Does it actually do anything for skin?

What this archive is for. Trials of the compound come first, ranked by how many people were actually given it. Studies that only observed people are below them and labelled.

1. 01MelittinPeptideModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 658 people given it.4 reported

   538 people given it1 trial

   • This tested whole bee venom, not melittin. Five hundred and thirty eight people with knee arthritis got weekly skin injections of venom, or of a control substance, for twelve weeks. Pain and physical function improved more on the venom. The gains were modest in size. Reactions where the needle went in were uncommon. Melittin is one ingredient of bee venom, and nothing here tells you what melittin alone would do. The paper does not say who paid.

     The numbers Whole purified venom, not melittin. 538 patients with knee osteoarthritis randomised 1:2 to histamine control or 100 mcg venom in 15 dermal injections at acupuncture points weekly for 12 weeks. WOMAC pain improved 1.1 points more than control (95% CI 0.3 to 2.0, p = 0.001) and physical function 3.1 points (p = 0.0046). Injection site reactions under 5 percent. Described as a phase 3; funding not stated in the abstract.

     Journal of Alternative and Complementary Medicine, 2019· 538 people

2. 02ArgirelinePeptideModerate. At least one finished study in people, and at least 100 people who took it. 4 completed trials, 155 people given it.7 reported

   131 people given it3 trials, 2 watch-only1 found nothing

   • In a short trial the cream beat a dummy cream, mostly on what people said about their own faces. Sixty people used one or the other for four weeks. Just under half the treated group counted as responding, against none of the dummy group. Measured skin roughness moved the same way. A gap that wide is unusual in cosmetic trials. Four weeks and sixty people is small, brief, and judged in part by opinion.

     The numbers 60 subjects, 4 weeks: 48.9% subjective anti-wrinkle response versus 0% with placebo; roughness parameters decreased.

     American Journal of Clinical Dermatology, 2013· 60 people

   • Wrinkles improved, and every author works for L'Oreal. Two studies were run, 50 people for still wrinkles and 42 for the wrinkles that appear when the face moves. After twelve weeks the still-wrinkle scores improved a lot and the moving-wrinkle scores improved a little. Nothing here can be credited to acetyl hexapeptide-8 on its own. Four other active ingredients sat in the same serum and changed at the same time. The authors are employed at L'Oreal research centres in China, the United States and Japan.

     The numbers Two clinical studies, 50 subjects for static wrinkles and 42 for dynamic wrinkles, of a serum containing acetyl hexapeptide-8 with four other actives. Static wrinkle scores improved 35 to 69 percent at 12 weeks and dynamic wrinkle scores 10 to 13 percent (all p<0.001). Every author is employed at a L'Oreal research and innovation centre in China, the United States or Japan, and the peptide is one of five actives, so no part of the result is attributable to it alone.

     International Journal of Cosmetic Science, 2026· 50 people

   • A small three-way test in which this peptide came last. 21 Indonesian women aged 26 to 55 were sorted by chance into three creams: acetylhexapeptide-3, palmitoyl pentapeptide-4, or a dummy. That is about seven women per group. Over eight weeks, instruments and a wrinkle scale put palmitoyl pentapeptide-4 ahead of both acetylhexapeptide-3 and the dummy. The authors call the work initial and say it needs a proper sample size. Seven people per group is too few to measure an effect from. No conflicts were reported.

     The numbers 21 Indonesian women aged 26 to 55 randomized to acetylhexapeptide-3 cream, palmitoyl pentapeptide-4 cream or placebo for eight weeks, roughly seven per arm, assessed by Corneometer, Tewameter, Cutometer and a crow's feet grading scale. The authors report palmitoyl pentapeptide-4 performing better than acetylhexapeptide-3 and placebo, and describe the work as initial, needing an adequate sample size. No conflicts reported.

     Journal of Clinical and Aesthetic Dermatology, 2023· 21 people

   • found nothingThis one had no seller behind it, and it found nothing. 19 women put the same hyaluronic acid serum on both sides of the face for four weeks, with Argireline added on one side only. Nobody involved knew which side was which, and a camera system read the wrinkles. Scores drifted down slightly on both sides, not enough to count on either, and the two sides ended up the same. The author declares no competing interests, and states the companies involved had no say in the study.

     The numbers Split-face double-blind study in 19 women: the same hyaluronic acid serum with and without Argireline on opposite sides of the face for four weeks, read by VISIA imaging. Wrinkle scores fell non-significantly on both sides (right p=0.060, left p=0.176) and the two sides did not differ (p=0.829). The author declares no competing interests and states the companies involved had no influence on the study, its analysis or its publication.

     GMS Interdisciplinary Plastic and Reconstructive Surgery DGPW, 2023· 19 peopleobserved only, nobody was given it

3. 03MatrixylPeptideModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 114 people given it.7 reported

   93 people given it1 trial

   • This is the best designed trial any of these cosmetic peptides has, and the peptide won. Ninety three women put the active cream on one side of the face and a plain moisturiser on the other for twelve weeks. Each woman was her own comparison, which removes most of the ways skin studies mislead. Wrinkles and fine lines improved more on the treated side. The comparison was a plain moisturiser, not nothing at all, and the change is a cosmetic one measured over three months.

     The numbers 93 women, 12-week split-face trial: pal-KTTKS significantly reduced wrinkles and fine lines versus placebo moisturizer.

     International Journal of Cosmetic Science, 2005· 93 people

4. 04Argireline with Matrixyl and SNAP-8BlendLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 60 people given it.6 reported

   60 people given it1 trial1 found nothing

   • found nothingArgireline cream reduced wrinkle roughness in a small, short, four week test. 60 people were put by chance, three to one, on argireline or a dummy cream, twice a day around the eyes. Judges scoring by eye rated about half the argireline group as improved overall, and the dummy group not at all. Silicone moulds of the skin agreed. They showed a measured drop in roughness that the dummy group did not show. Sixty people, four weeks, one patch of face, and argireline on its own.

     The numbers 60 subjects randomised 3 to 1 to argireline or placebo applied to peri-orbital wrinkles twice daily for four weeks. Subjective global assessment gave total anti-wrinkle efficacy of 48.9% for argireline against 0% for placebo. Objective analysis of silicone skin replicas found roughness parameters decreased in the argireline group at p < 0.01 with no significant decrease in placebo. Argireline alone, four weeks, on one facial area.

     American Journal of Clinical Dermatology, 2013· 60 people

   What people using it report

   • Fine lines around the eyes looking softer after several weeks.
5. 05SNAP-8PeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 24 people given it.7 reported

   24 people given it1 trial, 1 watch-only

   • One eye got the active patch and the other got a plain one, which is a fair way to test a face. Twenty four healthy people wore them for four weeks. The treated side showed better wrinkle improvement, held water in the skin better and was more elastic, with no side effects reported. As in the earlier patch study, this peptide was one of several active ingredients. The result belongs to the patch and not to the peptide.

     The numbers 24 healthy subjects wore a hyaluronic acid microneedle patch containing acetyl octapeptide-3 on one eye and a hyaluronic-acid-only placebo patch on the other for 28 days. The active side showed better eye-wrinkle improvement, lower transepidermal water loss and improved elasticity with no adverse effects. As in the 2020 patch study, acetyl octapeptide-3 was one of several actives, so the result is not attributable to SNAP-8 alone.

     Annals of Dermatology, 2024· 24 people

   • A patch containing this peptide reduced fine lines, but the peptide cannot take the credit. People used it for twelve weeks and finished with about a quarter fewer fine lines. The patch carried several active ingredients at once, along with hyaluronic acid and the tiny needles that deliver it. Nothing in the design separates one ingredient from another. There is no trial of this peptide on its own in a patch like this.

     The numbers 12-week study of a multi-ingredient patch containing acetyl octapeptide-3 reported 25.8% fewer fine lines; not attributable to SNAP-8 alone.

     Journal of Cosmetic Dermatology, 2020· number of people not givenobserved only, nobody was given it

6. 06SetmelanotidePeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 38 people given it.4 reported

   nobody was given it1 watch-only study

   • In rare genetic forms of obesity most patients lost serious weight, and there was nobody to compare them against. After about a year, 8 of 10 people with one gene fault and 5 of 11 with the other had lost at least a tenth of their body weight. Reported hunger fell by roughly a third in one group and nearly half in the other. Nearly everyone got darker skin and reactions where they injected. These gene faults are very rare, and this says nothing about ordinary obesity.

     The numbers At about one year, 8 of 10 (80%) POMC-deficiency and 5 of 11 (45%) LEPR-deficiency participants lost at least 10% of body weight, with hunger scores down 27% and 44%; hyperpigmentation and injection-site reactions were near-universal.

     The Lancet Diabetes & Endocrinology, 2020· number of people not givenobserved only, nobody was given it

Vitamins, minerals, amino acids and botanicals sold over the counter, held to the same standard.

1. 01Collagen peptidesSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 69 people given it.4 reported

   69 people given it1 trial

   • This is the skin study the ads lean on. 69 women aged 35 to 55 took 2.5 grams or 5 grams of a branded collagen peptide, or a dummy pill, for 8 weeks. Skin stretch, the measure they named first, improved against the dummy in both dose groups. Moisture and water loss did not clearly change. Some authors have ties to the maker of the peptide. A dummy comparison cannot tell you whether ordinary protein would have done the same.

     The numbers 69 women aged 35 to 55 randomised to 2.5 g or 5.0 g collagen hydrolysate or placebo daily for 8 weeks. Skin elasticity, the primary outcome, improved versus placebo in both dose groups. Moisture and transepidermal water loss did not reach significance. Manufacturer-affiliated authors.

     Skin Pharmacology and Physiology, 2014· 69 people

2. 02IdebenoneSupplementModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 732 people given it.

   41 people given it1 trial

   • A skin cream study with no honest comparison. 41 women aged 30 to 65 with sun damaged skin used an idebenone lotion twice a day for six weeks. Graders scored the stronger version as cutting roughness and dryness by about a quarter, cutting fine lines by about a third, and raising hydration by a third. Nobody used the same lotion base without idebenone in it. Any moisturiser improves these scores, so there is no way to know what the active ingredient did.

     The numbers 41 women aged 30 to 65 with moderate photodamage used 0.5 or 1.0 percent idebenone lotion twice daily for six weeks. With the 1.0 percent formula, graders scored a 26 percent reduction in roughness and dryness, 29 percent reduction in fine lines and wrinkles, 37 percent increase in hydration and 33 percent global improvement. The paper describes itself as a nonvehicle control study, so the lotion base itself was never controlled for.

     Journal of Cosmetic Dermatology, 2005· 41 people

Supplements

1. 01Ginsenoside Rg3SupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 24 people given it.

   1 animal or lab study

   Measured in animals or in the lab

   • In a dish. The 20(S) form brought worn-out human skin cells back to a younger state by restoring their energy supply and changing growth and repair signals. The 20(R) form did not. This is bringing worn-out cells back, not clearing them.

     The numbers Cultured human dermal fibroblasts. 20(S)-Rg3 reversed replicative senescence by restoring ATP and the NAD+ to NADH ratio and modulating Akt, mTOR and sirtuin signalling; the 20(R) isomer did not. Reversal of senescence, not clearance of senescent cells.

     Journal of Ginseng Research, 2020· lab (cells in a dish)