Blood Circulation, Hair loss, and Apple Polyphenols

OverMachoGrande

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Nature's Rogaine, Apple (Polyphenols).

This purpose of this article is to understand how minoxidil effects the blood flow and epithelial response in the scalp, influencing the growth of hair. Further on, how the same blood circulating effects as the drug are found in various natural sources, emphasizing in apples, due to the several studies which have been completed in Japan.

Below I give studies based on how minoxidil works, and four more studies on how apple polyphenols work, providing the similar blood circulatory effects and epithelial activity, both resulting in hair re-growth, and further, how apple polyphenols can be up to three times more effective.

The four studies below demonstrate how minoxidil, partially if not completely, increases blood circulation to help battle hair loss in men. This is important to know, since we can get an understanding of how blood circulation in the scalp has a direct influence over hair loss.

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http://www.ncbi.nlm.nih.gov/pubmed/...ed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=10

Nippon Yakurigaku Zasshi. 2002 Mar;119(3):167-74.
[Hair growth effect of minoxidil]
[Article in Japanese]

Otomo S.

Pharmacological Evaluation Laboratory, Taisho Pharmaceutical Co., Ltd., 403, Yoshino-cho 1-chome, Saitama-shi, Saitama 330-8530, Japan.
The length and size of hair are depend on the anagen term in its hair cycle. It has been reported that the some cell growth factors, such as VEGF, FGF-5S, IGF-1 and KGF, induce the proliferation of cells in the matrix, dermal papilla and dermal papillary vascular system and increase the amount of extra cellular matrix in dermal papilla and then maintain follicles in the anagen phase. On the other hand, negative factors, like FGF-5, thrombospondin, or still unknown ones, terminate the anagen phase. If the negative factors become dominant against cell proliferation factors according to fulfilling some time set by the biological clock for hair follicles, TGF beta induced in the matrix tissues evokes apoptosis of matrix cells and shifts the follicles from anagen to catagen. Androgenetic alopecia is caused by miniaturizing of hair follicles located in the frontal or crown part of scalp and are hereditarily more sensitive to androgen. In their hair cycles, the androgen shortens the anagen phase of follicles and shifts them to the catagen phase earlier than usual. The mode of action of hair growth effect of minoxidil is not completely elucidated, but the most plausible explanation proposed here is that minoxidil works as a sulfonylurea receptor (SUR) activator and prolongs the anagen phase of hair follicles in the following manner: minoxidil (1) induces cell growth factors such as VEGF, HGF, IGF-1 and potentiates HGF and IGF-1 actions by the activation of uncoupled SUR on the plasma membrane of dermal papilla cells, (2) inhibits of TGF beta induced apoptosis of hair matrix cells by opening the Kir 6.0 channel pore coupled with SUR on the mitochondrial inner membrane, and (3) dilates hair follicle arteries and increases blood flow in dermal papilla by opening the Kir 6.0 channel pore coupled with SUR on the plasma membrane of vascular smooth muscle cells.

http://www.ncbi.nlm.nih.gov/pubmed/...ed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=14

Med Hypotheses. 1999 Nov;53(5):402-6.
Minoxidil and male-pattern alopecia: a potential role for a local regulator of sebum secretion with vasoconstrictive effects?
Kurbel S, Kurbel B, Zani?-Matani? D.

Department of Physiology, Osijek Clinical Hospital, Croatia. sven.kurbel@public.srce.hr
Regulation of the hair cycle takes place at the pilo-sebaceous unit with the sebaceous gland as a sex hormone-dependent part. Although minoxidil stimulates proliferation of follicular cells and activation of prostaglandin endoperoxide synthase-1, it was suggested that other mechanisms, such as an increase in the local blood flow, might mediate the drug effect on hair growth. If that is the case, it is possible that minoxidil counteracts some vasoconstrictive mediator of male-pattern alopecia. This hypothetical vasoconstrictive mediator X would have to meet some criteria: (I) vasoconstriction both in the general circulation and in the hair-growing skin; (II) local vasoconstrictive activity in the hair growing skin should be related to the circulating testosterone level; (III) only an increase in the local mediator X activity causes male-pattern alopecia, since hypertensive patients are not balder than expected. The sebaceous gland is a possible place of the mediator X secretion since it is a sex-hormone-dependent part of the pilo-sebaceous unit. ET-1 might be a suitable candidate for the mediator X, since male hormones raise ET-1 plasma levels and female hormones lower them. The speculation presented here is that ET-1, beside vasoconstriction in the general circulation, might also regulate the sebum secretion, by triggering contractions of the myoepithelial cells. This hypothetical mechanism would normally remain confined to the sebaceous gland. During puberty, sex hormones stimulate growth of sebaceous glands in both sexes. In women hypertrophied sebaceous glands under estrogen control would not increase its ET-1 content, while in men, testosterone would increase ET-1 secretion that might affect the neighboring arterioles. Induced vasoconstriction might reduce the hair growth and promote hair loss. If ET-1 plays the described role, then an ET-1 antagonist, i.e.


http://www.ncbi.nlm.nih.gov/pubmed/...ed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=20

Plast Reconstr Surg. 1996 May;97(6):1109-16; discussion 1117.
Transcutaneous PO2 of the scalp in male pattern baldness: a new piece to the puzzle.
Goldman BE, Fisher DM, Ringler SL.

Department of Plastic Surgery, Butterworth Hospital, Grand Rapids, Mich., USA.
Our study was designed to measure the transcutaneous PO2 of the scalp to determine if there was a relative microvascular insufficiency and associated tissue hypoxia in areas of hair loss in male pattern baldness. A controlled prospective study was performed at Butterworth Hospital, Grand Rapids, Michigan. Eighteen nonsmoking male volunteers aged 18 years and older were studied. Nine men had male pattern baldness (Juri degree II or III), and nine were controls (no male pattern baldness). Scalp temperature and transcutaneous PO2 were obtained at frontal and temporal sites in each subject. Peripheral circulation was assessed from postocclusive transcutaneous PO2 recovery time by means of maximum initial slope measurements. Statistical significance was assessed at p < 0.05. There was no significant difference in scalp temperature between male pattern baldness subjects and controls. Temporal scalp blood flow was significantly higher than frontal scalp blood flow in male pattern baldness subjects; however, there was no significant difference in controls. Transcutaneous PO2 was significantly lower in bald frontal scalp (32.2 +/- 2.0 mmHg) than in hair-bearing temporal scalp (51.8 +/- 4.4 mmHg) in men with male pattern baldness. In controls, there was no significant difference in transcutaneous PO2 of frontal scalp (53.9 +/- 3.5 mmHg) and temporal scalp (61.4 +/- 2.7 mmHg). Transcutaneous PO2 also was significantly lower in the frontal scalp of male pattern baldness subjects (32.2 +/- 2.0 mmHg) than in either frontal or temporal scalp of controls (53.9 +/- 3.5 mmHg and 61.4 +/- 2.7 mmHg, respectively). There is a relative microvascular insufficiency to regions of the scalp that lose hair in male pattern baldness. We have identified a previously unreported tissue hypoxia in bald scalp compared with hair-bearing scalp.


http://www.ncbi.nlm.nih.gov/pubmed/...ed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=26

J Dermatol. 1990 Apr;17(4):240-6.
A new apparatus for hair regrowth in male-pattern baldness.
Toshitani S, Nakayama J, Yahata T, Yasuda M, Urabe H.

Department of Dermatology, School of Medicine, Fukuoka University, Japan.
A newly devised apparatus (Scalp-Tension-Relaxer, STR) can efficiently promote hair regrowth in patients with male-pattern baldness. When this apparatus is applied, the scalp is pushed up to relieve tension on the vertex. The efficacy rate of hair regrowth in alopecia patients was 40%. An investigation into the basis for the hair regrowth caused by this apparatus was directed toward the changes in hemodynamics and skin temperature of the scalp. During and after use of this apparatus, subjects exhibited an increase both in the cutaneous blood flow rate (as determined by laser Doppler flowmetry) and in the cutaneous temperature (as determined by thermography).

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Now to take a look a 'Polyphenols' in specific, Apple Polyphenols, Their effects when topically applied and supplemented, how they are shown to be more effective, and from a natural source.

Here a few studies, as their are some more, I only included those in direct relevance to Hair growth, to see all of them visit these websites;

http://www.applepolyphenols.com/studies/hairgrowth.htm#Phytother Res. 2001

http://www.applepoly.com/procyanidin-b-2/



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Department of Dermatology, Toyama Medical and Pharmaceutical University
The Hair-Growing Activity of Procyanidin Oligomers

Department of Dermatology, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, JP.

Procyanidins are a family of condensed tannins we have identified in apples, which act as a hair-growing factor in the murine model both in vitro and in vivo. We have previously reported that the growth-promoting effect on murine hair epithelial cells attributable to procyanidin B-2, one species of procyanidin oligomer, reaches about 300% relative to controls; and have also shown that procyanidin B-2 possesses intensive anagen-inducing activity in the C3H in vivo mouse model. This presentation describes our investigations during a 12-month clinical trial of highly purified procyanidin oligomers isolated from unripe apples, chiefly comprising procyanidin B-2, procyanidin B-1, and procyanidin C-1. The clinical trial was performed in a total of 21 subjects showing male pattern baldness on the head. The test agent (about 1.8 ml per dose) was applied to the subjects’ affected scalp area twice a day, giving a daily dose of 16 mg of procyanidin oligomers. During the 12 months of twice-daily application of the agent, the hair-growing effects were evaluated according to the following parameters: the macrophotographically recorded change in the number of hairs in the designated scalp area, the changes in the diameter of hairs clipped from the designated scalp area, and the changes in the photographically recorded global view of the subjects’ heads. No side effects were observed in any subjects. After 12 months of use, 71% of the subjects showed an increased number of hairs in the designated scalp area relative to pre-trial measurements. The numbers of total hairs in the designated scalp area after the 12-month trial were significantly greater than the measured values at the start of the trial (paired t-test, p < 0.005). We also observed a clear trend towards increased number of non-vellus hairs (> 40 µm) in the designated scalp area after the 12-month trial compared to the values measured at the start of the test. A number of the subjects showed cosmetically satisfactory changes. Procyanidin therapy shows promise as a potential cure for male pattern baldness.

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Journal of Investigative Dermatology 112, 310-316 (1999)
Procyanidin Oligomers Selectively and Intensively Promote Proliferation of Mouse Hair Epithelial Cells In Vitro and Activate Hair Follicle Growth In Vivo1

Tomoya Takahashi, Toshikazu Kamiya, Atsuhiro Hasegawa,* and Yoshiharu Yokoo

Tsukuba Research Laboratories, Kyowa Hakko Kogyo, Tsukuba, Ibaraki, Japan; * Tokyo Research Laboratories, Kyowa Hakko Kogyo, Machida, Tokyo, Japan

Reprint requests to: Dr. Tomoya Takahashi, Tsukuba Research Laboratories, Kyowa Hakko Kogyo Co., 2, Miyukigaoka, Tsukuba, Ibaraki 305-0841, Japan. 1The authors disclosed conflict of interest. 2Wilson C, Walkden V, Powell S, Shaw S, Wilkinson J, Dawber R: Contact dermatitis in reaction to 2% topical minoxidil solution. J Am Acad Dermatol 24:661–662, 1991 (brief communications)

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 µM) 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 µM). 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.

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Phytomedicine. 2000 Dec;7(6):529-36
Investigation of topical application of procyanidin B-2 from apple to identify its potential use as a hair growing agent.

Kamimura A, Takahashi T, Watanabe Y.

Tsukuba Research Laboratories, Kyowa Hakko Kogyo Co., Ibaraki, Japan. ayako.kamimura@kyowa.co.jp

Procyanidin B-2 is a polyphenol compound we have identified in apple which acts as a hair-growing factor in the murine model both in vitro and in vivo. This report describes our investigation of the effects of 1% procyanidin B-2 tonic on human hair growth after sequential use for 6 months. A double-blind clinical test involving a total of 29 subjects was performed. Nineteen men in the procyanidin B-2 group and 10 men in the placebo control group were subjected to analyses. No adverse side effects were observed in either group. The hair-growing effect was evaluated using a macrophotography technique combined with measurements of the hair diameter of clipped hairs. The increase in number of total hairs in the designated scalp area (0.5 cm square = 0.25 cm2 area) of procyanidin B-2 group subjects after the 6-month trial was significantly greater than that of the placebo control group subjects (procyanidin B-2, 6.68 +/- 5.53 (mean +/- SD)/0.25 cm2; placebo, 0.08 +/- 4.56 (mean +/- SD)/0.25 cm2; P < 0.005, two-sample t test). The increase in number of terminal hairs, which are defined as hairs more than 60 microm in diameter, in the designated area (0.5 cm square = 0.25 cm2 area) of the procyanidin B-2 group subjects after the 6-month trial was significantly greater than that of the placebo control group subjects (procyanidin B-2, 1.99 +/- 2.58 (mean +/- SD)/0.25 cm2; placebo, -0.82 +/- 3.40 (mean +/- SD)/0.25 cm2; P < 0.02, two-sample t test). Procyanidin B-2 therapy shows potential as a safe and promising cure for male pattern baldness.

Publication Types:
· Clinical Trial
· Randomized Controlled Trial

PMID: 11194183 [PubMed - indexed for MEDLINE]

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Phytother Res. 2001 Jun;15(4):331-6.
The first clinical trial of topical application of procyanidin B-2 to investigate its potential as a hair growing agent.

Takahashi T, Kamimura A, Yokoo Y, Honda S, Watanabe Y.

Tsukuba Research Laboratories, Kyowa Hakko Kogyo Co., 2, Miyukigaoka, Tsukuba, Ibaraki 305-0841, Japan. tomoya.takahashi@kyowa.co.jp

Procyanidin B-2 is a compound we have identified in apple which acts as a growth-promoting factor on murine hair epithelial cells. This report describes our investigation of the hair-growing effects of 1% procyanidin B-2 tonic after sequential use for 4 months. A double-blind clinical trial was performed, involving a total of 29 subjects (procyanidin B-2, 19 men; placebo, 10 men). No adverse side effects were observed in either group. In the procyanidin B-2 group, 78.9% showed an increased mean value of hair diameter, whereas only 30.0% in the placebo group showed any increase (p < 0.02, Fisher's exact probability test). The increased ratio of hairs measuring more than 40 microm in diameter after 4 months of procyanidin B-2 treatment was significantly higher than that of the placebo controls (p < 0.05, two-sample-t-test). The increase in number of total hairs in the designated scalp area (0.25 cm(2)) of procyanidin B-2 subjects after a 4 month trial was significantly greater than that of the placebo controls (procyanidin-B-2, 3.67 +/- 4.09 (mean +/- SD)/0.25 cm(2); placebo, -2.54 +/- 4.00/0.25 cm(2); p < 0.001, two-sample t-test). Procyanidin B-2 therapy shows potential as a promising cure for male pattern baldness. Copyright 2001 John Wiley & Sons, Ltd.

Publication Types:
· Clinical Trial
· Randomized Controlled Trial

PMID: 11406858 [PubMed - indexed for MEDLINE]

Apple polyphenols applied topically have shown they can be as much as 300% more effective than Minoxidil!
 
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