I know you just said you "don't know what to say there", but I'm going to ask anyways because you usually do have an answer for everything

. Do you think it has to do with deficiency as some people have suggested? And since you didn't mention SNPs, does that mean you don't think the reaction is due to certain SNPs? My symptoms continued for 5 weeks until I stopped methylfolate. I suppose someone could make an argument that the high dose of folic acid I was taking at the time was constantly causing a deficiency, but I'm not yet convinced.
Hehe I wish I had answers for everything.
Honestly I don't know. This aspect has really puzzled me. Clearly there is a lot of anecdotal evidence to support that people are simply very intolerant of even small amounts. What confuses me most is that some people are talking about 20-30 mcg setting them off, maybe even less. While most plant based food sources are not high in methylfolate in terms of percent of total composition of folate, animal meat is. So a question is do these same individuals get the same result from eating oysters, mussels, etc? Or even three normal servings of meat a day (7-10 mcg methylfolate per serving roughly)? In theory methylfolate is methylfolate, and is well absorbed in the gut provided no ascorbic acid.
Methyl b12 is arguably a different story since in reality oral absorption is so poor that very little makes it through the gut in food sources. But then some people claim they have awful symptoms on small doses of oral mb12 so I don't know what to say there at all.
I am not convinced either that folic acid you were taking was somehow making you intolerant to methylfolate. The argument is that folic acid drives you to deficiency so that you are suddenly overnight so low in methylfolate that tiny amounts drive you into bad symptoms for five weeks? That argument does not sit well with me.
On the other hand that does not absolve folic acid for having its own issues. Iif you take folic acid in high amounts, one of two things is going to happen:
a) you convert it just fine and you increase THF levels which may or may not lead to l5mthf and increased methylation based on your MTHFR efficiency and other factors (like b12 etc.).
or
b) you don't convert folic acid well in your liver, you don't get the bang for the buck with THF increase and methylation is not increased, and the pileup in folic acid leads to issues with other folate intermediates in terms of transport and cellular uptake.
Case (b) clearly is not desirable. Case (a) is at best a long way around with possible inefficiencies along the way that could have been shortcut and optimized with methylfolate or at least folinic acid. Hence my viewpoints on folic acid the synthesized oxidized version that mankind's genome never really experienced until the last few decades.
If someone comes to me and says they can't stand methylfolate but they tolerate well folic acid or folinic acid, I have to scratch my head. The end game is methyfolate unless the folate cycle is blocked. In the latter scenario taking folic or folinic acid means we are masking a folate deficiency with placebo and maybe doing harm in the process. If it converts to methylfolate then great but then why does methylfolate cause such a problem if titrated properly.
So yeah I am still confused on this topic, sorry. And so far I have not seen a convincing argument.
I think it is hard to argue for phantom SNPs we don't know about only because of the questions I raised above. One remote possibility is there a gut dysbiosis that loves the methyfolate directly supplemented. But if that is true then how can their be "growth" from doses that are commensurate with what is found in animal protein sources in a normal diet.
So around and around and still confused.
The last option is there is something else in the formulation that sets a person off. But the brands being used, don't seem to have many problems in that respect. The exception for me is Solgar Metafolin. Since it has corn and I have bad IgG reactions to corn, my inflammation takes off in a couple of days.
Anyways I will stop rambling now
