Pomegranate and 27-OH Cholesterol

Jacob Schor, ND, FABNO

June 15, 2016

www.DenverNaturopathic.com

 

This is interesting once you get past some of the big words.

 

We’ve been following the research on pomegranate and breast cancer for years.  The first mention in the literature I recall seeing was Ephraim Lansky’s 1999 paper that reported pomegranate extracts had antioxidant effects comparable to green tea and the preservative BHA.

https://www.ncbi.nlm.nih.gov/pubmed/10432202

 

This was followed by Lansky’s 2002 report suggesting that pomegranate might be useful in treating breast cancer.

https://www.ncbi.nlm.nih.gov/pubmed/12002340

 

Since then we’ve seen a regular stream of interesting pomegranate papers.  In particular the UCLA clinical trials suggesting benefit in advanced prostate cancer.  We’ve sent out newsletters about some of these various studies over the years.  Links to these older DNC newsletters will be at the end of this piece.

 

At one point Naturopathy Digest published a piece I had written, an article titled that Alchemist and the Capitalist, that compared Lansky, who is something of an eccentric ex-hippy turned MD/PhD researcher with Lynda Reznick, the owner of PomWonderful, who is quite his opposite; she’s the quintessential, Type A business entrepreneur.

http://www.naturopathydigest.com/archives/2006/apr/schor.php

 

Over the years various explanations have been put forth as to why pomegranate has so many health benefits, starting with the archaeological or perhaps Biblical explanation that pomegranate was actually that apple in the Garden of Eden that all the fuss was about.  Usually credit is given to pomegranate’s high content of ellagic acid, or the synergistic action ellagic acid has with the quercetin also found in the fruit.

 

The oil pressed from the seeds acts as an aromatase inhibitor and that action alone could account for much of the benefit especially in older breast cancer patients.  Still, not too long ago, something else caught our attention.

 

 

A paper published back in February suggests that pomegranate changes production of 27-hydroxycholesterol (27-OH).  This is fascinating.  I wrote about the action of this cholesterol metabolite for both the Natural Medicine Journal and the Townsend Letter.  The article provides a decent review of the chemistry and research. http://www.naturalmedicinejournal.com/journal/2014-04/27-hydroxycholesterol-promotes-some-breast-cancer-growth

 

 

In a February 2016 article, Vini, Juberiya, and Sreeja reported that an extract made from pomegranate binds to the estrogen receptors on breast, ovarian and endometrial cancer cells and down regulates the estrogen response while at the same time having a heart protecting effect similar to estrogen.  The pomegranate extract blocked the action of the 27 hydroxycholesterol.

https://www.ncbi.nlm.nih.gov/pubmed/26756990

 

 Recall the reason we don’t like this obscure cholesterol metabolite is that when it binds to estrogen receptors it stimulates tumor growth; the cancer cells apparently think it is potent estrogen.

 

This is interesting because it in a way gives us a description of which women may benefit the most from drinking pomegranate juice.  They are the overweight women with elevated cholesterol with a concern (past or present) about estrogen receptor positive breast cancer.  This of course doesn’t help us narrow down which men with prostate cancer will benefit the most from pomegranate juice.

 

Well I may be speaking or writing too quickly.  Another paper published last February reported on the effect of 27-OH cholesterol on prostate cancer cells.  Raza et all tell us that 27-OH cholesterol  “… stimulates proliferation and increases androgen receptor (AR) transcriptional activity. 27-OHC also increased prostate-specific antigen expression and enhanced AR binding to the androgen response element compared to controls. Silencing AR expression with siRNA markedly reduced the 27-OHC-induced proliferation. Furthermore, 27-OHC blocked docetaxel-induced apoptosis. Altogether, our results suggest that 27-OHC may play an important role in PCa and BPH progression by promoting proliferation and suppressing apoptosis.” 

https://www.ncbi.nlm.nih.gov/pubmed/26732475

 

 

Translating that into English, this 27-OH cholesterol encourages prostate cancer cells to grow faster and helps them survive chemotherapy treatment.  Thus we have another argument for drinking pomegranate juice with prostate cancer and during treatment with docetaxel as well.

 

There’s another paper worth mention, that you will find interesting if I can translate is clearly and simply enough.  Published inNovember 2015, just the title may slow you down: “Differential epigenetic reprogramming in response to specific endocrine therapies promotes cholesterol biosynthesis and cellular invasion.”

 

One of the challenges with long-term use of the aromatase inhibiting drugs by women with ongoing metastatic breast cancer is that eventually the drugs stop working.  The drug blocks estrogen production but over time the cancer cells lose their need for estrogen to stimulate growth; they become hormone independent…. They don’t need estrogen anymore.

 

This paper describes part of the reason why.  These cells figure out that they can increase their production of 27-OH cholesterol.  Cholesterol or actually the 27-OH metabolite of cholesterol, becomes a stand in for estrogen.  The paper goes on to suggest that statin drugs by lowering cholesterol makes it harder for these cancer cells to get away with this. 

 

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/26610607

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674692/pdf/ncomms10044.pdf

 

Granted that this starts to sound complicated but the bottomline is simple.  These ex estrogen dependent drugs figure out how to use 27-OH cholesterol instead so they can start to grow fast again.  Stopping 27-OH production could be really useful for these women.

 

Recall Vini et al, reported that pomegranate may hinder 27 OH cholesterol production.  See why this is so interesting?

 

So pomegranate now looks important for women taking aromatase inhibitors for advanced cancer.  It may keep the drugs working longer.

 

 

 

 

 

 

 

Past Denver Naturopathic Clinic newsletters about pomegranate:

 

2008: Synergy between green tea and pomegranate

http://www.denvernaturopathic.com/boardmeetingsandicedtea.htm

 

2008: Pomegranate research update: http://denvernaturopathic.com/pomegranateSeptember08.html

 

2006: Pomegranate and prostate cancer; the UCLA clinical trial http://denvernaturopathic.com/news/PomandPC.html

 

2005: Pomegranates and Pregnancy

http://denvernaturopathic.com/news/pomegranatesandpregnancy.html