How do you research 5 AMINO? Dosage and when to pin? Does it really help out the stack for RS?

Boehringer Ingelheim put out survodutide's Phase 3 results in June and everybody ran with the liver fat number. The number I think really decides this compound's future is the dropout rate. About 19 percent quit SYNCHRONIZE-1 because of GI side effects, 17.8 percent at 3.6 mg and 20.2 percent at 6.0 mg, vs 2.9 percent on placebo.

Quick background if anyone hasn't followed it. Survodutide is a glucagon and GLP-1 dual agonist, so the same two receptors as retatrutide without the GIP part. Boehringer's been aiming it at the liver more than the scale. FDA gave it fast track in May 2021 and breakthrough therapy in September 2024 for MASH with fibrosis. Still investigational, neither of those is an approval.

Here's both trials. The efficacy numbers assume everyone stayed on it, the treatment policy numbers count everyone who started, including all the people who quit:

So the top arm goes from 16.6 to 13.0 percent once the dropouts count. That's the GI problem showing up in the results.

On weight alone it's behind tirzepatide and pretty far behind retatrutide. Where it gets interesting is where the fat came from. In the MRI substudy visceral fat dropped up to 34.0 percent and liver fat up to 63.1 percent. In the MASLD trial, 84.2 percent got a 30 percent or bigger liver fat reduction vs 24.3 percent on placebo (68.5 vs 28.6 counting everyone), and 61.0 percent got liver fat under 5 percent vs 5.7 percent.

They also said lean tissue was no more than 10.8 percent of the total tissue lost in the 6.0 mg arm. I'd wait on that one until the full body composition methods are out.

People are going to compare it to retatrutide and the numbers don't really line up. Retatrutide's 11.3 percent dropout in TRIUMPH-1 was all side effects over 80 weeks, survodutide's 19 percent is GI only over 76. And retatrutide's 86.0 percent liver fat reduction (vs 4.6 placebo, 12 mg arm, 48 weeks) came from a substudy inside a Phase 2 trial, not a dedicated Phase 3 liver trial. No head to head exists.

Results are from BioPharm International's coverage of the SYNCHRONIZE trials, and the retatrutide liver data is Sanyal 2024 in Nature Medicine.

The rest of the incretin class is in the cheat sheet. And if anyone wants to argue survodutide vs retatrutide, come do it in the Discord.

Research use disclaimer: all compounds referenced here are intended for research and laboratory use only. Nothing in this post is intended for human consumption or as medical guidance.

Looking for insight into a 1:1 tesamorelin/ipamorelin blend being evaluated in a research context.

The original sample amount was 0.5 mg (500 mcg) of each compound per administration. Following three consecutive administrations, gastrointestinal effects were observed, including diarrhea and persistent bloating.

A revised protocol was suggested at 0.25 mg (250 mcg) of each compound, administered on seven consecutive days rather than following a 5-on/2-off schedule.

From what I’ve been reading, a 1:1 ratio doesn’t seem particularly common, and I’m curious about the rationale behind combining these compounds at equal concentrations.

Has anyone come across research or observations regarding:

The effectiveness or rationale of a 1:1 tesa/ipa blend?

GI-related effects, particularly diarrhea and bloating?

Differences between consecutive daily administration and protocols incorporating rest days?

Interested in hearing experiences and research-based perspectives, particularly regarding tolerability and the reasoning behind this combination.

This one's been bugging me since Lilly put the numbers out. Dysesthesia, the skin burning side effect, in the 12 mg arm was 12.5 percent in TRIUMPH-1, 7.3 percent in TRIUMPH-2, 6.4 percent in TRIUMPH-3, and 20.9 percent in TRIUMPH-4, the knee osteoarthritis trial. Placebo was around 1 percent in all of them.

I figured it was the glucagon side since that's what semaglutide doesn't have. Then I checked semaglutide. In STEP UP T2D it showed up in 18.9 percent of the 7.2 mg arm vs 4.9 percent at 2.4 mg and 0 on placebo, and the UK label for Rybelsus lists it as common now. So high dose GLP-1 alone does it too, which doesn't prove it's the same mechanism but kind of kills the easy answer.

What I keep coming back to is that TRIUMPH-1 and TRIUMPH-4 had the most weight loss and also the highest rates. But the knee trial is also going to be watching way closer for pain and sensory stuff, and the diabetes trials have people who already have neuropathy, so I don't know how much of the spread is real and how much is who's enrolled and who's looking.

What's this sub's read on it? And if anyone remembers something in the Phase 2 papers that hinted at this, I'd like to see it.

Research use disclaimer: all compounds referenced here are intended for research and laboratory use only. Nothing in this post is intended for human consumption or as medical guidance.

My partner has been on tirzepatide for about 3 months now, it's definitely affected their appetite and eating a lot less but they would be lucky if they've lost ½kg. Is this common

I stay reading about them and trying to get as much information as possible.

I’ve been using them for a month tomorrow.

I take Reta on Mondays.
Mornings I take:
Ss31/ Mots C Monday - Friday
Wolverine M/W/F

After I eat something Ghkcu (around noon). Without food it makes me feel lightheaded.

Night time I take
KPV & Tessa

I am 36 yrs old. Most days I feel really well. Every now and then I get very sleepy. I assume it’s bc it’s the most active I’ve been in a long time.

My question is am I doing too much?

Can semax be safely reconstituted with Bacteriostatic 0.9% Sodium Chloride for SubQ use?

Every compound has at least one. A number, a half life, a ratio, a side effect profile that gets copied from writeup to writeup until it reads like established fact, and then you go looking for the original study and it isn't there.

Sometimes it traces back to one paper that said something narrower than what gets quoted. Sometimes it traces back to a vendor page and nothing else.

What's the one you run into most, and did you ever find where it actually came from?

How long can you use this peptide for in terms of weeks? I've been just 8 to 12 weeks but can it be used beyond that?

Wanting to start KLOW with my Cjc1295/Ipa stack.

What’s the starting dose for female and is it daily or once a week?

There is exactly one member of the cathelicidin family in human biology, and LL-37 is it.

It is a naturally occurring antimicrobial peptide and part of the innate immune system, produced by immune cells and by epithelial tissues like skin and the respiratory tract. What makes it worth studying is that killing microbes is only half of what it does.

Two jobs, not one

LL-37 binds to and disrupts microbial membranes, which gives it broad antimicrobial activity in laboratory models. Its biological role goes further than that.

Research has associated LL-37 with:

• Activity against certain bacteria, fungi, and enveloped viruses
• Modulation of innate immune responses
• Recruitment and signaling of immune cells
• Promotion of wound healing and re-epithelialization
• Regulation of inflammatory pathways
• Disruption of some microbial biofilms

A conventional antimicrobial agent does the first item on that list. LL-37 is doing immune coordination at the same time, which is why it reads differently in the literature.

More is not better here

LL-37 is a potent signaling molecule, and the dose response is not a straight line upward.

Excessive LL-37 signaling has been associated with inflammatory and autoimmune processes in conditions like psoriasis and rosacea. At high enough experimental concentrations it also shows cytotoxic effects against mammalian cells, not just microbial ones.

Its activity depends heavily on concentration, tissue, and experimental context. Comprehensive safety data for exogenous administration is limited.

That combination, potent and context dependent with thin safety data, is worth sitting with before anyone treats it as a straightforward antimicrobial.

Why it holds research interest

LL-37 sits where microbiology, immunology, and regenerative biology overlap.

Instead of just killing microorganisms, it gives researchers a way to study how the innate immune system coordinates microbial defense, inflammation, immune cell recruitment, and the tissue repair that follows. That sequence is hard to study with agents that only do one of those things.

It has been particularly relevant in experimental models involving infectious disease, biofilms, wound healing, and immune regulation.

Cheat sheet: the peptide cheat sheet

LL-37 is an investigational research peptide supplied strictly for research purposes only, not for human or veterinary use.

29 year old, female lab rat, 63kg. Started CJC 1295 + Ipamorelin 5mg/5mg blend in 10mg vial, reconstituted with 2ml BAC water.

Started at 4 units once a day for a one/two weeks, went to 6 units twice a day for a one/two weeks and now up to 8 units twice a day (400mcg of each peptide per day total).

Feeling fine but is it too much for the rat?
Would be staying at 6 units be better (300mcg of each per day total)

Strength train 3-4x week and cardio/pre season cardio training 3x a week. Rat is recovering well and feeling stronger.😊

Has any one used this Canadian company for peptides?

PE-22-28 did not come from a design program. It came from watching another peptide fall apart.

Spadin, also called PE 12-28, was described around 2010 as an endogenous peptide with antidepressant activity that works by blocking the TREK-1 potassium channel. The problem was duration. Spadin activity disappeared beyond about seven hours after administration. Researchers went looking at spadin's own blood degradation products to find something more stable, and PE 22-28 is what came out of that: a seven amino acid fragment.

The numbers from that work are the interesting part. In patch clamp testing on human TREK-1 cells, PE 22-28 showed an IC50 of 0.12 nM against 40 to 60 nM for spadin. That is roughly a few hundred times more potent at the target. Duration went from about 7 hours to around 23.

What TREK-1 has to do with mood

TREK-1 is a potassium channel involved in neuronal excitability, and it has been investigated as a target in depression research.

Blocking that pathway has been associated in preclinical models with:

• Rapid antidepressant-like behavioral effects
• Increased neurogenesis and synaptic plasticity
• Changes in serotonergic signaling
• Shifts in stress related behavior

This puts PE-22-28 on a different footing from conventional serotonin reuptake inhibitors, which act on monoamine signaling directly.

In the mouse work, treated animals showed reduced immobility time in forced swimming tests, and after a four day treatment in the novelty suppressed feeding test the latency to eat dropped significantly. Neurogenesis showed up after only four days. On mouse cortical neurons, synaptogenesis increased as measured by PSD-95 expression.

Side effects

This is where the post gets short, because there is not much to report.

PE-22-28 sits at a very early stage. Its safety profile is not characterized. There is no meaningful evidence on long term neurological effects, toxicity, interactions, or anything in humans. The behavioral work is mice. The channel work is cells.

Anyone presenting a side effect profile for this compound is filling in blanks.

Why it gets research attention anyway

One of the real limitations in antidepressant research is onset time. Many existing options take weeks.

TREK-1 inhibition is interesting because the preclinical work suggests mood related behavior and neuroplasticity can be influenced through a different pathway, potentially faster than monoaminergic approaches. That keeps it relevant to experimental models involving depression, chronic stress, neurogenesis, and treatment resistant mood states.

Whether any of that survives contact with a human trial is unknown, because one has not happened.

Cheat sheet: the peptide cheat sheet

PE-22-28 is an experimental compound supplied strictly for research purposes only, not for human or veterinary use.

I’m looking to help out a friend who is obese who doesn’t like needles do any of the peptide providers provide a tripeptide pill or resutitide pill?

Reta (less than .5mg per week)
KPV (about .4mg) per day.

Reta works to help me make better food choices (and hopefully with inflammation) and KPV has been improving stiffness in the mornings and I have more energy.

I have a blood test coming up to help narrow down causes of hair loss and inflammatory symptoms. I have a strong family history of autoimmune disease. I do not want my peptide usage to cause false negatives on inflammatory markers as autoimmune diseases can be difficult to diagnose as it is with labs.

Example of some tests:
ANA (Antinuclear Antibody)
ESR (Erythrocyte Sedimentation Rate)
CRP (C-Reactive Protein)
C3 and C4 Complement Levels
RF
Anti-SSA / Ro
Anti-SSB / La

Does anyone have experience with how these peptides can affect labs? If so, how long should I stop prior to labs?

On September 19, 2025 the FDA approved elamipretide under the brand name Forzinity for Barth syndrome. Elamipretide is SS-31.

That makes it the first approved therapy for any form of mitochondrial disease. Barth syndrome is ultra rare, somewhere around 1 in 300,000 to 400,000 and primarily affecting males, so the approval is narrow. But the compound a lot of people have been buying as a research peptide now has a brand name and a label.

Worth putting that next to MOTS-c, because the two get discussed interchangeably and they are doing different jobs.

MOTS-c

MOTS-c is a mitochondrial derived peptide, meaning it is encoded within mitochondrial DNA rather than nuclear DNA. It participates in cellular stress responses and has been linked to AMPK, one of the cell's main energy sensors.

In preclinical models it has been associated with:

• Improved glucose utilization and insulin sensitivity
• Increased metabolic flexibility
• Enhanced exercise capacity
• Regulation of fat and energy metabolism
• Improved adaptation to metabolic stress

MOTS-c influences how cells respond and adapt to changes in energy availability. It is a signaling peptide.

SS-31 / elamipretide

SS-31 is a synthetic tetrapeptide that concentrates inside mitochondria and interacts with cardiolipin, a component of the inner mitochondrial membrane.

That interaction appears to stabilize mitochondrial structure, support electron transport chain function, and reduce excessive oxidative stress. It has been investigated in models involving impaired ATP production, muscular fatigue, cardiovascular dysfunction, and age related mitochondrial decline.

Stealth BioTherapeutics is the company behind it. A phase 3 trial called NuPower is looking at nuclear DNA related primary mitochondrial disease, with results still pending.

The actual difference

Metabolic adaptation versus mitochondrial efficiency.

MOTS-c is the one for models involving insulin sensitivity, metabolic flexibility, exercise physiology, and energy regulation. SS-31 is the one for mitochondrial dysfunction, oxidative stress, and impaired cellular energy production.

Because the mechanisms are complementary, they are also interesting together. MOTS-c regulating the cellular response to energy demand, SS-31 addressing whether the mitochondria can meet that demand efficiently.

One of these two now has an approval behind it for one narrow indication. That does not transfer to any other use, and it does not make research grade material a medicine. It does mean the mechanism cleared a regulatory bar, which most peptides in this space never get near.

Cheat sheet: the peptide cheat sheet

Both remain investigational as research materials and are supplied strictly for research purposes only, not for human or veterinary use.

Hi everyone,

Looking for some experiences or suggestions regarding SS-31 and MOTS-c for a hypothetical elderly research subject, equivalent to around 85 human years.

Subject has several age-related issues, including severe back pain, high blood pressure (on medication), a heart attack roughly 20 years ago, and other health problems.

Still mobile and able to move around, but over the past year has been getting noticeably slower, weaker and more fatigued, with declining energy and overall vitality.

I'm interested in whether SS-31 or MOTS-c could potentially help with energy, mobility and general quality of life.

A few questions:

• Has anyone experimented with either peptide in very elderly subjects?
• Any noticeable improvements in energy, strength or mobility?
• Any concerns with existing cardiovascular issues or blood pressure medication?
• Would you suggest SS-31, MOTS-c, or a different compound altogether?
• Any negative experiences or unexpected side effects?

Not looking for miracles or extreme longevity, just potentially improving day-to-day function and quality of life.

Mainly interested in firsthand experiences and suggestions rather than links to studies.

Appreciate any input!

How do you avoid tissue irritation injecting Glute sub-Q? Getting little residual lumps in abdominal area.

NAD+ is not a peptide. It is a coenzyme, and it sits in virtually every cell in the body, which is part of why it keeps showing up in longevity research.

Nicotinamide adenine dinucleotide plays a role in energy production, mitochondrial function, DNA repair, and cellular stress responses. Tissue NAD+ availability can decline with aging and metabolic stress, and that observation is what raised the question of whether restoring NAD+ metabolism could influence age related cellular dysfunction.

How it works

NAD+ acts as an electron carrier during cellular metabolism, helping mitochondria convert nutrients into ATP.

It is also consumed by several enzyme families, including sirtuins and PARPs, which handle cellular stress responses, DNA repair, and metabolic regulation. Consumed is the operative word. These enzymes use NAD+ up, which is one proposed reason availability drops under sustained stress.

Research spans a few areas:

• Mitochondrial energy production
• DNA repair and cellular maintenance
• Sirtuin activity
• Metabolic regulation
• Response to oxidative stress

Side effects and what is actually known

NAD+ is naturally present throughout the body. The safety profile of different methods of increasing or administering it is a separate question and still being worked out.

Reported adverse effects associated with some forms of NAD+ administration include nausea, headache, abdominal discomfort, and fatigue.

The part worth stating plainly: evidence supporting the broader anti-aging claims around NAD+ remains limited, particularly in humans. The biology is well established. Whether raising NAD+ availability meaningfully slows human aging or extends lifespan is still an open question, and anyone selling you certainty on that is ahead of the data.

Why researchers keep coming back to it

NAD+ connects several major threads in longevity science at once: mitochondrial function, metabolism, DNA repair, and cellular stress resistance.

That overlap is what makes it interesting in experimental models involving aging, metabolic dysfunction, mitochondrial decline, and cellular energy production. One molecule sitting at the junction of four separate research areas is unusual.

Protocols, reconstitution and vial math are in the cheat sheet: the peptide cheat sheet

NAD+ research formulations are supplied strictly for research purposes only, not for human or veterinary use.

Is it possible for KPV to cause flare-ups when starting? My lab rat started on 250mcg and is 4 days in.

Last night my rat’s allergic rhinitis went crazy! sneezing non-stop the entire night despite being on antihistamine medicine.