Interesting information on coal tar and DHT

…perhaps this is why there was that Neutragena “placebo effect” in those 2 year finasteride trials all those years ago for the first six months, when many in the placebo group pretty much held onto their hair…just a thought.

http://www.patentstorm.us/patents/5609858/description.html

"…It is this investigator’s finding that a specific co-enzyme present in LCD (a coal tar extract–B) serves to block the conversion of DHA and testosterone to DHT.

The formulation of the topical solution referenced above was developed to facilitate the delivery of LCD to the cell membranes of the sebaceous glands adjacent to the hair shaft and to the dermal papilla and contiguous cellular areas. In vivo studies demonstrated that hair loss was significantly retarded with regular application of a LCD formulation.

An initial comparative study of published findings on alopecia and review of coal tar applications for dermatological disease treatment revealed no explanation for the activity cited above to i.e., the inhibition of the conversion of testosterone to dihydrotestosterone. However, the study of the co-enzymes required for this reaction, namely the interaction of 5a-reductase and NADP (nicotinamide adenine dinucleotide phosphate) revealed a mechanism of action that would explain lower levels of DHT is patients regularly applying the LCD solution. The conversion of testosterone to DHT is catalyzed by 5a-reductase which serves to donate the extra hydrogen atom carried by DHT. To release this atom, 5a-reductase requires the presence of the co-enzyme NADP.

To clarify this point, it may be helpful to review the role of enzymes in human metabolism. Enzymes are protein molecules of high molar mass which serve to catalyze reactions, making it possible for changes to occur faster and/or with reduced levels of energy. Most enzymes contain a non-protein element called a co-enzyme that must be present if the enzyme is to fulfill its function. In some cases, the co-enzyme is a metal cation such as Zn2+, Cu2+ or Co2+. In others, it is an organic molecule, most often a vitamin (such as the B vitamin niacin). DHT is a ligand. Ligands are molecules which are bonded to the central metal in a complex ion (ligands can also be defined as any molecule with an unshared pair of electrons). DHT requires an extra hydrogen atom to convert from testosterone. If this extra hydrogen atom is not available, the conversion cannot occur. Testosterone uses 5a reductase as its substrate. This substrate is one of the family of dehydrogenases, a class of enzymes which serve to remove two electrons and two hydrogen ions from the substrate. Dehydrogenases are very specific to their substrate. The electron acceptor for some dehydrogenases is NADP+, others Use NAP+. If this acceptor is deactivated by the presence of LCD, as is generally recognized (See U.S. Pat. No. 4,102,0995 to Peter Hebborn, Jul. 25, 1978, entitled Tar Gel Formulation, cited below), then the catalytic function of 5a-reductase is inhibited.

Coal tar is credited with an inhibitory action on the pentose cycle in cellular metabolism, which is particularly active in psoriasis. As a result there is a reduction in the activity of the enzymes G6PD and NADP. This inhibitory action is said to reduce DNA and RNA synthesis, resulting in the inhibition of mitotic activity and protein synthesis. A reduction of mitosis, or cell division, is beneficial to the psoriasis patient because . . . one of the factors in psoriasis is the extreme acceleration of epidermal cell production.

The patent excerpt above concerned itself with tar gel formulation and makes reference to the inhibition of the co-enzyme NADP found in coal far as the mechanism of action for the retardation of excessive skin cell reproduction occurring in psoriasis conditions. LCD, a liquid, diluted form of coal tar gel, is likely to have the same or similar inhibiting action on NADP within the cellular metabolism of the hair follicle cells and sebaceous glands. With the deactivation of NADP, 5a-reductase is disabled as the catalyst for T/DHT conversion. The diagram below details the metabolic pathway in human skin of testosterone to dihydrotestosterone.1 ##STR1##

1 The importance of the role of dehydrogenase activity within the sebaceous glands of scalp tissue exhibiting androgenic alopecia is documented by Marty E. Sawaya, et. al., in her published article, “-- 5-3β-Hydroxysteroid Dehydrogenase Activity in Sebaceous Glands of Scalp in Male-Pattern Baldness” (The Society for Investigative Dermatology, December 1987). Their work suggests that bald areas of the scalp have a greater propensity for converting testosterone into DHT through the heightened activity of another dehydrogenase, – 5-3β-Hydroxysteroid.

By way of example, it is suggested here that as women enter menopause and naturally-produced estrogen levels decline, they experience hair loss due to the concurrent rise in DHT which is no longer being inhibited or neutralized at the same rate due to the lower amounts of circulating estrogens. It is believed that the application of the LCD solution at the onset of menopause or androgenic alopecia would serve to perform a similar metabolic function as the estrogens, limiting DHT production and its effects on deleterious DNA protein expression.

The mechanism of action in the Topical Lotion for the Retardation of Alopecia (patent application Ser. No. 08/343,647) to which this is a CIP, is thus primarily based on the single ingredient LCD and the claims for its singular discovery as a retardant to androgenic alopecia should be reconsidered in light of its inhibition of the essential co-enzyme NADP in the catalytic role of the 5a-reductase substrate for T to DHT conversion."

Me again…I think using T-Gel a couple of times a week, and leaving it in for a few minutes just like the directions tell you to, would probably be beneficial in “helping” your finasteride along with usage of nizoral a couple of other days a week. Just my opinion. The “placebo” effect in the 2 year finasteride trial was seen in a control group of some 1200+ men, so it could not have been a fluke. They were all given T-gel (Coal Tar shampoo), and 6 months is about how long a bottle of that would last. They pretty much held onto their hair for that six month period before starting to lose it thereafter. The study is at hlt, I dont have the link handy here.

» …perhaps this is why there was that Neutragena “placebo effect” in
» those 2 year finasteride trials all those years ago for the first six
» months, when many in the placebo group pretty much held onto their
» hair…just a thought.
»
»
» http://www.patentstorm.us/patents/5609858/description.html
»
»
»
» “…It is this investigator’s finding that a specific co-enzyme present in
» LCD (a coal tar extract–B) serves to block the conversion of DHA and
» testosterone to DHT.
»
» The formulation of the topical solution referenced above was developed to
» facilitate the delivery of LCD to the cell membranes of the sebaceous
» glands adjacent to the hair shaft and to the dermal papilla and contiguous
» cellular areas. In vivo studies demonstrated that hair loss was
» significantly retarded with regular application of a LCD formulation.
»
» An initial comparative study of published findings on alopecia and review
» of coal tar applications for dermatological disease
» treatment revealed no explanation for the activity cited above to i.e., the
» inhibition of the conversion of testosterone to dihydrotestosterone.
» However, the study of the co-enzymes required for this reaction, namely
» the interaction of 5a-reductase and NADP (nicotinamide adenine dinucleotide
» phosphate) revealed a mechanism of action that would explain lower levels
» of DHT is patients regularly applying the LCD solution
. The conversion
» of testosterone to DHT is catalyzed by 5a-reductase which serves to donate
» the extra hydrogen atom carried by DHT. To release this atom,
» 5a-reductase requires the presence of the co-enzyme NADP.
»
» To clarify this point, it may be helpful to review the role of enzymes in
» human metabolism. Enzymes are protein molecules of high molar mass which
» serve to catalyze reactions, making it possible for changes to occur faster
» and/or with reduced levels of energy. Most enzymes contain a non-protein
» element called a co-enzyme that must be present if the enzyme is to fulfill
» its function. In some cases, the co-enzyme is a metal cation such as Zn2+,
» Cu2+ or Co2+. In others, it is an organic molecule, most often a vitamin
» (such as the B vitamin niacin). DHT is a ligand. Ligands are molecules
» which are bonded to the central metal in a complex ion (ligands can also be
» defined as any molecule with an unshared pair of electrons). DHT
» requires an extra hydrogen atom to convert from testosterone. If this extra
» hydrogen atom is not available, the conversion cannot occur.

» Testosterone uses 5a reductase as its substrate. This substrate is one of
» the family of dehydrogenases, a class of enzymes which serve to remove two
» electrons and two hydrogen ions from the substrate. Dehydrogenases are very
» specific to their substrate. The electron acceptor for
» some dehydrogenases is NADP+, others Use NAP+. If this acceptor is
» deactivated by the presence of LCD, as is generally recognized (See U.S.
» Pat. No. 4,102,0995 to Peter Hebborn, Jul. 25, 1978, entitled Tar Gel
» Formulation, cited below), then the catalytic function of 5a-reductase is
» inhibited.

»
» Coal tar is credited with an inhibitory action on the pentose cycle in
» cellular metabolism, which is particularly active in psoriasis. As a result
» there is a reduction in the activity of the enzymes G6PD and NADP. This
» inhibitory action is said to reduce DNA and RNA synthesis, resulting in the
» inhibition of mitotic activity and protein synthesis. A reduction of
» mitosis, or cell division, is beneficial to the psoriasis patient because .
» . . one of the factors in psoriasis is the extreme acceleration of
» epidermal cell production.
»
» The patent excerpt above concerned itself with tar gel formulation and
» makes reference to the inhibition of the co-enzyme NADP found in coal far
» as the mechanism of action for the retardation of excessive skin cell
» reproduction occurring in psoriasis conditions. LCD, a liquid, diluted form
» of coal tar gel, is likely to have the same or similar inhibiting action on
» NADP within the cellular metabolism of the hair follicle cells and
» sebaceous glands. With the deactivation of NADP, 5a-reductase is disabled
» as the catalyst for T/DHT conversion. The diagram below details the
» metabolic pathway in human skin of testosterone to dihydrotestosterone.1
» ##STR1##
»
» 1 The importance of the role of dehydrogenase activity within the
» sebaceous glands of scalp tissue exhibiting androgenic alopecia is
» documented by Marty E. Sawaya, et. al., in her published article, “–
» 5-3β-Hydroxysteroid Dehydrogenase Activity in Sebaceous Glands of
» Scalp in Male-Pattern Baldness” (The Society for Investigative Dermatology,
» December 1987). Their work suggests that bald areas of the scalp have a
» greater propensity for converting testosterone into DHT through the
» heightened activity of another dehydrogenase, – 5-3β-Hydroxysteroid.
»
» By way of example, it is suggested here that as women enter menopause and
» naturally-produced estrogen levels decline, they experience hair loss due
» to the concurrent rise in DHT which is no longer being inhibited or
» neutralized at the same rate due to the lower amounts of circulating
» estrogens. It is believed that the application of the LCD solution at the
» onset of menopause or androgenic alopecia would serve to perform a similar
» metabolic function as the estrogens, limiting DHT production and its
» effects on deleterious DNA protein expression.
»
» The mechanism of action in the Topical Lotion for the Retardation of
» Alopecia (patent application Ser. No. 08/343,647) to which this is a CIP,
» is thus primarily based on the single ingredient LCD and the claims for
» its singular discovery as a retardant to androgenic alopecia should be
» reconsidered in light of its inhibition of the essential co-enzyme NADP in
» the catalytic role of the 5a-reductase substrate for T to DHT
» conversion.”

»
»
»
»
»
» Me again…I think using T-Gel a couple of times
» a week, and leaving it in for a few minutes just like the directions tell
» you to, would probably be beneficial in “helping” your finasteride along
» with usage of nizoral a couple of other days a week. Just my opinion. The
» “placebo” effect in the 2 year finasteride trial was seen in a control
» group of some 1200+ men, so it could not have been a fluke. They were all
» given T-gel (Coal Tar shampoo), and 6 months is about how long a bottle of
» that would last. They pretty much held onto their hair for that six month
» period before starting to lose it thereafter. The study is at hlt, I dont
» have the link handy here.

great post! Thanks for the effort.

So are you just saying that we should get some t-gel shampoo and use it if we take propecia?

Sounds easy enough.

What if we only take dutas? Will it still help or should I add propecia to my regiment?

I appreciate all your work in this forum

hopeful

And now, for the standard question #1 regarding anything that fights DHT . . .

Are we talking about topical-only effects, or was there just as much systemic influence from the stuff?

With this study on coal tar being basically an accidental discovery in men, and the other notations are about its effects on women, it doesn’t sound like we have a way to know about the systemic issue yet.

On page 9 of the 2 year finasteride study at HLT, you can see a chart.
Ive got the study posted near the bottom of my post there in the “New Treatments, Studies, and Discoveries” forum under my moniker there, Michael Barry. Click the link, as I cannot post it here.

Go to page 9 in that study. There is a chart. The trialees in the PLACEBO groups had higher hair counts at 6 months than when they started. Everybody was given Nuetragena T-gel at the beginning of the study. A bottle lasts about 6 months. Notice how after the six month period was up, even the rate of increase of the finasteride group slowed? They also probably weren’t instructed to follow the instructions on the T-Gel bottles (which say to leave on the scalp for SEVERAL minutes after lathering).

Cal, Ive never heard of ANYONE logging onto a hairloss site and saying they were getting side effects from T-gel (or nizoral for that matter).

How does T-gel (coal tar, what liquor carbonis detergens is a mere one component of) work? There is a co-factor called NADP upstream of alpha five reductase necessary for alpha five reductase to be synthesized. Alpha five reductase is made and degenerates constantly in the body just like androgen receptors are constantly made and degenerating. Coal tar inhibits NADP, therefore there is much less DHT being made in the scalp, because there will be much less alpha five reductase around.
Combine this with finasteride (or a couple of dutasteride pills a week, which would probably equal daily finasteride usage) and your scalp will have an extremely low amount of DHT available to attatch to androgen receptors.

The bottle says to use T-gel at least twice a week for best results. So if a guy uses T-Gel twice a week (and leaves in for a couple of minutes), and uses Nizoral a couple of times a week and does the same (one study showed nizoral was about as effective as 2% minoxidil), a mere “shampoo” regimine could almost assuredly dramatically slow the progression of MPB. Add finasteride…and very few men should lose their hair doing this. It would “up” the anti-androgenic potency in the scalp of the finasteride for certain.

There were 1200+ men in that placebo group, so this result can’t be some kind of “fluke”.

That’s a very interesting method of action you’re hitting on.

So if the classical attempts to fight the actual 5-alpha conversion can’t be kept non-systemic enough, then maybe we can hinder something a step earlier in the chain of events leading to that conversion in a more localized way.

(And you’re right, the 1200 number is too big to be any fluke. I’ve often wondered about the Propecia trials and the plecebo effect results. Everyone likes to talk about how strong the placebo effect is in medicine in general, but the placebo-effected gains in the Fin trials always seemed pretty monstrous even for that.)

» Go to page 9 in that study. There is a chart. The trialees in the
» PLACEBO groups had higher hair counts
» at 6 months than when they started.

No they didn’t! The placebo users had LOWER hair counts 6 months after they started the trial!

The chart you specified above is only the one for “global photographic assessment”, not the one for haircounts. Global photographic assessment is a much more subjective thing, and isn’t nearly as precise as haircounts or hairweights. The haircount chart, on the other hand, is on page 7, and shows a decline after 6 months for both the Pbo—>Pbo and Pbo—>Fin groups.

What’s always interested me for a long time is that although the T-Gel appears to have helped a little by restraining hairloss in the placebo groups, the effect seems to have “worn-off” after only around 6 months to 1 year in the Pbo—>Pbo group, judging by the steeper decline in haircounts in the second year (with continued use of the shampoo) than in the first year. THAT is really a dome-scratcher (pardon the expression).

» Everybody was given Nuetragena T-gel at the beginning
» of the study. A bottle lasts about 6 months. Notice how after the
» six month period was up, even the rate of increase of the finasteride
» group slowed?

That’s not true either, Michael. All the study participants used the T-Gel shampoo for the entire duration of the study, they weren’t just given a single bottle at the very beginning. And other studies have also documented the fact that finasteride’s maximum effect is reached at about the 1-year point. The “plateau” wasn’t reached because of a lack of T-Gel! :slight_smile:

Bryan Im looking at page 7 now. The trialees in the “hair count” analysis (chart) had slightly less hair at 6 months on placebo…basically holding onto their hair, and then it turns down. Which is just weird.

On page 8, The investigator mean rating score was up for everything they tried, including placebo, for the entire duration of the study.

On page 9, the photographic assessment was up for the first 6 months of the study.

Are you SURE that they had T-gel for the full legnth of this study and not just 6 months? It makes no sense for it to “work” for 6 months and then basically stop? Minxoidil, wich is less effective in the long run than finasteride sees its effect begin to lessen alone after what…18 months or so.

If this was a double blind study, I wouldn’t rule out the investigator and photographic assessments that were done by disinterested third parties. The investigator mean score was still above baseline 2 years after the trial start…

Did you read the patent literature on liquor carbonis Detergens Bryan? Their reasoning seemed very solid to me. If NADP is upstream of alpha five reductase, and we can inhibit it to some extent with coal tar, then using coal tar as an “additive” to a finasteride regimine should increase the anti-androgenic effect loacally in the scalp in my opinion. I think that alone would be a great reason to pick up some T-gel and use it twice a week. 1200 people in the placebo group that even just maintained their hair for 6 months (hair count group) is reason enough to do so in my opinion.

BTW -Bryan…put that Stephen info up. I’d like to see it myself. :slight_smile:

» Bryan Im looking at page 7 now. The trialees in the “hair count” analysis
» (chart) had slightly less hair at 6 months on
» placebo…basically holding onto their hair, and then it turns
» down. Which is just weird.

It IS rather weird. I’ve wondered about that for years, ever since I first read that study. What makes it easier to believe (despite the weirdness) is that the methods they used in that study to make haircounts were EXTREMELY precise and dependable, with all that computer-assisted technology that hadn’t been used before.

Kinda makes you wonder if the same thing would happen if you used Nizoral shampoo, instead of T-Gel shampoo! Would Nizoral shampoo ALSO turn out to work for only a few months, just like the T-Gel did? :slight_smile:

» Are you SURE that they had T-gel for the full legnth of this study and not
» just 6 months?

Yes. It’s INCONCEIVABLE that they would have supplied only a single bottle of the shampoo, without carefully specifying that in the text of the study. BTW, Dr. Vera Price did the same thing a couple years later in her own study of finasteride (it was tested using almost the exact same methods that she used in her 1999 topical minoxidil study, the one whose graphs I’ve posted so frequently): she had all the test-subjects use T-Gel during the trial.

» It makes no sense for it to “work” for 6 months and then
» basically stop?

Yeah, I know. Makes no sense at all that I can see.

» Did you read the patent literature on liquor carbonis Detergens Bryan?

I haven’t read it yet.

» Their reasoning seemed very solid to me. If NADP is upstream of alpha five
» reductase, and we can inhibit it to some extent with coal tar, then using
» coal tar as an “additive” to a finasteride regimine should increase the
» anti-androgenic effect loacally in the scalp in my opinion. I think that
» alone would be a great reason to pick up some T-gel and use it twice a
» week. 1200 people in the placebo group that even just maintained their hair
» for 6 months (hair count group) is reason enough to do so in my opinion.

I’m a bit concerned about other possible health effects of coal-tar, so I’ll wait a while on that, especially considering the apparent temporary nature of its benefits to hair…

Interestingly, Sawaya said something somewhat similar in her article a few years ago about “Unapproved Treatments for MPB”. She said that topical zinc may work not so much by inhibiting 5a-reductase, but by inhibiting the production of NADPH, the necessary co-factor for 5a-reductase. I’ve always remembered that.

» BTW -Bryan…put that Stephen info up. I’d like to see it
» myself. :slight_smile:

Give me two or three days to get that posted. It’s just a rather little thing, but it’ll be fun to see Stephen try to squirm his way out of it, like he always tries to do! :smiley:

Youre reasoning is solid as Ive come to expect Bryan. Thanks for the information on the coal tar…

BTW…Im pretty sure you know this, but a Japanese study with Keto cream showed it to have efficacy for at least 12 months, with a couple of nice growth pictures,
http://www.hairsite.com/hair-loss/forum_entry-id-25116-page-0-category-0-order-last_answer.html

6 months is a pretty goddamn long time for one bottle of (any) shampoo to last. I would think surely they kept the trialists supplied with a consistent supply of whatever they were requiring them to use.