newish studies re: topical niacin derivatives, caffeine, and

[Dave001]

Nothing terribly special. I haven't posted in ages, so here's an icebreaker.

Effect of caffeine and testosterone on the proliferation of human hair follicles in vitro.

Int J Dermatol. 2007 Jan;46(1):27-35.
Fischer, TW; Hipler, UC; Elsner, P
Department of Dermatology and Allergology, Friedrich-Schiller-University, Jena, Germany. tobias.fischer@derma.uni-jena.de

BACKGROUND: Androgenetic alopecia (Androgenetic Alopecia) is a common problem in men of all ages, affecting approximately 50% at 50 years of age. The underlying cause is an androgen-dependent miniaturization of genetically predetermined hair follicles. Here, the hair organ culture model was used to investigate the effects of testosterone and caffeine; the latter being a promising candidate for hair growth stimulation. METHODS: Hair follicles from 14 biopsies, taken from the vertex areas from male Androgenetic Alopecia patients, were cultivated for 120-192 h in vitro with normal William's E medium (control) or William's E medium containing different concentrations of testosterone and/or caffeine. Hair shaft elongation was measured daily and at the end of cultivation, cryosections of follicles were stained with Ki-67 to evaluate the degree and localization of keratinocyte proliferation. RESULTS: Significant growth suppression was found in hair follicles treated with 5 microg/ml testosterone. This was counteracted by caffeine in concentrations of 0.001% and 0.005%. Moreover, caffeine alone led to a significant stimulation of hair follicle growth. These results were confirmed immunohistochemically by Ki-67 staining. CONCLUSIONS: Androgen-dependent growth inhibition of ex vivo hair follicles from patients suffering from Androgenetic Alopecia was present in the human hair organ culture model, a constellation which may serve for future studies to screen new substances against androgen-dependent hair loss. Caffeine was identified as a stimulator of human hair growth in vitro; a fact which may have important clinical impact in the management of Androgenetic Alopecia.

PMID: 17214716

(Sponsored by Starbucks...)

The additive effects of minoxidil and retinol on human hair growth in vitro.

Biol Pharm Bull. 2007 Jan;30(1):21-6.
Yoo, Hyeon Gyeong; Chang, In-Young; Pyo, Hyun Keol; Kang, Yong Jung; Lee, Seung Ho; Kwon, Oh Sang; Cho, Kwang Hyun; Eun, Hee Chul; Kim, Kyu Han
Department of Dermatology, Seoul National University College of Medicine, Korea.

Minoxidil enhances hair growth by prolonging the anagen phase and induces new hair growth in androgenetic alopecia (Androgenetic Alopecia), whereas retinol significantly improves scalp skin condition and promotes hair growth. We investigated the combined effects of minoxidil and retinol on human hair growth in vitro and on cultured human dermal papilla cells (DPCs) and epidermal keratinocytes (HaCaT). The combination of minoxidil and retinol additively promoted hair growth in hair follicle organ cultures. In addition, minoxidil plus retinol more effectively elevated phosphorylated Erk, phosphorylated Akt levels, and the Bcl-2/Bax ratio than minoxidil alone in DPCs and HaCaT. We found that the significant hair shaft elongation demonstrated after minoxidil plus retinol treatment would depend on the dual kinetics associated with the activations of Erk- and Akt-dependent pathways and the prevention of apoptosis by increasing the Bcl-2/Bax ratio.

PMID: 17202653

This last one isn't very recent at all, but it's probably the more interesting as some of you are using or have used niacin derivatives (possibly without knowing it).

A pilot study evaluating the efficacy of topically applied niacin derivatives for treatment of female pattern alopecia.

J Cosmet Dermatol. 2005 Dec;4(4):258-61.
Draelos, Zoe Diana; Jacobson, Elaine L; Kim, Hyuntae; Kim, Moonsun; Jacobson, Myron K
Department of Dermatology, Wake Forest University School of Medicine, NC.

Background Female pattern alopecia is a common dermatologic condition that manifests after puberty. The only approved drug treatment for this condition is 2% minoxidil for topical application. Aims This pilot study examined the effect of topical application of two niacin derivatives, octyl nicotinate and tetradecyl nicotinate, on hair fullness in female alopecia. Patients/methods Sixty female subjects with Ludwig types I-III female pattern hair loss were evaluated in a double-blinded, placebo-controlled (40 active, 20 placebo) design using standardized 35-mm photographic analyses for assessment of efficacy after 6 months of application. Results The niacin derivatives demonstrated a statistically significant increase in hair fullness (P = 0.04 compared to the placebo). Conclusion Whereas evaluation of hair growth in women is challenging, this 6-month pilot study demonstrated statistically significant increase in hair fullness on blinded 35-mm photographic analysis. Long-term topical application of nicotinic acid derivatives offers promise for providing benefit in female alopecia and warrants further study.

PMID: 17168873

 

[michael barry]

Dave,

I wrote alpecin way back when they introduced their product and asked them if caffeine had some sort of anti-androgenic activity topically, and they told me it did not. They told me that it kept the c-AMP "energy messenger" from being down-regulated in hair follicles and thats how Alpecin worked.

There were a few other things in the topical formula that are mentioned in various hairloss patents like limonene, linolool, and castor oil (two of those three are in a hairloss patent from 2001) and perhpas menthol (there has been a study showing that spearmint tea controls hirsutism in Turkish women, although I dont know if the menthol in Alpecin is derived from peppermint or spearmint).


I AM impressed by their "double effect" dandruff and hairloss shampoo that has pirictone olamine (shown to be about as helpful as ketoconazole in one study), BHT (an anti-oxidant that Proctor uses), caffeine, and salycic acid.


I took alot of grief on the forums for being a bit nosy about this product and was reassured by about everyone that it was snake oil. The reason I privately hoped that there may be "something" to it, was that a big company like Alpecin that isn't in financial trouble shouldn't want to tar its good reputation by putting out a dandruff shampoo that didn't control dandruff or a hairloss shampoo that did absolutely nothing for hairloss. All that being said........................I have no idea if the stuff works or not.



Dave, I dont know if you have read about the Androscience company working on a topical cream that ends receptor expression in targeted tissues and their development of an acne product and their possible expansion into hairloss with the same technology (apparently a derivitave of some natural substance), but I think thats really an elegant solution to baldness for young men if they can make that work. No DHT inhibition or any hormonal drug, just one topical for young men. That would be great, even though it wouldn't get me back what Ive lost.

 

[Dave001]

I wrote alpecin way back when they introduced their product and asked them if caffeine had some sort of anti-androgenic activity topically, and they told me it did not. They told me that it kept the c-AMP "energy messenger" from being down-regulated in hair follicles and thats how Alpecin worked.

The abstract I posted earlier says nothing of an antiandrogenic effect from caffeine, only that it prevented the inhibitory effect of testosterone. BTW, why don't you buy bulk caffeine and incorporate it into a suitable vehicle, instead of buying a presumably expensive shampoo? One would also imagine that a shampoo is of limited efficacy.

Dave, I dont know if you have read about the Androscience company working on a topical cream that ends receptor expression in targeted tissues and their development of an acne product and their possible expansion into hairloss with the same technology (apparently a derivitave of some natural substance), but I think thats really an elegant solution to baldness for young men if they can make that work. No DHT inhibition or any hormonal drug, just one topical for young men. That would be great, even though it wouldn't get me back what Ive lost.

What is the regrowth potential from androgen antagonists of any kind for a given individual? Can miniaturization (irrespective of any cosmetic effect)
be appreciably reversed?

Skin Pharmacol Physiol. 2006;19(3):168-76. Epub 2006 May 4.

Natural scalp hair regression in preclinical stages of male androgenetic alopecia and its reversal by finasteride.

Van Neste D.

Skinterface, Tournai, Belgium. info@skinterface.be

Using contrast-enhanced phototrichogram (CE-PTG) at monthly intervals during 48 months, we measured the duration of the hair cycle, i.e. anagen, catagen and telogen at the exclusion of exogen. Exogen, a recently identified phase of the hair cycle, is characterized by weakening of anchorage of the club hair to the surrounding epithelium. The processing of the club hair terminates at the time of exogen hair release, i.e. hair shedding. We combined a noninvasive exogen sampling before each CE-PTG so that the area contained only anagen, catagen and telogen hair or empty follicular openings. During the first 24 months of this study, natural regression of hair cycling in early i.e. preclinical stages of androgenetic alopecia (Androgenetic Alopecia) in androgen sensitive areas was documented. Shortening of the hair cycle of thicker hair characterized progression of Androgenetic Alopecia. During the next 24 months, finasteride (1 mg/day) was introduced into the system. Shortening of the hair cycle was reversed by finasteride in androgen sensitive sites as long as the affected follicle was able to produce a thick hair fiber at the time of treatment initiation. Compared to the baseline period, responding follicles did not produce thicker hair. On average, they initiated active growth more rapidly by reducing the duration of the lag phase by 40%. The duration of the anagen phase of thick hair showed an average 23% increase. In this particular experiment, the already miniaturized follicles producing thinner hair (<40 microm thickness) at the time of finasteride introduction regressed further on treatment. Our results seem to indicate that reversal of 'hair loss' by finasteride probably means that the terminal type follicles that are functionally deficient--a stage of reversible hypotrophy--will be reactivated by two non-mutually exclusive mechanisms: faster regrowth followed by extension of the duration of anagen. In our study, there was no clear evidence in favour of reversal of miniaturized hair into terminal hair. This new interpretation indicates that miniaturized hair follicles may be an important diagnostic marker of Androgenetic Alopecia in males but also that it might be less contributive to the therapeutic response to finasteride. Our results highlight that precise measurement of terminal type hair follicle functionalities opens up avenues for the selection of 'drug-responsive organs' in the human scalp in vivo and these may possibly serve to predict 'quality of response to treatment'. 2006 S. Karger AG, Basel

PMID: 16679818

 

[michael barry]

Dave,

If one adds hypertrichotics to total androgen ablation in the scalp, they would have the best chance possible of growing back the most abount of hair possible.

Dutas trumps finas, Dutas plus topical sprio trums dutas. This andro-product that can end receptor epxression would trump all of the above if it can truly do that. Then one can add things like minoxidil and prox-n and caffeine and aminexil and piricotone olamine and proanthocyandins and see what can be brought back. Im certain that long gone hairs wouldn't return, but we do know that on finas alone, one slowly loses hair over many years, and its effect can be improved with nizoral and spironolactone.


This product (andaderm) would enable YOUNG men to never lose their hair in the first place, and thats a good thing.

 

[Dave001]

This product (andaderm) would enable YOUNG men to never lose their hair in the first place, and thats a good thing.

There has already been considerable loss at the point one first notices.

 

[michael barry]

Dave wrote,

"There has already been considerable loss when one notices"


Dave, I imagine you'd do the same thing as I would if you could be an 18 year old again. Since I deeply suspected that I'd inherit baldness despite my then very good hair.......................Hell man, I'd start treating it as a precautionary measure with topical spironolactone and nizoral before I lost any if I thought I had those demon genes these days.

Dave,
I tell these young dudes of just how lucky they are to have hairlosstalk, hairlosshelp, hairsite, etc. these days. I imagine you are about my age (30's). Remember back in the day when we were told that nothing could be done about baldness, and minoxidil just worked on the back baldspot and it was a fluke? These young fellas will never have to go through that. Informative posts like yours and Bryans helps the young men. I wish I could be 20 now (when I first noticed recession) instead of way back when. I honestly think Id have kept my hair with what Ive learned about finas, spironolactone, minoxidil, nizoral, etc.

 

[wookster]

What does it mean when one uses a topical niacin preperation on their scalp and they get the "niacin flush" in their forehead and face :freaked: :freaked: :freaked:

 

[Dave001]

Dave, I imagine you'd do the same thing as I would if you could be an 18 year old again. Since I deeply suspected that I'd inherit baldness despite my then very good hair.......................Hell man, I'd start treating it as a precautionary measure with topical spironolactone and nizoral before I lost any if I thought I had those demon genes these days.

I don't disagree that such a topical would be highly desirable.
My comment was not to intended to suggest otherwise, just that the addition of a growth stimulant is almost always a good idea when there is any degree of noticeable loss. It has always been my position that a locally effective, topical antiandrogenic treatment should be one's primary concern. That's because blocking the androgen mediated process is the only known way to arrest the damage to the hair follicles. It may be possible to prevent the damage further downstream, but research is lacking.

 

[Dave001]

Michael,

Are you aware of the potential effectiveness of topical NAC? In particular, there is a possibility that it and other antioxidants may minimize or prevent tolerance to minoxidil. Dr. Proctor cited the following article from the New England Journal of Medicine in a Usenet post in 1998*:

J.D. Parker, and John Parker, "Nitrate Therapy for Stable Angina Pectoris", NEJM, Feb 19, 1998, pp520-531.

This was quoted from the NEJM article:

If these findings are correct, a new construct of nitrate tolerance can be developed, whereby the generation of reactive oxygen species with inactivation of nitric oxide has a role in the loss of responsiveness to nitrates. Such an effect could be a local, counterregulatory response, in which the stimulating effects of nitrate on nitric oxide production are diminished because of local degradation.

The concern is that nitric oxide (NO) stimulants and possibly even NO mimetics such as minoxidil** could also lead to the increased local production of superoxide as a feedback response, and such could have deleterious effects on hair growth by causing damage to blood vessel lining. The use of topical NAC and other antioxidants might therefore mitigate the damage (and hence tolerance) if Dr. Proctor's hypothesis is correct.

I have no idea whether this actually happens in the case of topical minoxidil. I certainly wouldn't assume that it does. Whether similar effects from minoxidil and other analogues can be inferred seems less likely because they do not stimulate NO production; they mimic its action. Long-term clinical trials have not demonstrated a harmful effect from topical minoxidil, but it is possible that its continued use masked the damage.

Here is a link to the relevant patent issued to Dr. Proctor:

Hair loss treatment with ascorbates
http://patft.uspto.gov/netacgi/nph-Pars ... er=6150405

* Here's a link to the post:
http://groups.google.com/group/alt.bald ... f233?hair loss=en

** This latter concern (about NO analogues) is not expressed in the article, but seems to be an inference added by Dr. Proctor.

 

[michael barry]

Dave,

The info on N-acetyl-L-cysteine is interesting, and it sure looks like it can keep minoxidil working even longer. Ive seen cysteine pop up in various hairloss concoctions and patents. I remembered something Ive seen Proctor say about patents, and it went a bit like.... "you can be reasonably sure something in a hairloss patent has at least some efficacy, because who'd go to the trouble of filing for an ingredient that absolutely didnt help", etc. When I look at the five year graph on minoxidil at the resource library here at HairLossTalk.com, it would seem that a man would only get back to baseline after year 12 or so on minoxidil alone. Im assuming that with finas and spironolactone, he'd keep his hair for a long, long time.

Thats my hope personally. Im hoping to keep it until Inercytex, Anaderm, some gene therapy or whatever new advance comes out that effectively "cures" the condition.


Currently, Im doing finas, spironolactone (even though Im out of that and am waiting on more in the mail), and prox-n. I use nizoral a couple of times a week. Reading over that patent that you linked that Proctor submitted, Im struck at how much he has looked into hair personally. Im satisfied with his regrowth formula, but sure wished that he was able to have found a receptor-blocker that didn't smell and worked for 24 hours a stretch and that was non-greasy and cheap and preferably alchohol based so I could spray it on (I know, asking for the moon). Im putting my spironolactone in a cream that Ive seen Old Baldy recommend from Swansons that is pretty affordable. Im impressed wtih this cream carrier and its ingredients (its gotta be good for the skin up there.....................even if I went bald up there someday, I dont want liver spots, etc.)

Ive tried to check up on patents etc. from time to time and see if there is anything a man might be able to whip up at home that would have efficacy. I remember reading a patent that detailed the "spirits of camphor" as a topical that inhibited alpha five reductase with other ingredients like salycic acid and coal tar for alopecia. Pickart supposedly is coming out with a new, improved folligen that is in trials now (at skinbio.com' s discussion forum, its talked about a bit, but he's pretty mum about it). I wish he'd come up with something very good, his stuff is cheaply priced as opposed to prox-n, which aint'.

Ive piddled with other topical anti-androgens, but everything Ive tried had drawbacks. I thought revivogen worked well as it reduced body hair impressively, but it stinks and its greasy in your hair. Pine oil, a bit less effective, makes the hair look oily and really does make a guy smell like a pine tree. After I piddle with this lavendar, and do a run with spearmint/peppermint tea (effective with women's hirsutism and probably a real longshot, but I have nothing better to do but try it------and I might like the tea anyway) and perhaps topical licorice or hops, I'll be pretty much fresh out of ideas as far as "finding" some topical anti-androgen. I'll probably be doing spironolactone ten years from now............................and trying different creams to see which smells the best.


Haven't seen you on the couple of hairloss-sites I look at recently. They can be frustrating cant' they? Ive been able to learn a little bit (namely that spironolactone and finas together will help a young guy keep his hair) and try to share that one very effective piece of info with newbies (because I wish someone would have told me about spironolactone in 1990), only to be frustrated by encountering so many people who inhabit forums who are neo-luddites that believe all medicine will totally emasculate someone, or wierd alternative theories about baldness that must fufill some deep psychological need in man to believe the condition isn't given to him by his own genetics. These sites never lived up to what they could have been. If it weren't for Bryan's steady participation, there is no telling what the tone of this forum would be or if the consensus about hair would have been by now........


One other topical that is being tested for baldness that appeared a while back (about the time you stopped posting) was topical roxythromicyn. There is info about it at clinicaltrials.gov. You might have known about that though. Other than that, nothing much is really new. Im pulling for anaderm and that curcumin analogue topical they are working on'. If thats a go, I wonder if its something a man could concoct himself (withough turning his kitchen yellow).



Dave,
Im assuming you put a few things in your shampoo that you buy? I noted that Proctor talked about putting NAC in shampoo in that patent? The fact that another shampoo ingredient, PO, has been shown to have some efficacy leads me to believe certain growth stimulants definitely cold be delievered in shampoo time. So stuff like NAC, BHT, caffeine, etc.......could perhaps be added to a bottle of gentle shampoo.....
I hope so anyway.

 

[CCS]

bump

 

[mumuka]

Does anybody know what happened to Dave? His last post is 6 months old....