Thoughts on the MITO Stack Protocol? SS-31, MOTS-c, and NAD+

[Jrammi]

Hello - Has anyone tried this with fatigue? I am 60, sleep 6-8 hours nightly, on a Keto diet with one cheat day a week, 15mg Tirz, but switched last week to 10 mg Tirz and 5 mg Reta. I pulled this from another site. Not sure if I am allowed to post links to other sites. TIA.

SS-31	Repairs mitochondrial membranes, reducing electron leak and oxidative damage
MOTS-c	Retrains metabolic signaling — improves fuel flexibility and builds new mitochondria
NAD+	Restores the redox currency cells need for energy production, DNA repair, and longevity enzymes
Protocol cadence	12-week cycles with loading and maintenance phases
Complementary
Primary applications	Fatigue, metabolic dysfunction, injury recovery support, and longevity support What Is a Mitochondrial Peptide Stack?​ This stack combines three compounds that target different aspects of mitochondrial function — structure (SS-31), signaling (MOTS-c), and redox support (NAD+). These are the three layers that determine whether mitochondria can keep up with the work being asked of them. MOTS-c is part of the body's exercise-response system — a peptide mitochondria release during physical stress to reprogram how cells use energy. SS-31 protects the membrane where energy production actually happens, the part that degrades with age, inflammation, and oxidative stress. NAD+ is the redox currency both processes run on, and it declines measurably with age and chronic load. Each addresses a different failure point. MOTS-c tells cells to build better mitochondria. SS-31 keeps existing ones from breaking down. NAD+ makes sure there's enough energy currency to power both. The Three Axes of Mitochondrial Health​ Cardiolipin integrity Anchors electron transport chain Oxidized membranes leak electrons Low ATP, high ROS, inflammation Redox currency (NAD+) Powers enzymes, activates sirtuins Depleted by stress, aging, alcohol Fatigue, DNA damage, metabolic rigidity Adaptive signaling (AMPK → PGC-1α) Drives mitochondrial biogenesis Blunted by cortisol, nutrient overload Slow recovery, weight gain Protocol: 12-Week Mito Stack Cycle​ Weeks 1–2 (loading) 5–10 mg daily × 5–7 days, then 3×/week n/a 100–250 mg IM 2–3×/week Electrolytes, zone-2 cardio Weeks 3–6 5–10 mg 3×/week 5–10 mg 2×/week 100–250 mg IM 2–3×/week Resistance training, protein ≥1.6 g/kg Weeks 7–12 5–10 mg 2–3×/week 5–10 mg 2×/week 100–150 mg IM 1–3×/week Sleep 7–9 hours, glycine + collagen Cycling: 12 weeks on, 4 weeks off. Repeat twice yearly or maintain lighter cadence (SS-31 weekly, MOTS-c pulses, NAD+ 50–150 mg weekly or 2×/week).

 

[eidos]

Ss-31 and MOTS-c are really effective at relieving fatigue. I don't take NAD+ injections because I take NR orally (the bioavailability is good; it just takes a little longer to take effect). I add 5-amino-1-methylquinolinium to it, which is truly magical.
Increase your dose slowly and see what works for you. I'm currently at 5 mg of 2S31; I'm going to cut back to 2.5 mg of MOTS-C when I start the next cycle (too much ISR), and I'm taking 5 mg of 5AMQ because 10 mg isn't having more effect on me.

 

[Crowreap]

Hello - Has anyone tried this with fatigue? I am 60, sleep 6-8 hours nightly, on a Keto diet with one cheat day a week, 15mg Tirz, but switched last week to 10 mg Tirz and 5 mg Reta. I pulled this from another site. Not sure if I am allowed to post links to other sites. TIA.

No, I have not tried this mitochondrial peptide stack, but I am on MOTSC at the moment. Just started four days ago. And really now, I've been researching SS31 and NAD+, and I'm probably gonna add them to my stack now because I've seen a fairly massive difference when I added MOTSC. I'm seeing I get a lot of energy before the gym, and after the gym, I have good sustained energy throughout the day. So I think it only makes sense with me adding SS31 and NAD+ to it.

Also, you being on a keto diet is probably the reason why you are more fatigued than usual. Carbs are not the enemy. If you cut carbs even on GLP-1s, you may not feel any hunger, but you will still feel like you have that super low energy feeling and wanting something to eat feeling because eating something will give you energy. so kinda counterintuitive when using glp1s

 

[Jrammi]

No, I have not tried this mitochondrial peptide stack, but I am on MOTSC at the moment. Just started four days ago. And really now, I've been researching SS31 and NAD+, and I'm probably gonna add them to my stack now because I've seen a fairly massive difference when I added MOTSC. I'm seeing I get a lot of energy before the gym, and after the gym, I have good sustained energy throughout the day. So I think it only makes sense with me adding SS31 and NAD+ to it.

Also, you being on a keto diet is probably the reason why you are more fatigued than usual. Carbs are not the enemy. If you cut carbs even on GLP-1s, you may not feel any hunger, but you will still feel like you have that super low energy feeling and wanting something to eat feeling because eating something will give you energy. so kinda counterintuitive when using glp1s

Thank you. I have been Type 2 Diabetic for 40 years and just never lose weight with carbs in my diet. I am sure you are correct about the reason for the fatigue. I follow my ketosis status using a KetoMojo blood meter.

 

[Crowreap]

Thank you. I have been Type 2 Diabetic for 40 years and just never lose weight with carbs in my diet. I am sure you are correct about the reason for the fatigue. I follow my ketosis status using a KetoMojo blood meter.

Hmm, that's pretty interesting. I think at the end of the day, it has to do with the energy expenditure equation in the body. So like, if you were to burn more calories than you consuming more calories, then you will lose weight, even if the macronutrient profile is different. So I've been testing something out for the past 2 months now ever since I got on reta . And what I do is carb cycle, and it's a 3 day cycle. The first two days are moderate to high carbs (180-220 carbs), and then the last day is low carbs (45-60 carbs) while incorporating dietary fat back into the diet. And then I repeat the 3 day cycle again. Maybe what your body needs is some sort of variety in the macronutrient profile and also be sure to lift weights at the gym consistently and be getting consistent daily protein. Maybe you can try that out cause for me, that keeps good enough carbs in my system overall so I don't experience fatigue on reta and still feel good while losing weight.

 

[Jrammi]

Hmm, that's pretty interesting. I think at the end of the day, it has to do with the energy expenditure equation in the body. So like, if you were to burn more calories than you consuming more calories, then you will lose weight, even if the macronutrient profile is different. So I've been testing something out for the past 2 months now ever since I got on reta . And what I do is carb cycle, and it's a 3 day cycle. The first two days are moderate to high carbs (180-220 carbs), and then the last day is low carbs (45-60 carbs) while incorporating dietary fat back into the diet. And then I repeat the 3 day cycle again. Maybe what your body needs is some sort of variety in the macronutrient profile and also be sure to lift weights at the gym consistently and be getting consistent daily protein. Maybe you can try that out cause for me, that keeps good enough carbs in my system overall so I don't experience fatigue on reta and still feel good while losing weight.

I do carbs on Friday nights, lol. 🙂 I will try this. For example, I was on a Keto diet before entering USMC boot camp. You could see my abs. I went to boot camp, and you have to imagine where you are active, running, and high-intensity exercising, 4-6 hours a day, but I inserted carbs into my diet and gained 15 lbs of fat during boot camp, which is unheard of. Sure, I probably ate too much, but still....