What did KLOW do for you?
Hard to tell to be honest. I don’t really know how to measure its effectiveness. I did recover quickly from a shoulder arthroscopic clean up last year
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Is the peptide craze backed by science? The promise behind the hype
Scarce science
Cohen began to get excited about peptides a couple of decades ago. He and his team had started mining mitochondrial DNA for peptide-encoding genes and synthesizing the molecules to study their function. One of their finds was MOTS-c.
In mice, the compound prevented obesity and insulin resistance and improved physical performance1. It even extended lifespan. It worked so well that CohBar, a company co-founded by Cohen and Nir Barzilai at the Albert Einstein College of Medicine in New York City, licensed the MOTS-c patent. CohBar tweaked the compound to make it more effective and more stable, and then, in 2018, tested it in a safety study.
Researchers first administered the compound to 65 healthy adults to determine dosing. They then randomized 20 people with obesity and non-alcoholic fatty liver disease and gave the compound to about half of them for four weeks. Participants who received the peptide had lower glucose levels, greater reductions in markers of liver injury and a trend towards weight loss compared with the placebo group2.
CohBar raised US$80 million to get the drug through an initial trial. But, says Cohen, “we couldn’t raise the next round to do a phase II”. In 2023, the company shut down. That hasn’t stopped MOTS-c from becoming one of the most popular unapproved peptides. “Guys it’s like you have unlimited energy,” raves one Instagram user.
Other popular unlicensed peptides have been studied in even fewer people. Flynn McGuire, a physician specializing in physical medicine and rehabilitation at the University of Utah in Salt Lake City, and his colleagues delved into the literature on BPC-157, a peptide that purportedly helps to repair tissue injuries3. They managed to dig up 3 pilot studies with a total of 30 participants. “The amount of human data that exists for it is of dubious enough quality that you can essentially just ignore it,” he says. “There are no long-term studies. There are no safety studies, even in animals.”
Shepherding a drug from the lab through clinical trials is enormously expensive. And pharmaceutical companies might not want to invest in a compound that is already readily available. Kaeberlein says that he suspects that many of these peptides simply don’t work well enough to grab the interest of pharmaceutical companies. “They have biological activity, and they may have benefits in certain indications for certain people,” he says. But “none of them are as effective as the GLP drugs. If they were, pharma would have developed them already”.
full article: Is the peptide craze backed by science? The promise behind the hype (Nature)
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Nothing new here. Aside from the GLP1s and amylin agonists, you can count on 2 hands the number of peptides that have phase 3 data behind them. Use at your own risk tolerance.
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make that one hand or 1/2 a hand LOL
Peptide I just discovered named Phoenixin PXN20/PXN-20. Looks really interesting but not currently available for human use. Looks promising in animal trials for increasing LH, FSH, kisspeptin and presumably testosterone by extension. Also appears to have anxiolytic effects and promotes mitochondrial biogenesis.
We don’t know if it will do to humans what it does to other animals, or if it will do anything at all.
I’ve put some studies below, but before that a ChatGPT summary:
Phoenixin (PNX) is a recently discovered neuropeptide derived from SMIM20 that acts through the orphan receptor GPR173 and plays a key regulatory role in the hypothalamic–pituitary–gonadal (HPG) axis. Across animal and cell studies, it enhances reproductive signaling by increasing GnRH activity, potentiating LH release, and upregulating kisspeptin pathways, with evidence that disrupting PNX signaling can prolong estrous cycles and impair normal reproductive function. In non-reproductive roles, PNX shows broad pleiotropic effects in preclinical research, including modulation of memory, anxiety, feeding behavior, cardiovascular function, inflammation, and cellular metabolism, suggesting it acts as a multi-system neuromodulator rather than a purely reproductive hormone. However, most findings are based on rodent, fish, and in vitro models, and its full physiological relevance in humans remains uncertain.
Key points
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Phoenixin is a neuropeptide produced from SMIM20, acting via the GPR173 receptor
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Strongly involved in reproductive hormone regulation through the HPG axis
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Increases GnRH signaling and enhances GnRH-stimulated LH release from the pituitary
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Promotes kisspeptin expression and broader reproductive gene activation
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Disruption of PNX signaling can alter reproductive cycles (e.g., extended estrous cycle in rats)
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In fish and rodent models, PNX-20 upregulates reproductive and steroidogenic genes
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Shows additional effects beyond reproduction:
- Anxiety modulation (generally anxiolytic in animal models)
- Memory and learning enhancement in experimental studies
- Effects on feeding behavior and energy balance
- Cardiovascular and anti-inflammatory actions (preclinical evidence)
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Functions across brain and peripheral tissues (gonads, liver, adipose tissue, pancreas)
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Overall characterized as a pleiotropic neuropeptide with endocrine, neural, and metabolic roles
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Human clinical significance is still unconfirmed; evidence is largely preclinical
“Phoenixin (PNX) is a newly discovered peptide that has been linked to reproductive function, both in the hypothalamus and pituitary. This review will focus on the most recent discoveries related to this novel neuropeptide. Initially, it was found that PNX increased gonadotropin releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release from pituitary cells. Importantly, knockdown of PNX in female rats extended the estrous cycle by 2.3 days. Using novel hypothalamic cell lines, we found that PNX has a stimulatory role on kisspeptin (Kiss) and GnRH gene expression and secretion. The PNX receptor was uncovered using siRNA knockdown of GPR173, an orphan receptor postulated to bind PNX. We have found that the PNX-R signaling through protein kinase A (PKA) in hypothalamic neurons. Althuogh a number of studies demonstrate that PNX plays an important role in reproductive function, there is also evidence that it may have other functions, regulating the heart, feeding, memory, and anxiety, both in the brain and the periphery.”
Phoenixin: uncovering its receptor, signaling and functions Phoenixin: uncovering its receptor, signaling and functions - PubMed
“Phoenixin-20 (PNX-20) is a bioactive peptide with hormone-like actions in vertebrates. In mammals, PNX stimulates hypothalamo-pituitary-gonadal hormones and regulate reproductive processes. Our immunohisto/cytochemical studies show PNX-like and the putative PNX receptor, SREB3-like immunoreactivity in the gonads of zebrafish, and in zebrafish liver (ZFL) cells. Intraperitoneal injection of zebrafish PNX-20 upregulates mRNAs encoding both salmon gonadotropin-releasing hormone (GnRH), and chicken GnRH-II and kisspeptin and its receptor in zebrafish hypothalamus. Similarly, luteinizing hormone receptor mRNA expression in the testis, follicle-stimulating hormone receptor in the ovary, and the kisspeptin system were upregulated in the gonads of PNX-20 injected fish. We also observed the upregulation of genes involved in the sex steroidogenic pathway (cyp11a1, cyp17a1, 17βhsd, cyp19a1a) in the gonads of PNX-20 administered fish. PNX-20 upregulates the expression of vitellogenin isoforms and estrogen receptor (esr2a and 2b) mRNAs in ZFL cells in vitro. Meanwhile, siRNA-mediated knockdown of PNX-20 resulted in the downregulation of all vitellogenin transcripts, further suggesting its possible role in vitellogenesis. PNX-20 treatment resulted in a significant increase in germinal vesicle breakdown in zebrafish follicles in vitro. Collectively, these results provide strong evidence for PNX-20 effects on the HPG axis and liver to promote reproduction in zebrafish.”
Phoenixin-20 Stimulates mRNAs Encoding Hypothalamo-Pituitary-Gonadal Hormones, is Pro-Vitellogenic, and Promotes Oocyte Maturation in Zebrafish Phoenixin-20 Stimulates mRNAs Encoding Hypothalamo-Pituitary-Gonadal Hormones, is Pro-Vitellogenic, and Promotes Oocyte Maturation in Zebrafish | Scientific Reports
“Sexual maturation and maintenance of reproductive function are regulated by neurohormonal communication between the hypothalamus, pituitary, and gonads (referred to as the HPG axis). Phoenixin (PNX) is a newly identified, endogenous peptide abundantly produced in the hypothalamus and shown to be an important mediator of ovarian cyclicity. However, the underlying mechanisms by which phoenixin functions within the HPG axis are unknown. Previous in vitro studies demonstrated a direct action of PNX on gonadotrophs to potentiate gonadotrophin-releasing hormone (GnRH) induced luteinizing hormone (LH) secretion. Therefore, we hypothesized that centrally derived phoenixin regulates the preovulatory LH surge required for ovarian cyclicity. We observed a significant dose-related increase in the level of plasma LH in diestrous, female rats that were given an intracerebroventricular injection of PNX compared with vehicle-treated controls. While this suggests that even under low-estrogen conditions, PNX acts centrally to stimulate the HPG axis, further characterization is contingent on the elucidation of its cognate receptor. Using the “deductive ligand receptor matching strategy,” we identified the orphan G protein-coupled receptor, Gpr173, as our top candidate. In cultured pituitary cells, siRNA-targeted compromise of Gpr173 abrogated PNX’s action to potentiate GnRH-stimulated LH secretion. In addition, siRNA-mediated knockdown of endogenous Gpr173, which localized to several hypothalamic sites related to reproductive function, not only significantly extended the estrous cycle but also prevented the PNX-induced LH secretion in diestrous, female rats. These studies are the first to demonstrate a functional relationship between PNX and Gpr173 in reproductive physiology and identify a potential therapeutic target for ovulatory dysfunction.”
Hypothalamic action of phoenixin to control reproductive hormone secretion in females: importance of the orphan G protein-coupled receptor Gpr173 https://journals.physiology.org/doi/full/10.1152/ajpregu.00191.2016
“Phoenixin is a recently discovered brain peptide initially thought to be restricted to reproductive functions. The subsequent identification of phoenixin’s expression in peripheral tissues was accompanied by the description of several other actions of this hormone, such as effects on behavior, sensory perception, memory retention, the cardiovascular system as well as food intake, pointing towards a pleiotropic role of this peptide. The present review will discuss the present knowledge on phoenixin and the signaling involved as well as highlight gaps in knowledge to stimulate further research.”
Phoenixin—A Pleiotropic Gut-Brain Peptide Phoenixin—A Pleiotropic Gut-Brain Peptide - PMC
“Phoenixin (PNX) neuropeptide is a cleaved product of the Smim20 protein. Its most common isoforms are the 14- and 20-amino acid peptides. The biological functions of PNX are mediated via the activation of the GPR173 receptor. PNX plays an important role in the central nervous system (CNS) and in the female reproductive system where it potentiates LH secretion and controls the estrus cycle. Moreover, it stimulates oocyte maturation and increases the number of ovulated oocytes. Nevertheless, PNX not only regulates the reproduction system but also exerts anxiolytic, anti-inflammatory, and cell-protective effects. Furthermore, it is involved in behavior, food intake, sensory perception, memory, and energy metabolism. Outside the CNS, PNX exerts its effects on the heart, ovaries, adipose tissue, and pancreatic islets. This review presents all the currently available studies demonstrating the pleiotropic effects of PNX.”
Phoenixin: More than Reproductive Peptide Phoenixin: More than Reproductive Peptide - PMC
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This is the key, the cause of all the controversy. Some of us respond, while others don’t.
After my wife’s Meniscus root repair surgery last December we have done everything possible to restore the function of her knee. This included two PRP injections, extensive physical therapy, and now peptides along with hyaluronic acid injections. Recent research suggest that Semaglutide along with these injections can improve cartilage thickness by 17%.
We are also using BPC 157 and TB 500. We walked 7 miles at good pace yesterday and have been riding our mountain bikes on easy trails.
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People can say what they want about the lack of human data but if you are recovering from surgery or some other type of injury, it would be kind of silly not to try BPC157 & TB500. Worst that can happen is you spend your money with little result (No you will not get cancer).
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Here’s the Archive.org non-login version of the Guardian article, that RapAdmin posted above:
Medicines watchdog to investigate UK peptide clinics over health claims | Health | The Guardian
I do find this thread interesting, although I haven’t tried peptides, but I am wary of the lack of responsible human testing. I have no problem with Russian science but I judge the “unknown unknowns” are too risky for me at present.
I missed this last night, but will try to make the next one (purely out of curiousity)
Just be a spectator though. I wouldn’t trust trying a peptide at a party unless the host is the one pictured with the tongue out (brochure), in which case I’d try anything LOL
BTW, and just FYI there were couple people hospitalized with severe issues on a similar party in Nevada about 6 months ago.
Where is a good place to source raw peptides? I was interested in making capsules at home of pinealon and a few other things. I’m finding premade 1mg x60 pinealon capsules for $150-300, it is a ludicrous price I’m sure for what is 1mg + a few 100mg of flow agent/fillers in a capsule. Something I can easily do at home if I had the raw peptide powder.
China.
It took me years to establish relations with the suppliers I use. It cost me time and money to be where I am today. I doubt any peptide vendor is going to give up their supplier.
I’m also very skeptical of any Vladimir Khavinson research, due to who did the research, how it was “peer” reviewed and the journals it was published in. While very few peptides in the “hobby” have peer reviewed studies and even fewer with RCT.
I tried Epitalon for 6 months while stopping the use of NMN to see if the telomere support claim worked for me. I’ve had my telomere length measured by Trudiagnostic 5 times over 4 years and there was a trend indicating they were getting longer for the first 4 tests. They got shorter on the 5th test.
Some of the papers his group published.
https://orcid.org/0000-0001-7547-7725
A Perplexity review of he and his work. This AI remembers my research interests and threw GHK-cu in at the end to show an example of what a well validated peptide would look like.
Vladimir Khavinson russian peptide researcher, whe.pdf (457.7 KB)
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…they were getting longer for the first 4 tests. They got shorter on the 5th test.
What is your takeaway from that outcome?
To expand on @bluffsman 's question above, was NMN the culprit (good one) that resulted in telomere lengthening in first 4 test (to best of your knowledge) and was Epitalon the culprit (bad one) for the shortening of telomeres on your fifth test (best of your knowledge). Your message above is a bit murky.
I’m not trying to compete with anyones business I want to make my own capsules to save money.
I think I meant lyophilized powder, not raw.
Just to be clear 
You can’t get lyophilized power out side of a vial. So you would be purchasing vials. There is probably a dozen or more selling “kits” 10 vials to a kit for decent prices. There are group buy groups on some chat apps that do that and send off a sample for testing.
Lyo adds a significant amount of filler (manitol) as part of the freeze drying process. Nothing wrong with that but you need to carefully weight it to be able to divide up the powder for encapsulation
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NMN works - as per my first 4 tests
Epitalon does not work - as per test #5