#61

Steve_Combi,

Okay. Tell me more. What was your protocol for the first cycle and what were the results?

1 Like
#62

Beth,

ChatGPT responses are always questionable. But, for what it’s worth, here is what chatGPT has to say about SS‑31 (Elamipretide / MTP‑131):

Route Molecular Weight Consideration Potential Absorption / Effectiveness
Sublingual 640 Da Likely poor absorption; small enough for some passive uptake, but peptides >500 Da generally have low bioavailability.
Nasal spray 640 Da Moderate potential; nasal mucosa can absorb small peptides, so some systemic exposure is possible.
Subcutaneous injection 640 Da High absorption; SC injection bypasses barriers, giving reliable systemic delivery.
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#63

First cycle was 5mg 2 x per day SubQ (100mg total) with 1 injection per day for 10 days. Did not notice much

Second cycle about 2? weeks later 10mg 2 x per day for 10 days (200mg total), for me the lights turned on.

I’m looking forward to doing that cycle again starting Monday and my wife will be on the same protocol this time. I’m her personal guinea pig :slight_smile:

After that cycle is done we will then try a much lower daily dose to see if maintains the effect.

#64

That just really seems strange to me. She must know better, i.e. that there’s no way this peptide is getting absorbed sublingually to any significant degree and there’s no reason to believe that it should be effectively absorbed this way. Her answer about individual peptides behaving differently just seems defensive and deflective.

I can’t help but speculate that she’s not actually taking a sublingual product but doesn’t want to talk about what she’s doing or where she gets it from, which as a researcher with a reputation to uphold is perfectly understandable.

4 Likes
#65

A little more context is in order: She’s a retired researcher (left Cornell a number of years ago, and only has her own non-profit group now). Also, She talked about personally trying most all the peptides during her presentation to the crowd, so she seems to share freely without academic “reputation” concerns
 she’s out of academia. So I can’t understand why she wouldn’t tell the truth; there’s no financial incentive here.

Lastly - delivery mechanisms (like subliqual vs. SubQ injection) reallly seem like the type of research a company might do, not the optimization process that a hardcore researcher would do. See her list of publications
 nothing related to delivery mechanisms. See here: â€ȘHazel Szeto‬ - â€ȘGoogle Scholar‬

#66

Then I’m even more mystified why she’s taking it sublingually. Seems like such a waste of such a promising peptide.

#67

I can actually related to her taking it sublingually. Most people, and I include myself in that group, are highly reluctant to start doing injections on themselves. It conjures up images of heroin addicts, etc
 that we saw in our youth (or that we see on the streets today in major cities); there is an almost visceral reaction to the idea. Sublingual, even if much less effective, is entirely acceptable and the path I’ll choose initially.

1 Like
#68

That is understandable, just keep in mind that heroin users are injecting directly into veins. Peptides are injected via small insulin syringes (or fancy-looking pens) into a little roll of skin on the abdomen, just like a diabetic who takes insulin. It’s really pretty tame, especially with the pens.

2 Likes
#69

I do get it. I panicked when a doctor told me I had to start giving myself daily b12 injections. I got used to it in a of couple days. They didn’t even give me insulin syringes (I only discovered those from all of you
 life changing!!).

Then years later, repatha injections


Then years after that, the vet told me I needed to give sub q fluids to TWO cats EVERY SINGLE DAY. I was overwhelmed and thought no way can I do that and cried
. Fast forward
 now I teach friends how to do it!

Now I wish all my supplements could be given by injection!

2 Likes
#70

If you think insulin syringes are great, wait until you try an injection pen :joy:

3 Likes
#71

I’ve been hearing talk of this unicorn


I was intimidated by the description
 can you teach me!!! :slight_smile:

#72

At some point in the future, this may be something I could consider. Is this the process / protocol that people use for these “injection pens” and peptides?

Peptide mix / injection Pen Protocol From Google Gemini: https://gemini.google.com/share/ee37139668fa

1 Like
#73

Yes, with exception that it is way simpler than that LOL. I skip the part which says to use lower gage needles (thicker ones) and just use the same type 31 gage insulin needles to mix BAC into the vial which contains the lipolyzed product/peptide/GLP1. The only thing is with insulin needles it takes a bit longer to draw the desired amount since the needle hole is so small it is barely noticeable with naked eye.

Then grab another insulin needle (the first one might get too dull) and draw the desired amount out into the needle and just pin it into abdomen anywhere 2-4 inches away from belly button. Too close to belly button might have some more sensitive nerve endings. There is never any pain and never any blood whatsoever. On one occasion trying to convince a lady friend that it is so simple and pain free I just grabbed the needle and pinned myself continuously for 10-15 times in a raw. It is literally that easy and pain free.

The only thing to watch is to disinfect the needles and tops of vials often with alcohol pads, or every time you pin them just to keep it clean and disinfected, and you also need to rub the area in your abdomen pre and after pinning. Make sure to use BAC water for mixing. I do it exactly how this dude does it. Others as I said use bigger needles to get to reconstitute just because it is easier/faster, but it is really same end result. Just when you are drawing you have to be a bit patient since it will take a while to draw.

I have never done pens since it just adds one more step of loading the peptide into the pen, but pinning with the pen is even less noticeable. Pen is literally the same as when you prick your finger for glucose monitoring, but pinning/pricking into abdomen is easier.

Take Retatrutide the RIGHT Way (Avoid These Mistakes)

2 Likes
#74

Here’s a YouTube Short on how to load a vial into a pen cartridge and shows how easy it is to use the pen:

3 Likes
#75

One nice part about using a pen is since you’re transferring to a cartridge anyway, you can filter at the same time.

Anyways I used a pen for SS31 and had no injection pain at all. 31-32g needles are painless.

4 Likes
#76

I’ve had another idea
 perhaps SS-31 could be used in a topical serum formulation, and driven down into the skin via derma-electroporation or microneedling
 Dermo-electroporation for Aging Skin Health and Rejuvenation

Google Deep Research likes the general idea of topical use:

The intersection of mitochondrial biology and dermatological science has emerged as a frontier in the quest to retard, arrest, or reverse the phenotypic manifestations of skin aging. As the largest organ of the human body, the skin is subjected to a unique barrage of intrinsic metabolic decay and extrinsic environmental aggression, collectively termed the “exposome.” Central to the cellular response to these stressors is the mitochondrion, an organelle that functions not merely as a generator of adenosine triphosphate (ATP) but as a critical signaling hub regulating inflammation, apoptosis, and senescence. The therapeutic modulation of mitochondrial function, therefore, represents a logical and potent strategy for skin rejuvenation. Within this therapeutic class, Elamipretide (SS-31), a synthetic aromatic-cationic tetrapeptide, has demonstrated a unique mechanism of action that differentiates it from classical antioxidants and earlier mitochondrial-targeted therapies.

This report provides a comprehensive, expert-level analysis of the evidence supporting the topical application of SS-31 for improving skin mitochondria and combating skin aging. While Elamipretide—recently granted accelerated FDA approval under the brand name FORZINITYℱ for the treatment of Barth syndrome—is primarily recognized for its systemic application in rare metabolic and cardioskeletal disorders, a robust body of preclinical data, patent literature, and translational wound healing studies substantiates its efficacy in the dermal context.

Our analysis reveals that SS-31 operates through a distinct structural mechanism: the selective binding and stabilization of cardiolipin, a phospholipid exclusive to the inner mitochondrial membrane (IMM). By preventing cardiolipin peroxidation, SS-31 preserves cristae architecture, optimizes electron transport chain (ETC) efficiency, and reduces the intrinsic production of reactive oxygen species (ROS). This “upstream” prevention of oxidative stress contrasts sharply with “downstream” scavenging approaches.

Evidence derived from dermal fibroblast models indicates that SS-31 can reverse age-associated mitochondrial fragmentation, restore ATP synthesis required for collagen production, and modulate the secretory phenotype of senescent cells. Furthermore, in vivo studies utilizing advanced hydrogel delivery systems in diabetic wound models have provided definitive proof of topical bioactivity, demonstrating accelerated closure, enhanced neovascularization, and a critical immunological shift in macrophage polarization from pro-inflammatory to pro-reparative phenotypes.

Despite the absence of a dedicated dermatological drug approval, the intellectual property landscape—dominated by patents filed by N.V. Perricone LLC—signals a longstanding industry recognition of SS-31’s potential as a high-potency cosmeceutical.

Full Gemini Analysis: https://gemini.google.com/share/91f8c15e236f

1 Like
#77

More on the Perricone patents related to SS-31 for skin:

This monograph presents an exhaustive analysis of the intellectual property landscape surrounding the use of Szeto-Schiller (SS) peptides by Dr. Nicholas V. Perricone for the treatment and prevention of skin aging. The research synthesizes data from a specific cluster of patent applications—principally US20110245183, US20110245182, WO2011126940, and EP2436390—to construct a comprehensive view of a novel therapeutic approach that redefines skin aging as a mitochondrial bioenergetic crisis.

Unlike traditional cosmeceutical strategies that focus on surface hydration or broad-spectrum antioxidant protection, the Perricone patent portfolio disclosed herein leverages the unique physicochemical properties of aromatic-cationic peptides, most notably SS-31 (Elamipretide). These patents articulate a mechanism where the primary driver of the aging phenotype—ranging from fine lines to the structural collapse observed in menopausal skin—is the Mitochondrial Permeability Transition (MPT) and the unchecked production of Reactive Oxygen Species (ROS) within the inner mitochondrial membrane (IMM).

Document ID Title (or related subject) Key Claims/Disclosures Relevance to Skin Aging
US20110245183 Topical Uses of Szeto-Schiller Peptides Methods for treating skin conditions using SS peptides. Primary source for general anti-aging claims.
WO2011126940 Topical Glutathione Formulations for Menopausal Skin Compositions comprising SS peptides for menopausal skin. Defines “Menopausal Skin” symptoms (dryness, dullness).
EP 2 436 390 Topical Anesthetic Uses
 Claims “anti-skin aging agents” comprising SS-31. Links anesthetic effects to anti-aging properties.
US 7,576,061 Aromatic-Cationic Peptides
 Methods for reducing MPT and ischemia injury. Provides the foundational mechanistic data (MPT inhibition).
US 9,198,930 Treatment
 (Various) Discusses exclusions (“not for hair growth”). Clarifies the scope of facial vs scalp applications.

Full Google Deep Search Result on this topic: https://gemini.google.com/share/f66ff7da65f2

1 Like
#78

Diving deeper into optimal dosing levels and frequencies given the degradation rate of mitochondria:

Prompt:

Given the degradation rates of mitochondria in the human body, what would be the hypothetical optimal dosing level (mg) and frequency to counteract the diminishing ATP and power output of the mitochondria in the body (for organs where we have an idea of the degradation rates of mitochondria). Assume the person is age 50 years old, or 60 years old, in average health.

Gemini Response:

Chronopharmacology of Mitochondrial Therapeutics: Optimizing Dosing Regimens for Age-Related Bioenergetic Decline via Cardiolipin Stabilization

The rate at which mitochondria are turned over (mitophagy followed by biogenesis) determines the “half-life” of the organelle’s functional capacity. Research utilizing stable isotope tracers (e.g., L-[1-13C]leucine) provides granular data on these rates in human skeletal muscle.

Current evidence indicates that mitochondrial protein synthesis is not maintained at youthful levels into middle age. A pivotal study comparing young (24 ± 1 years) and middle-aged (58 ± 2 years) subjects reveals a dramatic decline. The fractional synthesis rate (FSR) of muscle mitochondrial protein is, on average, 40% lower ($P < 0.01$) in middle-aged subjects compared to their younger counterparts.1

Full Gemini analysis: https://gemini.google.com/share/697c45d58f28

2 Likes
#79

Anything to avoid subcutaneous injection i guess :rofl:. Too bad, since they are fast and painless with the right equipment.

Given my reading of other people’s experiences at much higher subcutaneous doses, and the hit or miss nature of this peptide, sublingual spray seems like a poor choice. If the patient doesn’t respond to the spray, it won’t be clear whether the delivery route or dosage is the issue.

1 Like
#80

It’s super easy. This is all we provide for our Cdn clients.

Here is my current collection for personal use. I buy several different brands and try them all. There are 2 standouts, both Lilly Pens. The brown one and the 2 tone blue one at the far right back. The lower cost no-names work well but not as “smooth” in operation. The cost difference is about $10 per pen for the higher spec ones. Expected operational life is about 2 years.

Don’t get any of the plastic ones.

There are a couple little tricks when filling cartridges.

  1. max fill is 3.0mL so you need to keep that in mind when reconstituting.
  2. when transferring into a cartridge, it is “air tight” and requires a “vent” to prevent blowing out the bottom stopper
  3. use a second syringe with the plunger removed as the vent

I would never go back to filling dozens of syringes a week for 3 people.

PXL_20251130_140306663

This one is the second nicest pen, the super duper pen is twice and much and I can’t find a volume wholesaler for that one. I have only 1 of these and use it for a specific purpose at the lab.

This is the green version of the brown one in my fridge.

HumaPen Luxura HD patient guide.pdf (480.2 KB)

3 Likes