Equol inhibits Hormone Feedback

[hairrific]

Equol (7-hydroxy-3[4'hydroxyphenyl]-chroman) is the major metabolite of the phytoestrogen daidzein, one of the main isoflavones found abundantly in soybeans and soy foods.....The significance of equol's ability to specifically bind and sequester DHT from the androgen receptor have important ramifications in health and disease and may indicate a broad and important usage for equol in the treatment of androgen-mediated pathologies.

.....In performing these studies, we discovered that equol had only a modest affinity for ERß and little or no affinity for ER{alpha}; however, the results from our studies indicate that equol can act as an anti-androgen. The anti-androgenic properties of equol are unique in that equol does not bind the androgen receptor (AR) but specifically binds 5{alpha}-dihydrotestosterone (DHT) with high affinity, and thereby prevents DHT from binding the AR.

.....Equol's anti-androgenic action is due to its unique ability to specifically bind DHT without binding the androgen receptor. As a result, equol can sequester DHT from binding the androgen receptor. It is known that soy-derived phytoestrogens (isoflavones) have positive benefits in protecting against hormone-dependent (breast and prostate cancer) and age-related diseases (such as cardiovascular disease and osteoporosis.....

....equol also blocked circulating DHT's androgenic trophic influence on the prostate and epididymis without significantly altering circulating DHT levels....

....other androgen-responsive tissues may also benefit from equol therapy. Such conditions include [42 female- and male-pattern baldness–44]; facial and body hair growth [42–44]; skin health (acne, anti-aging, and anti-photo aging) [42, 45]; skin integrity (collagen and elastin robustness) [42, 45]; and emotional and mental health issues, such as, mood, depression, anxiety, learning, and memory [46, 47].

http://www.biolreprod.org/cgi/content/full/70/4/1188

 

[hairrific]

http://www.ajcn.org/cgi/content/full/81/5/1072

...Our pharmacokinetic studies show that equol is rapidly absorbed from the intestine, but its formation after the initial intake of daidzein or of soy foods containing daidzin or daidzein is a time-dependent process. It generally takes >12 h for equol to appear in the plasma, and, in some adults, it may not appear for 36 h, which indicates that the colon is the site of its formation (18, 28, 48). Identification of the bacteria responsible for equol production has thus far been elusive.

...Attempts to identify the species of bacteria involved in equol production have yielded some information regarding strains that are capable of hydrolyzing the ß-glucoside of daidzin (50, 51) or of converting daidzein to dihydrodaidzein (52), and one report claimed that Streptococcus intermedius spp, Ruminococcus productus spp, and Bacteroides ovatus in vitro perform the required conversion (53).

 

[squeegee]

Abstract: Intestinal bacteria are involved in estrogen metabolism. Thus, inter- individual differences in intestinal bacterial populations may contribute to variation breast cancer risk via effects on estrogen metabolism. One-third to one-half of the population harbors the yet-to be-identified bacteria that metabolize daidzein, a soy isoflavone, to equol. Studies suggest that equol production may be associated with reduced breast cancer risk, but mechanisms for this relationship are unknown. Our objective was to determine whether fecal bacterial metabolism of estrogens differs according to equol-producer phenotype. A method was developed for the extraction and gas chromatography-mass spectrometry quantification of estrogens from fecal incubations. Previously frozen fecal samples from female equol producers (n=20) and non-producers (n=l3) were incubated anaerobically in media for 5d at 37C with the following estrogens: estrone, estradiol, estriol, 2-hydroxyestrone, l6alpha- hydroxyestrone, and 2-methoxyestrone. Fecal bacteria from equol-producers were more likely than non-producers to convert 2-hydroxyestrone to 2- hydroxyestradiol. Furthermore, equol-producers, compared to non- producers, converted significantly more estrone to estradiol, and l6alpha-hydroxyestrone to estriol. These findings suggest diffenences may exist between equol-producers and non-producers in bacterial estrogen metabolism. However, the conversion of 16alpha-hydroxyestrone to estriol, and the conversion of estrone to estradiol could represent potentially beneficial and detrimental, respectively, pathways in terms of breast cancer risk.

The intestinal microbial transformation of daidzein, one of the principal isoflavones from soy, into the isoflavan equol is subjected to a high interindividual variability. The latter compound is considered to have a higher biological activity than its precursor; hence, there is interest in dietary applications that modulate this important biotransformation. In 2 separate experiments, we administered a mixed microbial culture (EPC4), which we had isolated previously and which efficiently transforms daidzein into equol, to the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The SHIME was fed soy germ powder and inoculated with fecal samples from two nonequol-producing individuals. Equol production was induced in the distal colon compartments in both experiments, 5-6 d after the start of the treatment; 2 wk after interrupting the addition of EPC4, equol was still produced in high amounts. There are large interregional differences in daidzein metabolism in the simulated colon. Furthermore, no major shifts in the composition and activity of the microbial communities were caused by the supplementation with the microbial consortium. Although further confirmation in in vivo studies is required, these results validate the concept that administering EPC4 could constitute a novel means for converting a nonequol-producer into a producer.

 

[Bryan]

....equol also blocked circulating DHT's androgenic trophic influence on the prostate and epididymis without significantly altering circulating DHT levels....

I don't understand why you think that statement is so significant that you decided to put those last few words in bold. Again, it doesn't really make any difference whether you stop the production of DHT or bind a chemical to it, rendering it inactive. Either way, the level of functional DHT is greatly reduced! For that reason, it's misleading and dishonest to say that levels of circulating DHT aren't significantly altered.

 

[squeegee]

This stable mixed culture, which efficiently transforms daidzein into equol, consists of 4 dominant bacterial strains: Enterococcus faecium EPI1, Lactobacillus mucosae EPI2, Finegoldia magna EPI3, and a Veillonella sp.-related strain EP.


http://jn.nutrition.org/cgi/content/full/136/4/946

 

[squeegee]

Equol, a derivative of daidzein produced by enterobacteria, has greater activity as a phyto-oestrogen compared with daidzein. Difructose anhydride III (DFAIII) is a newly manufactured non-digestible disaccharide with unique fermentation properties. The present study evaluated the prebiotic effects of DFAIII on equol production and on plasma cholesterol concentrations related to the changes in equol production. We compared plasma equol concentrations at 10.00 and 18.00 hours and faecal isoflavone excretion in three groups of seven rats (male Wistar-ST strain, 6 weeks old) fed a basal diet or a DFAIII or fructooligosaccharide (15 g/kg diet) diet containing 1 g soya isoflavones/kg diet for 20 d. Equol concentrations in the DFAIII group were higher than in the control and fructooligosaccharides groups, especially in the later phase of the light period (18.00 hours) throughout the experiment. Daizein and genistein concentrations did not change between the diet groups. The faecal ratios of equol:daidzein were very high in all groups, but the ratios were higher in the DFAIII group than the control and fructooligosaccharide groups on day 3, and this tendency continued throughout the experiment. On day 20, the plasma total cholesterol concentration was lowest in the DFAIII group. Additionally, the cholesterol concentrations were inversely correlated to plasma equol concentration in all the rats. In conclusion, DFAIII efficiently enhanced plasma equol concentrations, which may be associated with an increase in equol production and a decrease in equol degradation by enterobacteria. Higher plasma equol concentrations may contribute to the hypocholesterolaemic effect of DFAIII feeding.


Equol is formed exclusively by bacteria in the gut, but only about a third of all Caucasians possess the necessary gut microflora capable of converting daidzein into equol. The health benefits of soy food diets are reported to more efficient in so-called 'equol producers'.

Marian Verbruggen, co-author of the study and head of medical sciences and regulatory affairs for Frutarom Netherlands told NutraIngredients.com that the study helps us to understand the large individual variation we observe in physiological response to isoflavones in clinical trials and the complex metabolism of isoflavones.

"The more we understand of the metabolism and in relation to this the bio-availability, the industry gets knowledge and tools to select the right ingredients for their products," she said.

"In the end the consumer will benefit from this, with the availability of high quality products."

Lead author Selin Bolca, from Ghent University, and co-workers recruited 100 postmenopausal women (average age 57, average BMI 23.9 kg per sq. m) and, after an initial four-day stabilisation period, randomly assigned them to a receive three portions per day of soymilk or soy germ containing 28.51 and 37.99 mg isoflavone aglycone equivalents per portion for five days.

Urine samples, taken over the 24 hours of the last day, showed that genistein and daidzein concentrations were higher when the isoflavones were consumed from soymilk rather than the soy germ tablets.

By classifying the individuals as poor, moderate, and strong equol producers, the researchers observed that higher counts of the bacteria Clostridium coccoides-Eubacterium rectale were associated with less equol, while increased sulfate-reducing bacteria counts was associated with increased equol production.

Moreover, an increased dietary intake of polyunsaturated fatty acids (PUFAs) was associated with increased equol production.

"PUFA are concentrated in foods such as fish and seafood, which are not generally consumed on a daily basis in western countries," wrote the researchers.

"In Japan and Korea, however, the diet is low in red meat and often rich in fish; thus, PUFA accounts for a larger proportion of the total fat intake, which may explain why the prevalence of strong equol producers is higher in these countries," they added.

The researchers noted a good correlation between the urinary excretion profiles and equol production and the subjects' phenotypes based on the daidzein metabolism by faecal cultures.

This shows "the potential of faecal incubations to identify equol producers without dietary intervention," they said.

The study was funded by Alpro NV and Frutarom Netherlands. The study and analyses were independent, however, state the researchers.

Source: Journal of Nutrition

Volume 137, Pages 2242-2246

"Microbial and Dietary Factors Are Associated with the Equol Producer Phenotype in Healthy Postmenopausal Women"

 

[hairrific]

....equol also blocked circulating DHT's androgenic trophic influence on the prostate and epididymis without significantly altering circulating DHT levels....

I don't understand why you think that statement is so significant that you decided to put those last few words in bold. Again, it doesn't really make any difference whether you stop the production of DHT or bind a chemical to it, rendering it inactive. Either way, the level of functional DHT is greatly reduced! For that reason, it's misleading and dishonest to say that levels of circulating DHT aren't significantly altered.

There might be a big difference between your body seeing that there is a lack of DHT floating around due to finasteride or dutasteride, and then reacting to that lack accordingly, as compared to your body sees plenty of DHT floating around at the proper amounts even though it is inactivevated by Equol.

How so? There has to be a difference between having a lack of DHT compared to having the right quantities of DHT that are just not able to screw up your hair.

Why? I am still researching.

 

[Bryan]

There might be a big difference between your body seeing that there is a lack of DHT floating around due to finasteride or dutasteride, and then reacting to that lack accordingly, as compared to your body sees plenty of DHT floating around at the proper amounts even though it is inactivevated by Equol.

Nope. There's no difference at all. The only way your body "sees" DHT is through the androgen receptor. If you do something to all those DHT molecules to keep them from binding to androgen receptors, then they are invisible to the body (at least, to androgen-sensitive tissues like the prostate, hair follicles, sebaceous glands, etc.).

How so? There has to be a difference between having a lack of DHT compared to having the right quantities of DHT that are just not able to screw up your hair.

Nope. Androgens (ncluding DHT) work through the androgen receptor. If you fiddle with the chemical structure of DHT molecules to prevent them from binding to androgen receptors, then it's the same as if they aren't there at all. You can't fool your body THAT easily with just something like equol! :shock: :smack:

 

[hairrific]

OK, good enough for me. Stay with me then, one more thought.

Does it not make more since to #1: directly deactivate DHT with Equol so it can't damage scalp hair, rather than #1: directly inhibiting 5ar so that #2: testosterone can't convert to DHT and damage scalp hair.

Why would we want to screw around with or inhibit 5ar which is has many other important roles to play in our bodies besides converting Test. to DHT when we could just take the more direct route of just deactivating DHT with Equol, why risk screwing around with our 5AR.

 

[Bryan]

Why would we want to screw around with or inhibit 5ar which is has many other important roles to play in our bodies besides converting Test. to DHT when we could just take the more direct route of just deactivating DHT with Equol, why risk screwing around with our 5AR.

I think that would be the only legitimate reason to pick equol over finasteride/dutasteride. I just wish we knew for sure how important those other conversions are that 5a-reductase performs.

 

[goata007]

Sex hormone-binding globulin and saliva testosterone levels in men with androgenetic alopecia.
Cipriani R, Ruzza G, Foresta C, Veller Fornasa C, Peserico A.

Sex hormone binding globulin (SHBG), plasma testosterone and saliva testosterone were measured in sixty-four men with androgenetic alopecia and in forty males within the same age range without alopecia. There was a significant reduction in SHBG levels in bald men, compared with controls. Plasma testosterone levels were not raised in bald men, but their salivary testosterone levels were significantly higher than in controls.


Bryan, the above study directly co-relates SHBG levels with androgenetic-alopecia. If Equol's method of action is similar to SHBG then it makes sense to boost equol in body to help with androgen action supression and avoid finas sideeffects?

 

[Bryan]

What do you think specifically causes finasteride side effects?

 

[goata007]

What do you think specifically causes finasteride side effects?

Don't get me wrong, I get your androgen receptor point of view i.e. doesn't matter if the androgen recepotor is blocked or dht is bound to shbg, the end result as interpreted by the brain should be the same and the response should be to jack up androgen production. However, the above study doesn't say anything about side effects infact the people without Androgenetic Alopecia are normal people and they have higher levels of SHBG than the bald men. If higher SHBG levels had the same sideeffects as finas, then many young men should experience side effects similar to finas(without being on it). But they don't, so maybe the method of action of SHBG and also equol(since it also binds to DHT) is different than finas.

 

[Bryan]

However, the above study doesn't say anything about side effects infact the people without Androgenetic Alopecia are normal people and they have higher levels of SHBG than the bald men. If higher SHBG levels had the same sideeffects as finas, then many young men should experience side effects similar to finas(without being on it). But they don't, so maybe the method of action of SHBG and also equol(since it also binds to DHT) is different than finas.

Here's where I think your argument fails: while I don't doubt that non-balding men do have a little higher level of SHBG than balding men on average, having a too-low level of SHBG isn't the cause of male pattern baldness. Having hair follicles that are too sensitive to the effects of androgens is the primary cause. For that reason, you can't just supply enough equol to reduce the effect of DHT to a slight degree and expect it to work as well as Propecia, and with none of the side effects; you'd have to supply AMPLE amounts of equol, enough to disable DHT to about the same extent that finasteride does. And the side effects of the equol will therefore be about the same, too.

 

[hairrific]

Well we shall soon see about that! Well actually more like years from now probably. :sobbing:

Equol study:

http://clinicaltrials.gov/ct2/show/NCT00787007?spons="Ausio+Pharmaceuticals,+LLC"&spons_ex=Y&rank=1