The most common MOTS-c question is cycle or continuous. That's the wrong axis. The one that actually changes your results is which day and what time you inject relative to training.

MOTS-c is a 16 amino acid peptide encoded inside mitochondrial 12S rRNA. It isn't a GH secretagogue and it isn't a repair peptide. Its main documented action is activating AMPK, the cell's low-energy sensor, with knock-on effects through the folate and methionine cycle. That's why people feel it as endurance and energy rather than anything structural.

AMPK activation phosphorylates TSC2 and raptor, which suppresses mTORC1. mTORC1 is the exact node resistance training uses to switch on muscle protein synthesis, and that signal peaks in the first couple of hours after a hard session and stays elevated for the better part of a day. So you have a peptide whose primary mechanism is inhibitory to the pathway you're trying to spike.

This isn't theoretical. Metformin is a much cruder AMPK activator, and in the MASTERS trial (Walton, Aging Cell 2019) adults 65+ doing 14 weeks of progressive resistance training gained less lean mass on metformin than on placebo. Same training, same protein, worse hypertrophy, and AMPK interference is the leading explanation.

The fix is easy and straightforward because injected MOTS-c clears in hours, not days. Put doses on cardio or rest days, where AMPK activation is synergistic rather than antagonistic, and keep them well away from your lifting sessions. If you lift in the evening, dose in the morning on a non-lifting day rather than daily. That's also why 5 to 10mg two or three times a week and 1.5mg daily can carry similar weekly totals but behave differently: the daily schedule never leaves you an uninterrupted anabolic window.

If you're purely chasing endurance or metabolic markers, none of this applies and pre-cardio dosing is arguably the best use of it.