Biotinoyl Tripeptide-1 (Procapil)
Biotinoyl Tripeptide-1 with Oleanolic Acid and Apigenin (marketed as Procapil)
Three-ingredient complex with plausible biology but widely misrepresented marketing claims and no peer-reviewed human trial of the peptide alone.
How Biotinoyl Tripeptide-1 (Procapil) works — and how well we know it
Procapil is a three-ingredient complex: biotinoyl tripeptide-1 (biotin-conjugated GHK matrikine peptide that stimulates ECM proteins like laminin-5, collagen IV, and vimentin for hair anchoring and delivers biotin to follicular cells), oleanolic acid (an olive leaf triterpene that inhibits 5-alpha reductase and DHT production), and apigenin (a citrus-derived flavonoid with vasodilatory effects for scalp microcirculation). The anti-DHT activity comes from oleanolic acid, not from the peptide.
topical
3% Procapil in topical lotion or serum, applied daily
Cosmeceutical ingredient. Not approved by any regulatory agency for hair loss. Marketed as a cosmetic active by Sederma (Croda International).
Cosmetic adjunct to proven treatments; not a standalone therapy.
Evidence distribution across 6 claims
Why the grade is D. No peer-reviewed clinical trial has ever tested biotinoyl tripeptide-1 alone in humans. The only placebo-controlled human trial of the full Procapil complex (N=18 active) was the manufacturer's unpublished pilot. The key marketing claims (58% hair loss reduction, 35% density increase) are misrepresentations of ex vivo and response-rate data.
What the studies actually showed
Unknown from rigorous data. The Sederma pilot measured at 4 months and reported effects at that timepoint. The Samadi 2024 trial showed physician-assessed improvement at 6 weeks. Marketing materials suggest 2-4 months for initial effects, but this is not supported by controlled data for Procapil alone.
Unknown. No study has tracked Procapil alone long enough with adequate methodology to establish peak effect. The Fahim 2024 trial (12 months) showed continued benefit through the study period, but tested Procapil combined with minoxidil.
Yes — must continue indefinitely
Unknown. No published data exists on what happens to hair after stopping Procapil. By analogy with other non-curative topicals (e.g., minoxidil), any gains would likely reverse over months after discontinuation, but this has never been studied for Procapil.
Side effects, contraindications, and special populations
| Adverse event | Rate | Placebo | Notes |
|---|---|---|---|
| Scalp irritation (redness, itching, dryness) | Not formally quantified; zero cases reported in the Samadi 2024 (N=20) and Garre 2018 (N=56) trials | — | Possible with any topical product, particularly in individuals with sensitive skin. More likely related to the vehicle/excipients (alcohol base in Sederma formulations) than to Procapil's active ingredients. Patch testing recommended for sensitive individuals. |
| Contact dermatitis / allergic reaction | Not formally quantified; no cases reported in published trials | — | Individuals with known allergies to olive-derived compounds should use caution due to the oleanolic acid component (olive leaf extract). Apigenin (citrus-derived) could theoretically cause reactions in individuals with citrus sensitivities. No published case reports of allergic reactions to Procapil specifically. |
| Changes in hair texture (oiliness or dryness) | Anecdotal reports only; not documented in any clinical trial | — | Some consumer reports mention changes in hair texture. This may be attributable to the formulation vehicle rather than the active ingredients. |
- None reported in published literature (0% across all published studies) — No serious adverse events have been attributed to Procapil or biotinoyl tripeptide-1 in any published study. However, total patient exposure in published trials is very small (fewer than 200 patients across all studies and indications), so rare events could easily be missed. The absence of reported serious AEs reflects an inadequate safety database rather than a demonstrated superior safety profile.
- Known allergy to olive-derived compounds (Relative) — Procapil contains oleanolic acid derived from olive leaf extract. Individuals with documented olive or Olea europaea allergy should avoid Procapil products or perform patch testing before use.
- Known allergy to citrus-derived compounds (Relative) — Procapil contains apigenin, a flavonoid derived from citrus. Individuals with citrus sensitivities should exercise caution.
- Known hypersensitivity to biotin or any component of the formulation (Absolute) — Standard contraindication for any cosmetic product. The peptide component is a biotin-conjugated tripeptide.
- Active scalp dermatitis, eczema, or psoriasis (Relative) — No specific data, but individuals with active inflammatory scalp conditions should consult a dermatologist before applying any new topical active. The alcohol-based vehicle used in some Procapil formulations may exacerbate these conditions.
- None established (N/A) — No drug interactions have been formally studied or reported for topical Procapil or biotinoyl tripeptide-1. Systemic absorption from topical scalp application of a peptide at cosmetic concentrations (3%) is expected to be negligible, making clinically significant systemic interactions extremely unlikely.
- 5-alpha reductase inhibitors (finasteride, dutasteride) (Theoretical — likely additive, not harmful) — Oleanolic acid in Procapil inhibits 5-alpha reductase. Co-use with oral 5-ARIs could theoretically produce additive DHT reduction. No interaction data exists, but the topical concentration and low systemic absorption make a clinically meaningful interaction unlikely. More plausibly a rationale for combination therapy than a safety concern.
- Biotin supplements (high-dose) (Informational) — Biotinoyl tripeptide-1 delivers biotin to follicular cells. Concurrent high-dose oral biotin supplementation is unlikely to interact but represents redundant biotin delivery. Note: high-dose biotin (>5 mg/day) can interfere with laboratory assays (troponin, TSH, etc.) — this is a biotin supplement concern, not a Procapil interaction.
No reproductive toxicity studies have been conducted for Procapil or biotinoyl tripeptide-1. The effects on fetal development are completely unknown. Oleanolic acid has shown some reproductive effects in animal studies at high systemic doses, but topical scalp application at 3% concentration involves negligible systemic exposure. Despite the low theoretical risk, the only responsible recommendation is avoidance during pregnancy given the complete absence of safety data.
No sex-specific safety concerns identified. Procapil has been tested in mixed-sex populations (Garre 2018 included both men and women) without sex-specific adverse signals. The mechanisms (ECM remodeling, 5-AR inhibition via oleanolic acid, vasodilation via apigenin) are not hormone-dependent in a way that would create sex-specific risks. Women are a primary target market for Procapil products.
Not recommended. No pediatric safety data exists. Procapil products are marketed for adult use only. Hair loss in children warrants medical evaluation, not cosmeceutical treatment.
Every claim, traced back to its source
We took every major claim made about Biotinoyl Tripeptide-1 (Procapil) and matched it to the specific experimental model behind it. Click a claim to see the model, the finding, and our assessment of how much weight it deserves.
6 claims · evidence-by-evidence breakdown
1Ex VivoWeight: Low to ModerateBiotinoyl tripeptide-1 produces a 58% reduction in hair lossMisrepresented ex vivo follicle elongation data, not clinical hair loss reduction; minoxidil doubled it in the same assay.
Ex vivo -- human hair follicle organ culture (follicles maintained alive in culture medium for 14 days). This experiment was conducted by BIOALTERNATIVES (a contract research organization) on behalf of Sederma. It tested the peptide alone (not the full Procapil complex).
At 2 ppm biotinyl-GHK (equivalent to 1% Procapil), hair follicles showed +58% superior hair growth compared to untreated controls at day 14. At 5 ppm, the same +58% increase. For comparison, minoxidil at 2 ppm (10 micromol/L) achieved +121% growth vs control in the same assay.
Here's the critical detail: the "58%" refers to hair follicle elongation in an organ culture dish over 14 days. It has been widely repackaged in marketing as a "58% reduction in hair loss" -- which sounds like a clinical trial result showing 58% fewer hairs falling out. It's not. It's ex vivo data showing follicles in a lab dish grew 58% longer with the peptide than without it. That's a meaningful biological signal, but (a) it's never been published in a peer-reviewed journal (only in the Sederma technical file), (b) organ culture doesn't replicate the scalp environment (no blood flow, hormones, or immune system), and (c) minoxidil outperformed it 2:1 in the same assay.
- Sederma / BIOALTERNATIVES (2012). Sederma Technical File: Procapil. Proprietary (not peer-reviewed)
2Open-LabelWeight: Very LowBiotinoyl tripeptide-1 produces a 35% increase in hair densityMisquoted response rate from multi-ingredient study; no study reports a 35% measured density increase.
Unverifiable. After extensive searching, no study was found that reports a 35% increase in measured hair density for biotinoyl tripeptide-1 or Procapil.
The number "35.7%" does appear in one clinical study (Garre et al., 2018), but it refers to the percentage of participants (35.7% of 56 patients) who were rated as having "thicker, more voluminous hair" by clinical assessment -- NOT a 35% increase in hair density. This appears to be the origin of the misquoted claim: "35.7% of people rated as improved" was transformed into "35% increase in density" somewhere in the marketing pipeline.
Same pattern we saw with Capixyl's claims: a real number gets pulled out of context and transformed into a different, more impressive-sounding metric. 35.7% of patients showing subjective improvement is a very different claim than 35% measured density increase. Be wary of any product citing this number.
- Garre et al. (2018). Multi-ingredient study (open-label, no control group). Journal of Cosmetic Dermatology
3Ex VivoWeight: Low to ModerateBiotinoyl tripeptide-1 strengthens hair anchoring through structural proteinsUnpublished manufacturer data showing ECM protein upregulation in organ culture; never validated in vivo or peer-reviewed.
Ex vivo -- human hair follicle organ culture, 14 days, treated with biotinyl-GHK. Measured via fluorescent antibody staining and DNA array analysis. Conducted by Sederma (proprietary data).
Peptide-treated follicles maintained laminin-5 and collagen IV layer thickness, while untreated follicles lost most of their structural proteins over the culture period. DNA array analysis showed adhesion complex proteins (vimentin, desmoglein, desmocollin, fibronectin receptor, laminin-binding protein) and cell proliferation markers were upregulated by 30-90% over baseline.
The protein data is biologically interesting -- these are the right proteins for hair anchoring, and the upregulation is meaningful in magnitude. But: (1) this is manufacturer data that has never been peer-reviewed, (2) it's ex vivo organ culture, not human scalp in vivo, (3) no direct measure of anchoring force (like a pull test) was performed, and (4) whether these protein changes translate to clinically meaningful hair retention on a living scalp is unknown.
- Sederma (2012). Sederma Technical File: Procapil. Proprietary (not peer-reviewed)
4In VivoWeight: LowProcapil inhibits DHT through 5-alpha reductase inhibitionDHT inhibition is real but comes entirely from oleanolic acid (plant extract), not the peptide component.
In vitro and in vivo -- the DHT inhibition comes from oleanolic acid (the olive leaf extract component), NOT from biotinoyl tripeptide-1.
Oleanolic acid inhibited 5-alpha reductase enzyme by 68% and inactivated 54% of testosterone conversion to DHT in a 3% formulation on skin (in-vitro/manufacturer data). In a 2023 mouse study (Zhang 2023, J Appl Biomed), oleanolic acid was reported to reduce DHT, 5-alpha reductase, TNF-alpha, and TGF-beta1 in dorsal skin and to stimulate VEGF and Wnt/beta-catenin. Interpret with caution: that study also reported minoxidil lowering DHT and 5-alpha reductase, which contradicts established pharmacology -- minoxidil is a vasodilator, not a 5-alpha reductase inhibitor, and does not meaningfully reduce DHT. A study whose comparator shows an implausible DHT effect casts doubt on its DHT/5-AR measurements for oleanolic acid too, so the 'greater than minoxidil' framing is not reliable.
Like Capixyl's biochanin A, the anti-DHT effect is real but belongs to the plant-derived component, not the peptide. If you're buying a product "because of the peptide" and the mechanism you care about is DHT reduction, you're attributing the effect to the wrong ingredient. Oleanolic acid is widely available and doesn't require an expensive peptide delivery vehicle.
- Sederma (2012). Sederma Technical File: Procapil. Proprietary
- Mouse skin study authors (2023). Oleanolic acid effects on DHT and hair growth pathways in mouse skin PMID 37016778
5RCTWeight: Low to ModerateClinical trials demonstrate Procapil's efficacy for hair lossOnly placebo-controlled test was an unpublished manufacturer pilot (N=18); independent trials combine Procapil with other actives.
Multiple human studies, but all testing multi-ingredient formulations: Study A (Sederma pilot, ~2005): N=35 (18 active), RCT, 3% Procapil lotion vs placebo, 4 months. 67% of treated volunteers showed improved anagen/telogen ratio. Never peer-reviewed. Study B (Fahim et al., 2024): N=140, RCT, 12 months. 5% Procapil alternated with minoxidil vs minoxidil alone. Combination showed better hair count, satisfaction, and dermatologist assessment. Does not isolate Procapil from minoxidil synergy. Study C (Samadi et al., 2024): N=20, single-arm (no control), 12 weeks. Caffeine + Procapil 3%. 84.2% rated as improved. Tested with caffeine, no control group. Study D (Pavithra & Rajashekar, 2023): N=54, RCT, 6 months. Procapil+PRP vs Redensyl+PRP. Procapil+PRP showed 11.9% improvement vs Redensyl combo's 21.9% -- Procapil was the LESS effective group.
The manufacturer's pilot shows a signal vs placebo. The largest independent RCT (N=140) shows benefit when combined with minoxidil. The head-to-head with Redensyl combination was unfavorable for Procapil.
The clinical evidence is real but weak. Key issues: (1) The only placebo-controlled test of Procapil alone was the manufacturer's unpublished pilot with just 18 active subjects. (2) The strongest independent trial (N=140) tested Procapil WITH minoxidil, not alone. (3) The one head-to-head comparison that included a Procapil arm (Pavithra 2023) showed it performed worse than a Redensyl combination. (4) No study has ever tested biotinoyl tripeptide-1 in isolation in humans.
- Sederma (2005). Sederma Technical File: Procapil pilot clinical trial. Proprietary (not peer-reviewed)
- Fahim et al. (2024). Procapil with minoxidil vs minoxidil alone for androgenetic alopecia. J Pak Assoc Dermatol
- Samadi et al. (2024). Caffeine and Procapil 3% for hair loss. J Cosmet Dermatol
- Pavithra & Rajashekar (2023). Procapil+PRP vs Redensyl+PRP for androgenetic alopecia. Cureus PMID PMC10246929
6In VivoWeight: Low to ModerateBiotin-GHK conjugation enhances follicular delivery and has applications in wound healingIndependent, peer-reviewed wound healing data in rats; delivery enhancement plausible but unproven for human hair.
In vitro and in vivo (rat dermal wound model). The wound healing evidence comes from Arul et al. (2005, 2007), who incorporated biotinylated GHK into collagenous matrices and tested them on rat dermal wounds. Also: Ferraro et al. (2023) synthesized Cu(II)-BioGHK and demonstrated antioxidant, antiglycant, and anti-amyloid aggregation properties in vitro.
Biotinylated GHK in collagen matrices improved wound contraction, increased cell proliferation, and showed high antioxidant enzyme expression in rat wounds. The Cu(II)-BioGHK complex showed greatest anti-aggregant activity against amyloid-beta aggregation, suggesting potential neuroprotective applications. The biotin conjugation preserves GHK's copper-binding ability while potentially enhancing cellular uptake and delivery.
The wound healing data is peer-reviewed and from independent academic labs, which gives it more credibility than the hair-specific claims. The Alzheimer's/amyloid-beta finding is early-stage but interesting. The delivery enhancement rationale (biotin enabling better cellular uptake) is biologically plausible. However, these are rat wounds and test-tube experiments -- translation to human applications needs clinical validation.
- Arul et al. (2005). Biotinylated GHK peptide incorporated collagenous matrix for dermal wound healing. J Biomed Mater Res PMID 15803494
- Arul et al. (2007). Biotinylated GHK peptide in collagen matrix for wound repair PMID 17049946
- Ferraro et al. (2023). Cu(II)-BioGHK complex: antioxidant, antiglycant, and anti-amyloid aggregation properties. Molecules PMID PMC10538196
What's still missing from the science
- Any peer-reviewed clinical trial testing biotinoyl tripeptide-1 alone for hair.
- Any peer-reviewed publication of the Sederma pilot clinical trial data.
- An independent, placebo-controlled trial of Procapil alone (not combined with minoxidil, caffeine, or other actives).
- Proof that biotin conjugation actually enhances follicular delivery compared to unconjugated GHK or biotin alone.
- Verifiable sources for the "58% reduction in hair loss" and "35% increase in density" claims as commonly marketed.
- Head-to-head comparison of Procapil vs standard-of-care (5% minoxidil or finasteride) with adequate sample size.
Our verdict on Biotinoyl Tripeptide-1 (Procapil)
Not in our formulary yet
We don't carry this ingredient. We only formulate around actives where the evidence — and the safety profile — is strong enough to recommend with confidence. As the data matures, we may revisit.
From the Anagen blog
Long-form analysis and primary-source breakdowns that go beyond the summary above.
Related treatments
How does Biotinoyl Tripeptide-1 (Procapil) stack up against its closest peers?
Two-component complex with plausible mechanisms but thin clinical evidence and key claims traceable to fabricated citations.
Read the breakdown →Strong preclinical rationale from wound healing and genomics, but no rigorous human trial of topical GHK-Cu alone for hair loss.
Read the breakdown →Strongest preclinical hair biology of any peptide, but zero human hair trials -- best evidence is for wound healing, dry eye, and cardiac repair.
Read the breakdown →