NATURAL AROMATASE INHIBITORS

[Logan-]

“White button mushroom (WBM, Agaricus bisporus) is the most common edible mushroom in the U.S.A. Accumulated evidence demonstrates that WBM has beneficial effects on various kinds of cancers. Lectins isolated from the WBM increase the sensitivity of lung, colon, and glioblastoma cancer cells to chemotherapeutic drugs.20 In addition, the WBM lectins inhibit colon cancer cell proliferation,20 and they enhance cellular antioxidant defense mechanisms.21 As we previously demonstrated, by inhibiting aromatase activity, both total WBM extract and certain isolated fractions effectively decrease breast cancer cell proliferation.22 In these active WBM fractions, conjugated linoleic acid was an important component; it was an inhibitor of both breast cell proliferation and aromatase activity.22, 23 In addition to breast cancer cells, we evaluated the effect of WBM on PC cell lines in vitroand vivo. According to our results, in all prostate cancer cell lines, WBM extract significantly inhibits cell proliferation; this occurs through induction of apoptosis of cancer cells.24 In mice gavaged with mushroom extract, tumor size and cell proliferation decreased while apoptosis increased. Similarly, for mushroom-fed mice, microarray analysis of tumors identified significant changes in gene expression. Particularly altered were the gene networks involved in cell death; growth and proliferation; lipid metabolism; the TCA cycle; and immune response.22, 23”

Twardowski, P., Kanaya, N., Frankel, P., Synold, T., Ruel, C., Pal, S. K., Junqueira, M., Prajapati, M., Moore, T., Tryon, P., & Chen, S. (2015). A phase I trial of mushroom powder in patients with biochemically recurrent prostate cancer: Roles of cytokines and myeloid-derived suppressor cells for Agaricus bisporus-induced prostate-specific antigen responses. Cancer, 121(17), 2942–2950. https://doi.org/10.1002/cncr.29421

 

[Logan-]

First published online November 1, 2010

Commonly consumed and specialty dietary mushrooms reduce cellular proliferation in MCF-7 human breast cancer cells​

Keith R Martin and Sara K BrophyView all authors and affiliations
Volume 235, Issue 11
https://doi.org/10.1258/ebm.2010.010113https://journals.sagepub.com/doi/10.1258/ebm.2010.010113#bibliography

Abstract​

Worldwide, over one million women will be newly diagnosed with breast cancer in the next year. Moreover, breast cancer is the second leading cause of cancer death in the USA. An accumulating body of evidence suggests that consumption of dietary mushrooms can protect against breast cancer. In this study, we tested and compared the ability of five commonly consumed or specialty mushrooms to modulate cell number balance in the cancer process using MCF-7 human breast cancer cells. Hot water extracts (80°C for 2 h) of maitake (MT, Grifola frondosa), crimini (CRIM, Agaricus bisporus), portabella (PORT, Agaricus bisporus), oyster (OYS, Pleurotus ostreatus) and white button (WB, Agaricus bisporus) mushrooms or water alone (5% v/v) were incubated for 24 h with MCF-7 cells. Cellular proliferation determined by bromodeoxyuridine incorporation was significantly (P < 0.05) reduced up to 33% by all mushrooms, with MT and OYS being the most effective. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction, an often used mitochondrion-dependent marker of proliferation, was unchanged although decreased (P > 0.05) by 15% with OYS extract. Lactate dehydrogenase release, as a marker of necrosis, was significantly increased after incubation with MT but not with other test mushrooms. Furthermore, MT extract significantly increased apoptosis, or programmed cell death, as determined by terminal deoxynucleotidyl end labeling method, whereas other test mushrooms displayed trends of ∼15%. The total numbers of cells per flask, determined by hemacytometry, were not different from control cultures. Overall, all test mushrooms significantly suppressed cellular proliferation, with MT further significantly inducing apoptosis and cytotoxicity in human breast cancer cells. This suggests that both common and specialty mushrooms may be chemoprotective against breast cancer.

From: Martin KR, Brophy SK. Commonly consumed and specialty dietary mushrooms reduce cellular proliferation in MCF-7 human breast cancer cells. Experimental Biology and Medicine. 2010;235(11):1306-1314. doi:10.1258/ebm.2010.010113

 

[Logan-]

Good post:

Does she consume any polyunsaturated fats (they are estrogenic)? Is her liver function not working well? The liver detoxes estrogen. Is she constipated? If yes, the extrogen the liver moved out via the intestine can get reabsorbed. Is she hypothyroid? Hypothyroidism can happen if the liver has a lot of estrogen to detox because then the liver won't be as efficient in converting T4 to T3.

 

[Logan-]

Important:

My GF gets so tired, negative image of herself, is depressed, and sleeps poorly when she is off her progesterone half of the month.

Sounds like hypothyroidism.

 

[Logan-]

I am using guava instead of orange juice with good results. Ray has mentioned that guava has a similar nutrient profile to OJ. When I tried to increase my OJ consumption I had an allergic reaction to it.
But once I switched to guava juice I have done really well and now I love it. Depending on where you live it might be hard to find. I get mine from the frozen section in a Mexican grocery store. Or I will drink the Kern's kind if I am desperate. I would think an Indian grocery store might have it too.
I take the frozen guava and blend them with sugar and water to make juice. I do peel mine but I don't think you have to.

"Breast Cancer
Orange juice and guavas contain aromatase inhibitors, and aspirin and progesterone are other inhibitors. Aspirin and progesterone also oppose the effects of HER2/neu on aromatase and estrogen. (Reference)"

Ray Peat Email Exchanges - Ray Peat Forum Wiki

There is a clip posted here: KMUD: Fasting, Alzheimers, Fish oil, Testosterone,...

have you not heard about Melanon. Main ingredient is Naringenin, as an anti estrogen -

http://raypeat.com/articles/articles/th ... trix.shtml
"...Substances that inhibit inflammation are likely to also inhibit excessive collagen synthesis, serotonin secretion, and the formation of estrogen. Besides aspirin, some effective substances are apigenin and naringenin, found in oranges and guavas. These flavonoids also inhibit the formation of nitric oxide and prostaglandins, which are important for inflammation and carcinogenesis (Liang, et al., 1999). Increased CO2, which has a variety of anti-inflammatory effects, can decrease collagen formation and tissue collagen content significantly (Ryu, et al., 2010)."

Naringenin:
Citrus flavanone naringenin enhances melanogenesis through the activation of Wnt/β-catenin signalling in mouse melanoma cells. - PubMed - NCBI
Hydrolysates of citrus plants stimulate melanogenesis protecting against UV-induced dermal damage. - PubMed - NCBI
Enhancement of transglutaminase activity and polyamine depletion in B16-F10 melanoma cells by flavonoids naringenin and hesperitin correlate to red... - PubMed - NCBI
In vitro cytotoxic activity of extracts and isolated constituents of Salvia leriifolia Benth. against a panel of human cancer cell lines. - PubMed - NCBI
Stimulation of melanogenesis by the citrus flavonoid naringenin in mouse B16 melanoma cells. - PubMed - NCBI
Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity. - PubMed - NCBI
Naringenin Inhibits UVB Irradiation-Induced Inflammation and Oxidative Stress in the Skin of Hairless Mice. - PubMed - NCBI
Chemopreventive and therapeutic potential of "naringenin," a flavanone present in citrus fruits. - PubMed - NCBI
Induction of apoptosis and antiproliferative activity of naringenin in human epidermoid carcinoma cell through ROS generation and cell cycle arrest. - PubMed - NCBI
Myricetin and naringenin inhibit human squamous cell carcinoma proliferation and migration in vitro. - PubMed - NCBI
Tumor growth attenuating effects of naringenin. - PubMed - NCBI
Inhibitory effect of GB-2a (I3-naringenin-II8-eriodictyol) on melanogenesis. - PubMed - NCBI
Preparation and Characterization of Naringenin-Loaded Elastic Liposomes for Topical Application. - PubMed - NCBI
The inhibitory effect of naringenin on atopic dermatitis induced by DNFB in NC/Nga mice. - PubMed - NCBI
Protective effects of fermented Citrus unshiu peel extract against ultraviolet-A-induced photoageing in human dermal fibrobolasts. - PubMed - NCBI
Naringenin protects HaCaT human keratinocytes against UVB-induced apoptosis and enhances the removal of cyclobutane pyrimidine dimers from the genome. - PubMed - NCBI
Inhibition of mammalian collagenase, matrix metalloproteinase-1, by naturally-occurring flavonoids. - PubMed - NCBI
Correlation of in vitro chemopreventive efficacy data from the human epidermal cell assay with animal efficacy data and clinical trial plasma levels. - PubMed - NCBI

Naringenin, Naringin Supplements?

Are there any supplements out there which contain only Naringenin and/or Naringin ? I get some good effects from OJ, unfortunately I also seem to have an allergy to oranges, with sneezing, runny nose, short breath... Since no other fruit juices produce the beneficial effects of orange juice...

raypeatforum.com

 

[Logan-]

Is it even possible to get them in pure powder form or something like that?

I won't do that.
Naringin and naringenin are potent inhibitors of cytochrome P450 3A4 (Cytochrome P3A4 or CY P3A4) and to a lesser extent of CYP1A2 and CYP3A5. Naringenin from grapefruit and certain polyphenols, such as polyphenols from red wine, slow down the activity of an enzyme, especially CY P3A4, which is very useful in the first phase of hepatic detoxification. Note, however, that some genetically predisposed people are more sensitive than others on this point (factor varying from 1 to 8).

Grapefruit juice, and grapefruit in general, is therefore a powerful inhibitor of the CYP3A4 enzyme. Half-life of the CYP3A4 enzyme Human CYP3A4 turnover varies widely depending on location. At the hepatic level, the half-life in vivo is between 70 and 140 hours. At the intestinal level, the half-life of cytochromes is linked to the turnover/renewal of the intestinal cells themselves. Otherwise expressed: The process is reversible. We can recover normal functioning as soon as the inhibitors are stopped... It is also dose-dependent.

36% of drugs are metabolized by the CYP450 3A4 enzyme. Almost half of the drugs metabolized are via CYP3A4.

Explained differently, naringin and naringenin prolong the half-life of quite a few drugs/toxins, which can overtax the liver and kidneys.

 

[Logan-]

But natural Vitamin E in itself is a fertility agent, and that alone has endowed it with a bull's eye for big pharma. The same COVID conspirators that want a lower earth population are one and the same with the anti-Vitamin E conspirators that date from 80 or so years back.

You don't need to add its anti-estrogen and anti-PUFA properties, much less its anti-cardiovascular issues properties.

Vitamin E succinate decreases melanoma size by 650% in vivo

How to combat being irritated after taking for of this? I can't say I like the mental state I am put in by a very small dose of it. Maybe it lowers estrogen too much? Symptoms of too much or too few overlap. @yerrag @burtlancast in case you haven't seen this thread, you might like it.

raypeatforum.com

 

[Logan-]

Vitamin e and estrogen

https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/documents/104/275/t3126pis.pdf