MOTS-c Subcutaneous Research Dosing Protocol
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For research use only. Not medical advice.
Overview
MOTS-c is a 16–amino-acid mitochondrial-derived peptide (MDP) involved in metabolic regulation, AMPK activation, insulin sensitivity, and cellular stress responses.
No completed human trials exist, so research protocols rely on preclinical data and conservative titration patterns.
Most researchers administer MOTS-c once daily subcutaneously with a gradual ramp-up.Daily Dosing Protocol (Subcutaneous)
Standard Daily Range
200–1,000 mcg once daily
Higher end of the range is used in exercise-capacity or metabolic-enhancement models.
Titration Schedule
Weeks 1–2
200 mcg daily
Establishes initial tolerability.
Weeks 3–4
400 mcg daily
Weeks 5–6
600 mcg daily
Weeks 7–8
800 mcg daily
Weeks 9–10+
1,000 mcg (1 mg) daily
Considered the upper daily dose for current research use.
Researchers typically spend ~2 weeks at each level before escalating.
Timing
Once daily, commonly in the morning due to MOTS-c’s association with energy metabolism and AMPK pathways.
Some researchers use pre-workout dosing to explore exercise-performance effects.
Cycle Length
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Typical MOTS-c research cycles:
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8–12 weeks, depending on goals
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Optional 2–4 week break before repeating
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Some metabolic studies use 10-week ramps, then maintain at 1 mg daily
Continuous long-term daily use is less common due to lack of human data.
Common Research Notes
- MOTS-c activates AMPK and behaves somewhat like an exercise-mimetic peptide; mild energy shifts or appetite modulation are possible.
- Some subjects report improved exercise endurance, reduced fatigue, or enhanced glucose handling.
- Side effects are typically mild (fatigue, warmth, slight nauea early in titration).
Because no human trials exist yet, conservative dosing and slow titration are strongly recommended.
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Currently doing 2.5mg MOTS plus 100mg NAD every other day. Feel freaking awesome now. Has anyone experimented with 5-10mg sub-q MOTS every other day paired with NAD+ 100mg-150mg (or higher)? I want to try super aggressive. Healthy researcher targeting mitochondrial rejuvenation and health. I'd be keen to hear results from a researcher who has tried this or similar. Cheers-
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@peptidepete I've done something not to dissimilar to this: 5mg of NAD MWF and 100mg NAD+ daily (for 10 days) (note: I highly recommend just doing NAD+ every other day or MWF).
My general recommendation on MOTS-C is to titrate up slowly to that 5 mg dose. There have been reports of folks getting histamine reactions with MOTS-C up to and including mild anaphylaxis. Titrating up reduces those risks.
All of that said: yes - I felt incredible

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@peptidepete I've done something not to dissimilar to this: 5mg of NAD MWF and 100mg NAD+ daily (for 10 days) (note: I highly recommend just doing NAD+ every other day or MWF).
My general recommendation on MOTS-C is to titrate up slowly to that 5 mg dose. There have been reports of folks getting histamine reactions with MOTS-C up to and including mild anaphylaxis. Titrating up reduces those risks.
All of that said: yes - I felt incredible

@PeptideEd said in MOTS-c Subcutaneous Research Dosing Protocol:
@peptidepete I've done something not to dissimilar to this: 5mg of NAD MWF and 100mg NAD+ daily (for 10 days) (note: I highly recommend just doing NAD+ every other day or MWF).
My general recommendation on MOTS-C is to titrate up slowly to that 5 mg dose. There have been reports of folks getting histamine reactions with MOTS-C up to and including mild anaphylaxis. Titrating up reduces those risks.
All of that said: yes - I felt incredible

Wow, great to hear your experience! Thank you for sharing (I know you meant MOTs for NAD 5mg).
Histamine/MOTs-C, absolutely to be respected! Great point to be amplified. Titration FTW. For those suffering this, consider HistaminX (Amazon) plus Fexofenodine.
This AM I moved from previous EOD 2.5mg MOTs to 5mg followed by a full 100mg NAD (buffered). After several months of lower doses I'm apparently conditioned to it and had no ISR at all. Crazy eh? Like you, I feel great!
Based on the latest research I have done, I plan to stick with this for months, perhaps even going to 100mg NAD per day and keeping MOTs EOD. No downregulations/desensitization's with NAD.
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Currently doing 2.5mg MOTS plus 100mg NAD every other day. Feel freaking awesome now. Has anyone experimented with 5-10mg sub-q MOTS every other day paired with NAD+ 100mg-150mg (or higher)? I want to try super aggressive. Healthy researcher targeting mitochondrial rejuvenation and health. I'd be keen to hear results from a researcher who has tried this or similar. Cheers-
This is awesome and looking to go there. Curious what your age is for context?
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This is awesome and looking to go there. Curious what your age is for context?
@harrisfrank said in MOTS-c Subcutaneous Research Dosing Protocol:
This is awesome and looking to go there. Curious what your age is for context?
65 years old. Feel awesome. Doing "all the things".
BTW and while I am posting, I have updated my regimen to 2.5mg MOTS every day. I have found, for me, back of the arm results in essentially no ISR, no pain, no itch. I would not have tolerated this protocol when starting out. With that said, 5mg EOD gives more of a "rush" (which some enjoy, some do not).
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Have you had any problems with going IM on back of arm? I had to stop when I lost weight because my Tirz was hitting muscle and I was bruising since I can’t pinch and shoot. Or are you using a short needle so no problem? Thx.
(For Tirz, subjectively, back of arm is my preferred location. Now doing muffin top. Still effective, but I need all the real estate I can get.
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Have you had any problems with going IM on back of arm? I had to stop when I lost weight because my Tirz was hitting muscle and I was bruising since I can’t pinch and shoot. Or are you using a short needle so no problem? Thx.
(For Tirz, subjectively, back of arm is my preferred location. Now doing muffin top. Still effective, but I need all the real estate I can get.
)@ResearchCat said in MOTS-c Subcutaneous Research Dosing Protocol:
Have you had any problems with going IM on back of arm? I had to stop when I lost weight because my Tirz was hitting muscle and I was bruising since I can’t pinch and shoot. Or are you using a short needle so no problem? Thx.
(For Tirz, subjectively, back of arm is my preferred location. Now doing muffin top. Still effective, but I need all the real estate I can get.
)Short needle 5/16", never an issue (so far) keeping it sub-q and no accidental IM. Least ISR's, easiest skin to penetrate.
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Yesterday Dr Sawicki posted a short on YouTube about how antioxidants block Mot-C from entering cells. She recommended taking Mot in the morning and taking antioxidants and any of their precursors at night. Just throwing this information out there.
Mot-C half life is 4.4 hours. The half-life of NAD+ is estimated at 1 to 2 hours in the nucleus and cytoplasm, and up to 8 hours in the mitochondria.
My take away is dose Mot-C first thing in morning and NAD+ 6-8hrs later.
https://youtube.com/shorts/W2a9qZ7vP1k?si=LHLm4izgWK7cxms1