Product Ingrediants Research

Botanical composition found in HairGenesis™ based on substances that have demonstrated biochemical activity useful in the context of pattern hair loss

Numerous Independent, Third-party Scientific Studies
Supporting HairGenesis™ Botanical Ingredients

Epigallocatechin-3-gallate (EGCG)

1)  Peer reviewed, indepedent, medical study in support of epigallocatechin-3-gallate:

Phytomedicine. 2007 Aug;14(7-8):551-5. Epub 2006 Nov 7.
Links
Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG).
Kwon OS, Han JH, Yoo HG, Chung JH, Cho KH, Eun HC, Kim KH.
Department of Dermatology, Seoul National University College of Medicine, Laboratory of Cutaneous Aging and Hair Research, Seoul National University Hospital, Institute of Dermatological Science, Seoul National University, 110-744 Seoul, Republic of Korea.

Green tea is a popular worldwide beverage, and its potential beneficial effects such as anti-cancer and anti-oxidant properties are believed to be mediated by epigallocatechin-3-gallate (EGCG), a major constituent of polyphenols.. Recently, it was reported that EGCG might be useful in the prevention or treatment of androgenetic alopecia by selectively inhibiting 5alpha-reductase activity. However, no report has been issued to date on the effect of EGCG on human hair growth. This study was undertaken to measure the effect of EGCG on hair growth in vitro and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. EGCG promoted hair growth in hair follicles ex vivo culture and the proliferation of cultured DPCs. The growth stimulation of DPCs by EGCG in vitro may be mediated through the upregulations of phosphorylated Erk and Akt and by an increase in the ratio of Bcl-2/Bax ratio. Similar results were also obtained in in vivo dermal papillae of human scalps. Thus, we suggest that EGCG stimulates human hair growth through these dual proliferative and anti-apoptotic effects on DPCs.

LSESr (liposterolic extract of serenoa repens)

Saw Palmetto is a small shrubby palm native to Florida and has a long folk history in various healing properties. Recent studies have implicated saw palmetto as an effective treatment for benign prostatic hyperplasia (BPH). Studies point to the fatty and sterolic extracts (fatty acids: capric, caprylic, caproic, lauric, palmitic, and oleic; sterols: beta-sitosterol, stigmasterol, cycloartenol, luepol, lupenone and 24 methyl-cycloartenol) as the active molecular components responsible for its therapeutic action.

1)  Peer reviewed, indepedent, medical study in support of LSESr:

"In a large European study, one in which a pharmaceutical clinical trial model was closely followed, a saw palmetto product (permixon) was found to cause no change in standard blood tests and no change in serum prostate specific anagen levels (PSA) during a six month treatment period." Carraro et al. Prostate vol. 29 pp.231-240 1996

2)  Peer reviewed, indepedent, medical study in support of LSESr:

"Among 1,098 patients with BPH (benign prostatic hyperplasia) in that study, the general safety profile of saw palmetto compared favorably with that of Finasteride (the chemical used in the drugs Propecia [for hairloss treatment] and Proscar [for prostate treatment] ), and sexual side effects were less common with the extract than with the drug Finasteride. In particular, the use of extract has not been associated with erectile dysfunction, ejaculatory disturbance, or altered libido." Carraro et al. Prostate vol. 29 pp.231-240 1996

3)  Peer reviewed, indepedent, medical study in support of LSESr:

"Aside from an occasional instance of GI upset, side effects of saw palmetto extract have not been reported" Bach et al. Phytomedicine pp. 105-111, 1996.. "Pharmaceutical style evaluations have not yet been performed in the United States, partly because they are not required by law, and partly because the cost of such evaluations would be difficult to recoup with non-patentable products." Marks and Tyler, Urology, vol. 53, 457-461, 1999

4)  Peer reviewed, indepedent, medical study in support of LSESr:

"LSESr was found to be a three fold more potent competitor of 5AR (5-Alpha-Reductase) than Finasteride when comparing the recommended therapeutic dose by the manufacturers for the treatment of BPH. (5mg per day vs. 320mg per day LSESr Note: The hairloss treatment drug Propecia = 1mg per day Finasteride." (This suggests a fifteen-fold greater efficacy dose for dose in favor of LSESr) Delos et al., J. Steroid Biochem. Molec. Biol., vol. 48, pp 347-352, 1994

5)  Peer reviewed, indepedent, medical study in support of LSESr:

"Finasteride is a selective inhibitor of the type two isoform of 5AR (5-Alpha-Reductase), whereas LSESr markedly inhibited both type one and type two isoforms of 5-Alpha-Reductase." (Type one 5-Alpha-Reductase predominates in tissue specific to the hair follicle morphology, whereas with type two there is evidence for the expression of both) Lehle et al., J. Steroid Biochem. Molec. Biol., vol 54, 273-279, 1995

"Naturopathic physicians have used LSESr as a tonic to naturally support the body in the treatment of genital/urinary tract disturbances, in men to increase testicle function, and in women with mammary gland disorders." Murray, Vital Comm. 1990 pp 1-14

6)  Peer reviewed, indepedent, medical study in support of LSESr:

Human prostatic steroid 5 Alpha-Reductase isoforms--a comparative study of selective inhibitors.
Author
Lehlé C; Délos S; Guirou O; Tate R; Raynaud JP; Martin PM
Journal
J Steroid Biochem Mol Biol, 54: 5-6, 1995 Sep, 273-9

Abstract
The present study describes the independent expression of the Type 1 and 2 isoforms of human 5-Alpha-Reductase in the baculovirus-directed insect cell expression system and the selectivity of their inhibition. The catalytic properties and kinetic parameters of the recombinant isozymes were consistent with published data. The Type 1 isoform displayed a neutral (range 6-8) pH optimum and the type 2 isoform an acidic (5-6) pH optimum. The Type 2 isoform had higher affinity for testosterone than did the Type 1 isoform (Km = 0.5 and 2.9 microM, respectively). Finasteride and turosteride were selective inhibitors of the Type 2 isoform (Ki (type 2) = 7.3 and 21.7 nM compared to Ki (type 1) = 108 and 330 nM, respectively). 4-MA and the lipido-sterol extract of Serenoa Repens (LSESr) markedly inhibited both isozymes (Ki (type 1) = 8.4 nM and 7.2 micrograms/ml, respectively; Ki (type 2) = 7.4 nM and 4.9 micrograms/ml, respectively). The three azasteroids were competitive inhibitors vs. substrate, whereas LSESr displayed non-competitive inhibition of the Type 1 isozyme and uncompetitive inhibition of the Type 2 isozyme. These observations suggest that the lipid component of LSESr might be responsible for its inhibitory effect by modulating the membrane environment of 5-Alpha-Reductase. Partially purified recombinant 5-Alpha-Reductase Type 1 activity was preserved by the presence of lipids indicating that lipids can exert either stimulatory or inhibitory effects on human 5-Alpha-Reductase.

Beta Sitosterol

Alone and in combination with similar phytosterols, beta-sitosterol reduces blood levels of cholesterol, and is sometimes used in treating hypercholesterolemia. In the published HairGenesis™ trial (described elsewhere in this website), betasitosterol showed a positive effect on male hair loss in combination with Saw palmetto.  In Europe beta-sitosterol plays a major role in treatment of herbal therapy of benign prostatic hypertrophy (BPH).

1)  Peer reviewed, indepedent, medical study in support of betasitosterol:

Beta-sitosterol for the treatment of benign prostatic hyperplasia: a systematic review.
Author
Wilt TJ; MacDonald R; Ishani A
Address
The VA Coordinating Center of the Cochrane Collaborative Review Group in Prostatic Diseases and Urologic Malignancies, 13/Minneapolis, VA, USA.
Source
BJU Int, 83(9): 976-83 1999 Jun

Abstract
Objectives: To conduct a systematic review of the evidence for the efficacy of beta-sitosterol in men with symptomatic benign prostatic hyperplasia (BPH). METHODS: Studies were identified through Medlinetrade mark (1966-98), EMBASEtrade mark, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with study authors and pharmaceutical companies. Randomized trials were included if: men had symptomatic BPH; plant extract preparations contained beta-sitosterols; a control group received placebo or a pharmacological therapy; and treatment duration was >/=30 days. Study characteristics, demographic information, enrolment criteria and outcomes were extracted.

Results
Four trials comprising a total of 519 men met the inclusion criteria. All were double blind and lasted 4-26 weeks. Three studies used nonglucosidic beta-sitosterols and one used a preparation that contained only beta-sitosterol-beta-d-glucoside. Compared with placebo, beta-sitosterol improved urinary symptom scores and flow measures. For the two studies reporting the International Prostate Symptom Score (IPSS), the weighted mean difference (WMD) against placebo was -4.9 IPSS points (95% confidence interval, CI, -6.3 to-3.5). The WMD for peak urinary flow rate was 3.91 mL/s (95% CI 0.91 to 6.90, four studies) and for residual volume the WMD was -28.62 mL (95% CI-41.42 to-15.83, four studies). Beta-sitosterol did not reduce prostate size.The trial using pure beta-sitosterol-beta-d-glucoside (WA184) showed no improvement in urinary flow measures. Withdrawal rates for men assigned to beta-sitosterol and placebo were 7.8% and 8.0% (not significant), respectively. CONCLUSION: beta-sitosterol improves urological symptoms and flow measures. However, the existing studies are limited by short treatment duration and lack of standardized beta-sitosterol preparations. Their long-term effectiveness, safety and ability to prevent the complications of BPH are unknown.

2)  Peer reviewed, indepedent, medical study in support of betasitosterol:

1: J Altern Complement Med. 2002 Apr;8(2):143-52.
Links
Erratum in:
J Altern Complement Med. 2006 Mar;12(2):199.
A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia.
Prager N, Bickett K, French N, Marcovici G.
Clinical Research and Development Network, Aurora, CO, USA.

BACKGROUND: Androgenetic alopecia (AGA) is characterized by the structural miniaturization of androgen-sensitive hair follicles in susceptible individuals and is anatomically defined within a given pattern of the scalp. Biochemically, one contributing factor of this disorder is the conversion of testosterone (T) to dihydrotestosterone (DHT) via the enzyme 5-alpha reductase (5AR). This metabolism is also key to the onset and progression of benign prostatic hyperplasia (BPH). Furthermore, AGA has also been shown to be responsive to drugs and agents used to treat BPH. Of note, certain botanical compounds have previously demonstrated efficacy against BPH. Here, we report the first example of a placebo-controlled, double-blind study undertaken in order to examine the benefit of these botanical substances in the treatment of AGA. OBJECTIVES: The goal of this study was to test botanically derived 5AR inhibitors, specifically the liposterolic extract of Serenoa repens (LSESr) and beta-sitosterol, in the treatment of AGA. Subjects: Included in this study were males between the ages of 23 and 64 years of age, in good health, with mild to moderate AGA. RESULTS: The results of this pilot study showed a highly positive response to treatment. The blinded investigative staff assessment report showed that 60% of (6/10) study subjects dosed with the active study formulation were rated as improved at the final visit. CONCLUSIONS: This study establishes the effectiveness of naturally occurring 5AR inhibitors against AGA for the first time, and justifies the expansion to larger trials.

Pygeum africanum

Pygeum africanum is an herbal remedy containing extracts from the bark of Prunus africana. It has been used as to alleviate discomfort caused by inflammation in patients suffering from benign prostatic hyperplasia. In the UK, small short randomised studies using Pygeum provided moderate relief of some of the symptoms of BPH.  A selective dichloromethane extract from the stem barks of Pygeum africanum revealed the highest antiandrogenic effect. Bioactivity-directed fractionation of this extract led to the isolation of N-butylbenzenesulfonamide (NBBS) indicating that extracts of the stem bark of P. africanum harbour androgen antagonistic activity. This compound may provide a novel approach for the prevention and treatment of BPH and human prostate cancer.

1)  Peer reviewed, indepedent, medical study in support of Pygeum africancum:

Urology. 2003 Feb;61(2):474-8.
Effect of Pygeum africanum tadenan on micturition and prostate growth of the rat secondary to coadministered treatment and post-treatment with dihydrotestosterone.
Yoshimura Y, Yamaguchi O, Bellamy F, Constantinou CE.
Department of Urology, Fukushima Medical University, Fukushima, Japan.

OBJECTIVES: Pretreatment with oral tadenan (TAD) has been shown to possess a protective effect on bladder dysfunction-induced obstruction. We evaluated the functional influence of cotreatment and post-treatment with oral TAD on the frequency/volume characteristics of micturition of conscious rats stimulated with exogenous dihydrotestosterone (DHT) to induce experimental prostate growth.

METHODS: Studies were done on 36 adult Sprague-Dawley male rats, treated daily for 6 weeks and grouped as follows: group 1, sesame oil during weeks 1 and 2, peanut oil during weeks 3 to 6; group 2, DHT (1.25 mg/kg subcutaneously) dissolved in sesame oil as vehicle during weeks 1 and 2 and peanut oil during weeks 3 to 6; group 3, DHT (1.25 mg/kg subcutaneously) dissolved in sesame oil as vehicle and TAD (100 mg/kg orally) in peanut oil during weeks 1 and 2 and TAD during weeks 3 to 6; and group 4, DHT in sesame oil during weeks 1 and 2 and TAD in peanut oil during weeks 3 to 6. The characteristics of frequency/volume were monitored biweekly and at the sixth week. RESULTS: Controls showed no significant changes from baseline values in volume or frequency during the entire study period. DHT treatment produced a significant increase in frequency (1.9 +/- 0.3 to 3.0 +/- 0.4/hr) and a significant decrease in volume (1.8 +/- 0.3 to 1.2 +/- 0.1 mL). In groups 3 and 4, no significant changes occurred in frequency or volume. By the sixth week of observation, the effects of DHT treatment decreased to control values in all groups. A significant increase in prostatic weight (1191 +/- 11 to 1434 +/- 17 mg/kg) was produced by DHT treatment and TAD cotreatment suppressed growth to 1390 +/- 8.4 mg/kg. CONCLUSIONS: TAD cotreatment or post-treatment suppressed the effects of DHT on micturition, and TAD cotreatment regressed a developing increase in prostatic weight. Post-treatment TAD administration did not reduce already established growth.

Essential Fatty Acids

GLA, ALA, Linoleic Acid and Palmitoleic Acid

Gamma Linolenic Acid (GLA), Alpha Linolenic Acid (ALA), Linoleic and Oleic Acid are essential fatty acids found in plant oils. These fatty acids have been individually proven to inhibit 5-Alpha Reductase. The essential fatty acids are among the most powerful inhibitors of 5-Alpha Reductase known today. They have been demonstrated to inhibit both Type 1 and Type 2 isoforms of the enzyme 5AR. This is in marked contrast to finasteride, which has been shown efficacious only in the inhibition of Type 2 5AR. Importantly for the purposes of considering value in combating pattern hair loss; the Type 1 isoenzyme is present in high concentrations in the scalp, sebaceous glands, and the skin. It has also been shown that GLA, ALA and Oleic acid have potent anti-inflammatory properties.

1)  Peer reviewed, indepedent, medical study in support of GLA:

Author
Liang T; Liao S
Journal
Journal of Investigational Dermatology: 1997 Aug; 109 (2): 152-7

Abstract
Certain unsaturated aliphatic fatty acids, such as gamma-linolenic acid, inhibit 5alpha-reductase activity in vitro and in vivo. Hamster flank organ growth, as measured by the increase in the area of pigmented macule, is dependent on androgen. When one of the paired flank organs of a castrated hamster was treated topically with testosterone, the treated organ, but not the contralateral flank organ, became larger and darker. Topical application of gamma-linolenic acid to the testosterone-treated flank organ suppressed this testosterone effect. Other fatty acids that were not inhibitors of 5alpha-reductases were not active. Topical treatment of hamster flank organs with 5alpha-dihydrotestosterone also stimulated the growth of the organ. This 5alpha-dihydrotestosterone-dependent activity, however, was not significantly affected by gamma-linolenic acid, suggesting that flank organ growth was dependent on 5alpha-dihydrotestosterone and that gamma-linolenic acid acted by inhibiting 5alpha-reductase. With intact male hamsters, the endogenous androgen-dependent growth of flank organs is also suppressed by topical treatment with gamma-linolenic acid.

The effect of gamma-linolenic acid is localized at the site of its application; topical application of gamma-linolenic acid did not affect the androgen-dependent growth of other organs such as testis, epididymis, seminal vesicle, and prostate. Gamma-linolenic acid, with low toxicity and absence of systemic effect, may be potentially useful for treatment of androgen-dependent skin disorders.

2)  Peer reviewed, indepedent, medical study in support of GLA:

Author
Liang T; Liao S
Journal
Journal of Biochemistry, 1992 Jul 15, 285 (Pt 2): 557-62

Abstract
Human or rat microsomal 5-Alpha-Reductase (5AR) activity, as measured by enzymatic conversion of testosterone into 5 alpha-DiHydroTestosterone or by binding of a competitive inhibitor, [3H] 17 beta-NN-diethulcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one ([3H] 4-MA) to the reductase, is inhibited by low concentrations (less than 10 microM) of certain polyunsaturated fatty acids. The relative inhibitory potencies of unsaturated fatty acids are, in decreasing order: gamma-linolenic acid greater than cis-4, 7,10,13,16,19-docosahexaenoic acid = cis-6, 9,12,15-octatetraenoic acid = arachidonic acid = alpha-linolenic acid greater than linoleic acid greater than palmitoleic acid greater than oleic acid greater than myristoleic acid. Other unsaturated fatty acids such as undecylenic acid, erucic acid and nervonic acid, are inactive. The methyl esters and alcohol analogues of these compounds, glycerols, phospholipids, saturated fatty acids, retinoids and carotenes were inactive even at 0.2 mM. The results of the binding assay and the enzymatic assay correlated well except for elaidic acid and linolelaidic acid, the trans isomers of oleic acid and linoleic acid respectively, which were much less active than their cis isomers in the binding assay but were as potent in the enzymatic assay. Gamma-linolenic acid had no effect on the activities of two other rat liver microsomal enzymes: NADH: menadione reductase and glucuronosyl transferase. Gamma-linolenic acid, the most potent inhibitor tested, decreased the Vmax. And increased Km values of substrates, NADPH and testosterone, and promoted dissociation of [3H] 4-MA from the microsomal reductase. Gamma-linolenic acid, but not the corresponding saturated fatty acid (stearic acid), inhibited the 5 alpha-reductase activity, but not the 17 beta-dehydrogenase activity, of human prostate cancer cells in culture. These results suggest that unsaturated fatty acids may play an important role in regulating androgen action in target cells.

Palmitoleic acid

Palmitoleic acid, or (Z)-9-hexadecenoic acid, is a omega-7 monounsaturated fatty acid that is a common constituent of the glycerides of human adipose tissue. It is present in all tissues, but generally found in higher concentrations in the liver. It is biosynthesized from palmitic acid by the action of the enzyme delta-9 desaturase.

1)  Peer reviewed, indepedent, medical study in support of palmitoleic acid:

Title
Enhancement of propylene glycol distribution in the skin by high purity cis-unsaturated fatty acids with different alkyl chain lengths having different double bond position.
Author
Taguchi K; Fukushima S; Yamaoka Y; Takeuchi Y; Suzuki M
Address
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Source
Biol Pharm Bull, 22(4): 407-11 1999 Apr

Abstract
Enhancement of skin distribution of propylene glycol (PG) in the skin by high purity cis-unsaturated fatty acids with different alkyl chain lengths was studied in the rat using Fourier transform/attenuated total reflection (FT-IR/ATR) analysis. Two fatty acids with the double bond at the delta9 position, palmitoleic acid (omega7, delta9) and oleic acid (omega9, delta9), enhanced PG flux into the dermis and increased the dermal steady state level of PG. In contrast, myristoleic acid (omega5, delta9) was extremely weak in its action. A positional effect of the omega chain was observed. The rate of skin structural alteration increased in proportion to omega chain length. The application of three fatty acids with the double bond at the omega9 position, oleic acid (omega9, delta9), gondoic acid, (omega9, delta11), erucic acid (omega9, delta13) enhanced PG distribution in the skin. While nervonic acid (omega9, delta15) did not increase PG distribution in the skin, the relationship of the delta/omega ratio to parameters characterizing the action of enhancers (PG (peak area max), T (max alteration), and the slope) suggest that skin distribution increases as the position of the double bond is shifted toward the hydrophilic end. It is therefore likely that the ratio of the delta/omega chain length of the cis-unsaturated fatty acid determines the efficacy of these compounds as skin penetration enhancers. An adequate molecular volume may be required for cis-unsaturated fatty acids to act as enhancers..

Biotin

Biotin, also known as Vitamin H, aids in the utilization of protein, folic acid, Pantothenic acid, and Vitamin B-12, and has also been shown to promote healthy hair. A deficiency of biotin may lead to extreme exhaustion, drowsiness, muscle pain, loss of appetite, depression, loss of skin tone, and hair loss.

1)  Peer reviewed, indepedent, medical study in support of biotin:

Title
Vitamin and dermatology
Author
Yoshikawa K Address Department of Dermatology, Osaka University Graduate School of Medicine
Source
Nippon Rinsho, 57(10): 2385-9 1999 Oct

Abstract
Vitamin A, B1, B2, B6, B12, biotin, nicotinic acid, panthotenic acid, vitamin C, E and K has been used for various skin disorders. The use is mostly based on the similarity of the skin manifestations seen in their deficiencies, except for the rare cases of clear deficiency like pellagra. Recent introduction of vitamin A and D analogues for psoriasis and keratinization disorders resulted in significant progress in clinical dermatology. Application of vitamin C, E and beta-carotene++ for UV-induced skin damages are being studied, and the vitamins will be more important in dermatology in the future.

Procyanidin Oligomers

Procyanidin Oligomers (also known as Proanthocyanidin) are naturally derived ingredients that have shown to stimulate hair growth with a mechanism of action thought by some investigators to be similar to that of Minoxidil (Rogaine™). Recent studies have shown that Procyanidin Oligomers promote growth stimulation activity of hair epithelial cells in vitro and stimulate anagen induction in hair follicles in vivo.

1)  Peer reviewed, indepedent, medical study in support of procyanidin oligomers:

Title
Procyanidin Oligomers selectively and intensively promote proliferation of mouse hair epithelial cells in vitro and activate hair follicle growth in vivo.
Source
J Invest Dermatol 1999 Mar; 112 (3): 310-6
Author
Takahashi T, Kamiya T, Hasegawa A, Yokoo Y Tsukuba Research Laboratories, Kyowa Hakko Kogyo, Ibaraki, Japan.

Abstract
We have previously reported that proanthocyanidins extracted from grape seeds possess growth-promoting activity toward murine hair epithelial cells in vitro and stimulate anagen induction in hair cycle progression in vivo.. This report constitutes a comparison of the growth-promoting activity of procyanidin oligomers and the target cells of procyanidins in the skin. Results show that procyanidin dimer and trimer exhibit higher growth-promoting activity than the monomer. The maximum growth-promoting activity for hair epithelial cells with procyanidin B-2, an epicatechin dimer, reached about 300% (30 microM) relative to controls (=100%) in a 5 d culture. Optimum concentration of procyanidin C-1, an epicatechin trimer, was lower than that of procyanidin B-2; the maximum growth-promoting activity of procyanidin C-1 was about 220% (3 microM). No other flavonoid compounds examined exhibit higher proliferative activities than the procyanidins. In skin constituent cells, only epithelial cells such as hair keratinocytes or epidermal keratinocytes respond to procyanidin oligomers. Topical application of 1% procyanidin oligomers on shaven C3H mice in the telogen phase led to significant hair regeneration [procyanidin B-2, 69.6% +/- 21.8% (mean +/- SD); procyanidin B-3, 80.9% +/- 13.0%; procyanidin C-1, 78.3% +/- 7.6%] on the basis of the shaven area; application of vehicle only led to regeneration of 41.7% (SD = 16.3%). In this paper, we demonstrate the hair-growing activity of procyanidin oligomers both in vitro and in vivo, and their potential for use as agents to induce hair growth.
PMID: 10084307, UI: 99181798