MOTS-C and Shortness of Breath During Training

[jmon1977]

MOTS-C is something I normally use 20-30 minutes ahead of training. What I've run into is that occasionally, while I'm working out, a pretty severe breathing difficulty hits me. The pattern seems to show up mainly on the heavier days (Legs/Back). Eventually it fades, but I'm wondering whether anyone else has experienced this same response? What time do you use your MOTS-C?

Also, I'm not on the high end of MOTS-C dosing the way some people are. My intake is 1-2 mg/day.

 

[Jone5y87!]

jmon1977 said:

MOTS-C is something I normally use 20-30 minutes ahead of training. What I've run into is that occasionally, while I'm working out, a pretty severe breathing difficulty hits me. The pattern seems to show up mainly on the heavier days (Legs/Back). Eventually it fades, but I'm wondering whether anyone else has experienced this same response? What time do you use your MOTS-C?

Also, I'm not on the high end of MOTS-C dosing the way some people are. My intake is 1-2 mg/day.

Have you thought about using it right after waking up, mate?

 

[LabRatts]

jmon1977 said:

MOTS-C is something I normally use 20-30 minutes ahead of training. What I've run into is that occasionally, while I'm working out, a pretty severe breathing difficulty hits me. The pattern seems to show up mainly on the heavier days (Legs/Back). Eventually it fades, but I'm wondering whether anyone else has experienced this same response? What time do you use your MOTS-C?

Also, I'm not on the high end of MOTS-C dosing the way some people are. My intake is 1-2 mg/day.

My protocol is 2.5 mg on alternate days, and I have not run into any problems at all. My wife is on 3 mg and she has been fine too.

My suggestion would be to drop your dose and check whether the symptom sticks around. It’s possible you’re a “cheap date” when it comes to Mots, or maybe a different factor is behind what you’re feeling.

 

[igottapee]

Anything else in the mix for you?

 

[Chili777]

My dose is 4 mg, taken every other day, and that hasn't been an issue for me. Since I live at altitude, I've found that on pin days it bothers me nowhere close to as much. Running up 3 flights of stairs is doable, and I bounce back almost right away.

 

[Turbo-Farmer]

My experience goes the other way. Every morning before work I go running with my dog, and it feels like my pace has gotten quicker compared to how it was before I started the mots-c.

According to my Fitbit, my v02 max has gone up from 39 to 43

My wind is better than it used to be

 

[jmon1977]

Turbo-Farmer said:

My experience goes the other way. Every morning before work I go running with my dog, and it feels like my pace has gotten quicker compared to how it was before I started the mots-c.

According to my Fitbit, my v02 max has gone up from 39 to 43

My wind is better than it used to be

Do you dose MOTS right before going for a run? Since I don't do any high intensity cardio, I've got nothing to compare it against. On days when I'm not training, taking it causes no issues for me. The problem shows up almost exclusively when I use it shortly before lifting heavy weight. Looks like my only option is to begin dosing much earlier ahead of my workout.

 

[Turbo-Farmer]

jmon1977 said:

Turbo-Farmer said:

My experience goes the other way. Every morning before work I go running with my dog, and it feels like my pace has gotten quicker compared to how it was before I started the mots-c.

According to my Fitbit, my v02 max has gone up from 39 to 43

My wind is better than it used to be

Do you dose MOTS right before going for a run? Since I don't do any high intensity cardio, I've got nothing to compare it against. On days when I'm not training, taking it causes no issues for me. The problem shows up almost exclusively when I use it shortly before lifting heavy weight. Looks like my only option is to begin dosing much earlier ahead of my workout.

I've gone running daily for 30 months straight. My dog makes sure of it — we're out the door each morning, whether it's raining or sunny. So everything I do fits around that routine. Getting to the gym is harder for me than running up the mountain in the woods behind my house.

 

[Researcher6076]

jmon1977 said:

MOTS-C is something I normally use 20-30 minutes ahead of training. What I've run into is that occasionally, while I'm working out, a pretty severe breathing difficulty hits me. The pattern seems to show up mainly on the heavier days (Legs/Back). Eventually it fades, but I'm wondering whether anyone else has experienced this same response? What time do you use your MOTS-C?

Also, I'm not on the high end of MOTS-C dosing the way some people are. My intake is 1-2 mg/day.

jmon1977 said:

MOTS-C is something I normally use 20-30 minutes ahead of training. What I've run into is that occasionally, while I'm working out, a pretty severe breathing difficulty hits me. The pattern seems to show up mainly on the heavier days (Legs/Back). Eventually it fades, but I'm wondering whether anyone else has experienced this same response? What time do you use your MOTS-C?

Also, I'm not on the high end of MOTS-C dosing the way some people are. My intake is 1-2 mg/day.

Turbo-Farmer said:

jmon1977 said:

Turbo-Farmer said:

My experience goes the other way. Every morning before work I go running with my dog, and it feels like my pace has gotten quicker compared to how it was before I started the mots-c.

According to my Fitbit, my v02 max has gone up from 39 to 43

My wind is better than it used to be

Do you dose MOTS right before going for a run? Since I don't do any high intensity cardio, I've got nothing to compare it against. On days when I'm not training, taking it causes no issues for me. The problem shows up almost exclusively when I use it shortly before lifting heavy weight. Looks like my only option is to begin dosing much earlier ahead of my workout.

I've gone running daily for 30 months straight. My dog makes sure of it — we're out the door each morning, whether it's raining or sunny. So everything I do fits around that routine. Getting to the gym is harder for me than running up the mountain in the woods behind my house.

MOTS C Wrecked My Training Sessions — The Explanation

Taken before a workout, MOTS C is meant to deliver an energy lift. Yet at times what I got was the reverse. To figure out why, I had to look into the biology, and what I found was that MOTS C only works properly when it matches what is already happening inside your body.

MOTS C = AMPK Stressor

AMPK gets switched on by MOTS C, and that is the very same cellular energy stress pathway that exercise sets off.

•Hard training puts stress on your mitochondria.

•AMPK is activated by that stress.

•From there, AMPK pushes adaptation toward better mitochondrial efficiency, improved fuel use, and occasionally a burst of energy partway through a workout, an AMPK shift.

But There’s a Limit: Overtraining

If you have overtrained, you know the feeling: you turn up at the gym, and your body just refuses to cooperate. Fatigue, sluggishness, and less strength than the previous day.

Your AMPK has been stressed beyond its limit and has not bounced back. Mitochondria can only tolerate so much AMPK activation before they resist and signal, “enough.”

What Stresses AMPK?

•Exercise that is intense or done often

•Calorie deficit / fasting

•Medications such as metformin (prescribed for diabetes and sometimes for longevity)

•MOTS C itself

On its own, each one can be handled. The trouble starts when they are stacked.

My Mistake: I Was Stacking Everything

All of these were happening at once:

•Frequent, intense workouts

•A mini cut with an ongoing calorie deficit

•Metformin for longevity

•And on top of that, I introduced MOTS C

One of those alongside MOTS C might have been fine, but not the whole set together: for MOTS C that amounts to a full contraindication, since AMPK gets pushed beyond what recovery can absorb.

The Results Were Ugly

Midway through, I had to abandon the workout. There was simply no energy left. An hour afterward, I bent down to pick something up, stood back up, and felt lightheaded and dizzy.

Those are textbook indicators of AMPK over activation combined with inadequate recovery.

How to Combine MOTS C With Exercise

MOTS C is not a free energy boost. Since it triggers the same AMPK pathway as hard training, the best results come on days when recovery is solid, calories are not heavily restricted, and no other AMPK stressors are being stacked. Reserve MOTS C for training days when you are well fed and well rested. Keep the signal inside the “adaptive” zone rather than the “overstressed” zone, at a point when your mitochondria have the capacity to respond, instead of adding stress upon stress.

 

[jmon1977]

Researcher6076 said:

jmon1977 said:

MOTS-C is something I normally use 20-30 minutes ahead of training. What I've run into is that occasionally, while I'm working out, a pretty severe breathing difficulty hits me. The pattern seems to show up mainly on the heavier days (Legs/Back). Eventually it fades, but I'm wondering whether anyone else has experienced this same response? What time do you use your MOTS-C?

Also, I'm not on the high end of MOTS-C dosing the way some people are. My intake is 1-2 mg/day.

jmon1977 said:

MOTS-C is something I normally use 20-30 minutes ahead of training. What I've run into is that occasionally, while I'm working out, a pretty severe breathing difficulty hits me. The pattern seems to show up mainly on the heavier days (Legs/Back). Eventually it fades, but I'm wondering whether anyone else has experienced this same response? What time do you use your MOTS-C?

Also, I'm not on the high end of MOTS-C dosing the way some people are. My intake is 1-2 mg/day.

Turbo-Farmer said:

jmon1977 said:

Turbo-Farmer said:

My experience goes the other way. Every morning before work I go running with my dog, and it feels like my pace has gotten quicker compared to how it was before I started the mots-c.

According to my Fitbit, my v02 max has gone up from 39 to 43

My wind is better than it used to be

Do you dose MOTS right before going for a run? Since I don't do any high intensity cardio, I've got nothing to compare it against. On days when I'm not training, taking it causes no issues for me. The problem shows up almost exclusively when I use it shortly before lifting heavy weight. Looks like my only option is to begin dosing much earlier ahead of my workout.

I've gone running daily for 30 months straight. My dog makes sure of it — we're out the door each morning, whether it's raining or sunny. So everything I do fits around that routine. Getting to the gym is harder for me than running up the mountain in the woods behind my house.

MOTS C Wrecked My Training Sessions — The Explanation

Taken before a workout, MOTS C is meant to deliver an energy lift. Yet at times what I got was the reverse. To figure out why, I had to look into the biology, and what I found was that MOTS C only works properly when it matches what is already happening inside your body.

MOTS C = AMPK Stressor

AMPK gets switched on by MOTS C, and that is the very same cellular energy stress pathway that exercise sets off.

•Hard training puts stress on your mitochondria.

•AMPK is activated by that stress.

•From there, AMPK pushes adaptation toward better mitochondrial efficiency, improved fuel use, and occasionally a burst of energy partway through a workout, an AMPK shift.

But There’s a Limit: Overtraining

If you have overtrained, you know the feeling: you turn up at the gym, and your body just refuses to cooperate. Fatigue, sluggishness, and less strength than the previous day.

Your AMPK has been stressed beyond its limit and has not bounced back. Mitochondria can only tolerate so much AMPK activation before they resist and signal, “enough.”

What Stresses AMPK?

•Exercise that is intense or done often

•Calorie deficit / fasting

•Medications such as metformin (prescribed for diabetes and sometimes for longevity)

•MOTS C itself

On its own, each one can be handled. The trouble starts when they are stacked.

My Mistake: I Was Stacking Everything

All of these were happening at once:

•Frequent, intense workouts

•A mini cut with an ongoing calorie deficit

•Metformin for longevity

•And on top of that, I introduced MOTS C

One of those alongside MOTS C might have been fine, but not the whole set together: for MOTS C that amounts to a full contraindication, since AMPK gets pushed beyond what recovery can absorb.

The Results Were Ugly

Midway through, I had to abandon the workout. There was simply no energy left. An hour afterward, I bent down to pick something up, stood back up, and felt lightheaded and dizzy.

Those are textbook indicators of AMPK over activation combined with inadequate recovery.

How to Combine MOTS C With Exercise

MOTS C is not a free energy boost. Since it triggers the same AMPK pathway as hard training, the best results come on days when recovery is solid, calories are not heavily restricted, and no other AMPK stressors are being stacked. Reserve MOTS C for training days when you are well fed and well rested. Keep the signal inside the “adaptive” zone rather than the “overstressed” zone, at a point when your mitochondria have the capacity to respond, instead of adding stress upon stress.

Thanks — that was a good read and full of useful detail. As for me, I wouldn't go so far as to say MOTS-C has wrecked my performance. I follow progressive overload and I'm still setting PRs on a regular basis. The only thing I run into is breathlessness, and it tends to show up right after the heavy compound movements (those are normally what I do 1st in a session). So I changed my timing: instead of dosing right before training, I now take it a couple of hours ahead, and that appears to have cleared up the problem.

 

[Turbo-Farmer]

jmon1977 said:

Researcher6076 said:

jmon1977 said:

MOTS-C is something I normally use 20-30 minutes ahead of training. What I've run into is that occasionally, while I'm working out, a pretty severe breathing difficulty hits me. The pattern seems to show up mainly on the heavier days (Legs/Back). Eventually it fades, but I'm wondering whether anyone else has experienced this same response? What time do you use your MOTS-C?

Also, I'm not on the high end of MOTS-C dosing the way some people are. My intake is 1-2 mg/day.

jmon1977 said:

MOTS-C is something I normally use 20-30 minutes ahead of training. What I've run into is that occasionally, while I'm working out, a pretty severe breathing difficulty hits me. The pattern seems to show up mainly on the heavier days (Legs/Back). Eventually it fades, but I'm wondering whether anyone else has experienced this same response? What time do you use your MOTS-C?

Also, I'm not on the high end of MOTS-C dosing the way some people are. My intake is 1-2 mg/day.

Turbo-Farmer said:

jmon1977 said:

Turbo-Farmer said:

My experience goes the other way. Every morning before work I go running with my dog, and it feels like my pace has gotten quicker compared to how it was before I started the mots-c.

According to my Fitbit, my v02 max has gone up from 39 to 43

My wind is better than it used to be

Do you dose MOTS right before going for a run? Since I don't do any high intensity cardio, I've got nothing to compare it against. On days when I'm not training, taking it causes no issues for me. The problem shows up almost exclusively when I use it shortly before lifting heavy weight. Looks like my only option is to begin dosing much earlier ahead of my workout.

I've gone running daily for 30 months straight. My dog makes sure of it — we're out the door each morning, whether it's raining or sunny. So everything I do fits around that routine. Getting to the gym is harder for me than running up the mountain in the woods behind my house.

MOTS C Wrecked My Training Sessions — The Explanation

Taken before a workout, MOTS C is meant to deliver an energy lift. Yet at times what I got was the reverse. To figure out why, I had to look into the biology, and what I found was that MOTS C only works properly when it matches what is already happening inside your body.

MOTS C = AMPK Stressor

AMPK gets switched on by MOTS C, and that is the very same cellular energy stress pathway that exercise sets off.

•Hard training puts stress on your mitochondria.

•AMPK is activated by that stress.

•From there, AMPK pushes adaptation toward better mitochondrial efficiency, improved fuel use, and occasionally a burst of energy partway through a workout, an AMPK shift.

But There’s a Limit: Overtraining

If you have overtrained, you know the feeling: you turn up at the gym, and your body just refuses to cooperate. Fatigue, sluggishness, and less strength than the previous day.

Your AMPK has been stressed beyond its limit and has not bounced back. Mitochondria can only tolerate so much AMPK activation before they resist and signal, “enough.”

What Stresses AMPK?

•Exercise that is intense or done often

•Calorie deficit / fasting

•Medications such as metformin (prescribed for diabetes and sometimes for longevity)

•MOTS C itself

On its own, each one can be handled. The trouble starts when they are stacked.

My Mistake: I Was Stacking Everything

All of these were happening at once:

•Frequent, intense workouts

•A mini cut with an ongoing calorie deficit

•Metformin for longevity

•And on top of that, I introduced MOTS C

One of those alongside MOTS C might have been fine, but not the whole set together: for MOTS C that amounts to a full contraindication, since AMPK gets pushed beyond what recovery can absorb.

The Results Were Ugly

Midway through, I had to abandon the workout. There was simply no energy left. An hour afterward, I bent down to pick something up, stood back up, and felt lightheaded and dizzy.

Those are textbook indicators of AMPK over activation combined with inadequate recovery.

How to Combine MOTS C With Exercise

MOTS C is not a free energy boost. Since it triggers the same AMPK pathway as hard training, the best results come on days when recovery is solid, calories are not heavily restricted, and no other AMPK stressors are being stacked. Reserve MOTS C for training days when you are well fed and well rested. Keep the signal inside the “adaptive” zone rather than the “overstressed” zone, at a point when your mitochondria have the capacity to respond, instead of adding stress upon stress.

Thanks — that was a good read and full of useful detail. As for me, I wouldn't go so far as to say MOTS-C has wrecked my performance. I follow progressive overload and I'm still setting PRs on a regular basis. The only thing I run into is breathlessness, and it tends to show up right after the heavy compound movements (those are normally what I do 1st in a session). So I changed my timing: instead of dosing right before training, I now take it a couple of hours ahead, and that appears to have cleared up the problem.

Because my test results came back showing pre-diabetes, I am extremely cautious about metformin and any other medication that could drive my blood sugar down. My PCP advised against combining metformin with tirzepatide, since doing so could drop your blood sugar level too far. I still have more than a year's supply sitting in my medicine cabinet, since the side effects were more than I could tolerate.

Newer studies have shown that metformin might cancel out part of what aerobic exercise gives you.

The thinking is that these opposing effects occur because metformin works on mitochondria to bring oxidative stress down, which, oddly enough, ends up blocking the cellular adaptations that exercise promotes, including a rise in mitochondrial activity.

The NIH article is attached below my summary

Key Benefits Negated by Metformin:

• Aerobic Fitness & Fitness Gains:Participants combining exercise with metformin showed reduced VO2max (aerobic capacity) improvements, indicating limited progress in cardiovascular fitness.
  
• Vascular Function: Metformin reduces the improvements in blood vessel dilation and blood flow, which are crucial for lowering blood pressure and enhancing muscle insulin sensitivity.
  
• Cardiometabolic Health: The combination may hinder improvements in insulin sensitivity, reduce fat mass loss, and limit the reduction of inflammatory markers and fasting glucose levels.
  
• Muscle Adaptations: Metformin can inhibit mitochondrial adaptations and slow muscle hypertrophy in response to resistance training, particularly in older adults.

Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults