Is leucine, methionine, or isoleucine worse? (in context of high protein diets) Is leucine or isoleucine easier to restrict?

[Alex K Chen]

https://www.nature.com/articles/s42255-024-00984-2

 

[TomBAvoider]

I'm not a huge fan of basing my protein intake on mouse studies. That said, MR has pointed out that true methionine restriction in humans (equivalent to that in rodents) is very difficult short of hospital level feeding, i.e., largely impractical. One could nonetheless make an argument for moderating methionine intake in the diet. There is are some very definite cautionary studies in humans when it comes to BCAA consumption, and excess seems pretty detrimental especially for CV health. Further investigation seems to have partcularly zeroed in on isoleucine as the biggest culprit, more so than leucine with valine being next. The argument against leucine seems to be mostly theoretical, centered around mtor activation, but actual live bad outcomes as opposed to mechanistic speculation seems to be lacking.

Bottom line, current speculative recommendations seem to be to definitely minimize isoleucine, moderate methionine, and not fret excessively over leucine.