# The Twenty-Two Sources

> References — Primitive Peptides — The twenty-two peer-reviewed sources and regulatory documents behind every quantitative claim on Primitive Peptides, covering NAD+, KPV, PT-141 (bremelanotide) and GHK-Cu.

**SOURCES**

Every bracketed number on this site resolves here.

## How to read this list

The list below is fixed. It was assembled and citation-audited before any page on this site was written, and the writing stage could select from it but not add to it. Every bracketed number in the text resolves to one entry here, and every quantitative claim on the site carries one.

The sources are grouped by compound in the order the site presents them: NAD+, KPV, PT-141 (bremelanotide) and GHK-Cu. They include randomised controlled trials, mechanistic and neuroimaging studies, animal-model work, review articles, and one regulatory label. Where a claim rests on an animal model or a single research group, the page making the claim says so.

## References

[1] Vinten KT, Trętowicz MM, Coskun E, van Weeghel M, Cantó C, Zapata-Pérez R, Janssens GE, Houtkooper RH. NAD(+) precursor supplementation in human ageing: clinical evidence and challenges. Nat Metab. 2025;7:1974-1990. https://pubmed.ncbi.nlm.nih.gov/41083806/
[2] Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience 2023. 2023;45:29-43. https://pubmed.ncbi.nlm.nih.gov/36482258/
[3] Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372:1224-1229. https://pubmed.ncbi.nlm.nih.gov/33888596/
[4] Covarrubias AJ, et al. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021. https://pubmed.ncbi.nlm.nih.gov/33353981/
[5] Conze D, Brenner C, Kruger CL. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Sci Rep. 2019;9:9772. https://pubmed.ncbi.nlm.nih.gov/31278280/
[6] Zhang D, et al. PepT1-targeted nanodrug based on co-assembly of anti-inflammatory peptide and immunosuppressant for combination treatment of acute and chronic DSS-induced colitis. Front Pharmacol. 2024;15:1442876. https://pubmed.ncbi.nlm.nih.gov/39211778/
[7] Xiao B, Xu Z, Viennois E, et al. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Mol Ther. 2017;25(7):1628-1640. https://pubmed.ncbi.nlm.nih.gov/28143741/
[8] Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, Yan Y, Sitaraman S, Merlin D. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008;134(1):166-178. https://pubmed.ncbi.nlm.nih.gov/18061177/
[9] Kannengiesser K, Maaser C, Heidemann J, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2008;14(3):324-331. https://pubmed.ncbi.nlm.nih.gov/18092346/
[10] Brzoska T, Luger TA, Maaser C, Abels C, Bohm M. Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Endocr Rev. 2008;29(5):581-602. https://pubmed.ncbi.nlm.nih.gov/18612139/
[11] Bonfiglio V, Camillieri G, Avitabile T, Leggio GM, Drago F. Effects of the COOH-terminal tripeptide alpha-MSH(11-13) on corneal epithelial wound healing: role of nitric oxide. Exp Eye Res. 2006;83(6):1366-1372. https://pubmed.ncbi.nlm.nih.gov/16965771/
[12] Getting SJ, Schiöth HB, Perretti M. Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. J Pharmacol Exp Ther. 2003;306(2):631-637. https://pubmed.ncbi.nlm.nih.gov/12750433/
[13] Borland JM, Kohut-Jackson AL, Peyla AC, Hall MA, Mermelstein PG, Meisel RL. Female Syrian hamster analyses of bremelanotide, a US FDA approved drug for the treatment of female hypoactive sexual desire disorder. Neuropharmacology. 2025;267:110299. https://pubmed.ncbi.nlm.nih.gov/39793696/
[14] Thurston L, Hunjan T, Mills EG, Wall MB, Ertl N, Phylactou M, Muzi B, Patel B, Alexander EC, Suladze S, Modi M, Eng PC, Bassett PA, Abbara A, Goldmeier D, Comninos AN, Dhillo WS. Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder. J Clin Invest. 2022;132(19):e152341. https://pubmed.ncbi.nlm.nih.gov/36189794/
[15] Kingsberg SA, Clayton AH, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Simon JA. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol. 2019;134(5):899-908. https://pubmed.ncbi.nlm.nih.gov/31599840/
[16] Simon JA, Kingsberg SA, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Clayton AH. Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder. Obstet Gynecol. 2019;134(5):909-917. https://pubmed.ncbi.nlm.nih.gov/31599847/
[17] U.S. Food and Drug Administration / DailyMed. Bremelanotide Injection — US Prescribing Information (DailyMed/FDA). DailyMed (US FDA structured product label). 2019. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=8c9607a2-5b57-4a59-b159-cf196deebdd9
[18] Mortazavi SM, Mohammadi Vadoud SA, Moghimi HR. Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective. BioImpacts. 2025;15:30071. https://pmc.ncbi.nlm.nih.gov/articles/PMC11830136/
[19] Pickart L, Margolina A. Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. International Journal of Molecular Sciences. 2018;19(7):1987. https://pmc.ncbi.nlm.nih.gov/articles/PMC6073405/
[20] Lee WJ, Sim HB, Jang YH, Lee SJ, Kim DW, Yim SH. Efficacy of a Complex of 5-Aminolevulinic Acid and Glycyl-Histidyl-Lysine Peptide on Hair Growth. Annals of Dermatology. 2016;28(4):438-443. https://pmc.ncbi.nlm.nih.gov/articles/PMC4969472/
[21] Pickart L, Vasquez-Soltero JM, Margolina A. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. BioMed Research International. 2015;2015:648108. https://pmc.ncbi.nlm.nih.gov/articles/PMC4508379/
[22] Hostynek JJ, Dreher F, Maibach HI. Human skin penetration of a copper tripeptide in vitro as a function of skin layer. Inflammation Research. 2011;60(1):79-86. https://pmc.ncbi.nlm.nih.gov/articles/PMC3016279/

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Primitive Peptides traces four research compounds back to the molecules the body makes on its own, and treats endogenous origin as a starting hypothesis rather than a safety claim — a literature digest, not a clinic, a vendor, or a source of dosing advice.