Grape Seed Extract: Effective for Menopausal Symptoms, Especially Hot Flashes... a Curious Contradiction

Recently, I have started to suggest to patients that they take grape seed extract (GSE) to reduce menopausal symptoms, especially hot flashes.

There is a problem with this, though. Theoretically, grape seed extract should not help hot flashes. Or at least I wouldn't think it should, but in real women, experiencing very real hot flashes, it has shown to be effective.

The reason that grape seed extract should theoretically not help hot flashes is because it acts as an aromatase inhibitor. After menopause, a woman's ovaries stop producing estrogen. Instead she relies on her adrenal glands to make a chemical, androstenedione, that is converted by the enzyme aromatase into estrogen. At menopause, estrogen levels only drop about 60 percent because this adrenal and aromatase process continues to supply estrogen.

First in 2003 and then in 2006, researchers from the City of Hope Cancer Center 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 curious contradiction: if grape seed extract decreases estrogen, it should worsen menopausal symptoms.

But it doesn't seem to. In fact, in my experience to date, it does quite the opposite.

In response to an email query for an explanation to this phenomenon, Michael Uzick, ND, currently teaching oncology at Southwest College of Naturopathic Medicine, forwarded me an article on Pycnogenol and hot flashes. Pycnogenol is a proprietary extract made from the bark of maritime pine trees that grow along the Mediterranean Sea. It is a rich source of proanthocyanidins (PCO), a class of flavonoids. These proanthocyanidins are the same chemicals as those found in grape seed extract.

Even though not about grape seed extract, the Pycnogenol article Uzick forwarded is still relevant. Published in a 2007 issue of Acta Obstetricia et Gynecologica, Taiwanese 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 menopausal symptoms improved, along with cholesterol levels. Remember, grape seed extract contains the same proanthocyanidins as Pycnogenol.

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 beneficial "side effects" make it worth taking even without hot flashes.

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.

Researchers believe that one way GSE works is by hindering angiogenesis, 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 extract acts as a vascular epithelial growth factor inhibitor (VEGF). In laymen's terms, this means that GSE inhibits a protein involved in angiogenesis. According to one of the papers, "... this study indicates that GSE is a well-tolerated and an inexpensive natural VEGF inhibitor and could potentially be useful in cancer prevention or treatment."

Grape seed extract does other things in regard to cancer. A study released in early 2009 showed that GSE can inhibit the proliferation of a particular breast cancer cell (MCF-7) by stopping its normal cell cycle and decreasing gene expression of survivin, an essential regulator of cell division and apoptosis that is over-expressed in cancer. GSE has also been shown to increase the effect of the chemotherapy drug Doxorubicin in killing breast cancer cells, "independent of estrogen receptor status of the cancer cell."

So with its promise in cancer prevention and/or treatment, why are we in such a rush to figure out how well grape seed extract works on hot flashes?

Women who have been, or who are currently 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 extract 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 it 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.

So although in theory grape seed extract should not help, and indeed should theoretically make menopausal symptoms worse, real women are finding relief with this most contradictory of supplements.

I've been suggesting a dose of 200 mg of grape seed extract morning and evening.

References available on request.