Understood. To be clear though I was implying that the 81% probably can mobilize folinic acid at some level (they used big dosages if I remember right). And that the 19% left over may NOT be able to do so. In other words if we view folinic acid as a storage intracellular buffer form which is perfectly natural, that most people at some level can shuttle around and convert for multiple uses. While not as optimal as taking straight methylfolate for methylation they would get some conversion dependent on MTHFR status and of course there are other reasons folates are used than just methyation, i.e. dUMP, thymidine synthase, etc. (though those other uses I doubt need high levels). Clearly the 81% were at some level able to deal with a stockpile of folinic acid. But for those who cannot it could be really devastating. Folinic acid levels when they rise high enough without proper activity of MTHFS will strongly downregulate SHMT1 and more importantly SHMT2 in the mitchondria. At which point you can kiss the folate cycle goodbye, since you are stuck at THF. Sure you could massively dose methylfolate but that will only last so long, if SHMT is blocked. This would lead to a folinic acid / methylfolate arms race which would not be good. In any event I don't see why high dose folinic acid would ever be a good thing. If you want methylation then take l5mthf and bypass a lot of issues. If you want some folates for other uses and want some regulatory control of SHMT and other folate enzymes, then take small amounts of folinic acid. Folinic acid as you know has a long half-life and can sit right in the CNS and take days to clear out. Overdoing it with say 800 mcg folinic acid (imo over doing it) could really "pile-up" over time. But 200 mcg? I doubt that is a big issue with most people based in part on the 81% study and the .high frequencies of many MTHFS and SHMT1 haplotypes.