One of the vexing problems faced by men intrigued by PCa-Polyphenol study results, is how to improve bioavailability. This is particularly true for curcumin & resveratrol. While micronized versions of these now exist, bioavailability issues remain for a dozen others.
The primary reason for poor bioavailability is the CYP3A4 enzyme. Oral polyphenols, taken up in the portal vein to the liver, may be largely metabolized by this enzyme.
Chrysin, a flavone in the flavonoid family, is an aromatase inhibitor - it can reduce the conversion of testosterone [T] to estradiol [E2]. As many bodybuilders have found, it is not very effective at lowering E2. Life Extension has a T booster called MiraForte [1]. Two of the seven ingredients are chrysin (750 mg) & Bioperine (7.5 mg). Bioperine contains piperine, which inhibits CYP3A4. Until I found a doctor willing to prescribe Arimidex, I used the product to keep E2 at ~20 pg/mL. (Meanwhile, the Chrysin Wikipedia page insists that it has no aromatase activity.
The MiraForte label has two warnings:
"If you are taking any medication, use only under physician supervision."
"Do not take more than 15 mg per day of Bioperine®."
It's all a bit vague, & the warnings are probably soon forgotten, but perhaps half of all drugs are partially metabolized by CYP3A4 in the "first pass" through the liver.
It's very odd that it is considered natural to take massive amounts of a pharmaceutical drug, on the basis that perhaps less than a tenth will survive the liver. One wonders about the stress on the liver & the effect in the body of all the metabolites, as well as the extra work the kidneys must do.
The active amount of a drug that gets into circulation depends in part on how much CYP3A4 the liver has produced. Too much & one might not receive a therapeutic dose; too little & side effects might be stronger. Various foods (& supplements) can inhibit or stimulate CYP3A4 production - including black pepper, which is 5-9% piperine. The most well-known is grapefruit juice, which is a potent inhibitor.
As for CYP3A4 inducers, St. John's wort stands out - but see [2] for 18 drugs that increase CYP3A4; they may make other drugs less effective. 35 CYP3A4 pharma inhibitors are also shown.
I take most of my supplements after breakfast & take my prescription drugs at bedtime. I figure it is safe to use Bioperine at breakfast.
[3] (2012 - U.S.) "Co-administration of piperine and docetaxel results in improved anti-tumor efficacy via inhibition of CYP3A4 activity."
A Taxotere (Docetaxel) injection escapes the first pass effect, but the drug is ultimately metabolized by CYP3A4. Bioperine would potentially extend the half-life of the drug.
"The synergistic administration of piperine and docetaxel significantly improved the anti-tumor efficacy of docetaxel in a xenograft model of human CRPC."
"The pharmacokinetic profile of docetaxel is characterized by substantial inter-individual variability, with up to 10-fold differences in drug clearance even in patients with normal hepatic function. The importance of docetaxel’s clearance is highlighted by a previous study documenting that a 50% decrease in docetaxel clearance is associated with a greater than 430% increase in the odds of developing severe-grade 3 or 4-neutropenia."
"In the United States, average daily intake of black pepper has been estimated at 359 mg [26]. Piperine accounts for between 5% and 9% of black pepper content, implying a daily intake of approximately 60 to 110 μmol of piperine. Results of our study demonstrate that such an amount of piperine could potentially modulate pharmacokinetics of docetaxel in cancer patients."
[4] (2013 - U.S.) "Piperine ... Exerts Therapeutic Effects on Androgen Dependent and Androgen Independent Prostate Cancer Cells"
[5] (2013 - China) "Piperine inhibits the proliferation of human prostate cancer cells via induction of cell cycle arrest and autophagy."
Summary:
a) Bioperine might be useful for those taking supplements known to have poor bioavailability.
b) Bioperine may have anti-PCa activity.
c) Bioperine may improve the effectiveness of Taxotere.
Bioperine is sold under various brand names. e,g.:
swansonvitamins.com/swanson...
-Patrick
[1] lifeextension.com/Vitamins-...
[2] pharmacytimes.com/publicati...
[3] ncbi.nlm.nih.gov/pmc/articl...
