The Mitochondrial Master Switch: Rethinking Cellular Energy as the Locus of Chronic Disease

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#25

The problem (forgetting the expense) is the short half-life of SS-31. We need something that does the same thing with a longer half-life. I hope someone is working on this.

The elimination half-life of subcutaneously (SC) injected SS-31 (elamipretide) in the human body is approximately 2 hours.

Key pharmacokinetic details for SC administration in humans include:

  • Absorption: Peak plasma concentrations are typically reached within 0.5 to 1 hour after injection.
  • Bioavailability: The absolute bioavailability of a subcutaneous dose is high, at approximately 92%.
  • Distribution: It is distributed throughout total body water with a volume of distribution of roughly 0.5 L/kg and approximately 39% protein binding.
  • Metabolism & Elimination: It undergoes sequential C-terminal degradation into inactive metabolites (M1 and M2). Roughly 100% of the dose and its metabolites are recovered in the urine within 48 hours in individuals with normal renal function.
  • Accumulation: There is minimal accumulation of the parent drug with standard once-daily dosing.

Here is some prescription dosing information. Ref

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#26

That is an issue, but it still works for Barth’s syndrome. So half-life is not an impediment for that condition.

This is also why I split my high dose 20mg per day into 2 injections of 10mg, morning and night. with a 5 day cycle. Total 100mg used

I’m currently into about day 20 of a 30 day low dose (3.33mg per day) routine.

Keep in mind this compound “fixes” a particular problem in mito’s that themselves have 5 to 11 day life. With this kind of turnover, repairing the damaged mito’s and getting rid of the damaged mito’s, then replacing the old with new mito’s ones is still “probably” a benefit,

I see this as a 2 or 3 step process.

  1. repair existing damaged mito’s with a high dose cycle
  2. support mitophagy and production of healthy new ones
  3. do this in cycles for “normal” people that are aging.

I don’t think it would be necessary to do this as a daily intervention to get some benefit.

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#27

Because they work very differently, I don’t know that it matters. But I’d probably start with the SS 31.

If I had any indication of CKD I’d be taking a GLP1-ra. - see page 6 of this PDF.

GLP1-RA - how do they work, explain the science, u.pdf (846.2 KB)

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#28

I had never heard of that particular syndrome because:

Barth syndrome (BTHS) is an ultra-rare, life-threatening genetic disorder that primarily affects males. It is a multisystem metabolic condition characterized by heart problems, muscle weakness, and a weakened immune system.
Ref1

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#29

This is the mitochondrial condition that SS 31 is FDA approved to treat and where all the good data comes from.

Barth syndrome is a genetic mitochondrial disorder in which defective remodeling of the phospholipid cardiolipin disrupts many aspects of mitochondrial structure and function, especially in heart and skeletal muscle cells

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#30

Hard to say much on this in one post… Being a member of Alex Kikels TPC-Army skool, $200/mo, Anthony Castor’s Skool (free and super excellent coach), and Chris Duffin’s Skool, free and decent, and off course Hunter/Campbell on youtube;

There is not one dose fits all for any of the peptides especially the mitochondrial family; MOTSC, SS-31. Small molecules SLU-pp-332, 5AminoMq and probably more. There is a point where the mito can be over stimulated and you experience a caffeine like brain fog / and over stimulation. So more is not better especially when adding in SLU and maybe BAM15 which are amplifiers.

I’ve learned that the personal dosing, protocol, is layered, cycled, and slowly built up. Finances can be the limiitor. Unless you buy from places like nexaph.com or even closer to China, then SS-31 in the mgs’s /day are possible, but with likely over doing it.

Folks can say peptides dont work. And that may be true for them at the doses and at their metabolic health/dis-health/BMI/SAD diet inputs… Lots of bodies are not ready for peptides its a waste. Fix metabolic health first starting with HRT!!! and Lifting some weights and fixing the diet. THEN GLP-1s, in a few months and pounds lost then the mitochondria stacks. I’ll add though its ok to start Urilithin-a any time and possibly continuously. But Kikel will cycle even Urolithin-a… Using epigenetic nudging, hormesis, to stair step health and function up.

Just tersely summarizing a complicated topic of dosing, layering, cycling peptides.

At least join the 2 free Skool groups I know of. Probably a few others that are useful re peptides, health, muscle growth. Kikel’s TPC is not a general tutorial type group. Anthony Castore’s group covers a wide range of topics rifle shots at a time.

A bit of a sales pitch-y peptide/bioregulator education site: https://peptidescienceinstitute.com, I just received their Peptide Master book. An encyclopedia. TBD the value. But its; education for education’s sake at the least. The gap all along is: case studies, dosing protocols combining many inputs to effect a health improvement. Too much talk about just one peptide, one thing.

Best to all, curt

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#31

How do you promote only healthy mitochondria to be replenish? My understanding is that you need some kind of stressor to eliminate the weak ones.

#32

The myopothy model strikes me as an extreme case, a degree of illness that many of us are not contending with yet. The dosing protocol may be different, and much less expensive, for the more generic problems of aging.

That’s what I am trying to do. In one of his videos, Alex Kikel recommends SS-31 specifically for the kidneys. As does Hazel Szeto. I think SS-31in combination with retatrutide would have the most benefit.

40 mg/day, but that’s for Barth syndrome, also an extreme case.

I took a quick look at his group. In my opinion, this is still the best site on the web.

Me either.

There is a wide price range on Amazon, from $25 to $125. Does anyone have a recommendation?

Researchers have also shown that Urolithin B is as biologically active as its sibling. In particular, it reduces fibrosis and improves renal function in rats.

https://www.sciencedirect.com/science/article/pii/S1756464619306723

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#33

Could you do an oral glucose tolerance test? 75g pure glucose at once fasted while wearing a CGM.
That would be a good standard data point.

I did that some time ago to compare glucose handling with and without rapamycin: Hyperglycemia caused by rapamycin

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#34

Since new mito’s are created by the division of existing mito’s, i.e. fusion, then “quality control” through mitophagy is important. As dysfunctional mito will generate more dysfunctional mito’s.

Theoretically if one were to use SS 31 to repair one aspect of a damaged mito, when it comes time to divide and produce new ones. that repaired mito may produce healthier mito’s.?

With respect to MOTS-c

In cell and animal studies, MOTS‑c increases expression of mitophagy‑associated genes such as PINK1, PARK2 (Parkin), and ATG7, alongside genes for mitochondrial biogenesis and fusion, suggesting coordinated activation of mitochondrial turnover

mitophagy and aging (1).pdf (687.9 KB)

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#35

Re Urolithin A I wish I could find the testing report on actual content. Like NMN et al, there’s a wide actual content issue. BUT one can hopefully side step that by going with higher quality vendors: https://www.hansensupplements.com

donotage.com (??). Of course Time Line… ;(

best of luck, curt

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#36

Also in Kikels group, TPC-army, is “The kidney Doc” Fiona Chin. Google for Fiona’s youtube channel, videos. She LOVES klotho for kidney rejuvination. Us TPC members have access to buying a private source of 1-Klotho, a daily dose. A publicly available of a-klotho, dosed every 2 weeks from Biolongevitylabs.com. Fiona is taking the TPC version 300mcg every other day.

Fiona has detailed kidney protocols in her videos, her website (google) and may do consults from here home in Australia.

FWIW, curt

3 Likes
#37

I bought a few of the timeline gummies 50% off (still expensive though, but they are YUMMY)
I also bought Codeage during the big holiday sales.

When I run out, I’ll switch to Neurogan which are priced the best.

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@curt504
“ Could you do an oral glucose tolerance test? 75g pure glucose at once fasted while wearing a CGM.
That would be a good standard data point.”
I’ve never done anything similar to that. I’ve been wearing CGMs on and off for years, and this was the very first time I only went over 140 1 time, which was yesterday. Normally it’s once per day, even on medication.

Today, I’ll put a new CGM on, so I’ll know in couple of days if my CGM from the last two weeks was a fluke.

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#38

I have UA, 98% = $1.50 per gm bulk powder

#39

@Steve_Combi

UA at 98% at $1.50/gr.
Where?

=== SS-31 dosing, MOTSC dosing.

Maybe this Chris Duffin Skool URL will force bringing up a join link then good, its free. This video in Chris’s post is good, worth watching. Jump over the first 20min of small talk.

The Video off the skool post seems to be a public youtube URL: https://www.youtube.com/watch?v=fVJTRUFRpKo

The SS-31 / MOTSC dosing after 1:15hr

8 week cycle of SS-31 at 5mg/day, then MOTSC for 8 weeks at 5mg/day. +/-

This is alot more then I’ve been doing. So I’ll up dosing. At upon waking I do HGH secretagoge: Ipa/CJC/Tesa + SS-31. 300mcg Ipa and CJC/Tesa sits on top at what ever my mix includes. There’s a risk of wasting some secretagoges since the body can’t put out any more then the nudge of Ipa/CJC/Tesa can push. More is wasted. . I’ll up the SS-31 to 3mg ish from 1mg. One should ramp up slowly noticing side effects.

Best to all, curt

curt

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#40

neurogan urolithin A

Great, the red bottle. Thats the one I buy off Amazon for $99/120 caps at 1000mg.

tnx for the chart!!!

No systemic CGM glucose tolarance test. An idea though. Good luck with your CGM use. I just take an SGLT-2, dapa, ALA, dihtydro berberine. I can’t take metformin, makes me feel litharigic. I’m told by the body builders I needd to take 1g AM + PM to get over the hump. Then there’s the issue of metformin being toxic to mitochondria, so I don’t do metformin…

curt

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#41

I sell it, it’s one compound in my MAX5 super mix.

I buy compounds in bulk, been doing that for 5 years.

Ingredient Name Daily Dose - mg
Spermidine 98% 25.0
Ergothionene 99% 20.0
Urolithin A 97% 1000.0
Ca-AKG 100% 800.0
NMN 99.5% 800.0
#42

There are clinical trials on SS 31, have you looked at the doses used in those? much higher with no side effects. I’ve done 20mg per day broken in 2 x 10mg doses, morning and evening for 5 days

Just finished a 30 day SS 31 cycle of 3.33mg per day.

I’ve done 10mg x 2 daily doses of MOTS-c as well for 4 days

Just started a planned 20 day MOTS-c cycle taking 12mg x 2 doses per day. Based on HED doses from mouse trials.

#43

All the clinical trial data, and research papers on SS-31 are in this thread: Hazel Szeto, SS-31 peptide, the World's First FDA-Approved Mitochondria-targeted Drug (Longevity Summit, 2025)

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#44

Provided as 500mg caps so 2 caps = 1000mg for 60 doses at that level.

This bottle contains 60.0gm of UA at $99 = $1.65 per gram which is a very reasonable price.