Is curcumin contraindicated while on Xtandi?
There have been a few recent posts on this subject. Rather than respond to them individually, I'm starting yet another thread. LOL
This is also a follow-up to an old post, which was a response to Cromone, who had been told to avoid curcumin, because:
"the Oncologist consulted the Pharmacist who suggested that I should stop the Curcumin as he was not familiar with Curcumin supplementation and was unsure of what, if any, inter-reaction their could be."
More recently, Daddysdaughter:
"My father is on Xtandi and he was told to stop taking tumeric because it decreases the effectiveness for the Xtandi.. he also was told to stop green tea."
Rexwaterbury responded:
"I am on Xtandi. Dr Myers also told me to stop turmeric."
I can't find any studies that support a contraindication.
Dr. Myers had positive things to say about curcumin in 2010:
askdrmyers.wordpress.com/20...
This video was re-posted on Sep 04, 2015, with the following comment:
"In the past few weeks we’ve received several questions about curcumin. So, this week we’re re-running a video Dr. Myers prepared about curcumin back in 2010."
But in the 2 years before retirement, Dr. Myers seems to have found reason to suspect an interaction.
...
Xtandi [Enzalutamide, MDV3100] is a nonsteroidal antiandrogen. It binds to the androgen receptor [AR], but unlike Casodex, the AR does not translocate to the nucleus. Also unlike Casodex, Xtandi remains an AR antagonist (Casodex can eventually become an agonist for mutant AR).
{Dihydrotestosterone [DHT] (the natural AR ligand) strongly competes with Xtandi for AR binding, so it is just as well to use Avodart, even with castrate testosterone [T], since PCa has been known to manufacture DHT via a back-door path that does not involve T.}
Curcumin does not bind to the AR, so does not compete with Xtandi.
Curcumin does, however, target the AR. Why might that be a problem? Seems that there might be synergy with Xtandi. The team behind the following study (2016) [1] clearly think so:
{Note: ASC-J9(® is a synthetic curcumin analog with greater bioavailability.}
"The detailed mechanisms how CRPC develops Enz {Enzalutamide - Xtandi} resistance remain unclear and may involve multiple mechanisms. Among them, the induction of the androgen receptor (AR) mutant AR-F876L in some CRPC patients may represent one driving force that confers Enz resistance. Here, we demonstrate that the AR degradation enhancer, ASC-J9(®), not only degrades wild-type AR, but also has the ability to target AR-F876L."
A 2002 paper first reported curcumin-related AR activity [2]:
"... curcumin has a potential therapeutic effect on prostate cancer cells through down-regulation of AR and AR-related cofactors (AP-1, NF-kappaB and CBP)."
The following is from a full-text review of curcumin & PCa [3]:
"Uncontrolled AR gene amplification, AR mutations, and increase of AR expression appear to be a selective driving force for the progression of prostate cancer to the hormone refractory state. Curcumin was shown to have an influence on the expression level of typical prostate marker proteins. In fact, in response to curcumin treatment, the AR expression was strikingly down-regulated as well as the AR binding activity to the androgen response element of the prostate-specific antigen protein (PSA) gene, and the PSA expression in LNCaP cells. This phenomenon is expected to deprive these cells of a critical growth advantage and classifies thus this phytochemical as a non-toxic approach to the management of AR-dependent prostate cancer"
In 2013, the ASC-J9(® people [4]:
"examined the existing data on PCa patients treated with ADT plus anti-androgens to analyze ADT effects on primary tumor size, prostate-specific antigen (PSA) values, and metastatic incidence. We found that the current ADT with anti-androgens might lead to primary tumor reduction, with PSA decreased yet metastases increased in some PCa patients. Using in vitro and in vivo metastasis models with four human PCa cell lines, we evaluated the effects of the currently used anti-androgens, Casodex/bicalutamide and MDV3100/enzalutamide, and the newly developed anti-AR compounds, ASC-J9® and cryptotanshinone, on PCa cell growth and invasion. In vitro results showed that 10 μm Casodex or MDV3100 {Xtandi} treatments suppressed PCa cell growth and reduced PSA level yet significantly enhanced PCa cell invasion. In vivo mice studies using an orthotopic xenograft mouse model also confirmed these results. In contrast, ASC-J9® led to suppressed PCa cell growth and cell invasion in in vitro and in vivo models."
Which suggests to me that curcumin + Xtandi might be a good partnership, provided that the curcumin used was truly bioavailable (most products are not - turmeric certainly isn't).
Also in 2013 [5]:
"Here we found that ADT with the currently used Casodex (bicalutamide) and the newly developed MDV3100 (enzalutamide) promoted PCa metastasis via enhancing macrophage infiltration in both in vitro co-culture systems and in vivo mouse models. In contrast, the newly developed AR degradation enhancer ASC-J9 showed an opposite effect, suppressing the macrophage infiltration and consequent PCa metastasis."
...
"Enzalutamide is a moderate to strong inducer of multiple cytochrome P450 enzymes including CYP3A4, CYP2C9, and CYP2C19 and hence has a high potential for clinically relevant drug interactions." [6] i.e. greater clearance & reduced effectiveness.
That is certainly a problem when using supplements with poor bioavailability due to CYP3A4 clearance. Adding piperine might help, but one would need to start with a good curcumin product, such as LongVida (CurcuBrain).
...
Obviously, I haven't answered the question. {The answer is not to be found on PubMed.} There seems to be a good case for curcumin use to degrade up-regulated AR. Unfortunately, Xtandi might accelerate clearance of curcumin. Given the poor availability of most curcumin products, it's difficult to visualize curcumin getting in the way of Xtandi.
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/272...
[2] ncbi.nlm.nih.gov/pubmed/122...
[3] ncbi.nlm.nih.gov/pmc/articl...
[4] jbc.org/content/288/27/1935...
more possibilities after exhausting SOC?: Enzalutamide-resistant castration-resistant prostate cancer: challenges and solutions
