T-Plus contains three proprietary blends one of which is Anti-Estro Blend responsible for blockingthe testosterone conversion to estrogen. T-Plus has the ability to increase testosterone levels butthere is more to it than that. Increasing testosterone levels may increase your levels of estrogen.The reason for this is that testosterone is converted into estradiol which in turn is converted intoestrogen. Increased levels of testosterone tends to bring about feminizing characteristics which canlead to decreased libido, hair loss, and enlarged breasts. For that reason, Onnit has formulated theproprietary blend known as Anti-Estro Blend that allows you to maintain the extra testosterone you are producing. This proprietary blend of red clover, luteolin and resveratrol acts as an effective estrogen blocker which allows for maintaining higher levels of testosterone. Each component contributes to inhibiting aromatase activity responsible for testosterone conversion to estrogen with slightly different mechanisms. Anti-Estro Blend may help to inhibit the unwanted side effects seen with higher testosterone levels.


Red Clover

Red clover contains the biochanin A isoflavone which resembles the structure of estrogen. Thismolecule is believed to display agonistic and antagonistic interactions with the estrogen receptor. Overexposure to estrogen is a major factor in developing breast cancer, and the cytochrome P450 enzyme known as an aromatase (CYP19 gene), catalyzes the conversion of testosterone to estrogen. Recent research has demonstrated that biochanin A is involved with gene regulation and enzyme activity of aromatase. Biochanin A has been shown to inhibit aromatase activity as well as decrease CYP19 mRNA production. It was also demonstrated that biochanin A repressed the transcriptional control dictated by the promoter regulation. So, biochanin A has the ability to inhibit CYP19 activity and gene expression. This suggests that biochanin A found in red clover may bean effective estrogen blocker.

Luteolin is yet another aromatase inhibitor. Research has demonstrated that luteolin has an inhibitoryeffect on the biosynthesis of estrogen in human ovarian granulosa cells by suppressing aromatase(CYP19 gene). Researchers reported that luteolin decreased aromatase mRNA expression and destablized aromatase protein (increased protein degradation) in human granulosa cells which is themajor source of estrogen in premenopausal women. This study suggests luteolin may be a potentialtreatment for estrogen-dependent cancers. This indicates that luteolin is an effective estrogen blocker.

For those of you who are familiar with chrysin, luteolin may be considered to be a superior aromatase inhibitor in comparison to chrysin. Chrysin is another popular flavonoid-based aromatase inhibitor. Chrysin is an effective aromatase inhibitor as demonstrated in vitro studies however, it has low bioavailability in the gut. Luteolin has high bioavailability meaning it is easily absorbed.

Resveratrol as a polyphenolic flavonoid has many functions, however what is of concern here is that ithas the ability to inhibit the transcription of an enzyme known as aromatase thus inhibiting a positivefeedback pathway involving the production of estrogen. The aromatase enzyme is known as cytochrome P450 (CYP19 gene) and is a rate-determining step in the synthesis of estrogen. CYP19 is the gene that codes for the cytochrome P450 enzyme. This gene has a transcriptional control that is different for different types of cells. Researchers have demonstrated that Resveratrol reduces estradiol-induced CYP19 mRNA abundance (aromatase gene transcription). This doesn’t take place in the nucleus where estrogen receptors are located on the genome but rather by an extracellular signal-regulated kinase (ERK) which can be activated by estradiol, a precursor of estrogen.

In other words, resveratrol obstructs the non-genomic induction of estrogen on CYP19 gene from outside the cell. This inhibits the production of estrogen when testosterone levels are high. Keep in mind that testosterone is converted to estradiol and then the aromatase enzyme (cytochrome P450) convertsestradiol to estrogen. Resveratrol blocks ERK so it can’t interact with estradiol. Resveratrol turns out to be an effective estrogen blocker.

Anti Estro-Blend combines red clover, luteolin, and resveratrol to block testosterone conversion to estrogen. Red clover contains biochanin A which inhibits aromatase enzyme (cytochrome P450)activity by binding to its active site and decreases CPY19 mRNA transcription (aromatase genetranscription). Luteolin also decreases CPY19 mRNA transcription and destabilizes the aromataseenzyme (enzyme degradation). Resveratrol binds to cell surface estradiol receptors effectivelyblocking the binding of estradiol and thus blocking aromatase gene expression. Less aromatase around means less conversion of testosterone to estrogen. By inhibiting the enzyme aromatase directly and/or blocking the gene that codes for it inhibits the conversion of testosterone to estrogen. So, Anti Estro-Blend aids in keeping testosterone levels higher while preventing unwanted side effects of feminization that other supplements can generate because they don’t inhibit testosterone conversion to estrogen.

Suggested Reading

The red clover (Trifolium pratense) isoflavone biochanin A inhibits aromatase activity and
expression.
http://www.ncbi.nlm.nih.gov/pubmed/17761019

http://www.silverhydra.com/2011/09/aromatase/

Inhibitory Effect of Luteolin on Estrogen Biosynthesis in Human Ovarian Granulosa Cells by
Suppression of Aromatase (CYP19).
http://www.ncbi.nlm.nih.gov/pubmed/22838964

Fighting cancer with red wine? Molecular mechanisms of resveratrol.
http://www.ncbi.nlm.nih.gov/pubmed/20443159

Finding a Target for Resveratrol
http://www.cell.com/abstract/S0092-8674(12)00098-0