Simplex Res; Mushrooms and Grape Seeds in Breast Cancer Prevention

Jacob Schor, ND

December 26, 2007

[This article appeared in the May 2008 issue of NDNR]

There is a huge Korean grocery near our office.  I drove over the other day to study the mushrooms that they sell. 

My new found interest in mushrooms is sparked by the publication of a study on mushroom consumption and breast cancer risk in the International Journal of Cancer this past February.

Researchers from Seoul, South Korea recruited 362 women between the ages of 30 and 65 years who had breast cancer and matched them to controls by age and menopausal status. All the women were questioned carefully to determine how often and how many mushrooms they ate.

The researchers took this information and calculated that eating mushrooms lowers risk of breast cancer.

The women who ate mushrooms the most frequently had a 52% reduction in overall risk when compared to the women who ate mushrooms the least often.  Those who ate the most mushrooms had a 46% reduction in risk.  When this basic data was analyzed by menopausal status, a much stronger effect was seen.  In postmenopausal women, there was an 84% reduction in risk for the frequent mushroom eaters. Likewise, there was an 83% reduction in risk for those who ate the most mushrooms.  No benefit was apparent in premenopausal women.

Numbers like these should get our attention.  What is going on here?

We generally promote mushroom consumption and mushroom polysaccharide extracts as “Immune Boosters.”  My typical explanation to patients for eating and taking those mushroom pills has to do with the whole N-K Killer cell SWAT team story.  This explanation does not explain the effect seen in these Korean women based on menopausal status.  There is another and possibly better explanation for these results.

It is all about estrogen and aromatase inhibition.  So first, we need to recall a bit of basic biology .

About three quarters of all breast cancers are hormone sensitive; estrogen makes the tumor cells grow.  Blocking estrogen stimulation is a key component in the treatment of these cancers. Think Tamoxifen. Or flax seeds.  The FDA approved Tamoxifen in 1977 and it has been the standard of care for treating metastatic breast cancer and in preventing recurrent breast cancer ever since.  Tamoxifen binds to estrogen receptors and blocks estrogen from attaching and stimulating the cancer cells.  This has made Tamoxifen the largest selling breast cancer treatment in the world. Estimates are that five years of tamoxifen therapy reduces mortality from breast cancer by 31%. Of course, Tamoxifen does have its down sides, like increasing risk of endometrial cancer by 2.4 times or thromboembolitic disease by 1.9 times.  Let’s not digress.

Tamoxifen is outdated, rapidly being replaced by a new class of drugs called aromatase inhibitors. 

Aromatase inhibiting drugs arrived on the market about ten years ago and have recently replaced Tamoxifen as the accepted standard of care in post-menopausal breast cancer patients.  Tamoxifen continues to be the standard for premenopausal women. The top three aromatase inhibiting drugs are Arimidex (anastrozole), Aromasin (exemestane), and Femara (letrozole).

These drugs work differently than Tamoxifen.  The estrogen in menopausal women comes from the adrenal glands rather than the ovaries.  The adrenal glands secrete a chemical called androstenedione which is converted into estrogen.  The enzyme that converts the androstenedione is called aromatase.  Blocking aromatase provides a means to block estrogen production.  The drugs used as aromatase inhibitors can reduce estrogen production by 90 to 95%.

Although these new drugs are safer than Tamoxifen, they do seem to cause more symptomatic complaints than Tamoxifen.  The most common complaint we have seen in patients is arthralgia or what patients call aching joints. 

The symptoms can be severe enough that some patients refuse to continue treatment with aromatase inhibitors.  As much as these drugs provide long term benefit in treating cancer, these patients cannot tolerate the short-term discomfort.  As a result, we have been watching for alternatives, especially reports that suggest foods might block aromatase action. Here is where the grapes and mushrooms come into the story.

Dr. Shiuan Chen at the City of Hope in Duarte, California has been steadily publishing research for the last half dozen years on dietary aromatase inhibitors.  At first, Chen found that polyphenols called procyanidin B dimmers were aromatase inhibitors.  Knowing that grape seeds are a good source of this chemical they ran out to their local health food stores and bought every grape seed product they could fine.  They tested the aromatase inhibition action of 13 different brands of grape seed extracts in cell and animal studies and found that ten worked. They published this initial research in December 2003, reporting that grape seed extracts lowered estrogen levels and slowed tumor growth.   They confirmed these early findings in detail in a Cancer Research published paper in June 2006.   The grape seed extracts could inhibit aromatase by at least 80%.

Chen looked at other foods looking for aromatase inhibition and curiously found that white button mushrooms were particularly effective.  Other mushrooms including shitake, portabella and crimini also had an effect when tested but Chen’s efforts have focused on the white buttons as they are the most available.

At this point Chen’s team begun a Phase I human trial using four different doses of grape seed extract, from 50 mg to 300 mg per day, in women at high risk for developing breast cancer. 

If mushrooms act as aromatase inhibitors, this might explain the Korean effect.  It would especially explain why the protection was only found in post-menopausal women.  Aromatase inhibition has no effect on estrogen levels before menopause.

There is an overwhelming variety of different mushrooms at our local market.  Fresh and especially dried mushrooms are piled up.  There are pallets filled with bags of dried mushrooms.  I cannot read Korean and the English translations on the packages don’t help me.  The bag labels tell me all the bags contain dried “mushrooms.”  Some I recognize as shitake mushrooms.  The sliced ones are beyond my recognition.

Luckily, our esteemed colleague Michael Uzick has studiously perused the text of the original paper with his typical care and so informed me that the paper reported which mushrooms Koreans eat the most frequently.  The ‘favored’ mushrooms were in order of preference, Shiitake, Oyster and Enokitake mushrooms.

Does it matter which kind?  Perhaps not, as our common white button mushrooms may be just as effective.

How many mushrooms does a menopausal woman need to eat to make a difference?

The United States Department of Agriculture (USDA) tells me that in 2001, the average American ate 3.94 pounds of mushrooms.  That is about 4.9 g/day per capita. Asian Americans ate more mushrooms, averaging 8.9 pounds or about 11.1 g/day, twice the national average.

In this Korean mushroom study, the participants ate an average 9.6 g/day of mushrooms.  The women with breast cancer averaged only 7.8 g/day but the control group that did not have breast cancer averaged 11.4 g/day.   Here comes Math for Dummies or how I do the  math.  Round that last amount, 11.4 g/day, up to 14 something grams, and call it half an ounce. Then pretend there are 8 days in a week or 4 ounces of mushrooms per week. We are talking about only a quarter a pound of mushrooms a week, or about a pound a month to possibly lower breast cancer risk by three quarters. 

How shall we translate this into practice?  We can easily encourage menopausal women to eat loads of mushrooms.  This makes sense, unless of course the women are complaining of hot flashes, in which case they might appreciate more aromatase activity and the resultant estrogen.

I do not know whether mushrooms or grape seed extracts are useful for a woman being treated with an aromatase inhibiting drug. Will adding either increase the effect or has the drug already suppressed aromatase as far as it will go?

Aromatase inhibiting drugs have their limits.  Breast cancer cells eventually become estrogen independent and the estrogen lowering effect of the drugs will no longer slow the cancer growth.  Could alternating or cycling aromatase inhibiting drugs with ‘food’ inhibition, slow the development of estrogen independent tumor cells? 

Certainly, there are women who cannot tolerate the side effects of the aromatase inhibitors and refuse to take them.  These women may be perfect candidates for dietary aromatase inhibition.  Some combination of grape seed extracts and mushrooms may prove to be almost as effective as the current drugs.

Eating mushrooms seem like such a little thing to tell a patient about when compared to the excitement surrounding these new drugs.  Each new study on aromatase drugs comparing survival and disease progression statistics that I read lulls me into thinking that the drug companies are finally on to something great.  In truth though, these data from the mushroom studies are just as exciting, perhaps even more so.  It’s the simplicity that fools me.  What could be less glamorous or more humble than a mushroom? 

This story reminds me of many of the other things we do as naturopathic doctors.  We do tend to gravitate to the simplest, lowest tech, lowest cost drugless intervention when searching out treatments.   Perhaps we need to add another one of those Latin phrases to our definition of naturopathy.  Along with Vis Medicatrix and Tolle Causam  and the rest, perhaps we need to define ourselves as the physicians who choose Simplex Res, the simple things.  Like that Shaker song…..

 

Hong SA, et al. A case-control study on the dietary intake of mushrooms and breast cancer risk among Korean women.  Int J Cancer. 2008 Feb 15;122(4):919-23.

Eng ET, et al. Suppression of estrogen biosynthesis by procyanidin dimers in red wine and grape seeds. Cancer Res. 2003 Dec 1;63(23):8516-22.

Kijima I, et al. Grape seed extract is an aromatase inhibitor and a suppressor of aromatase expression. Cancer Res. 2006 Jun 1;66(11):5960-7.

Chen S, et al. Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus). Cancer Res. 2006 Dec 15;66(24):12026-34. 

Grube BJ, et al. White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell proliferation. J Nutr. 2001 Dec;131(12):3288-93.