The science is super duper thin on this topic. Hence we're all researchers.
Lets go into the data we have first:
Human MOTS-c:
There is no published dose-finding RCT that tested 1x vs 2x vs 3x vs daily in people and showed one schedule wins. The completed human work is mostly on a MOTS-c analog (CB4211), and that was dosed daily (single doses, then daily for 7 days, one cohort 28 days). That tells you daily is tolerable for an analog. It does not prove native MOTS-c needs to be daily.
Pharmacokinetics:
Human plasma half-life is not well published. Estimates people throw around are short (minutes to a few hours). Downstream AMPK / metabolic effects last longer than the peptide sitting in blood. That is why a short half-life does not automatically mean daily injections. It also does not prove once a week is enough.
What the science does not say:
It does not say 5 mg 3x/week is the human dose. That number is clinic/community convention scaled from mice.
It does not say once weekly is optimal.
It does not say daily 5–10 mg is better. Daily in papers ≠ daily at forum bolus doses.
It does not settle AMPK “desensitization.” Chronic AMPK vs mTOR is a real pathway conflict in principle, but nobody has mapped MOTS-c injection frequency onto that in humans.
Honest take from the data, not the vendor blogs, plus I can pull from some personal experience as I'm currently on a cycle of MOTS-c....
Pulsed exposure is consistent with how endogenous MOTS-c behaves (it rises with exercise, but not 24/7).
If you want to stay closest to published schedules, the animal record is daily or 3x/week, and the one analog human trial is daily.
If you want to stay closest to published biology, you pulse AMPK, pair it with a low-insulin / training window, and don’t assume more injections = more effect.
2–3x a week is the zone where I have been administrating and it works well for me. Your mileage may vary. I think a reasonable approach is daily for 1 week as a loading phase and then going to 2 or 3x a week aiming for 10mg total per week. Also remember to administer when fasted, which we do have data suggesting this is the correct method.
So if someone asks “what does the science say, 1x, 2x, 3x, or daily?” the accurate answer is: the science does not pick a human frequency. It supports that MOTS-c can work when given repeatedly over days to weeks, with daily and 3x/week both appearing in the animal literature, and daily in analog human work. Everything else is protocol folklore from Reddit and the like. Sorry not sorry, but I don't put much if any pedigree into anything coming out of the toxic waste dump known as Reddit.