The science of soy and soy isoflavones for menopause has experienced a bumpy ride. But now we know better. Turns out those bumps in the road came in the form of a little-understood metabolite called equol.

By now most of us have heard the recent news that eating soy can significantly increase longevity for breast cancer survivors. This has been updated by a 2017 study from Tufts University.

Soy for menopause has remained a bit more mysterious. Significant benefits have been proving that soy isoflavones – the medicinal elements of soy – can tremendously reduce menopause symptoms. But there may be an extra step in the process for some women – those who don’t effectively produce equol.

The soy isoflavones we’re talking about are genistein, daidzein, and glycitein. Let’s start with a recent study that focused not only upon a menopausal symptom, but equol production as well. Then we’ll look at how we got there.

Soy isoflavones reduce bone loss

The study comes from Purdue University. The researchers tested 24 menopausal women. At the beginning of the study the researchers screened each woman for their ability to convert diadzein to equol.

The researchers proceeded to give the women supplements that ranged from 52 to 220 milligrams of isoflavones. Different doses were given to each for 50 days with a 50-day washout period in between.

Throughout, the doctors measured the women’s ability to retain bone calcium. This is one of the central issues that affect menopausal women – bone loss.

Anyway, the study found that the most effective soy treatment had 105 total milligrams of isoflavones per day. But the proportions between genistein, daidzein, and glycitein that worked the best were those which matched soy’s natural isoflavone proportions.

These increased calcium retention by as much as 7.6 percent. Not bad.

But the interesting part of this study is the fact that the soy supplementation worked for women who were not equol producers as well as for equol producers.

Do equol producers have better results from isoflavones?

A 2016 study from Max Rubner and Max Planck Institutes studied the effects of soy isoflavones among humans, rats and mice. Because the rats and the mice were all equol producers, they all had a standard positive effect from soy isoflavones. But the humans had varying degrees of soy isoflavone benefits based upon whether they were equol producers.

Researchers from the Czech Republic’s Mlada Regional Hospital in Boleslav confirmed that consuming soy isoflavones decreases menopausal symptoms among women. But only among those who maintain particular intestinal probiotics that produce an isoflavone metabolite called S-equol.

Higher circulating levels of S-equol have been linked to decreases in bone loss, reduced prostate cancer and reduced menopausal symptoms, including hot flushes (or hot flashes), night sweats and irritability. Some research has also indicated that S-equol reduces the risk of breast cancer and endometrial cancer.

The Czech study tested 28 menopausal women who were each given 80 milligrams of soy isoflavones daily while being tested for S-equol within their urine and bloodstream(prior to the study, the researchers identified the “S-equol producers” versus “S-equol non-producers.”)

Among the S-equol producers, the S-equol urine levels went from 0.34 to 10.67 ng/ml after the isoflavone supplementation, while the non-producers’ levels went from 0.29 to a scant 0.34.

Meanwhile, Kupperman index ratings decreased substantially, but only for the S-equol producers. In the producers, Kupperman index values went from 23.44 to 14.44, while there was little change among the non-producers.

The Kupperman index measures hot flushes (or hot flashes), insomnia, nervousness, melancholia, vertigo, weakness, arthralgia or myalgia (muscle pain), headache, paresthesia (tingling sensations), palpitations (quickening heart beats), and formication (skin sensations). A reduction in the index indicates reduced menopausal symptoms.

Other studies have had similar results. In one, 96 menopausal Taiwanese women were given 135 milligrams of isoflavones daily for six months. The isoflavone group reported significantly decreased menopausal symptoms. But again, this effect was only among those who were S-equol producers.

Yet the bone retention results of the Purdue study indicate that non-equol producers also experience benefits from soy isoflavones. But in this study, the best results were found in those that had the combinations of the isoflavones that matched soybeans.

Equol is produced by probiotics after isoflavone consumption

S-equol (4′,7-isoflavandiol) – also called 5-hydroxy-equol – is produced by intestinal probiotics after they consume the isoflavonedaidzein and genistein we eat. Some have proposed that S-equol only comes from daidzein but other research clearly indicates that certain probiotics will also produce S-equol from genistein. That said, it is primarily daidzein that equol-producers convert to S-equol.

Isoflavonesdaidzein and genistein are not only in soy: Asparagus and many other types of beans such as fava beans, lupins, mung beans and lentils; seeds such as sesame, linseed and flax; and yams, apples, pomegranates, whole wheat and some others. Isoflavone-rich herbs include black cohosh, licorice root, fennel, anise, hops and chaste berry.

Equol production and intestinal probiotics

The missing piece relates to the health of our intestinal probiotics. Can probiotic supplements help increase S-equol production?

The research has indicated that many of the strains in our probiotic supplements do not increase S-equol production.

In a 2004 study from the University of Minnesota, isoflavone supplementation plus Lactobacillus acidophilus DDS+1 and Bifidobacteriumlongum did not generally increase S-equol production among a group of 20 women compared to controls (isoflavones alone). However, S-equol production went up significantly among a few of the women. The researchers concluded that:

“the large differences between plasma and urinary equol in some subjects suggest that equol producer status may be modifiable in some individuals.”

However, in a 2011 study from Italy with twelve menopausal women, Lactobacillus sporogenes supplementation resulted in a 24% increase in genistein-related equol, while daidzein metabolite equol production only went up for some of the women but not all.

Another 2011 laboratory study indicated that Lactobacillus rhamnosus increased daidzein S-equol production.

But a 2012 study from Germany’s Institute of Human Nutrition found that the intestinal probiotic bacteria (conveniently) named Slackiaisoflavoniconvertens will convert both genistein and daidzein to 5-hydroxy-equol.

The issue may simply be that the two strains of probiotics given in the University of Minnesota study were not equol-related probiotic strains, while L. rhamnosus and L. sporogenes and possibly others – are. This is what the research seems to be indicating.

Boosting probiotics

So while the hunt for the right combination of probiotics to turn “non-equol producers” into “S-equol producers” may continue, there is good reason to believe that we can increase our probiotic colonies and thereby increase our S-equol production with a varied species supplementation plan.

This isn’t just for women, by the way. Men also benefit from soy isoflavone supplementation. It helps the prostate and reduces blood pressure among other things. But again, some of these benefits relate to equol production.

The take-home message is that the health benefits of isoflavones – which include cancer protection, bone health and lower menopausal symptoms – relate directly to healthy intestinal probiotic populations, and eating whole soy – or natural proportions of soy isoflavones.