Ss-31 & Mots-c

[Jordaboo]

I am wanting to start Mots-C, after lots of reading it is apparently suggested to do or start a cycle with SS-31 to repair mitochondrial health before starting the. Mots-C or it’s basically a waste.

Any opinions on this subject would be appreciated!

 

[Skidude]

There are many opinions, you can find a lot here: SS31 THREAD

The protocol I have used a few times calls for 5mg SS31 5/2 for 4 weeks than overlap a few weeks with MOTS-C before stopping SS31.

There are those who believe the dosage is too small at 5mg or that the pep is too expensive to use a high enough dose.
I am satisfied with the cycle and "feel" it may have benefitted my long term strategy of optimizing all supplement/peps I use.

Take a look at that thread and I believe @Calm Logic has posted a great deal about this stack as well.

I am currently on the overlap portion of mots on second cycle of ss31/mots and "feel" it was worth the investment on a risk/reward comparison.

I also cut my food budget down by $400+ per month, so ss31 is now my door dash mad money..lol

 

[Jordaboo]

There are many opinions, you can find a lot here: SS31 THREAD

The protocol I have used a few times calls for 5mg SS31 5/2 for 4 weeks than overlap a few weeks with MOTS-C before stopping SS31.

There are those who believe the dosage is too small at 5mg or that the pep is too expensive to use a high enough dose.
I am satisfied with the cycle and "feel" it may have benefitted my long term strategy of optimizing all supplement/peps I use.

Take a look at that thread and I believe @Calm Logic has posted a great deal about this stack as well.

I am currently on the overlap portion of mots on second cycle of ss31/mots and "feel" it was worth the investment on a risk/reward comparison.

I also cut my food budget down by $400+ per month, so ss31 is now my door dash mad money..lol

When I originally searched SS31 in the search bar nothing popped up, than I went into the posts on the side and found it & did some reading!
So so many different opinions on how to dose/stack that’s for certain!
Next thing is finding the SS-31, I can find the mots all day but not the ss-31

 

[Jordaboo]

I see

When I originally searched SS31 in the search bar nothing popped up, than I went into the posts on the side and found it & did some reading!
So so many different opinions on how to dose/stack that’s for certain!
Next thing is finding the SS-31, I can find the mots all day but not the ss-31

I see HK Peptide has it for a decent price, just haven’t seen many reviews on here from that vendor…

 

[Skidude]

When I originally searched SS31 in the search bar nothing popped up, than I went into the posts on the side and found it & did some reading!
So so many different opinions on how to dose/stack that’s for certain!
Next thing is finding the SS-31, I can find the mots all day but not the ss-31

Nexa usually has reasonable prices when you compare 10mg to 30mg kits (theirs is 30mg)

 

[hexagonal]

I didn't notice anything doing the SS-31 -> SS-31/MOTS-C -> MOTS-C stack. I've had no luck with any of the mitochondrial enhancers though, peptide or otherwise.

 

[Calm Logic]

It seems to know if it did help at the cellular level (or how much), you would need expensive testing like an Organic Acids Test or telomere length test, before and after, and even then you wouldn't know for sure.

 

[Skidude]

It seems to know if it did help at the cellular level (or how much), you would need expensive testing like an Organic Acids Test or telomere length test, before and after, and even then you wouldn't know for sure.

my exact thought, how do you quantify this?
I don't know if it helped, but I thought it was worth a shot.

 

[PopTart]

I love ss-31….did 3 months @ 4mg daily pinned at night. Just felt much more alert. I’m also in my early 60s.

Been on mots-c for a month @ 5mg every other day and pinned in the A.M. ….started it when I started the 3rd month of ss-31. Didn’t feel any noticeable difference after being on the ss-31.

Going to add NAD+ on June 1 and run it for a couple months.

 

[TRS123]

I love ss-31….did 3 months @ 4mg daily pinned at night. Just felt much more alert. I’m also in my early 60s.

Been on mots-c for a month @ 5mg every other day and pinned in the A.M. ….started it when I started the 3rd month of ss-31. Didn’t feel any noticeable difference after being on the ss-31.

Going to add NAD+ on June 1 and run it for a couple months.

Hello
58 yr old male subject. Realizing some early age related memory issues just don’t feel as sharp mentally as I used to be. Have been on NAD for 4 weeks now 3x a week have ss-31 on the way should arrive next week. I’m interested in your experiment with ss31. On your protocol are you taking a break after x number of weeks? Did you take daily?

 

[RadicalCrimson]

I started Mots-C at 5mg/day 5/7 for a week, but interrupted to research SS-31. Will resume concomitantly after 10-14 days.
I'm following the 10mg/day for 30 days protocol, common due to being prescribed with a 300mg/6ml vial.
I blend 5 vials of the 30mg kit into a 3ml pen cartridge, use 18-20 units per injection.

 

[RocketGotRobbed]

I don't want to bring anyone down but I can tell you what the human trials of ss31 say. They had 0 luck in the human tests. The mechanism is legit but it just didnt translate to humans the way it did in vitro.

 

[TRS123]

I haven’t seen any cognitive human trials. Good or bad. If you have a link to the study you are referencing please post

 

[Calm Logic]

I don't want to bring anyone down but I can tell you what the human trials of ss31 say. They had 0 luck in the human tests. The mechanism is legit but it just didnt translate to humans the way it did in vitro.

If you are referring to the MMPOWER-3 trial:

Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy: a post hoc analysis of the MMPOWER-3 trial - Orphanet Journal of Rare Diseases

Background As previously published, the MMPOWER-3 clinical trial did not demonstrate a significant benefit of elamipretide treatment in a genotypically diverse population of adults with primary mitochondrial myopathy (PMM). However, the prespecified subgroup of subjects with disease-causing...

ojrd.biomedcentral.com

"Post hoc analyses indicated that elamipretide had a beneficial effect in PMM patients with mtDNA replisome disorders, underscoring the importance of considering specific genetic subtypes in PMM clinical trials. These data serve as the foundation for a follow-up Phase 3 clinical trial (NuPOWER) which has been designed as described in this paper to determine the efficacy of elamipretide in patients with mtDNA maintenance-related disorders."

Human studies of SS-31 with good results:

https://www.jacc.org/doi/abs/10.1016/j.jacbts.2018.12.005

"Treatment of explanted human hearts with elamipretide [SS-31] improves human cardiac mitochondrial function."

https://www.ahajournals.org/doi/full/10.1161/CIRCINTERVENTIONS.117.005487

"During PTRA, patients were assigned randomly to either elamipretide (0.05 mg/kg per hour, n=6) or identically prepared placebo (n=8) infusion, which started 30 minutes before PTRA."

"Adjunctive elamipretide during PTRA was associated with attenuated postprocedural hypoxia, increased RBF, and improved kidney function in this pilot trial. These data support a role for targeted mitochondrial protection to minimize procedure-associated ischemic injury and to improve outcomes of revascularization for human atherosclerotic renal artery stenosis."

Similarly, a dog study with good results for heart failure:

https://www.ahajournals.org/doi/full/10.1161/CIRCHEARTFAILURE.115.002206

"Long-term therapy with elamipretide improves LV systolic function, normalizes plasma biomarkers, and reverses mitochondrial abnormalities in LV myocardium of dogs with advanced HF. The results support the development of elamipretide for the treatment of HF."

 

[RocketGotRobbed]

If you are referring to the MMPOWER-3 trial:

Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy: a post hoc analysis of the MMPOWER-3 trial - Orphanet Journal of Rare Diseases

Background As previously published, the MMPOWER-3 clinical trial did not demonstrate a significant benefit of elamipretide treatment in a genotypically diverse population of adults with primary mitochondrial myopathy (PMM). However, the prespecified subgroup of subjects with disease-causing...

ojrd.biomedcentral.com

"Post hoc analyses indicated that elamipretide had a beneficial effect in PMM patients with mtDNA replisome disorders, underscoring the importance of considering specific genetic subtypes in PMM clinical trials. These data serve as the foundation for a follow-up Phase 3 clinical trial (NuPOWER) which has been designed as described in this paper to determine the efficacy of elamipretide in patients with mtDNA maintenance-related disorders."

Human studies of SS-31 with good results:

https://www.jacc.org/doi/abs/10.1016/j.jacbts.2018.12.005

"Treatment of explanted human hearts with elamipretide [SS-31] improves human cardiac mitochondrial function."

https://www.ahajournals.org/doi/full/10.1161/CIRCINTERVENTIONS.117.005487

"During PTRA, patients were assigned randomly to either elamipretide (0.05 mg/kg per hour, n=6) or identically prepared placebo (n=8) infusion, which started 30 minutes before PTRA."

"Adjunctive elamipretide during PTRA was associated with attenuated postprocedural hypoxia, increased RBF, and improved kidney function in this pilot trial. These data support a role for targeted mitochondrial protection to minimize procedure-associated ischemic injury and to improve outcomes of revascularization for human atherosclerotic renal artery stenosis."

Similarly, a dog study with good results for heart failure:

https://www.ahajournals.org/doi/full/10.1161/CIRCHEARTFAILURE.115.002206

"Long-term therapy with elamipretide improves LV systolic function, normalizes plasma biomarkers, and reverses mitochondrial abnormalities in LV myocardium of dogs with advanced HF. The results support the development of elamipretide for the treatment of HF."

No, I was referring to studies directly on humans. Not isolated mitochondria, not animal tests and not in vitro. We spent a few weeks in 2023 reviewing SS-31 and were unable to locate one test that confirmed success in humans. Granted we only searched, Eastern Europe and Southeast Asia. So there may be some out there that we didn't find. Don't get me wrong, I said the mechanism is legit, as I have read through most of the studies you shared. I don't dispute the mechanism, I just have not been able to verify actual human response. I will read thhrough that middle one you shared there as it is a new one to me. It looks promising.

 

[RocketGotRobbed]

I haven’t seen any cognitive human trials. Good or bad. If you have a link to the study you are referencing please post

There are several. I do not remember it but a google scholar search or if you have access to a scientific library like we do, should yield them. It was study on people with mitochondrial myeopathy, speciifically i believe it was inherited. The only success at all was slight and it was only in people who had a specific mutation of a specific cardiolipin. For all others, it failed. That does not mean that the mechanism is not intact but for its intended purpose, it failed. There is another one that shows it was beneficial for eyes, but since ss-31 targets cardiolipins specifically and in the human study looking for repair to cardiolipins, it only worked in people with a specific mutation.

https://www.sciencedirect.com/science/article/pii/S2666914524001647

There was also one that showed it helped a fetus in utero that was diagnosed with Barth as well. So, I mean, it does something, it just hasn't shown that it will do the thing we take it to do.

 

[lessthanhalf]

Unlike a lot of the available peptides, ss-31 has had multiple human trials. The problem was that they were not successful, not that they had no effect, but they did not achieve what was expected, and generally had minor improvements, this is especially the case when it was tried for problems that were not specific genetic mitochondrial dysfunction disorders, such as to reduce macular degeneration ( ReCLAIM (1 and 2)), to reduce heart failure after myocardial infarction ( EMBRACE-STEMI ), and to improve heart failure , ( PROGRESS-HF ). This sort of not very impressive clinical trial result usually results in abandoning it as a drug development candidate. or maybe trying it for some other disorder that looks promising when tested in rodents. This article has a good summary especially part 5 table 2. Unfortunately this is what happens to most interesting substances that show promising effects in the lab, or in mice , and in early human trials.
https://www.mdpi.com/1422-0067/26/3/944
The trials do indicate that it is generally safe, with minor side effects and the most serious adverse effect was urticaria in one patient.

 

[Calm Logic]

I was impressed with the dog study. We are obviously closer to dogs than mice.

From the review @lessthanhalf mentioned:

Table 1. Summary of the main preclinical studies investigating the properties of Elamipretide.

Model	Design	Results	Interpretation
Cardiovascular Disease	Preclinical studies in animal models of heart failure.	Chronic therapy improved LV function, reduced LVESV, increased EF, stroke volume, and cardiac output, while reversing mitochondrial dysfunction, hypertrophy, and fibrosis. Skeletal muscle mitochondrial function and morphology were also restored.	The intervention stabilizes cardiolipin, improves energy production, and prevents pathological remodeling, suggesting potential for treating heart failure and post-MI cardiac dysfunction.
Renal Disease	Murine models of ischemia–reperfusion injury and diabetic nephropathy.	The intervention reduced oxidative stress, restored ATP levels, and protected mitochondrial structure, leading to decreased kidney injury and fibrosis.	The results highlight the ability to mitigate acute and chronic kidney injury by improving mitochondrial function, offering therapeutic potential for renal diseases.
Neurodegenerative Disease	Murine models of Alzheimer’s and Parkinson’s diseases.	Treatment protected against amyloid-beta toxicity in Alzheimer’s models and preserved dopaminergic neurons in Parkinson’s models, improving mitochondrial function and reducing oxidative stress.	The intervention indicates neuroprotective potential by mitigating mitochondrial damage, offering promise for slowing neurodegeneration in Alzheimer’s and Parkinson’s diseases.

Table 2. Main clinical trials testing Elamipretide.

Name	Design	Results	Interpretation	Ref(s).
EMBRACE-STEMI	Multicenter, randomized, double-blind Phase 2a study in first-time anterior STEMI patients undergoing PCI for proximal or mid-LAD artery occlusion. Dose: 0.05 mg/kg/h for 1 h.	No reduction in myocardial infarct size; however, a reduced incidence of chronic heart failure was observed within 24 h post-PCI.	While Elamipretide did not impact infarct size, its potential to reduce chronic heart failure warranted further investigation into its cardioprotective effects.	[49]
PROGRESS-HF	Randomized, double-blind, placebo-controlled Phase 2 trial assessing left ventricular function in patients with stable HFrEF. Dose: 4 or 40 mg.	The primary endpoint (LVESV reduction) was not met; mitochondrial function and quality of life showed improvements, though secondary cardiac parameters were unchanged.	Longer therapy duration or evaluation during exercise may better capture the benefits of Elamipretide, particularly for cardiac remodeling and mitochondrial dynamics.	[50]
TAZPOWER	Randomized, double-blind, placebo-controlled crossover study in Barth syndrome, followed by a 168-week open-label extension. Dose: 40 mg.	Significant improvements in skeletal muscle strength, cardiac stroke volume, fatigue scores, and cardiac parameters (SV, LVEDV, LVESV) were observed.	Sustained efficacy and tolerability highlight the potential of Elamipretide as a therapy for Barth syndrome, with further research needed in younger patients.	[51]
ReCLAIM (1 and 2)	Randomized, double-blind, placebo-controlled Phase 2 trial in patients with dry AMD. Dose: 40 mg.	Primary endpoints (visual acuity and geographic atrophy area) were not met, but progressive EZ degradation, a predictor of vision loss, was slowed.	Elamipretide may preserve photoreceptor function by protecting mitochondria, potentially slowing AMD progression.	[52,53,54]
MMPOWER-3	Randomized, double-blind, placebo-controlled Phase 3 trial in patients with genetically confirmed PMM. Dose: 40 mg.	Primary endpoints, including 6MWT, were not met; however, reduced fatigue was reported, particularly in participants with DNA defects.	Subgroup benefits in DNA-related PMM highlight the need for targeted trials to confirm the efficacy of Elamipretide in specific genetic variants. Further investigations are needed to explain why some endpoints were not met.	[55]

 

[RocketGotRobbed]

I was impressed with the dog study. We are obviously closer to dogs than mice.

From the review @lessthanhalf mentioned:

The dog studies is always where I tend to first.