michael barry
Senior Member
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Found this old post from Bryan.............I thought it was interesting that curcumin and green teas anti-androgenic possibilities have been explored by at least some scientists:
Monday August 13, 2001 7:05 PM
Here is something else I posted on alt.baldspot, which I think has implications for some novel ways to treat balding!
Guys, I'm all excited about a new study which just came out. I have to give Waseda a tip of the hat for mentioning it on the newsgroup a couple of weeks ago. Since then, I've gotten the full study and carefully read it. I think it has some very interesting implications: "Growth suppression of hamster flank organs by topical application of catechins, alizarin, curcumin, and myristoleic acid", Shutsung Liao et al., Arch Dermatol Res (2001) 293:200-205.
Most of you know that I've been experimenting with a topical green tea extract (from http://www.beyond-a-century.com) that is supposed to be 45% EGCG (epigallo-catechin-3-gallate), which is one of the main antioxidant polyphenols found in green tea. The rationale for doing this is that EGCG and certain others of this chemical group have been found to be potent inhibitors of the 5alpha-reductase enzyme. This was first verified in an earlier study: "Selective inhibition of steroid 5alpha-reductase isozymes by tea epicatechin-3-gallate and epigallocatechin -3-gallate", Shutsung Liao and Richard Hiipakka, Biophys Biochem Res Commun 214:833-838. This was just an "in vitro" study, but it did find that EGCG and certain others of these compounds inhibited BOTH forms of 5a-R, although they were more potent against the type 1 version. However, as with all things like this, you can make up with quantity what you lack in quality! And near the end of this study, they added a little afterthought: they mentioned an "unpublished observation" of theirs, which was that the topical application of either GLA (gamma-linolenic acid) or EGCG to the foreheads of human male subjects decreased their sebum excretion rate. Since the activity of sebaceous glands is under androgenic control, this was a clear indication that these compounds are able to work topically in humans, at the very least in sebaceous glands.
Now we have a newer study by these same researchers, and this time they test these substances (and a few others) in an "in vivo" experiment, using hamster flank organs. And they made a *very* unexpected and fascinating finding which I will get to in just a moment, but first let me mention the more conventional results: in one part of the experiment they duplicated yet another earlier study, and tested a combination of testosterone and 1 mg of GLA on one flank organ of a group of hamsters, and found that the GLA reduced the growth of the pigmented macules (a direct function of the growth of the flank organ itself) by 82%, which agrees with the previous study. In other parts of the experiment they tested EGCG along with testosterone, and as you can guess, they got significant inhibitions that ranged up to 64% from 1 mg of EGCG, in one of the trials! Now think about that: 1 mg of the very inexpensive and easily obtainable EGCG (from green tea) was in the same general neighborhood of effectiveness as 1 mg of the extremely expensive, exotic, and exemplary GLA (yes, I just love alliteration)! Results from 1 mg of the tea catechins
alizarin and curcumin were even *more* impressive, with inhibitions of 87% for both of those compounds.
Ok, now we're getting closer to the real punchline of this study! Consider this: GLA, ALA, LA, oleic acid, and the other fatty acids have no effect whatsoever on DHT itself. In this new study and the older one, they were very effective at inhibiting hamster flank organs and hair follicles because they are good at stopping the conversion of testosterone to DHT, via the 5a-R enzyme. But they have no effect on the androgen receptor, so they cannot affect pre-existing DHT. When GLA and the other fatty acids are applied to hamster flank organs along with pure DHT, there is no effect at all; the growth of the flank organs is not inhibited at all.
Question: what would you expect to happen if you applied some cheap EGCG from green tea to hamster flank organs, along with pure DHT?? Would it also turn out to be ONLY a 5alpha-reductase inhibitor?? That's what Liao et al. wanted to know, and that's what they tried. (BTW, they found that pure DHT was almost exactly 50% more potent than the same dose of testosterone at stimulating flank organs: the extra testosterone-stimulated growth of the macules in control animals was 13.83 mm^2, and the DHT-stimulated growth was 20.80 mm^2)
Ok, here's the kicker: 1 mg of EGCG applied with pure DHT inhibited the flank organ growth by an absolutely *astonishing* 97%!! EGCG was even MORE effective against DHT than it was against testosterone!!
Suddenly, things are put in a whole new light. Previously it was assumed that cheap green tea might possibly function as an inexpensive additional 5alpha-reductase inhibitor; perhaps something to use as an adjunct to Propecia, to inhibit the type 1 form of the enzyme. But now it appears to be a distinct possibility that this substance performs not just as a *dual* inhibitor of 5a-R, but also as some kind of an agent that interferes directly with DHT! Could it be possible that the most effective antiandrogenic agent to date (at the very least, the most cost-effective) has been literally right under our noses all this time?? I think this is something to consider....
I now present the entire "Discussion" section of this new study. I've added a couple of comments of my own in brackets. Any comments afterwards are certainly welcome:
"DISCUSSION"
"In this study we showed that all four green tea catechins inhibited hamster flank organ growth to various degrees. Like gamma-LA (Liang and Liao 1992; Liao and Hiipakka 1995), in an in vitro enzyme assay ECG and EGCG have been shown to be potent inhibitors (IC50 10-20 uM) of 5alpha-reductase, while EC and EGC are not active inhibitors of 5alpha-reductase at 200 uM (Liao and Hiipakka 1995). Consistent with these in vitro tests, EGCG and ECG inhibited the testosterone-dependent growth of flank organs. However,
EC and EGC, though inactive against 5alpha-reductase in vitro, had an inhibitory effect on flank organ growth. The suppression of flank organ growth by catechins, therefore, does not appear to be due simply to inhibition of the formation of DHT from testosterone in flank organs. In line with this observation, EGCG was inhibitory even when DHT instead of testosterone was used as the androgen (Table 1). [That refers to the 97% figure --- Bryan] This is in contrast with GLA, which inhibited testosterone-stimulated flank organ growth but not DHT-stimulated flank organ growth (Liang and Liao 1997). Therefore, even though EGCG and EGC can inhibit 5alpha-reductase, inhibition of flank organ growth by catechins may occur through other mechanisms. Whether these catechins affect androgen receptor activity in hamster flank organs is not known.
"The possibility that polyphenolic catechins and other inhibitory compounds act simply by interacting with topically applied androgens and reduce androgenic activity is unlikely since these compounds when topically applied inhibited endogenous androgen-dependent growth of flank organs of normal (not castrated) male hamsters (results not shown). We have previously shown that topically applied GLA inhibits flank organ growth in normal hamsters (Liang and Liao 1997).
"Previous studies of the effect of fatty acids on flank organ growth suggest that compounds with fewer than 18 carbons are ineffective (Liang and Liao 1997). We showed here that MA [this is myristoleic acid --- Bryan], containing 14 carbons is as effective as GLA in inhibiting flank organ growth. In addition, the effects of MA and GLA in preventing testosterone-induced growth of flank organs were similar to the effect of EGC-gamma-linoleneate and EGC-myristoleate esters. No differences were noted in the effects of EGCG and that of the synthetic esters which contained GLA and MA in place of the gallate group of EGCG.
"Alizarin and curcumin may inhibit flank organ growth primarily by inhibiting 5alpha-reductase. This conclusion is supported by data showing that alizarin and curcumin inhibited testosterone-induced flank organ growth, but did not curb growth stimulated by DHT. Furthermore, in an in vitro enzyme assay, both compounds have been shown to be potent inhibitors of 5alpha-reductase (IC50 5-10 uM) (Hiipakka and Liao, unpublished results). These observations support our previous conclusion (Liang and Liao 1997) that flank organ growth is dependent on local conversion of testosterone to DHT as is prostate growth in rodents and humans. Histological observations show that pigments of flank organs were localized in the hair shaft and near the orifice of hair follicles. This finding suggests that catechins, alizarin, and curcumin inhibit androgenic effects not only in dermal melanocytes, but also in hair follicles of the flank organ.
"An inhibitor of a 5alpha-reductase with systemic activities would be teratogenic to embryos (Imperato-McGinley and Guatier 1986; Russell and Wilson 1994). For this reason a topical preparation of 5alpha-reductase inhibitor that does not produce systemic activity is desirable for treating androgen-dependent skin diseases. Since local application of GLA and other active compounds described in this report did not exhibit a systemic effect on the contralateral flank organs or on prostate organ weights in hamsters, they may be useful for treatment of androgen-dependent skin disorders. Additional studies are needed to determine whether the findings described in this report for the hamster model are applicable to human skin."
Monday August 13, 2001 7:05 PM
Here is something else I posted on alt.baldspot, which I think has implications for some novel ways to treat balding!
Guys, I'm all excited about a new study which just came out. I have to give Waseda a tip of the hat for mentioning it on the newsgroup a couple of weeks ago. Since then, I've gotten the full study and carefully read it. I think it has some very interesting implications: "Growth suppression of hamster flank organs by topical application of catechins, alizarin, curcumin, and myristoleic acid", Shutsung Liao et al., Arch Dermatol Res (2001) 293:200-205.
Most of you know that I've been experimenting with a topical green tea extract (from http://www.beyond-a-century.com) that is supposed to be 45% EGCG (epigallo-catechin-3-gallate), which is one of the main antioxidant polyphenols found in green tea. The rationale for doing this is that EGCG and certain others of this chemical group have been found to be potent inhibitors of the 5alpha-reductase enzyme. This was first verified in an earlier study: "Selective inhibition of steroid 5alpha-reductase isozymes by tea epicatechin-3-gallate and epigallocatechin -3-gallate", Shutsung Liao and Richard Hiipakka, Biophys Biochem Res Commun 214:833-838. This was just an "in vitro" study, but it did find that EGCG and certain others of these compounds inhibited BOTH forms of 5a-R, although they were more potent against the type 1 version. However, as with all things like this, you can make up with quantity what you lack in quality! And near the end of this study, they added a little afterthought: they mentioned an "unpublished observation" of theirs, which was that the topical application of either GLA (gamma-linolenic acid) or EGCG to the foreheads of human male subjects decreased their sebum excretion rate. Since the activity of sebaceous glands is under androgenic control, this was a clear indication that these compounds are able to work topically in humans, at the very least in sebaceous glands.
Now we have a newer study by these same researchers, and this time they test these substances (and a few others) in an "in vivo" experiment, using hamster flank organs. And they made a *very* unexpected and fascinating finding which I will get to in just a moment, but first let me mention the more conventional results: in one part of the experiment they duplicated yet another earlier study, and tested a combination of testosterone and 1 mg of GLA on one flank organ of a group of hamsters, and found that the GLA reduced the growth of the pigmented macules (a direct function of the growth of the flank organ itself) by 82%, which agrees with the previous study. In other parts of the experiment they tested EGCG along with testosterone, and as you can guess, they got significant inhibitions that ranged up to 64% from 1 mg of EGCG, in one of the trials! Now think about that: 1 mg of the very inexpensive and easily obtainable EGCG (from green tea) was in the same general neighborhood of effectiveness as 1 mg of the extremely expensive, exotic, and exemplary GLA (yes, I just love alliteration)! Results from 1 mg of the tea catechins
alizarin and curcumin were even *more* impressive, with inhibitions of 87% for both of those compounds.
Ok, now we're getting closer to the real punchline of this study! Consider this: GLA, ALA, LA, oleic acid, and the other fatty acids have no effect whatsoever on DHT itself. In this new study and the older one, they were very effective at inhibiting hamster flank organs and hair follicles because they are good at stopping the conversion of testosterone to DHT, via the 5a-R enzyme. But they have no effect on the androgen receptor, so they cannot affect pre-existing DHT. When GLA and the other fatty acids are applied to hamster flank organs along with pure DHT, there is no effect at all; the growth of the flank organs is not inhibited at all.
Question: what would you expect to happen if you applied some cheap EGCG from green tea to hamster flank organs, along with pure DHT?? Would it also turn out to be ONLY a 5alpha-reductase inhibitor?? That's what Liao et al. wanted to know, and that's what they tried. (BTW, they found that pure DHT was almost exactly 50% more potent than the same dose of testosterone at stimulating flank organs: the extra testosterone-stimulated growth of the macules in control animals was 13.83 mm^2, and the DHT-stimulated growth was 20.80 mm^2)
Ok, here's the kicker: 1 mg of EGCG applied with pure DHT inhibited the flank organ growth by an absolutely *astonishing* 97%!! EGCG was even MORE effective against DHT than it was against testosterone!!
Suddenly, things are put in a whole new light. Previously it was assumed that cheap green tea might possibly function as an inexpensive additional 5alpha-reductase inhibitor; perhaps something to use as an adjunct to Propecia, to inhibit the type 1 form of the enzyme. But now it appears to be a distinct possibility that this substance performs not just as a *dual* inhibitor of 5a-R, but also as some kind of an agent that interferes directly with DHT! Could it be possible that the most effective antiandrogenic agent to date (at the very least, the most cost-effective) has been literally right under our noses all this time?? I think this is something to consider....
I now present the entire "Discussion" section of this new study. I've added a couple of comments of my own in brackets. Any comments afterwards are certainly welcome:
"DISCUSSION"
"In this study we showed that all four green tea catechins inhibited hamster flank organ growth to various degrees. Like gamma-LA (Liang and Liao 1992; Liao and Hiipakka 1995), in an in vitro enzyme assay ECG and EGCG have been shown to be potent inhibitors (IC50 10-20 uM) of 5alpha-reductase, while EC and EGC are not active inhibitors of 5alpha-reductase at 200 uM (Liao and Hiipakka 1995). Consistent with these in vitro tests, EGCG and ECG inhibited the testosterone-dependent growth of flank organs. However,
EC and EGC, though inactive against 5alpha-reductase in vitro, had an inhibitory effect on flank organ growth. The suppression of flank organ growth by catechins, therefore, does not appear to be due simply to inhibition of the formation of DHT from testosterone in flank organs. In line with this observation, EGCG was inhibitory even when DHT instead of testosterone was used as the androgen (Table 1). [That refers to the 97% figure --- Bryan] This is in contrast with GLA, which inhibited testosterone-stimulated flank organ growth but not DHT-stimulated flank organ growth (Liang and Liao 1997). Therefore, even though EGCG and EGC can inhibit 5alpha-reductase, inhibition of flank organ growth by catechins may occur through other mechanisms. Whether these catechins affect androgen receptor activity in hamster flank organs is not known.
"The possibility that polyphenolic catechins and other inhibitory compounds act simply by interacting with topically applied androgens and reduce androgenic activity is unlikely since these compounds when topically applied inhibited endogenous androgen-dependent growth of flank organs of normal (not castrated) male hamsters (results not shown). We have previously shown that topically applied GLA inhibits flank organ growth in normal hamsters (Liang and Liao 1997).
"Previous studies of the effect of fatty acids on flank organ growth suggest that compounds with fewer than 18 carbons are ineffective (Liang and Liao 1997). We showed here that MA [this is myristoleic acid --- Bryan], containing 14 carbons is as effective as GLA in inhibiting flank organ growth. In addition, the effects of MA and GLA in preventing testosterone-induced growth of flank organs were similar to the effect of EGC-gamma-linoleneate and EGC-myristoleate esters. No differences were noted in the effects of EGCG and that of the synthetic esters which contained GLA and MA in place of the gallate group of EGCG.
"Alizarin and curcumin may inhibit flank organ growth primarily by inhibiting 5alpha-reductase. This conclusion is supported by data showing that alizarin and curcumin inhibited testosterone-induced flank organ growth, but did not curb growth stimulated by DHT. Furthermore, in an in vitro enzyme assay, both compounds have been shown to be potent inhibitors of 5alpha-reductase (IC50 5-10 uM) (Hiipakka and Liao, unpublished results). These observations support our previous conclusion (Liang and Liao 1997) that flank organ growth is dependent on local conversion of testosterone to DHT as is prostate growth in rodents and humans. Histological observations show that pigments of flank organs were localized in the hair shaft and near the orifice of hair follicles. This finding suggests that catechins, alizarin, and curcumin inhibit androgenic effects not only in dermal melanocytes, but also in hair follicles of the flank organ.
"An inhibitor of a 5alpha-reductase with systemic activities would be teratogenic to embryos (Imperato-McGinley and Guatier 1986; Russell and Wilson 1994). For this reason a topical preparation of 5alpha-reductase inhibitor that does not produce systemic activity is desirable for treating androgen-dependent skin diseases. Since local application of GLA and other active compounds described in this report did not exhibit a systemic effect on the contralateral flank organs or on prostate organ weights in hamsters, they may be useful for treatment of androgen-dependent skin disorders. Additional studies are needed to determine whether the findings described in this report for the hamster model are applicable to human skin."
