What causes a sensitivity to methyl donors?

[Hyperflux]

So we all know that some people are quite sensitive to methyl donors and cannot even tolerate the smallest dose of say, methylfolate, while others can take 5mg from the get-go and feel fine. It's a popular theory that COMT and CBS polymorphisms result in sensitivity to methyl donors because these individuals slowly degrade catecholamines and methyl donors increase said catecholamines, so there's a bottleneck that causes a whole host of issues. I believe this is from Yasko's interpretation of the literature, but I have read a few posts on this forum (some from @alicec) that say that the COMT correlation to methyl donors is just a coincidence and not substantiated in any good data.

That being said, what is the root cause to sensitivity to methyl donors? I wonder if trying to associate methyl donor intolerance to some SNP's is too reductionist but I can't think of anything else.

Also, does anyone know if caffeine, curcumin and melatonin are methyl donors?

 

[Learner1]

Perhaps another way of looking at it is how to keep the pathways moving - one needs the right ingredients in the right proportions given ones SNPs and environmental factors.

I suspect many of the complaints are people having the wrong mix of ingredients for them at a given point in time.

My methylation status has changed dramatically over the past few years as I acquired, fought, and beat cancer only to develop CFS. I have NutrEval tests tracking the entire saga over 8 years.

I have COMT and CBS SNPs, but need whopping amounts of MB12 as well as caffeine, curcumin, melatonin and other methyl donors. But I also take high doses of riboflavin, P5P, and magnesium, along with methionine and TMG.

As Ben Lynch says, "treat the patient, not the SNPs".

Time and again, testing has been better at helping than guessing.

 

[GreenMachineX]

@Learner1
What’s the caffeine for in your stack, just energy or does it do something else as well?

 

[Learner1]

Just energy.