Subject: MOTS-c & Morning Workout Timing — A Beginner-Friendly Breakdown
From: Derek from Peptide Price <[email-masked]>
To: [email-masked]
Date: Sat, 21 Mar 2026 12:24:20 +0000
List-Id: <derekpruski.substack.com>

View this post on the web at https://derekpruski.substack.com/p/mots-c-and-morning-workout-timing

Not medical advice, not personal advice. For educational purposes only. All use cases discussed are strictly research use only.
If a researcher is using MOTS-c and also hitting the gym in the morning, timing matters. Here’s why — broken down in plain language.
First, What Is MOTS-c?
MOTS-c is a small peptide encoded in mitochondrial DNA, which makes it unique among peptides. Most peptides are encoded in the cell’s nucleus. Mitochondria are the energy-producing organelles inside your cells — often called the “powerhouse of the cell.” MOTS-c is essentially a signal that mitochondria send out to communicate with the rest of the body about energy status.
In research, it has shown strong effects on metabolism, insulin sensitivity, fat utilization, and cellular energy regulation.
Two Pathways You Need to Understand
To understand why timing matters, a researcher needs to understand two opposing biological pathways. Think of them like two switches in the body that generally can’t both be fully on at the same time.
AMPK — The Low Fuel Switch
AMPK stands for adenosine monophosphate-activated protein kinase. Just think of it as the body’s low-energy alarm system. When cellular energy is running low — during fasting, cardio, or caloric restriction — AMPK activates. Once on, it tells the body to:
Burn fat for fuel
Improve how cells use glucose
Build new mitochondria
Conserve energy by slowing down expensive biological processes — including building new muscle tissue
MOTS-c is a potent AMPK activator. That’s largely where its metabolic benefits originate.
mTOR — The Build and Grow Switch
mTOR stands for mechanistic target of rapamycin. Think of this as the body’s anabolic — or growth — signal. When mTOR is activated, the body ramps up muscle protein synthesis, drives hypertrophy (muscle growth), and invests resources into repair and building.
Resistance training is one of the most powerful ways to stimulate mTOR. Eating adequate protein and carbohydrates after training also helps keep it elevated.
Why They Conflict
Here’s the key point: AMPK and mTOR are opposing signals. When AMPK is highly active, it puts the brakes on mTOR. Biologically this makes sense — the body doesn’t want to be building expensive new muscle tissue when it thinks it’s in an energy-deficient state. These two pathways actively suppress each other, which is why administering a potent AMPK activator right before resistance training creates a potential conflict worth thinking about.
The Important Nuance
Before getting into scenarios, this needs to be stated clearly because it gets misunderstood constantly.
Activating AMPK does not completely shut off mTOR. It does not eliminate muscle growth.
The relationship between these two pathways is nuanced — it depends on how strongly each is activated, the researcher’s nutrition status, training intensity, recovery, and a range of other factors. A research subject is not going to lose all their gains because MOTS-c was administered before a workout. The effect is more of a partial dampening under certain conditions, not a complete block.
There’s also a compelling wrinkle specific to MOTS-c: research has shown it can suppress myostatin. Myostatin is a protein the body produces that actively limits how much muscle can grow — it functions as a biological brake on muscle development. Lower myostatin means that brake is loosened, which can support greater skeletal muscle growth potential.
Whether this effect is enough to fully offset any mTOR dampening from AMPK activation is still an open research question — but it makes the picture considerably more complex than simply writing off MOTS-c as counterproductive to muscle growth.
Scenario 1 — The Optimal Approach (If Schedule Allows)
This is the approach that theoretically extracts the most from both MOTS-c and resistance training by keeping the two signals separated.
Step 1 — Administer MOTS-c fasted, first thing in the morning.
Step 2 — Follow with low-to-moderate intensity movement. A walk, steady state cardio, a light bike ride. Not resistance training. In a fasted state with low-intensity activity, AMPK is heavily biased and substrate availability is low — the body is primed to respond to MOTS-c’s metabolic signals. This is the environment where its effects on mitochondrial function, fat oxidation, glucose metabolism, and metabolic flexibility are operating at full capacity with no interference.
Step 3 — Remain in a fasted or semi-fasted state for roughly 2–4 hours. This gives the acute AMPK signaling window time to normalize.
Step 4 — Break the fast with a solid meal. Protein, carbohydrates, adequate calories. This refuels glycogen stores, raises circulating amino acid availability, and shifts the hormonal environment toward anabolism.
Step 5 — Train. With MOTS-c out of the acute signaling window and the body adequately refueled, resistance training can potently stimulate mTOR without meaningful AMPK interference. The anabolic response to training is uncompromised.
The end result is two clean, well-supported signaling environments — one optimized for metabolic and mitochondrial adaptation in the morning, one optimized for muscle growth later in the day. Both get their moment.
Scenario 2 — Morning Administration Before Resistance Training
Not every researcher has the schedule flexibility for Scenario 1, and that’s completely fine.
For a researcher who can only train in the morning: administer MOTS-c, train, and don’t overthink it.
The mechanistic concern around AMPK and mTOR is real, but it is not catastrophic in a practical context. The research subject is still going to produce a meaningful training stimulus, still going to drive muscle protein synthesis, and still going to see adaptation over time. The myostatin suppression effect from MOTS-c also adds a layer that may partially compensate for any attenuation of mTOR signaling.
Compared to Scenario 1, outcomes on the muscle growth side may be marginally less optimal — but results are still being produced on both fronts. This is not a failure mode. It is a practical, workable approach for researchers whose schedules demand it.
The Simple Version
Maximum benefit: Administer MOTS-c fasted in the morning, do light cardio, eat a solid meal a few hours later, then train.
Constrained schedule: Administer MOTS-c and train in the morning anyway. Still worth it.
For research use only, not for human consumption. This is not medical advice or personal advice — strictly educational.
I want to give a huge shoutout to Coach Cam because he provided a lot of different perspectives on this through his research as well.  
Questions or thoughts? Drop them in the comments.

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