The idea likely originated because of secondary interactions, not direct peptide mechanisms. When SS-31 improves mitochondrial efficiency and ATP output, it can ramp up a bunch of other ATP dependent processes, including methylation reactions that rely on SAMe. So if someone’s already got sluggish methylation, like higher homocysteine, low folate/B12, or an MTHFR variant, you might feel a bit off when their metabolism suddenly speeds up (fatigue, headaches, brain fog, etc.). In that case, adding something like TMG or B vitamins might help because it supports the body’s own capacity to handle the extra energy load. It’s not that SS-31 needs a methyl donor, it’s just that some people’s systems do better with that extra support when mitochondrial output increases. I am one of those people, without the added support I was non functioning. Is it needed by everyone? No, but it is a simple addition that can support your body so you are running ahead of the game and not behind.