Fatigue during third week of MOTS-c and whether to keep going

I already follow intermittent fasting with two meals a day, the first around noon and the second after my evening workout. That means the dose at 7 am is taken fasted and the workout is also fasted. I have been low-carb for four years and did a full year of keto so my system is used to pulling energy from fat rather than glucose.

That could be exactly what is happening because I have kept carbs low for years and rarely go above 50 g a day.

Then that is probably the cause. I have stayed between 10 and 25 g daily for six years yet still deal with stubborn blood-sugar problems and cannot reach ketosis. You might get better results from SS-31 instead.

So what do you recommend doing now? Should I raise carbs, keep going with MOTS-c for the full six weeks, and monitor how I feel?

If the low-carb approach has worked well for years I would stay with it. MOTS-c can help when insulin resistance shows up or as a partial stand-in for metformin, but older studies found that lowering calories to around 400 kcal with a low-carb diet produced similar improvements in insulin resistance and glucose control. The peptide itself is fairly stable so storing it for a couple of years should not be an issue.

Could the tiredness simply come from running too large a calorie deficit? On my first cycle I was at 1200 kcal daily and often felt drained. The second cycle came after reaching goal weight and raising calories and that time the energy benefits appeared. There is research on how GLP-1 medications interact with fatigue and calorie restriction.

A calorie deficit certainly does not help but after years at the same intake most people reach equilibrium so the fatigue here seems tied more directly to MOTS-c. Thanks for the reference. Retatrutide has cut my appetite sharply and some days it is hard to hit even 50-60 g of protein. Sodium drops and low blood pressure episodes have increased especially in the heat so electrolytes and a multivitamin have become necessary, yet the overall benefits still make it worthwhile.

Age matters because mitochondrial damage accumulates over time. In my late fifties I felt confident the compounds would help.

One mitochondrial protocol calls for 4 mg of SS-31 daily for six weeks. I ran SS-31 and MOTS-c one after the other. Newer ideas suggest combining them but those come from rat data. If someone is already running low on metabolic resources the peptides can make fatigue worse because they increase mitochondrial output that still has to come from somewhere. Keeping protein and carbohydrate intake adequate seems necessary to get results from the approach.

Whether it is useful depends on age and current health. Under roughly 50 with no heart, liver, or metabolic issues most people will not notice much benefit.

Thanks, that protocol is helpful. I already take 5-amino and NAD so that part is covered. I will pick up some SS-31 and try the six-week plan. For context I turn 62 this month, am generally healthy, and have been losing weight after gaining about 50 lb over thirty years. I have dropped 26 lb so far and am approaching 20 percent body fat, so I thought a mitochondrial reset might be useful.

One note from my experience: 5 mg of MOTS-c felt like too much, almost like rocket fuel, so I settled on 4 mg as the right amount. It also helps to start lower the first week to see how you respond because allergic reactions have been reported. I used 1 mg, then 2 mg, then 3 mg on Monday-Wednesday-Friday during that first week.

I am about to begin MOTS-c and was wondering about dosing. Some people use 2 mg five days a week while others do 10 mg split across three days such as Monday-Wednesday-Friday. Does the schedule itself matter?

I agree with that stack. Mine is almost identical except I use 3 mg of SS-31 every day. At 44 I have not had any fatigue or other side effects and I have noticed steadier energy during the day. Normally I feel drained right after work but lately that has improved.

What dosing schedule did you follow for MOTS-c? I am about to start it along with 2 mg of retatrutide.

The protocols I see online for MOTS-c and NAD+ vary widely. I chose a fairly conservative plan: 5 mg of MOTS-c every five days for a few weeks and a loading week of 50 mg NAD+ daily followed by 50 mg two or three times a week. Most suggestions are higher but I prefer to run my own smaller experiments.

I am not an expert on dosing. Some sources suggest very high amounts like 40 mg a week which gets expensive fast. Others I have spoken with say 2 mg per injection worked for them with modest but noticeable effects. I may increase the dose or stop depending on how things go. I do not understand how the studies used 40 mg three or four times a week because that would empty an entire vial in one go.

I have not heard of anyone injecting 40 mg of MOTS-c in a single day. That amount would be extreme and probably too much for me. My personal limit is 4-5 mg and I followed the protocol at 4 mg three days a week. I have heard of that kind of dosing with SS-31 though, which is a different compound.

I have seen study references to those high amounts but I do not know anyone who could afford them. Even 40 mg a week would be a stretch for me. The protocol you mentioned earlier already sounds intense. I showed it to my training partner and he was interested but wanted me to try it first because I could handle the cost better. Being a test subject is one thing but that schedule feels like too much.

I completed the full 14-week protocol and others have as well. SS-31 is daily while MOTS-c is three times a week so total MOTS-c comes to 15 mg weekly. I am not sure where the 40 mg figure came from because that protocol does not reach it. I have not heard of anyone using that much MOTS-c and it could be risky.