CFS patients in general. I could have missed some more recent studies and if you can point me to these I would be very happy to read them. I would certainly be interested in the study about SNPs relevant to BH4 recycling.

I note that Ron Davis has indicated that he has identified some candidate SNPs which might have relevance to his metabolic trap hypothesis. Very wisely though he has said that he needs more data to confirm and is trying to accumulate that now. I have contributed my exome sequence to help with that.

His caution underscores the fact that for genetic association studies to have any value, large numbers are needed (thousands, not hundreds) and I am not aware of any studies on ME/CFS which fulfill this criterion. Hopefully they are being done right now.

When such studies appear I will gratefully embrace them.

Such studies bear no resemblance to the ridiculous claims made by Yasko about common SNPs shared by millions in the population. There is simply no substance to them but they are good for selling supplements.

I think it is important to steer people away from falling into the trap of thinking that they have found solutions for their ill health. This is snake oil.

In the meantime, I agree it is valuable to try and understand one's own genetic legacy. Such understanding should be rooted in science, however, not whim and fanciful claim.