Diets high in Serine.

[Methyl Health]

First, these are my transulfuration related SNPS:

• CBS A13637G rs2851391 CT +/- Heterozygous
  
• CBS C19150T rs4920037 AG +/- Heterozygous
  
• CBS C699T rs234706 AA Homozygous
• SUOX rs10876864 AG Heterozygous

My dietary reactions: High protein diet, High thiol foods, high sulfite wines, NAC (the reaction I get from taking just 500mg of NAC is nothing short of disturbing; chills, anxiety, etc)
My main symptoms: anxiety, heart palpitations, GERD, rhinitis with no mucus, higher blood pressure, internal "shakiness", intention tremor.

I have been doing very well following a low protein, low non-essential amino acid, low thiol diet and taking varying amounts of pyridoxine 5 phosphate (B6 - 25mg to 100mg subligual) among other supplements, but there would always seem to be times when the B6 made me feel worse or that a food that was low in thiols would trigger slight sulfite reaction. What I stumbled upon this morning was serine.

Serine, a non-essential amino acid, is a cofactor for the CBS enzyme to make cysteine. I cannot eat eggs at all, and this makes sense because they are not only high in sulfur, they are high in serine.

So, some notes on serine and B6:

• The SHMT gene uses B6 to take up Serine to convert THF to 5,10 methylene THF. Here is another image.
  
• B6 is a cofactor to produce myelin via the serine palmitoyltransferase (SPT) enzyme.
• Serine is a driver of the TCA (krebs) cycle via Pyruvate, as is cysteine interestingly.
• This is also interesting: Cysteine metabolism in vivo of vitamin B6-deficient rats. Which shows that the L-cysteine catabolism in B6 deficient rats increases pyruvate but not taurine.
• During dietary protein restriction, it was found that de novo serine synthesis increased, but... Serine synthesis normally occurs at the kidney, but under these conditions it also takes place at the liver.
• The administration of ample amounts of pure B vitamins to rats on an experimental diet, receiving dl-serine by stomach tube, reduces considerably the mortality and the severity of the clinical symptoms. Of the B vitamins tested, pyridoxine was most effective.

So I am wondering if a diet high in serine, combined with the CBS SNP, leads to a deficiency in B6, which could effect myelin production as well as screw with the folate and TCA cycle causing fatigue and other neuro symptoms. By getting too much dietary serine we limit de novo synthesis of serine as well(?)

It makes me also think that B6 supplementation is not needed as much if you have low serine intake, and that supplementing with the B6 increases the transsulfuration pathway action and could make us feel worse.

(As an aside to ponder, I think the key to ME/CFS lies in the TCA cycle and how that cycle is driven my different macro nutrients. And I think that calorie restriction is important to to those of us with these mutations. Calorie restriction influences the SIRT3 gene which changes the TCA cycle.)

 

[Critterina]

Interesting. You could be right about dietary serine increasing the need for B6. But the body also makes serine, so if that mechanism is screwed for some reason, it's possible that you'll always need more B6. Other foods high in serine are soy protein isolate and turkey. Do you have trouble with them?

B6, you know, gets toxic in high doses. I thing that oral B6 has been shown safe except for one case at 100 mg. Sublingual dosing may make more of the dose available, I would guess, so you may reach toxicity sooner - just a guess. I wanted to start with that before saying anything else.

The second "introductory comment" is that I want to make sure you have eliminated some of the other things - the anxiety we talked about with respect to MTHFR. Have you a good read on your adrenal/thyroid status? Have you looked into histamine intolerance (which would include reactions to cooked then refrigerated meats and anything aged or fermented)? Have you had a serum amino acid profile done? Have you tried enzymes and/or Betaine HCl or zinc or any of those kind of things for GERD? Some stuff may be related to SNPs, but there are lots of other options to consider.

An acupuncturist suspected my B6 deficiency, so I took 100 mg for a few months before my amino acid profile showed that it was still deficient. I switched to P5P and my labs improved, most notably a reduction in taurine to normal levels.

 

[CFS_for_19_years]

I cannot get the docs to test any adrenals

I don't know if you've seen this resource, but if you can swing the $119, you could get some useful information from this salivary cortisol testing where you take four saliva samples throughout the day:

http://www.canaryclub.org/specializ...-zrt-stress-hormone-test-kit-c1-c2-c3-c4.html

If you have low levels of cortisol during the day, and show this to your doctor, they might be more interested in at least ordering an 8 a.m. serum cortisol, or if you've really hit the jackpot, they may also add an ACTH stimulation test.

A naturopath can help you treat low adrenals with things like hydrocortisone, pregnenolone, DHEA, adrenal extract and herbals.

 

[CFS_for_19_years]

Well if anything my cortisol should be through the roof during the day. Or would have been. I feel so much better now I so not really care or need the testing.

Excellent!