Grape seed extract to relieve menopausal hot flashes
Jacob Schor ND FABNO
April 11, 2009


In recent weeks both Dr. Bloom and I have started suggesting to patients that they take grape seed extract (GSE) to reduce menopausal symptoms, especially hot flashes. There is little published in the peer reviewed medical journals to support this recommendation. Nor is there a history of clinical use providing anecdotal support. We generally practice evidence based medicine so an explanation is in order for this notion that is an exception to the rule.



Dr. Bloom tells me that she first heard of using grape seed extracts for hot flashes from Nancy Rao, Lac, ND who began practicing in Boulder decades before we arrived in Colorado. Dr. Rao in turn tells me she heard of this from Tori Hudson, ND who runs advanced programs training doctors in women’s health issues in Portland. Dr. Hudson taught a number of our courses when Dr. Bloom and I attended National College of Naturopathic Medicine in the 1980s. She commands a great deal of respect in our profession and from both of us. If Tori says something works I tend to believe her (though please don’t let her know I’ve written that).



There is a problem though with this. Grape Seed Extract should not help hot flashes.
Or at least I wouldn’t think they should.



This is because grape seed extract acts as an aromatase inhibitor. In menopause a woman’s ovaries stop producing estrogen. Instead she relies on her adrenal glands to make a long named chemical, androstenedione, that is converted by the enzyme aromatase into estrogen. At menopause, estrogen levels only drop about 60% because this adrenal and aromatase process continues to supply estrogen.



First in December 2003 and then in 2006, researchers from the City of Hope reported in Cancer Research that grape seed extract blocks aromatase activity. This is significant because it suggests that grape seed extract lowers estrogen and should be of value in both preventing and treating breast cancer. But here’s the problem: if grape seed extract decreases estrogen, it should worsen menopause symptoms.



But it doesn’t seem to. In fact in our experience to date, it works well.


In response to an email query for an explanation to this phenomenon, the good Michael Uzick, ND, currently teaching oncology at Southwest College of Naturopathic Medicine. forwarded me an article on Pycnogenol and hotflashes. Pycogenol is a proprietary extract made from the bark of maritime pine trees (Pinus pinaster) that grow along the Mediterranean Sea. It is a rich source of proanthocyanidins or OPC-oligometeric proanthocyanidins. This is pretty much the same chemical we find in grape seed extract.



Ever since I read an article written by Michael Murray, ND back in the mid 1990s "PCO sources: Grape seed vs. pine bark," I’ve used the two products almost interchangeably. Both grape seed extract and Pycnogenol are well-defined chemically and both are excellent sources of PCOs. There is more experimental research published on grape seed extract though. In addition grape seed extracts tend to be cheaper than Pycnogenol because every year there are tons of grape seeds left over from grape juice and wine making. In contrast, to make Pycnogenol the trees must be killed to obtain the bark.



Even though not on grape seed extract, the Pycnogenol article Uzick forwarded is still relevant. Published in a 2007 issue of Acta Obstetricia et Gynecologica, Taiwnese researchers reported on a randomized, double-blind, placebo controlled trial examining Pycnogenol’s effect on menopausal symptoms. A total of 155 women completed the study. All climacteric symptoms improved along with cholesterol levels.


“During treatment, a rapid improvement of symptoms was reported from women in the Pycnogenol group, starting after 1 month…..In the placebo group, no ….significant changes of symptoms were reported…. Occasionally symptoms in the placebo group improved …, however later symptoms worsened. …. After 6 months, the difference between the Pycnogenol group and the placebo group became so clearly visible that no statistical evaluation was required to demonstrate the advantage of Pycnogenol treatment….” [2]

If Pycnogenol works for menopausal symptoms then why are we suggesting grape seed extract? It’s not just that it is less expensive. Grape seed extract may also lower risk of cancer and cardiovascular disease. For some people these ‘side effects’ make it worth taking even without hot flashes.

Some of the more interesting cancer research has focused on prostate cancer. Yes, I am aware men don’t have hot flashes. Grape seed extract is a complex mixture of polyphenols including gallic acid, catechin, epicatechins and procyanidins. It appears all of these, but particularly the gallic acid, have anticancer activity. [3] These chemicals act partly because they are NF Kappa B inhibitors. [4] Together in grape seed extract, these chemicals cause, “…strong suppression of cell cycle progression and cell proliferation and an increase in apoptosis” on prostate cancer cells. The result is that they, “…induce necrosis and apoptosis of PC-3 cells.” [6] A 2008 paper suggests that grape seed extract, “….can be used as a new drug in treatment of prostate cancer.” [7]

Evidence is also mounting the grape seed extracts may be useful in treating leukemia. Though early reports were published in March of 2006, the most notable report was just published in Clinical Cancer Research in January 2009.

In this experiment, grape seed extract caused human leukemia cells triggered apoptosis (a fancy term for cell suicide.)



Past studies of grape seed extract have shown effect against a number of laboratory cancer cell lines, including skin, breast, colon, lung, stomach and prostate cancers.[8] Up until this paper, grape seed extract had not been tested on hematological cancers such as leukemia. This new paper reports that treating human leukemia cells with varying doses of grape seed extract can have profound effect. When exposed to high doses of extract, 76 percent of leukemia cells had died in 24 hours. The extract did not affect normal cells.

The researchers think the grape seed extract acts through a signaling pathway called JNK, a protein that regulates the apoptosis pathway. Chemical agents that inhibit JNK made the grape seed ineffective.[9]

JNK disruption isn’t the only way that grape seed extracts can inhibit cancer growth, they also hinder angiogenesis. Angiogenesis is the growth of new blood vessels. If a growing tumor can’t build new blood vessels, it suffocates. Some of the newer more exciting cancer drugs work by blocking angiogenesis. In 2008, two papers reported that grape seed extracts act as vascular epithelial growth factor inhibitors (VEGF). [10.11] I know this is getting obscure for some or our readers, so trust me that it’s a desirable thing and we’ll move on. But let me add some words from one report first, “Taken together, this study indicates that GSE is a well-tolerated and inexpensive natural VEGF inhibitor and could potentially be useful in cancer prevention or treatment.” [12]


Grape seed extracts do other things in regard to cancer. They hinder metastasis of melanoma to the lungs. [13,14] It increases the effect of the chemotherapy drug doxorubicin in killing breast cancer cells, “…independent of estrogen receptor status of the cancer cell.” [15]


So why are we in such a rush to figure out how well grape seed extracts work on hot flashes?

Women who have been or are undergoing treatment for breast cancer are often left to suffer unbearable hot flashes that are far more intense than what other women experience. Fear of promoting cancer puts the standard therapies, especially hormone replacement, off limits. These women are often left to suffer by their doctors. It is for these women especially that grape seed extracts may be valuable. Use may decrease discomfort while at the same time working against cancer reoccurrence or progression. At the least, grape seed extract may provide relief and we can be fairly certain they won’t make the cancer worse. It is the old, “It’s not going to hurt and it might help” rationale but in this case it may help symptoms and cancer.


This is why we are interested in finding out whether and how well grape seed extracts work to calm hot flashes.


We’ve been suggesting a dose of 200 mg morning and evening and have been using a product purchased from Vital Nutrients, a company that has a reputation for making honest products of strong ingredients.





References:

1. Acta Obstet Gynecol Scand. 2007;86(8):978-85.
A randomised, double-blind, placebo-controlled trial on the effect of Pycnogenol on the climacteric syndrome in peri-menopausal women.
Yang HM, Liao MF, Zhu SY, Liao MN, Rohdewald P.
2. Acta Obstet Gynecol Scand. 2007;86(8):978-85.
A randomised, double-blind, placebo-controlled trial on the effect of Pycnogenol on the climacteric syndrome in peri-menopausal women.
Yang HM, Liao MF, Zhu SY, Liao MN, Rohdewald P.
3. Carcinogenesis. 2007 Jul;28(7):1478-84. Epub 2007 Feb 28.
Fractionation of high molecular weight tannins in grape seed extract and identification of procyanidin B2-3,3'-di-O-gallate as a major active constituent causing growth inhibition and apoptotic death of DU145 human prostate carcinoma cells.
Agarwal C, Veluri R, Kaur M, Chou SC, Thompson JA, Agarwal R
4. Int J Oncol. 2003 Sep;23(3):721-7.
Inhibition of NF-kappaB pathway in grape seed extract-induced apoptotic death of human prostate carcinoma DU145 cells.
Dhanalakshmi S, Agarwal R, Agarwal C.
5. Cancer Res. 2007 Jun 15;67(12):5976-82.
Oral grape seed extract inhibits prostate tumor growth and progression in TRAMP mice.
Raina K, Singh RP, Agarwal R, Agarwal C.
6. Zhonghua Nan Ke Xue. 2008 Dec;14(12):1090-3.
[Grape seed extract induces morphological changes of prostate cancer PC-3 cells]
[Article in Chinese]
Shang XJ, Yin HL, Ge JP, Sun Y, Teng WH, Huang YF.
7. Zhonghua Nan Ke Xue. 2008 Apr;14(4):331-3.
[Grape seed extract inhibits the growth of prostate cancer PC-3 cells]
[Article in Chinese]
Huang TT, Shang XJ, Yao GH, Ge JP, Teng WH, Sun Y, Huang YF
8. Mol Cell Biochem. 1999 Jun;196(1-2):99-108.
The cytotoxic effects of a novel IH636 grape seed proanthocyanidin extract on cultured human cancer cells.
Ye X, Krohn RL, Liu W, Joshi SS, Kuszynski CA, McGinn TR, Bagchi M, Preuss HG, Stohs SJ, Bagchi D.
9. Int J Oncol. 2003 Sep;23(3):721-7.
Inhibition of NF-kappaB pathway in grape seed extract-induced apoptotic death of human prostate carcinoma DU145 cells.
Dhanalakshmi S, Agarwal R, Agarwal C.
10. Cancer Prev Res (Phila Pa). 2008 Dec;1(7):554-61.
Grape seed extract inhibits angiogenesis via suppression of the vascular endothelial growth factor receptor signaling pathway.
Wen W, Lu J, Zhang K, Chen S.
11. Carcinogenesis. 2009 Apr;30(4):636-44. Epub 2009 Jan 8.
Grape seed extract inhibits VEGF expression via reducing HIF-1alpha protein expression.
Lu J, Zhang K, Chen S, Wen W.
12. Cancer Prev Res (Phila Pa). 2008 Dec;1(7):554-61.
Grape seed extract inhibits angiogenesis via suppression of the vascular endothelial growth factor receptor signaling pathway.
Wen W, Lu J, Zhang K, Chen S.
13. Histol Histopathol. 2005 Oct;20(4):1121-9.
The effect of the flavonoid diosmin, grape seed extract and red wine on the pulmonary metastatic B16F10 melanoma.
Martínez C, Vicente V, Yáñez J, Alcaraz M, Castells MT, Canteras M, Benavente-García O, Castillo J.
14. Clin Transl Oncol. 2005 Apr;7(3):115-21.
[Experimental model for treating pulmonary metastatic melanoma using grape-seed extract, red wine and ethanol]
[Article in Spanish]
Martínez Conesa C, Vicente Ortega V, Yáñez Gascón MJ, García Reverte JM, Canteras Jordana M, Alcaraz Baños M.
15. Breast Cancer Res Treat. 2004 May;85(1):1-12.
Synergistic anti-cancer effects of grape seed extract and conventional cytotoxic agent doxorubicin against human breast carcinoma cells.
Sharma G, Tyagi AK, Singh RP, Chan DC, Agarwal R.



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