lets talk bout Nizoral's anti DHT properties

[Lizzad]

Gotta agree with Vortex. Egos here frighteningly enormous. Never ending pissing contests mind-bending.

:laugh: I KNOW, it's amusing, sometimes hilarious. I suppose we're all pissed off because we have male pattern baldness!!! Maybe we should organise a fight club??? :rockon:

 

[Bryan]

Re: Answer to Bryan

Let's focus on testosterone (T). T is produced primarily in the testes and adrenals (in order of importance), with a tiny smattering coming from other tissues. T then circulates throughout the body where it can be transformed by 5AR into dihydroxytestosterone (DHT), the really potent male adrogen. Ketoconazole is not a 5AR inhibitor. It is an inhibitor of one or more of the enzymes responsible for converting precursor molecules into T.

As I indicated to Maddoc, it could well be the androgen receptor blocking ability of topical ketoconazole that inhibits sebaceous glands, and (putatively) helps hair follicles.

It is widely understood that ketoconazole, topically applied, has little or no systemic effects. So, topical keto will have an insignificant effect on steroidogenesis. Therefore, it has no impact on the amount of T that gets to your scalp from other parts of your body. It also has no impact (so far as we know) on the conversion of T to DHT in your scalp or any other part of your body.

I'll mention here briefly that it has no effect on SYSTEMIC steroidogenesis, but it may still have an effect on LOCAL steroidogenesis within the hair follicle when applied topically. There's a very recent article out by Hoffmann which talks about how apparently all the enzymes necessary for androgen production are present within the hair follicle. That may have a certain relevance for the course of male pattern baldness, although I still think that it's the AR-blocking aspect of topical keto which is probably more important.

So, I'm not saying topical antiandrogens can't work, if they work the right way. I'm saying that keto doesn't seem like it would be an effective topical antiandrogen, since, delivered topically, it has very little impact on the body's production of T.

Keep in mind that the strict definition of an "antiandrogen" is a substance which blocks androgen receptors. Ketoconazole meets that definition. It seems reasonable to me that that MAY be what accounted for the benefit seen in the Nizoral study.

Given this line of reasoning, how does Dr. Lee support his assertion that keto shampoo is an "anti-DHT" shampoo? I just don't see it. I'm not going to say that keto shampoo can't help with hair loss. Some of the preliminary research out there suggests it might be helpful. All I'm saying is it's not clear to me what mechanism keto uses to exert this beneficial effect. It's an interesting question to answer rigorously, IMO, as it might lead to better treatments for hair loss. I highly doubt inhibition of steroidogenesis is the reason, though.

Who knows? The inhibition of local steroidogenesis may play some minor role...

You mentioned in an earlier post that keto may be an androgen receptor antagonist. If that proves to be true, that could be the mechanism, who knows. Could you provide a link to that reference?

"Ketoconazole Binds to the Human Androgen Receptor", C. Eil, Horm Metab Res 24 (1992) pp. 367-370.

Here's a brief passage from the Discussion section, near the end: "...Because certain drugs which induce gynecomastia, such as cimetidine and spironolactone, are believed to have anti-androgenic properties on the basis of their ability to interfere with androgen binding to its receptor, ketoconazole was tested for this property as well. The results of the studies reported here indicate that ketoconazole is a competitive inhibitor of the human fibroblast androgen receptor, albeit with relatively weak affinity. Its potency in this regard is similar to that of cimetidine. While the dose of ketoconazole required for 50% occupancy of the androgen receptor is not likely to be achieved in vivo in serum by routine anti-fungal therapy, it is possible that the drug may be concentrated in target tissues, such as the breast, allowing for sufficient levels to interact with the receptor."

Bryan

 

[Loopydude]

Hrm...

I never got the impression there were any pissing contests here. I call it healthy debate. I don't think of debate as a brainiac contest, I think of it as a good way to get at the facts. I guess it's just that discussions of this type are so common where I work, I take for granted other people would find them useful.

I deal with pharmacology and cell biology issues for a living. I do care about accuracy, and if I disagree with somebody, it's not because I want to show I'm smarter, it's because I'm debating points of logic or science that matter. If I'm right, it's not because I've got a higher IQ necessarily, it might just be because I have experience in the field. And if I'm wrong, I learn something. Hence, such discussions are a win-win enterprise for all involved, as far as I can see. There's no reason to inject ego into the mix. I sure don't.

Anyway, for the sake of some of you other participants, I hope you don't get turned off by such discussions because what comes out of them isn't what you want to hear. I'm sure we'd all love to believe that we can find the magic hair tonic on the internet, and some genius dermatologist out there has all the answers for us. Through many years of experience, my impression is that if it sounds too good to be true, it almost certainly is. Belief will get you nowhere but ripped-off in this world. You've got to be educated and skeptical. Healthy, rigorous, and informed debate is what will keep your money out of the snake-oiler's pockets. And there's a hell of a lot of snake oil out there, so be on your guard.

Picking apart a vendor's claims and finding them less than convincing can be disappointing, especially if you've already shelled out a lot of dough. But I'm not somebody who thinks ignorance is bliss. Ignorance is a state that allows others take adantage of your insecurities. Remember that when you buy anything. And remember that about anyone who operates outside the mainstream and has something to sell. They may have found the Next Big Thing, but the odds are highly against that. Caveat emptor!

 

[Bryan]

No offense meant to you Bryan. I DID read every word of the thread but near the end it seemed to turn more into a "whose brain is bigger" thread rather than meaningful discussion.

Vortex, if you really think THIS thread is a "pissing contest", you oughtta see what happens over on hairsite! This thread is a Sunday School class, compared to other places! :lol:

Bryan

 

[Axon]

Re: Hrm...

I never got the impression there were any pissing contests here. I call it healthy debate. I don't think of debate as a brainiac contest, I think of it as a good way to get at the facts. I guess it's just that discussions of this type are so common where I work, I take for granted other people would find them useful.

While it would be nice if everything was a healthy debate, far too often does it become a "my brain is bigger than your brain" contest. Just can't let the other guy have the last word, I suppose.

Vortex, if you really think THIS thread is a "pissing contest", you oughtta see what happens over on hairsite! This thread is a Sunday School class, compared to other places!

Mmm...I agree. Some it pure flaming, though, where as here, some of these "contests" really do boil down to egos. Thankfully it is not often that this occurs.

 

[Loopydude]

Some points

Hey, Brian,

In vitro binding assays are great for some things, but it has to be understood that context is everything, and it's not unusual for such assays to give spurious results. They have to be followed up with more careful analysis, ultimately things like radioligand binding assays in vivo to colocalize receptor, known competator, and putative competator binding. Some people really go crazy and do the x-ray crystallography on the ligand-receptor complex, but that's a late-stage kinda study.

Check out this abstract:

Toxicol Ind Health. 1999 Jan-Mar;15(1-2):94-118.

Administration of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, p,p'-DDE, and ketoconazole) and toxic substances (dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat.

Gray LE Jr, Wolf C, Lambright C, Mann P, Price M, Cooper RL, Ostby J.

This study suggest that ketoconazole is NOT an adrogen receptor (AR) antagonist, by comparing it with several other known AR antagonists. The statement by Dr. Eli, that keto concentrations sufficient to achieve EC50 levels are unlikely to occur in vivo in the clinically relevant dose range, is a good cautionary, cover-your-*** kind of statement. All his/her paper really says is, hey, when I stick boatloads of keto on some fibroblasts at room temperature (your body is at 37 deg. C, not 22, and the amount of energy in the system has a big impact on intermolecular interactions), it competes for binding with a known AR ligand. By itself, unfortunately, this is not a very impressive result. Eli is very responsible in his/her wording; he/she merely suggests keto could be an AR antagonist. Unfortunately, the experimental conditions have little in vivo relevance, and would have to be followed-up in a much more realistic model to make the hypothesis convincing. I could find no such studies, unfortunately. At any rate, for clinical purposes, the antisteroidogenic effects of keto are so potent, I imagine it completely swamps any effect one might see by the tiny AR antagonistic properties it may have.

One could argue that local concentrations of keto are high enough in the skin with topical treatment to make its putative antiandrogenic properties important. This would be the purest conjecture without further study. Nothing in Eli's paper can justify such a leap.

As for skin steroidogenesis: If you cut your balls off, you stop losing hair. You may not regrow much, but you won't lose much more either. Sadly, your nuts are the major source of the problem. If the skin could produce enough testosterone to promote hair loss by itself, castration would have less of an effect on alopecia. However, it has a big effect, an abolishing effect, some would say. Trust me, if you snipped off your nads, your adrenals alone would still make many times more testosterone than the rest of your body put together, at least as far as anyone knows. I could swallow that local conversion of testosterone to DHT might be of some importance, but local synthesis of the pro-hormone? I can't see any reason to think that's a relevant concern, given the available evidence about eunuchs. So, if you still have your balls, what good is inhibiting the piddly amount of testosterone synthesis in your skin going to do you? You've still got relatively huge amounts coursing through your veins, testosterone moves very easily across cell membranes, and your exposure is thus still significant.

Now, having said all this, maybe the antiandrogen hypothesis is as good as any other. Unfortunately, none of the theories about keto's action in hair loss hold much water under scrutiny, so that's not saying a whole lot. Some people think that fungus makes you lose hair, which I'm sure is true in severe cases; but it seems to me that the average male-pattern-baldie didn't get that way because of a yeast infection or whatever. Besides, other antimycotics don't promote hair growth as far as I know, so there goes the fungus theory. Maybe, when all is said and done, you're completely right, but there's simply no way to make any sound judgements so far.

I kinda wonder if keto does something nobody knows about yet. Wouldn't that be interesting? I think so! I wish somebody would study it rigorously. They might find another key drug target and screen for good topicals that act more strongly than keto.

P.S. - This is NOT a pissing contest! I think you're a cool dude, a smart guy, etc. etc. Hope you don't take offense at the debate.

 

[Bryan]

Hey, Brian,

In vitro binding assays are great for some things, but it has to be understood that context is everything, and it's not unusual for such assays to give spurious results. They have to be followed up with more careful analysis, ultimately things like radioligand binding assays in vivo to colocalize receptor, known competator, and putative competator binding. Some people really go crazy and do the x-ray crystallography on the ligand-receptor complex, but that's a late-stage kinda study.

Gosh, it would be terrific if we had that kind of thorough testing, but we don't, unfortunately. However, the results of the study I cited along with the observed effect on sebaceous glands would appear to make keto's putative antiandrogenicity the most attractive theory to explain its beneficial effect on hairloss, IMHO.

Check out this abstract:

Toxicol Ind Health. 1999 Jan-Mar;15(1-2):94-118.

This study suggest that ketoconazole is NOT an adrogen receptor (AR) antagonist, by comparing it with several other known AR antagonists.

Thanks, Loopy! I've added that to my "Get" list. I'll read that with interest.

At any rate, for clinical purposes, the antisteroidogenic effects of keto are so potent, I imagine it completely swamps any effect one might see by the tiny AR antagonistic properties it may have.

Now you've lost me! With what you say later, it would appear to me that you'd say just the OPPOSITE of that (and I would certainly agree): the AR-blocking effect would surely swamp out the local antisteroidogenic effect, since the latter must surely be relatively minimal, compared to systemic levels of androgens. It looks like you've done a 180 on me! :lol:

One could argue that local concentrations of keto are high enough in the skin with topical treatment to make its putative antiandrogenic properties important. This would be the purest conjecture without further study. Nothing in Eli's paper can justify such a leap.

But we have additional EVIDENCE supporting that theory: the effect on sebaceous glands. I'm not sure why Maddoc, and now you, apparently, find that theory so difficult to believe.

As for skin steroidogenesis: If you cut your balls off, you stop losing hair. You may not regrow much, but you won't lose much more either. Sadly, your nuts are the major source of the problem. If the skin could produce enough testosterone to promote hair loss by itself, castration would have less of an effect on alopecia. However, it has a big effect, an abolishing effect, some would say. Trust me, if you snipped off your nads, your adrenals alone would still make many times more testosterone than the rest of your body put together, at least as far as anyone knows. I could swallow that local conversion of testosterone to DHT might be of some importance, but local synthesis of the pro-hormone? I can't see any reason to think that's a relevant concern, given the available evidence about eunuchs. So, if you still have your balls, what good is inhibiting the piddly amount of testosterone synthesis in your skin going to do you? You've still got relatively huge amounts coursing through your veins, testosterone moves very easily across cell membranes, and your exposure is thus still significant.

Oh, trust me on this: I was DEFINITELY thinking of Hamilton's castration studies when I wrote the previous posts! (God, that early work has been of ENORMOUS utility in many cases regarding hairloss, hasn't it?) In fact, I was a bit hesitant even to mention the _possibility_ that the inhibition of local steroidogenesis might be useful, so I was careful to mention it only in passing. I do have respect for Dr. Hoffmann's ideas, though, so I wanted to give at least a little bit of lip-service to it.

Now, having said all this, maybe the antiandrogen hypothesis is as good as any other. Unfortunately, none of the theories about keto's action in hair loss hold much water under scrutiny, so that's not saying a whole lot. Some people think that fungus makes you lose hair, which I'm sure is true in severe cases; but it seems to me that the average male-pattern-baldie didn't get that way because of a yeast infection or whatever. Besides, other antimycotics don't promote hair growth as far as I know, so there goes the fungus theory.

Yes, and there's one other point from the study I cited that I didn't mention before: other antimycotics were ALSO tested for AR-blocking, but they didn't have any, only keto! That makes it still more suggestive!

Maybe, when all is said and done, you're completely right, but there's simply no way to make any sound judgements so far.

I'm just saying that right now, it's the simplest and most obvious explanation.

BTW, Loopy, Maddoc appears to have bailed-out of this conversation. Can you take over HIS end of the conversation? Are you aware of any relationship between local fungal growth and the size of sebaceous glands and their sebum output? I seriously wanted him to find some evidence that would support his own claims, but he never met my challenge. I can't think of any other explanation for Nizoral's effect on sebaceous glands, other than what we've been talking about. Can YOU think of an alternative explanation?

Bryan

 

[maddoc23]

Bryan,

With respect to the size of a sebaceous gland you have assumed to many things. I do recognize it can be influenced by androgens, but at the same time you should recognize it can be influenced by other factors. One being s. dermatitis. If s. dermatitis is accompanied by increased sebum production why is it so difficult to extrapolate that the very treatment of s. dermatitis would bring the sebaceous gland back to baseline. Under this theory androgens would have nothing to do with the size of the gland.

Furthermore, I really don't see the point in debating Nizorals DHT properties if it has not been established nizoral can penetrate the skin (especially in 5 min) Dr. Lee has even said as much. Allow me to reiterate, NOBODY has established this. While nizoral may have some anti-androgenic properties, I find it far fetched to avdocate and promote nizoral as a shampoo that blocks DHT (in any capacity). For this to be done, you must show it can penetrate the skin (in 5 minutes) and the little affect it MAY have is responsible for the gains in the nizoral study. It has been proven the elimination of s. dermatitis helps with male pattern baldness and anti-inflammatory agents also help with male pattern baldness. Nizoral does both, and these actions are the most plausible explanation as to the benefit of Nizoral.

Unless you can demonstrate nizoral's ability to pentrate the scalp and to do so in sufficient quantities that enable the anti-androgenic properties to account for the clinical data........you should not aver it as a "DHT shampoo"

And to be fair I CAN demonstrate the penetration ability of nizoral is UNKNOWN and that eliminating s. dermatitis and inflammation promote hair regrowth.

D

P.S. My absence from this post was due to corroborating my position mainly in the form of a reply from Dr. Lee stating nizoral is not known to penetrate the scalp. I would be more than happy to include that response if requested.

 

[Bryan]

Bryan,

With respect to the size of a sebaceous gland you have assumed to many things. I do recognize it can be influenced by androgens, but at the same time you should recognize it can be influenced by other factors.

Sure. For example, I have a study which examines seasonal effects on sebum production, and the effects of temperature changes. And I don't believe they know to this very day why isotretinoin so profoundly reduces the size of sebaceous glands. The last time I checked, it was still a big mystery.

One being s. dermatitis.

And your evidence for that is...?

I'm not saying I don't believe you, I'd just like to see some clear evidence that it's the s. dermatitis that's causing the sebum, and not the sebum that's causing the s. dermatitis.

If s. dermatitis is accompanied by increased sebum production why is it so difficult to extrapolate that the very treatment of s. dermatitis would bring the sebaceous gland back to baseline.

Simple: association is not the same as causation. You probably have the CAUSE confused with the EFFECT. But if you can show me some evidence, I'll believe you.

Furthermore, I really don't see the point in debating Nizorals DHT properties if it has not been established nizoral can penetrate the skin (especially in 5 min)

What do you mean by "penetrate the skin"? BE SPECIFIC. Are you talking about penetrating the stratum corneum, or something else? Recent evidence indicates that a very significant fraction of the topical absorption of some drugs is right down through the hair follicle itself, in which case the difficulty of penetrating the stratum corneum is a rather moot point.

Dr. Lee has even said as much. Allow me to reiterate, NOBODY has established this. While nizoral may have some anti-androgenic properties, I find it far fetched to avdocate and promote nizoral as a shampoo that blocks DHT (in any capacity). For this to be done, you must show it can penetrate the skin (in 5 minutes) and the little affect it MAY have is responsible for the gains in the nizoral study.

Again: what does "penetrate the skin" mean? BE SPECIFIC.

P.S. My absence from this post was due to corroborating my position mainly in the form of a reply from Dr. Lee stating nizoral is not known to penetrate the scalp. I would be more than happy to include that response if requested.

You can include it if you like, but is it really relevant to what we're talking about?

Bryan

 

[Loopydude]

What can you say? Not much, unfortunately...

On the simple basis of principle, I have to agree with maddoc. Not only is there no good data, there's really none at all.

Sorry for the confusion about antisteroidogenesis swamping androgen antagonism: I was thinking about systemic keto, the only condition in which anyting approaching good data has been generated in regards to hormones. The reason I separated putative topical effects in my statements is because they are precicely that. One needs more than hypotheses to make confident claims about what a drug is doing in a particular context. Sadly, little data exists on topical keto that is of relevance to the questions at hand. One is forced to be agnostic on the whole subject. It looks like keto does all kinds of things that could effect sebacious glands. Which effect is the important one? Are they all? No one seems to know.

I consider a claim like "2% Nizoral or equivalent is an anti-DHT shampoo" to be something other than agnostic. If one is just speculating, fine. If one is selling the stuff using marketing based on that claim...well, that's a whole other story.

 

[maddoc23]

I concur with Loopy here. I really don't think there is any question ketoconazole slightly affects DHT acitivity when taking orally. However, to my knowledge, there hasn't been any studies to demonstrate how much DHT is inhibited or blocked when keto is taken orally AND what impact it will have in male pattern baldness. Furthermore, it is unknown if a keto shampoo will be absorbed through the skin (far enough) to impact DHT activity. With these questions unanswered it becomes irresponsible to cite its anti-androgenic (or such) properties as being responsible for the results in the nizoral study or having an affect on DHT activity, especially since there are other more plausible explainations.

D

 

[Bryan]

Re: What can you say? Not much, unfortunately...

It looks like keto does all kinds of things that could effect sebacious glands.

Can you name a few of those things, Loopy?
Thanks...

Bryan

 

[Bryan]

I concur with Loopy here. I really don't think there is any question ketoconazole slightly affects DHT acitivity when taking orally. However, to my knowledge, there hasn't been any studies to demonstrate how much DHT is inhibited or blocked when keto is taken orally AND what impact it will have in male pattern baldness.

We're mainly discussing TOPICAL keto (Nizoral shampoo), not oral keto.

Furthermore, it is unknown if a keto shampoo will be absorbed through the skin (far enough) to impact DHT activity. With these questions unanswered it becomes irresponsible to cite its anti-androgenic (or such) properties as being responsible for the results in the nizoral study or having an affect on DHT activity, especially since there are other more plausible explainations.

Maddoc, we've been over and over all this, and you still haven't been able to provide any evidence for your alternate theory. I think that my explanation is CLEARLY more plausible.

Bryan

 

[maddoc23]

I concur with Loopy here. I really don't think there is any question ketoconazole slightly affects DHT acitivity when taking orally. However, to my knowledge, there hasn't been any studies to demonstrate how much DHT is inhibited or blocked when keto is taken orally AND what impact it will have in male pattern baldness.

We're mainly discussing TOPICAL keto (Nizoral shampoo), not oral keto.

True, but if you can not establish the impact oral keto has on male pattern baldness than you can not establish the impact nizoral has.

Furthermore, it is unknown if a keto shampoo will be absorbed through the skin (far enough) to impact DHT activity. With these questions unanswered it becomes irresponsible to cite its anti-androgenic (or such) properties as being responsible for the results in the nizoral study or having an affect on DHT activity, especially since there are other more plausible explainations.

Maddoc, we've been over and over all this, and you still haven't been able to provide any evidence for your alternate theory. I think that my explanation is CLEARLY more plausible.

This is my point. Are you saying in the absence of scientific evidence we are to just assume nizoral just absorbs through the skin. Sadly, I must inform you the onus is on you to prove your point. Proving your point is not just disproving ours. Scientific law is not based on a lack of evidence, but confirming a hypothesis via valid, reproducible experiments. Until YOU can show the absorptive ability of nizoral there is nothing to debate.
Ultimately, through all the semantics, you still have not elucidated the one point your explanation is critical upon.......will the shampoo be absorbed through the skin far enough in 5 minutes. The reason this argument sounds repetitive is because neither you nor the scientific community has demonstrated the absorptive ability of nizoral. Remember, since you are making the "DHT shampoo" claim it is up to YOU to show it is absorbed through the skin (far enough) to make the impact in those studies you cite, and you can not show it.

Respectfully,

D

 

[Loopydude]

Response to Bryan

Heya, Bryan,

I guess I was under the impression that microbial infestation playss a big role in seborheic dermatitis (Malassezia yeast infection appears to be the most prevalent problem), and so keto's antifungal properties go a long way toward explaining its effects on sebacious glands.

CYP450 enzymes are expressed in skin, hair follicles, and sebaceous glands. Since keto is a known CYP450 inhibitor, it seems reasonable to wonder if it might have some impact on skin biology. Maybe this is the thing that could establish an important antisteroidogenic link, but I don't know: CYP450 enzymes (I can't remeber which one or ones, exactly) are involved in the conversion of cholesterol to steroid hormones. But CYP450 enzymes are involved in converting a whole host of other molecules into other things too, so it's hard to know what's important. I guess all I'm saying is keto, by acting on such an ubiquitously-expressed and important family of enzymes, impacts a lot of things.

Check out this link:

http://www.ncbi.nlm.nih.gov:80/entrez/q ... t=Abstract

 

[Bryan]

We're mainly discussing TOPICAL keto (Nizoral shampoo), not oral keto.

True, but if you can not establish the impact oral keto has on male pattern baldness than you can not establish the impact nizoral has.

That statement doesn't make any sense. Are you saying that the Nizoral study did not establish any impact that Nizoral has on male pattern baldness? Please explain.

This is my point. Are you saying in the absence of scientific evidence we are to just assume nizoral just absorbs through the skin.

No, I'm saying in the PRESENCE of scientific evidence, we can conclude that Nizoral absorbs into the pilosebaceous unit. As I've pointed out about 47 times so far, it was able to reduce the size of sebaceous glands. If you can't find any way to explain how a fungal infection would influence sebaceous glands in a similar fashion, well then...there's your evidence!

Sadly, I must inform you the onus is on you to prove your point. Proving your point is not just disproving ours. Scientific law is not based on a lack of evidence, but confirming a hypothesis via valid, reproducible experiments. Until YOU can show the absorptive ability of nizoral there is nothing to debate.
Ultimately, through all the semantics, you still have not elucidated the one point your explanation is critical upon.......will the shampoo be absorbed through the skin far enough in 5 minutes. The reason this argument sounds repetitive is because neither you nor the scientific community has demonstrated the absorptive ability of nizoral. Remember, since you are making the "DHT shampoo" claim it is up to YOU to show it is absorbed through the skin (far enough) to make the impact in those studies you cite, and you can not show it.

I already have shown it, about 47 times. And YOU have no evidence for any competing explanation.

Has this discussion reached an impasse now? Is this what they call a "Mexican StandOff"? :lol:

Bryan

 

[Bryan]

Re: Response to Bryan

I guess I was under the impression that microbial infestation playss a big role in seborheic dermatitis (Malassezia yeast infection appears to be the most prevalent problem), and so keto's antifungal properties go a long way toward explaining its effects on sebacious glands.

How would a fungal infection cause sebaceous glands to enlarge?

CYP450 enzymes are expressed in skin, hair follicles, and sebaceous glands. Since keto is a known CYP450 inhibitor, it seems reasonable to wonder if it might have some impact on skin biology. Maybe this is the thing that could establish an important antisteroidogenic link, but I don't know: CYP450 enzymes (I can't remeber which one or ones, exactly) are involved in the conversion of cholesterol to steroid hormones. But CYP450 enzymes are involved in converting a whole host of other molecules into other things too, so it's hard to know what's important. I guess all I'm saying is keto, by acting on such an ubiquitously-expressed and important family of enzymes, impacts a lot of things.

Yes, but an important point (for Maddoc's sake) is that even IF that explains Nizoral's action on sebaceous glands instead of the assumed antiandrogenic effect, that still apparently shows that keto is being absorbed by sebocytes, and is affecting their metabolism (albeit by a different mechanism).

Bryan