EstroQuench™ Herbs

Lepidium meyenii (Red maca) (4:1 root extract) is a cruciferous vegetable cultivated at high altitudes. It is a concentrated dietary component that is able to increase optimal estrogen metabolism. Like other cruciferous vegetables Red Maca is rich in glucosinolates, the precursor for indole-3- carbinol [1], which has both antiproliferative and proapoptotic actions specifically in regard to hormones sensitive tissues. Indole-3-carbinol (I3C), an autolysis product of glucosinolates present in cruciferous vegetables, such as red maca, has been indicated as a promising agent in preventing the development and progression of breast cancer [2].
The proapoptotic and anti-proliferative effects in hormone sensitive tissues is associated with a reduced risk to hormones sensitive tissues in both genders. The absolute content of glucosinolates in Maca hypocotyls is relatively higher than that reported in other cruciferous crops, so Maca is a potent promoter of healthy metabolic reduction of estrogen, such that red maca protects hormone sensitive tissues without affecting serum testosterone or estradiol levels [3].
The ability to affect hormone sensitive tissues and maintain sexual function makes Lepidium meyenii an important component of EstroQuench™. Lepidium meyenii improves sexual function in 21 to 56 year old men [4], as well as postmenopausal women [5]. Lepidium meyenii improves sperm production, sperm motility and semen volume by mechanisms directly not related to LH, FSH or prolactin [6], [7].
Lepidium meyenii improves testosterone function and spermatogenesis without increasing estrogen [8]. Lepidium meyenii (Red Maca) has been noted to reduce prostate size [9]. However, this inhibitory effect is believed to take place after 5-alpha-dihydrotestosterone conversion [10], meaning Lepidium meyenii does not interfere with endogenous 5-alpha-dihydrotestosterone production. This is congruent with the previously noted observation that estrogen formation is inhibited by endogenous 5 alpha- reduced androgens such as 5-alpha-dihydrotestosterone [11]. There is also some evidence that Lepidium meyenii can decrease stress induced rise in serum corticoid levels [12], which can help decrease cortisol caused increase in aromatase activity [13], [14].

Turnera diffusa (Damiana) (4:1 leaf extract) has compounds such as pinocembrin [1] and acacetin [2] which significantly suppress aromatase activity. Turnera diffusa has also been regarded as an aphrodisiac, with the ability to restore sexual vitality [3] and mimics testosterone through various actions such as engorgement of corpus cavernosum [4] and increased sexual behavior [5], even though it has not been found to raise testosterone levels. Damiana also contains apigenin [6], which has been described as one of the three most potent natural aromatase inhibitors [7], [8]. Extracts from Turnera diffusa have recently been shown to kill some breast cancer cells [9] suggesting that its protection against estrogens may extend beyond its ability to inhibit aromatase activity.

Hesperidin (hesperetin precursor) from Citrus sinensis is a flavanone glycoside that releases its aglycone hesperetin when ingested [1]. Therefore, hesperetin is the naturally occurring aglycone of hesperidin. Since hesperidin is more easily absorbed than hesperetin, hesperidin is a more efficient method of increasing blood levels of hesperetin. Hesperetin is considered one of the three of the most potent natural flavone aromatase inhibitors (as well as apigenin and chrysin) [2], [3]. The aromatase inhibiting properties of hesperetin were even able to inhibit growth of aromatase-expressing breast cancer cells [3]. In one study, hesperetin or letrozole could each reduce plasma estrogen level and inhibit tumor growth, but the letrozole-induced bone loss was reversed by hesperetin without compromising on the inhibition of tumor growth, suggesting that hesperedin could also be a potential adjuvant (co-therapeutic agent) to pharmacological aromatase inhibition [4].
Since dietary flavones and flavonones might regulate aromatase transcription differently, evidence suggests that multiple flavones are more effective than using only one flavone flavonone [5].
Therefore, the efficacy of hesperetin is enhanced when used with other flavanones and flavones such as naringenin and chrysin, as it is in the EstroQuench™ formulation. Hesperetin can also decrease stress induced rise in serum corticoid levels [6], which can help decrease corticoid caused increase in aromatase activity [7], [8].

Agaricus bisporus (White Button Mushroom) (8:1 extract) suppresses aromatase activity and estrogen biosynthesis, and were found to have antiproliferative properties [1].
Agaricus bisporous has been found to be a competitive aromatase inhibitor at the cellular level, preventing the conversion of testosterone to estradiol by competing against testosterone on aromatase binding sites [2]. The same study concluded that Agaricus bisporous can produce aromatase inhibition without toxic side effects.
In addition to inhibiting aromatase activity, Agaricus bisporus mushrooms also inhibits breast cell proliferation [2] and suppress aromatase activity and estrogen biosynthesis [3] they are considered a potential breast cancer chemopreventive agent [4], [5]. Agaricus bisporus also inhibited prostate tumor cell proliferation in a dose-dependent manner and induced apoptosis [6].
In addition to its aromatase inhibition properties, Agaricus bisporous contains a substance identified as 2-amino-3H-phenoxazin-3-one (APO), which may inhibit both COX-1 and COX-2 enzyme activity as well as IL-6 activity [7]. Since there is a strong linear association between aromatase expression and the sum of COX-1 and COX-2 expression as well as IL-6 activity [8], [9], the COX-1, COX-2 and IL-6 specific properties of Agaricus bisporous may contribute to its aromatase inhibition properties.
Immature Agaricus bisporus are white and commonly called White Button Mushrooms, while mature Agaricus bisporus is brown and commonly called Portabella Mushrooms [10], [11].

Brassaiopsis glomerulata (10:1 leaf Extract) is an effective aromatase inhibitor was shown to decreases the conversion of testosterone to estradiol by inhibiting aromatase activity in both enzyme- and cell-based aromatase inhibition (AI) assays [1]. In fact, that study showed that Brassaiopsis glomerulata leaf extract was found to be as active as letrozole (a prescription aromatase inhibitor) in a cell-based aromatase inhibition study. Brassaiopsis glomerulata is one of the herbs presented in a comprehensive documentation of natural aromatase inhibitors that can be used with reduced side effects [2]. The safety of Brassaiopsis glomerulata is further demonstrated in that its leaves have been used as a traditional medicine in North Vietnam to treat rheumatism and back pain [3], as well as being used to treat gastritis, ulcers and jaundice [4].
Eurycoma longifolia (Tongkat Ali) (100:1 root Extract) inhibits aromatase conversion of testosterone to estradiol and maintains testosterone levels in large part due to eurycomanone, the major quassinoid found in Eurycoma longifolia [1]. The anti-estrogen properties of Eurycoma longifolia has also been found to decrease the effects of estrogen and increase spermatogenesis and sperm counts in animal studies [2]. In one study, the anti-estrogenic effect were comparable to tamoxifen [3].

Eurycoma longifolia caused and increase in LH and FSH in animal studies, accompanied by an increase in testosterone, but a decrease of estradiol. The mechanisms of action include affecting the hypothalamic-pituitary-gonadal axis, while at the same time having aromatase inhibition properties [4]. After one month on Eurycoma longifolia extract, 91% of male patients had normal testosterone levels, whereas only 36 % had normal testosterone levels before taking the extract [5].
If interest, Eurycoma longifolia has even been shown effective as testosterone replacement therapy an alternative treatment to prevent and treat male osteoporosis without causing the side effects associated with testosterone replacement therapy [6]. As well as increasing testosterone, it also decreases stress induced rise in salivary cortisol [7]. This is important because increased levels of glucocorticosteroids can cause increased aromatase activity resulting in higher estrogen levels [8], [9].

Garcinia mangostana (Mangosteen fruit Extract) exhibits significant aromatase inhibitory activity due to the presence of xanthones [1]. Four xanthones in Garcinia mangostana were found to affect aromatase activity. Of those four, gamma—mangostin was found to be more active in inhibiting aromatase in cells than letrozole [2]. Gamma-mangostin has also been identified as being a powerful antioxidant with antiproliferative activity [3]. Xanthones in Garcinia mangostana have been found to induce apoptosis (cell death) and inhibit proliferation of estrogen sensitive cancer cells such as breast cancer and prostate cancer cells [4]. A recent review of over 60 papers mentioned that numerous studies have shown that the xanthones in Garcinia mangostana have significant anti-oxidant, anti- proliferative, pro-apoptotic, anti-inflammatory and anti-carcinogenic activities [5]. These additional properties work together synergistically with the aromatase inhibiting activity of Garcinia mangostana to make this an effective component of EstroQuench™.

Pomegranate Hull Extract (Punica granatum L.) (Standardized to 70% Ellagic Acid) has been demonstrated to inhibit aromatase activity by up to 80% [1]. The pomegranate fruit and hull is a rich source of ellagitannins (ET). On consumption, pomegranate ETs hydrolyze, releasing ellagic acid, which is then converted to 3, 8-dihydroxy-6H-dibenzo [b,d]pyran-6-one ("urolithin") derivatives by gut microflora. Six of these ET-derived compounds and have anti-aromatase activity, and all compounds exhibited antiproliferative activity [2].
Additional studies have validated that various constituents of pomegranates can inhibit aromatase and have antiestrogenic activity that could decrease breast cancer risk [3], [4], and may have beneficial effects in other hormone sensitive tissues [5].
The antiproliferative properties have also demonstrated an ability to decrease growth and proliferation of human prostate cancer cells [6], [7], [8].

Naringenin (Citrus grandis L., pomelo fruit) has consistently been recognized as a potent flavanone aromatase inhibitor [1], [2], [3]. It is considered one of the three of the most potent natural aromatase inhibitors (as well as apigenin and hesperetin) that will decrease estrogen activity in breasts [4]. In another study, naringenin inhibited aromatase activity in a study for phytotherapeutic agents that could be used for the treatment of endometriosis [3].
Naringenin is 70% as potent as aromatase inhibitor as chrysin and over 10 times as potent as biochanin A and quercetin [1]. In addition to decreasing estrogen biosynthesis naringenin also has
anti-estrogenic effects that are important in decreasing breast and prostate cancers [5]. The efficacy of naringenin is enhanced when used with other flavanones and flavones such as hesperetin and chrysin, as it is in the EstroQuench™ formulation [6]. Naringenin can also decrease stress induced rise in serum corticoid levels [7], which can help decrease corticoid caused increase in aromatase activity [8], [9].

Chrysin is a naturally occurring flavone that will inhibit the aromatization of androstenedione and testosterone to estrogens due to a potent competitive aromatase inhibition function [1], [2]. Flavones, like other flavonoids are extremely safe and associated with low toxicity [3].
When a number of substances that are commonly used in beverages where tested for their ability to inhibited estrogen production, chrysin was found to be the most potent [4]. Throughout the medical literature, chrysin is consistently recognized as one of the most potent flavonoid aromatase inhibitors [5], [6], [7], [8]. Research suggests that chrysin may be used in the treatment of breast cancer, including advanced or metastatic breast cancer [9]. Chrysin inhibited aromatase activity in human endometrial stromal cells, suggesting it can be a therapeutic agent for the treatment of endometriosis [10]. Chrysin reduces proliferation and induces apoptosis in the human prostate cancer [8]. In addition to its aromatase inhibiting properties, chrysin also has anticancer, antioxidation, and anti-inflammatory properties [11], and increases the vasodilatory effect of testosterone [12]., and increases nitric oxide mediated vasodilation [13]. The anticancer properties are due to a number of factors which are independent of its aromatase inhibiting properties including its ability to directly inhibit proliferation and induce apoptosis [14], [15]. The aromatase inhibiting properties of chrysin is enhanced when used with flavanones such as hesperetin and naringenin, as it is in the EstroQuench™ formulation [16].

Bioperine® is a patented extract of piperine which has been clinically tested in the United States and found to significantly enhance the bioavailability of various supplement nutrients and herbal extracts through increased absorption. An additional benefit in EstroQuench™ is that piperine enhances the neuroprotective effects of quercetin, an aromatase inhibiting flavonoid like chrysin, and reduced stress induced elevations of corticosterone [1] alone, and when given with quercetin [2]. This is very contributory to the goals of EstroQuench™ because increased levels of glucocorticosteroids (cortisol and corticosteroid) can cause increased aromatase activity resulting in higher estrogen levels [3], [4]. A number of papers discuss the ability of perperine to help decrease the effects of corticosterone while enhancing the bioavailability and action of herbal extracts [5], [6], [7], [8], [9]. Therefore Bioerpine® helps prevent aromatase activity cause by controlling increases in glucocorticosteroid activity. This may be due to the ability of perperine to modulate the function of the HPA (hypothalamic-pituitary- adrenocortical) axis [10]. Additional studies have shown that piperine has antiproliferative properties [11]. It also induces apoptosis in some forms of human prostate cancer, and some forms of breast cancer [12], [13], [14], [15], [16], [17].