Literature Review & Applicable Pharmacology
Modern active ingredients, supported by extensive and replicated clinical data.
Procyanindin B2
The most potent B-type procyanidin for hair growth. Included in systemK11 & TOPK11
Mechanism of Action
Counters TGF-β-induced telogen, elongating anagen
Best Practices for Formulations
Oral administration in gastric-resistant capsules, at 400mg BID. Pharmacokinetic enhancer (e.g. piperine) is recommended.
Study Citation
Participants, Duration & Design
Dose & Administration Route
Efficacy Outcomes
Safety, Adverse Events & Notes
De Biasio 2023; Yeniay 2022; Tenore 2018; Takahashi 2005; Takahashi 2001
442 adults; 2–6-month double-blind randomised controlled trials
400 mg BID (Procyanidin B2-enriched) or topical 0.7–1% BID
Topical: +13.8 to +24.8 hairs/cm² vs placebo (p<0.001); Oral: +14 to +19.2 hairs/cm² (significant); consistent gains across studies
Excellent tolerability; no serious AEs; occasional mild local scaling/itching with topical
Review studies in detail
Procyanindin B2
The most potent B-type procyanidin for hair growth. Included in systemK11 & TOPK11
Mechanism of Action
Counters TGF-β-induced telogen, elongating anagen
Best Practices for Formulations
Oral administration in gastric-resistant capsules. Pharmacokinetic enhancer (e.g. piperine) is recommended.
De Biasio 2023; Yeniay 2022; Tenore 2018; Takahashi 2005; Takahashi 2001
442 adults; 2–6-month double-blind randomised controlled trials
400 mg BID (Procyanidin B2-enriched) or topical 0.7–1% BID
Topical: +13.8 to +24.8 hairs/cm² vs placebo (p<0.001); Oral: +14 to +19.2 hairs/cm² (significant); consistent gains across studies
Excellent tolerability; no serious AEs; occasional mild local scaling/itching with topical
Review studies in detail
Procyanindin B2
The most potent B-type procyanidin for hair growth. Included in systemK11 & TOPK11
Mechanism of Action
Counters TGF-β-induced telogen, elongating anagen
Best Practices for Formulations
Oral administration in gastric-resistant capsules. Pharmacokinetic enhancer (e.g. piperine) is recommended.
Study Citation
Participants, Duration & Design
Dose & Administration Route
Efficacy Outcomes
Safety, Adverse Events & Notes
De Biasio 2023; Yeniay 2022; Tenore 2018; Takahashi 2005; Takahashi 2001
442 adults; 2–6-month double-blind randomised controlled trials
400 mg BID (Procyanidin B2-enriched) or topical 0.7–1% BID
Topical: +13.8 to +24.8 hairs/cm² vs placebo (p<0.001); Oral: +14 to +19.2 hairs/cm² (significant); consistent gains across studies
Excellent tolerability; no serious AEs; occasional mild local scaling/itching with topical
Review studies in detail
Bimatoprost
FDA-approved drug for glaucoma and eyelash hypotrichosis by increasing eyelash length & thickness.
Mechanism of Action
Prostaglandin F2α analog, elongating anagen
Best Practices for Formulations
0.3% bimatoprost showed the best results. Penetration enhancers are also recommended.
Study Citation
Participants, Duration & Design
Dose & Administration Route
Efficacy Outcomes
Safety, Adverse Events (AEs) & Notes
NCT01904721; NCT02170662; NCT01325337; NCT01325350; Aryaningrum 2018
874 adults with AGA; mostly 4–6-mo, double-blind Phase II RCTs; plus a small crossover and a single-arm
Topical 0.03–0.3% bimatoprost QD–BID; controls: placebo and 2–5% minoxidil
Best men’s arm: +13.1 hairs/cm² vs +4.1 placebo (p=0.005); Crossover +27.4% on-drug; small single-arm ↑ vellus diameter 88%; women’s not significant vs placebo;
Mostly mild local AEs (pruritus/dryness); some hypertrichosis; URTIs/rare serious events reported but judged unrelated; overall well tolerated
Review studies in detail
Bimatoprost
FDA-approved drug for glaucoma and eyelash hypotrichosis by increasing eyelash length & thickness.
Mechanism of Action
Prostaglandin F2α analog, elongating anagen
Best Practices for Formulations
0.3% bimatoprost showed the best results. Penetration enhancers are also recommended.
NCT01904721; NCT02170662; NCT01325337; NCT01325350; Aryaningrum 2018
874 adults with AGA; mostly 4–6-mo, double-blind Phase II RCTs; plus a small crossover and a single-arm
Topical 0.03–0.3% bimatoprost QD–BID; controls: placebo and 2–5% minoxidil
Best men’s arm: +13.1 hairs/cm² vs +4.1 placebo (p=0.005); Crossover +27.4% on-drug; small single-arm ↑ vellus diameter 88%; women’s not significant vs placebo;
Mostly mild local AEs (pruritus/dryness); some hypertrichosis; URTIs/rare serious events reported but judged unrelated; overall well tolerated
Review studies in detail
Bimatoprost
FDA-approved drug for glaucoma and eyelash hypotrichosis by increasing eyelash length & thickness.
Mechanism of Action
Prostaglandin F2α analog, elongating anagen
Best Practices for Formulations
0.3% bimatoprost showed the best results. Penetration enhancers are also recommended.
Study Citation
Participants, Duration & Design
Dose & Administration Route
Efficacy Outcomes
Safety, Adverse Events (AEs) & Notes
NCT01904721; NCT02170662; NCT01325337; NCT01325350; Aryaningrum 2018
874 adults with AGA; mostly 4–6-mo, double-blind Phase II RCTs; plus a small crossover and a single-arm
Topical 0.03–0.3% bimatoprost QD–BID; controls: placebo and 2–5% minoxidil
Best men’s arm: +13.1 hairs/cm² vs +4.1 placebo (p=0.005); Crossover +27.4% on-drug; small single-arm ↑ vellus diameter 88%; women’s not significant vs placebo;
Mostly mild local AEs (pruritus/dryness); some hypertrichosis; URTIs/rare serious events reported but judged unrelated; overall well tolerated
Review studies in detail
Cetirizine
FDA-approved antihistamine drug for allergies and hives, available OTC since 2007.
Mechanism of Action
Shifts prostaglandins balance (↓ PGD2, ↑ PGE2) and acts as an anti-inflammatory
Best Practices for Formulations
1% cetirizine HCl for improved solubility
Study Citation
Participants, Duration & Design
Dose & Administration Route
Efficacy Outcomes
Safety, Adverse Events (AEs) & Notes
Bassiouny 2022; Mostafa 2021; Zaky 2021; Rossi 2018
251 adults; 4–6-mo blinded randomised controlled trials and one pilot
1% topical cetirizine QD–BID; sometimes added to 5% minoxidil
Monotherapy: +8.5 to +30.3 hairs/cm² vs placebo; 43% new growth vs 0% placebo; as add-on, minoxidil + cetirizine > minoxidil + placebo (p<0.05)
Well tolerated; no systemic signals; AEs sparsely detailed in some trials
Review studies in detail
Cetirizine
FDA-approved antihistamine drug for allergies and hives, available OTC since 2007.
Mechanism of Action
Shifts prostaglandins balance (↓ PGD2, ↑ PGE2) and acts as an anti-inflammatory
Best Practices for Formulations
1% cetirizine HCl for improved solubility
Mostafa 2021; Bassiouny 2022; Zaky 2021; Rossi 2018
251 adults; 4–6-mo blinded randomised controlled trials and one pilot
1% topical cetirizine QD–BID; sometimes added to 5% minoxidil
Monotherapy: +8.5 to +30.3 hairs/cm² vs placebo; 43% new growth vs 0% placebo; as add-on, minoxidil + cetirizine > minoxidil + placebo (p<0.05)
Well tolerated; no systemic signals; AEs sparsely detailed in some trials
Review studies in detail
Cetirizine
FDA-approved antihistamine drug for allergies and hives, available OTC since 2007.
Mechanism of Action
Shifts prostaglandins balance (↓ PGD2, ↑ PGE2) and acts as an anti-inflammatory
Best Practices for Formulations
1% cetirizine HCl for improved solubility
Study Citation
Participants, Duration & Design
Dose & Administration Route
Efficacy Outcomes
Safety, Adverse Events (AEs) & Notes
Mostafa 2021; Bassiouny 2022; Zaky 2021; Rossi 2018
251 adults; 4–6-mo blinded randomised controlled trials and one pilot
1% topical cetirizine QD–BID; sometimes added to 5% minoxidil
Monotherapy: +8.5 to +30.3 hairs/cm² vs placebo; 43% new growth vs 0% placebo; as add-on, minoxidil + cetirizine > minoxidil + placebo (p<0.05)
Well tolerated; no systemic signals; AEs sparsely detailed in some trials
Review studies in detail
Modern ingredients, supported by smaller data sets or unique mechanisms of action
Adenosine
Naturally occurring nucleoside
Mechanism of Action
Promotes pro-anagen signalling through adenosine receptor activation at DP
Best Practices for Formulations
0.75% in aqueous-based solution for twice daily application
Tocotrienols
Potent anti-oxidants in the vitamin E family. Included in systemK11 & TOPK11
Mechanism of Action
Antioxidant - reduces oxidative linked with alopecia and TGF-beta expression.
Best Practices for Formulations
High-dose oral vitamin E has risks. Sub-15 mg/day suggested. Combine with astaxanthin or ergothioneine which directly improve mitochondrial function.
Rice Bran Extract
Topical phytosterol-rich extract that increases hair density in a rigorous human study.
Mechanism of Action
5-alpha reductase inhibition, via phytosterol derivatives.
Best Practices for Formulations
Topical application, with rice bran extracted via supercritical CO2.
Fenugreek Seed Extract
A culinary and medicinal seed rich in saponins, fibre, and nutrients; used traditionally for digestion and metabolism.
Included in systemK11 & TOPK11
Mechanism of Action
Steroidal saponins may blunt DHT activity and glucose metabolism modulation through 4-HIL.
Best Practices for Formulations
Oral administration. Standardised seed extracts for both saponin and soluble dietary fibre (galactomannan).
Sulforaphane glucosinolate
A broccoli-derived isothiocyanate.
Included in systemK11
Mechanism of Action
Upregulates 3α-HSD, an enzyme that degrades DHT into less damaging metabolites.
Best Practices for Formulations
Oral administration of sulforaphane glucosinolate (sulforaphane precursor) co-administered with myrosinase enzyme.
Equol
A metabolite of a legume isoflavone.
Currently used in prostate health.
Mechanism of Action
Reversibly binds to DHT directly with high specificity,
Best Practices for Formulations
Topical applications prevent equol from being conjugated. Dose-ranging and delivery studies are needed.
Review studies in detail
Adenosine
Naturally occurring nucleoside
Tocotrienols
Potent anti-oxidants in the vitamin E family. Included in systemK11 & TOPK11
Rice Bran Extract
Topical phytosterol-rich extract that increases hair density in a rigorous human study.
Fenugreek Seed Extract
A culinary and medicinal seed rich in saponins, fibre, and nutrients; used traditionally for digestion and metabolism.
Included in systemK11 & TOPK11
Sulforaphane glucosinolate
A broccoli-derived isothiocyanate.
Included in systemK11
Equol
A metabolite of a legume isoflavone.
Currently used in prostate health.
Review studies in detail
Adenosine
Naturally occurring nucleoside
Mechanism of Action
Promotes pro-anagen signalling through adenosine receptor activation at DP
Best Practices for Formulations
0.75% in aqueous-based solution for twice daily application
Tocotrienols
Potent anti-oxidants in the vitamin E family. Included in systemK11 & TOPK11
Mechanism of Action
Antioxidant - reduces oxidative linked with alopecia and TGF-beta expression
Best Practices for Formulations
Long-term high-dose vitamin E has risks. Sub-15 mg/day suggested. Combine with astaxanthin or ergothioneine which are associated with longevity.
Rice Bran Extract
Topical phytosterol-rich extract that increases hair density in a rigorous human study.
Mechanism of Action
5-alpha reductase inhibition, via phytosterol derivatives
Best Practices for Formulations
Topical application, with rice bran extracted via supercritical CO2.
Fenugreek Seed Extract
A culinary and medicinal seed rich in saponins, fibre, and nutrients; used traditionally for digestion and metabolism.
Included in systemK11 & TOPK11
Mechanism of Action
Steroidal saponins may blunt DHT activity and glucose metabolism modulation through 4-HIL
Best Practices for Formulations
Standardised seed extracts for both saponin and soluble dietary fibre (galactomannan)
Sulforaphane glucosinolate
A broccoli-derived isothiocyanate.
Included in systemK11
Mechanism of Action
Upregulates 3α-HSD, an enzyme that degrades DHT into less damaging metabolites
Best Practices for Formulations
Oral administration of sulforaphane glucosinolate (sulforaphane precursor) co-administered with myrosinase enzyme.
Equol
A metabolite of a legume isoflavone.
Currently used in prostate health.
Mechanism of Action
Specifically binds to DHT directly, reducing androgen receptor activation
Best Practices for Formulations
Topical applications prevent equol from being conjugated. Dose-ranging and delivery studies are needed.
Review studies in detail
