#41

Well, my personal rule is to try to stay as close as possible to administration methods that are used in studies. They aren’t giving mice tiny little mouth sprays and telling Stewart Little to hold it under his tounge.

I’d ask her what data give her confidence in her approach.

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#42

I’m in email contact with Hazel Szeto. I’ll ask her about this. My gut feeling is that she’s not too predisposed to needles and feels that taking 5mg sublingually “might” be effective, and the cost is not an issue as its a research expense (she’s probably accumulated lots of samples as part of the lab testing process). It’s a different calculus for people buying it at retail prices.

Anyway - I’ll get back to you when I hear more.

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#43

I used PGB’s SS31 for my trials. No complaints, good service. A bit of a funky web shop but easy once you get the hang of it.

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#44

Given the cost of SS-31, finding the dose that gives the best benefit to cost ratio is going to be important for most of us. Could you ask her, how she arrived at a 5mg dose? Other than the initial dose escalation study that went up to 0.25mg/kg, all of the studies using sub-q administration have used a fixed dose of 40mg/day. Another question would be dose vs age - should dose vary with age? Since SS-31 is more effective the older you are, does that mean the dose could be lower as you get older, or does that mean you could effectively take advantage of a higher dose? Does baseline mitochondrial function (for a given age) affect the effectiveness of SS-31? For example, consider the difference in muscle mitochondria in a 60 year old type-II diabetic vs the 60 year masters endurance athlete. Would SS-31 be equally effective in both of these cases?

#45

QSC has 10x50mg for $300, US Domestic in stock, but it tested at 45. Still good

Screenshot_20251212-071311
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#46

In the clinical trials SS 31 was administered by IV drip over 2 to 4 hours. So the 0.25mg people see is NOT the dose, it’s 0.25 mg/kg/hour

NOTE per hour…

At 4 hours that’s 1mg per kg of body weight, for me that would be 64mg. NOT 16mg

When I see a successful trail I ask 2 questions,

  1. what is the dose that worked
  2. how was it administered

Those are the 2 most important things to take away if one is going to do an N-1 experiment.

SS 31 is NOT orally bioavailable and I seriously doubt you could pump enough up ones nose to make it work in that manner either.

It is used at a relatively HIGH dose compared to many of the other peptides used by “researchers”. Anyone doing less that the clinically proven dose is probably wasting their money.

I compromised when I used it, was not gong to do an IV, so I broke my compromised daily dose of 20mg into 2x subQ doses of 10mg

Over a 5 day period I used 100mg (20mg x 5) - nexpah price for that = $425 / 3 = $142 same as what I charge. I charge by the mg and people can buy as much or as little as they want, from 1mg or 500mg, same price $4.25 per mg.

Again, anyone using less than the clinically proven effective dose is most likely experiencing the placebo effect. And wasting their money.

The placebo effect is very powerful and one of the reasons it takes so long to determine if a drug actually works.

In Phase 1 and 2 trials the objectives are to determine tolerability and safe dosing as well as a result. There is a lot of placebo effect in the early Phases, typically over 70%.and this effect drives the drug candidate forward, the researchers know this.

To reduce this effect then we see the results of RCT’s with double blind trials in large groups. Even then the placebo effect is strong as the participants know they are in a trail, they just don’t know if they are getting the real thing or the fake.

About 1% of drug candidates get approval. I feel that the placebo effect is costing us time and money in the process but how can that be eliminated?

For example, this is why AOD 9604 failed to make it to the approved drug stage. It showed “promise” in the early phases and failed in the Phase 3 trials. Abd yet I sell a fair bit of this to people who believe it’s the best weight loss product on the market. I provide them with the evidence it’s not and yet they swear by it.

Same goes for NAD - it is not used by the body the way it’s promoted on the 'net, it just cannot work, the biology and science completely dispels that myth and yet I still have clients who swear by it even after reading the evidence I give them. This one I attribute to “confirmation bias”. - I get this back, “clinics are charging $500 for a 2 hour IV drip, it must be working or people would not go back for more, so it works for me”

That particular bias is based on - “I spent $500 on this (anything) and it really works” few people want to admit they are getting fleeced.

SS 31 was administered by IV drip over 2 hours. (1).pdf (295.3 KB)

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#47

This is helpful info Steve, thanks.

So, the higher doses make sense, especially because you’ve done it and are still alive to type about it :slight_smile:

How often-ish do you do these 5 day rounds?

Do you know if each round is helping things improve… additive

Or is it that things then go back to your baseline and future rounds are just to start over and make improvements again.

#48

My initial interest was the potential cardio benefit as various CVD’s existed in my parents and myself. I didn’t expect much else as I’m pretty OK in most things or so I thought.

I’ve only done 2 cycles so far and I noticed a difference in a couple days on the 2’nd cycle.

  1. Sept 14 - first cycle (10mg per day for 10 days = 100mg) a low dose test run to evaluate my response no side effects
  2. Oct 1. - second cycle (10mg x 2 per day for 10 days = 200mg)

Did not notice much the first cycle.

For the second cycle it was an increase in overall physical energy, and more importantly mental acuity and mental energy. With a very welcome effect on longer focus time on deep work. Deep work for me is probably pretty shallow for some in this group :slight_smile: but I had really lost that over the past 4 or 5 years.

Because these 2 cycles were close together there was probably a bit of an priming and increase in blood plasma levels? as the gap was 2 weeks.

Any lasting benefit? I think it has faded. That’s about 8 weeks post cycle 2.

Next week will be cycle 3 and I’ll shorten the time to cycle 4 from 8 weeks to 6 weeks.

Interestingly studies show no benefit for young healthy people. But for older folks it does provide benefits, I guess you can’t fix what is not broken and you cannot improve an already functional thing with this peptide.

This cycle will include my wife so we will go through 400mg in 10 days.

This is half the dose approved for Barth syndrome, and over a much shorter period, where they used 40mg per day for 12 to 24 weeks which would cost a lot !!

1 Like
#49

This is a rare instance that being a tiny person is in my favor $$$$!!!

And yes, CVD is most of my interest as well… and then it’s apoe4 stuff (I figure my odds of dropping dead before apoe4 hits me is greater :slight_smile: … champagne problem?

Thank you!!!

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#50

I’m also considering a maintenance dose between the 20mg x 5 day cycles.

In between the 20 mg cycles I’d consider going for 2mg per day dose after this 3rd cycle, that would then be 2mg x 2 people = 4mg per day for 40 days = 160mg

I really did like the effect LoL! I’m my own best customer :rofl:

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#51

#1 rule of being a profitable drug dealer is ‘don’t get high on your own supply’

do I have to teach you EVERYTHING? :slight_smile:

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#52

I disagree here. The 40mg dose was chosen because they are treating a very sick population (Barth syndrome) with severe mitochondrial dysfunction. The pharma company chooses a high dose with sick patients in order to maximize the chances of seeing as large an effect as possible over as short of a time period as possible. Using it for anti-aging purposes and/or for other disorders with less severe mitochondrial dysfunction and for a longer time period could very well have significant benefits. We won’t know for sure without studies, but it’s certainly plausible.

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#53

I don’t disagree :slight_smile:

Treating a specific condition, with a specific dose is a solid consideration. It appears the high dose schedule is working for Barth and over an extended period of time of 24 weeks and still ongoing, this also establishes a modicum of safety.

This provides a bit of confidence to try other doses and why I’m taking half the dose (20mg) and for a much shorter period of time.5 days verses 24 weeks.

I now know I responded to 20mg per day but not 10mg per day in a 5 day cycle. Next step I’ve outlined above.

Personally I prefer guarantees of performance, just ask my wife of 50 years LoL! or don’t, cause I do want to live longer…

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#54

Ok - I received some feedback from Hazel Szeto on the bioavailability issue. I sent her my Gemini analysis that suggested peptides are not going to be bioavailable at much over 1% to 3% vs. the injection delivery method.

Here is her response:

As for what you found on Gemini, not all peptides are the same. SS-31 does not behave like other generic peptides, and that was what led me to 20 years of work. Just like the way the longevity doctors were discussing about using peptides in their practice, I am dumbfounded by the naïveté that all peptides behave the same way.

She’s definitely the world expert on SS31 (probably one on peptides in general too), so I now view “sublingual” as worth a try.

All of which I view as basically good news. I really doubt I’d get my father to do the injection method (much too biohackerish), and I’m even a question mark on these types of injections. I can definitely get him to try the sublingual approach. Even it its only 10% as bioavailable, I’d view it as a win because the alternative is zero.

I just stumbled upon this recent article on Dr. Szeto and her peptide discoveries:

and an older 2009 story:

Pharmacologist Szeto pioneers tiny compounds with big potential

Hazel Szeto, M.D., Ph.D. '77, professor of pharmacology at Weill Cornell Medical College (WCMC), was studying opioid receptors in the brain when her moment of serendipity struck years ago.

Now, following a path that began with one curious result, her research has branched out in directions she never would have predicted – and it could lead to a new class of drugs to treat conditions ranging from heart attacks and strokes, to diabetes and neurodegenerative diseases.

Szeto’s research centers on mitochondria, the organelle in every cell that produces energy in the form of ATP. Besides producing ATP, the mitochondrial electron transport chain also produces free radicals, and mitochondria are particularly vulnerable to damage by free radicals. Mitochondrial damage can cause a cascade of cellular reactions and ultimately lead to cell death by apoptosis or necrosis. Mitochondrial oxidative stress is thought to be the underlying cause of aging.

Szeto and her colleagues are developing new compounds that work in two ways: by promoting electron transfer and reducing free radical production by mitochondria, and by protecting the mitochondria against free radical damage. The compounds are small peptide molecules (Szeto-Schiller peptides) that easily penetrate into all cells and concentrate in the inner membrane of mitochondria where the electron transport chain resides. These compounds are simple to synthesize and can be administered easily with no need for an elaborate drug delivery mechanism.

So far, the researchers have shown the compounds to be effective in prevention and treatment of injury to heart, brain and kidney tissue after disrupted blood flow; insulin resistance; diabetic complications; neurodegenerative disorders such as Parkinson’s disease and Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig’s disease); heart failure; and muscle wasting associated with mechanical ventilation or long periods of immobilization.

Read the full story:
https://ezramagazine.cornell.edu/update/April11/EU.Szeto.profile.html

Here are all her research papers… mostly on peptides:

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#55

To be fair her answer seems a bit vague. Given her expertise on the matter, I would have appreciated a more direct answer from her, something like a % of absorption rather than just saying SS31 is different from other peptides. I guess we have to take her word for it…

I hear you about the needle part not being very appealing to your father, and I was actually one of those guys, I hate needles, but I mustered enough bravery LOL to try the insulin needles (the 31-gauge 1/4-inch length ones) and I’m glad I tried it. I have literally never felt the needle breaking/entering the skin and there were times I was pinning/microdosing a lot of peptides (10-20 times per day). I actually experimented with the 30 gauge and even such a small difference I did feel the pin on couple occasions.

So, you shouldn’t give up just yet LOL (with the 31 gauge) since that is a sure way to guarantee optimal/maximum absorption.

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#56

Wow on the above. I’m SOLD!! Thank you for following up with her.

Ok, so I AI’d (my new term instead of saying googled)

“For an oral spray (sublingual or mouth spray) using grey market SS-31 peptide, reconstitute the lyophilized powder with sterile saline (0.9% sodium chloride) or distilled water, then transfer to a clean glass nasal/mouth spray bottle. This mirrors DIY nasal spray protocols adapted for oral use, as SS-31 shows water solubility and some mucosal absorption potential”

IF AI is correct, we can mix it with saline or distilled water. Distilled water sounds like it would taste better?

And, the big question is:

Based on her expertise, we can now feel confident that sublingual is fine.

But, is it more effective, equal, or less effective if given sub q?

Like @Kelman, insulin needles are easy peasy for me, so I ask this in the spirit of making my money go the farthest.

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#57

I have to assume that the mechanism of action is the same regardless of the method, with the difference being in absorption rate and/or timing of peak concentration in the plasma, and that may or may not make a difference on outcome. I just wish she was more precise in her answer. Clearly, a very intriguing substance worth researching.

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#58

Yes, but I had asked that question (what is the % bioavailability for sublingual vs. injection) but she said she didn’t know, and hadn’t done the test. I can appreciate that for a scientist investigating the method of action, and functional impact of a given peptide, researching all the delivery mechanisms would be seen as more of a “development” issue, not a “research” issue.

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#59

Oh, there is virtually no chance that sublingual is more effective than SubQ. With direct injection you’re getting virtually 100% of the peptide into the bloodstream (medical professionals here please correct me if I’m wrong)… so the real question is if its 5% or 10% or 20% as bioavailable via sublingual, I think. And, unfortunately there are no blood tests to easily do to check on whether it’s working.

If you’re not needle adverse, SubQ would definitely be the way to go.

In my Google Deep Research with Gemini, it did suggest these as things to watch:

Biomarker Verification Panel

  • Efficacy Markers:
    • GDF-15: A sensitive marker of mitochondrial stress (look for reduction).
    • Exercise Tolerance: 6-Minute Walk Test (clinical standard) or Zone 2 output (biohacker standard).
    • Cardiolipin profile: (Research grade only) Lymphocyte cardiolipin content/oxidation status.
  • Safety Monitoring: Basic renal panel (Creatinine/eGFR) due to renal excretion path.

But…

Bottom Line Up Front: No, there is currently no direct-to-consumer (DTC) “add-to-cart” blood test for GDF-15 available from major aggregators (e.g., InsideTracker, WellnessFX, Ulta Lab Tests, Walk-In Lab).

While the academic longevity community recognizes Growth Differentiation Factor 15 (GDF-15) as a sensitive biomarker for mitochondrial stress and cellular aging, the clinical lab market restricts it to investigating specific pathologies (e.g., mitochondrial myopathy, cardiac risk).

To obtain this data, you must use a “provider-facilitated” workaround rather than a consumer-initiated purchase.

1. The Workaround: How to Get Tested

You cannot order this yourself, but you can instruct a cooperative physician (or functional medicine provider) to order it for you via specific reference laboratories. Provide them with the following exact test codes to remove friction:

Laboratory Test Name Test ID CPT Code Notes
Mayo Clinic Labs Growth Differentiation Factor 15, Plasma GDF15 83520 The “gold standard” reference test. Most hospital systems can send samples here.
Cleveland HeartLab Growth Differentiation Factor 15 (GDF15) GDF15 83520 Often used for cardiovascular risk stratification.
Quest Diagnostics Variable / Send-out N/A 83520 Quest does not perform this in-house; they will likely send it to Mayo Clinic or Cleveland HeartLab.

Export to Sheets

Practical Instruction: Ask your physician to write a script for “GDF-15 Plasma” using CPT code 83520. If they use a major commercial lab like Quest or LabCorp, ensure they mark it as a “Send-out to Mayo Clinic” if it is not in their standard menu.

2. Why It Is Not Consumer Accessible

  • Clinical Indication Lag: In standard medicine, GDF-15 is FDA-cleared/utilized primarily for diagnosing rare mitochondrial diseases (e.g., MELAS syndrome) or specific cancer prognostics. It has not yet crossed the regulatory threshold to be considered a “wellness” marker like HbA1c or hs-CRP.
  • Reference Lab Status: High-volume automated labs do not run this assay routinely. It is performed via ELISA (Enzyme-Linked Immunosorbent Assay) in specialized reference sections, making it too operationally complex for the low-cost DTC model.

3. Alternative: Functional Medicine “Mitochondrial Panels”

If you cannot find a provider to order GDF-15, you may encounter “Mitochondrial Health Panels” from functional medicine labs (e.g., Genova Diagnostics, vibrant Wellness).

  • Warning: These panels generally do not measure GDF-15.
  • What they measure instead: They utilize Organic Acids (OATs) in urine (e.g., lactate, pyruvate, succinate, fumarate) to infer mitochondrial efficiency and Krebs cycle stalling.
  • Comparison: While OATs provide a metabolic snapshot, they lack the specific specificity of GDF-15 as a “mitokine” signal of systemic mitochondrial stress response.

4. Interpretation for Longevity

If you successfully source a test, note that the reference ranges are calibrated for pathology (detecting disease), not optimization.

  • Standard Reference (Mayo): ≤750 pg/mL (for adults >3 months).
  • Longevity Context: In healthy aging cohorts, lower levels generally correlate with better health outcomes. Elevated GDF-15 in the absence of acute injury or pregnancy is strongly associated with “inflammaging,” mitochondrial dysfunction, and all-cause mortality in epidemiological studies (e.g., Framingham Heart Study ).

Details on the Testing and Costs, etc. from Gemini: https://gemini.google.com/share/eacfc25414ed

Additional prompt:

Is there any scientific or clinical evidence that SS-31 would lower HS-CRP levels in humans?

Gemini Response:

No, there is currently no direct clinical evidence that SS-31 (elamipretide) lowers hs-CRP in humans.

While preclinical (animal) models show it can powerfully suppress the “upstream” cytokines that trigger CRP release, this effect has not yet been translated into a confirmed reduction of serum hs-CRP in human clinical trials.

The Mechanistic Plausibility (The “Upstream” Argument) While human data is missing, the mechanism suggests it should theoretically lower CRP. hs-CRP is produced by the liver in response to IL-6 (Interleukin-6). Preclinical data confirms that SS-31 powerfully inhibits IL-6 production at the source:

  • NLRP3 Inflammasome: SS-31 has been shown to inhibit the NLRP3 inflammasome in mice. The inflammasome is the cellular “siren” that detects mitochondrial damage (ROS/mtDNA leak) and pumps out inflammatory cytokines (IL-1beta, IL-18).
  • Cytokine Suppression: In mouse models of atherosclerosis and ischemia, SS-31 significantly reduced TNF-α and IL-6. Since IL-6 is the direct trigger for CRP, SS-31 acts upstream of the CRP pathway.
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#60

No medical professional by any means, but a while back had a discussion with a doc friend of mine and if I remember it correctly, he’d mention that IV is almost 100%, IM is close, I think he mentioned over 95% and then SubQ is about 90%. supposedly a little is lost in the transport/absorption process. Nevertheless all these three should count as getting 100% IMO.

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