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One of the most profoundly significant developments in the past few years is the discovery of the action in the body of the plant sterols and sterolins. These are potent phytochemicals  found in a variety of botanical sources. There are a number of different  sterols and these include the principal phytosterol, which is known as sitosterol.

In addition to sitosterol the most common sterols include campesterol, sitostanol and stigmasterol. The glucoside of sitosterol is known as sitosterolin and in plants it is always found together with the sterol. The ratio of sterol  to sterolin varies in the plant kingdom ranging from 5% to 10% but in some  cases being higher as in the case of potatoes.

Sterols are essential cell membrane components and the maintenance of adequate serum levels in humans seems to be necessary for an efficient immune system. Seeds are the richest source of the sterols and sterolins and yet, the refining  processes applied by the food industry render the staple foods useless, because  they remove the sterols and sterolins to make the product more appealing to the eye.

For instance, in order to prevent precipitation of the fats in so-called "cold pressed oils," the oil is heated and refined to remove the sterols / sterolins. Sterols and sterolins have been shown to modulate the functions  of the T-Cells both in vitro and in vivo by enhancing their cellular division.

Recent research conducted by Professor Patrick Bouic and his research team at the University of Stellenbosch Medical Faculty and published in the International  Journal of Immunopharmacology is providing an entirely new medical approach to the treatment of autoimmune diseases and other chronic diseases that  only manifest themselves when the afflicted individuals are at cause. International medical and scientific interest on this breakthrough has been overwhelming.

Sitosterol assists in the conversion of linoleic acid to polyunsaturated fatty acids. This process is essential for the conversion of the Omega 6 fatty acids to prostaglandins and leukotrienes. Prostaglandins and leukotrienes  are hormone like substances that are involved in immune support; they assist in the reduction of thrombo-embolic disorders by reducing platelet aggregation  and they also assist in the reduction of inflammatory metabolites.

Sitosterol can be metabolized to pregnenolone and therefore to DHEA and  the other hormones derived from pregnenolone and its analogues. In the human body there is a steady decline with age in the production of DHEA, which is the master hormone responsible for the synthesis of estrogen, progesterone, testosterone, cortisol and others.

By the age of 70 the DHEA production can be down to 10% or 20% of the levels found in a twenty year old, thus sitosterol supplements have an enormous potential for supporting the endocrine system in elderly people and, by implication, increasing their longevity.

Research Abstract on Beta Sitosterol

Title
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.

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.

Research Abstract on Gamma-Linolenic Acid

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.

Research Abstract examining Gamma-Linolenic Acid against other Fatty Acids in the Inhibition of 5-Alpha-Reductase

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.

Research abstract on 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, 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.

Research Abstract on 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 (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.

Research Abstract on 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