Soy Eases Menopause Better with Equol Production
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.
Active phytoestrogens within soy isoflavones include genistein and daidzein. They are also found among many types of peas, beans, nuts and whole grains.
Bone research with soy isoflavones
A number of studies have shown that soy isoflavones can significantly boost bone health.
This is confirmed by a 2012 analysis of multiple studies from Sichuan University’s Hainan Medical College.
The researchers analyzed multiple published international clinical studies on the application of soy isoflavones to prevent osteoporosis, the central cause of hip fractures and other bone fractures around the world.
In their meta-analysis of the research, the medical researchers found that soy isoflavones increased bone density by 54% while reducing bone loss by 23% as measured by a bone loss marker called deoxypyridinoline, which is found in the urine, especially at higher levels among those women in postmenopause.
The research found that doses above 75 milligrams a day of soy isoflavones had the most effect among postmenopausal women.
Osteoporosis is the leading cause of disability among the elderly. Nearly half of women over 60 will have a hip fracture among industrialized nations.
However, at the same time there have been a few studies that have not showed significant bone health benefits for soy isoflavones. Why?
Soy isoflavones reduce bone loss with equol
Another study comes from Purdue University. This focused not only upon a menopausal symptoms, but equol production as well.
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. Why? Read on.
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 was that 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?
This conclusion has been born out of the research of late. For example, 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. They were 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, their 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 isoflavone daidzein 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.
Isoflavones daidzein 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 Bifidobacterium longum 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 Slackia isoflavoniconvertens 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.
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 lesson 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.
Zhang FF, Haslam DE, Terry MB, Knight JA, Andrulis IL, Daly MB, Buys SS, John EM. Dietary Dietary isoflavone intake and mortality in breast cancer survivors: The Breast Cancer Family Registry. survivors: The Breast Cancer Family Registry. Cancer. 2017 Mar 6. doi: 10.1002/cncr.30615.
Soukup ST, Helppi J, Müller DR, Zierau O, Watzl B, Vollmer G, Diel P, Bub A, Kulling SE. Phase II metabolism of the soy isoflavones genistein and daidzein in humans, rats and mice: a cross-species and sex comparison. Arch Toxicol. 2016 Jun;90(6):1335-47. doi: 10.1007/s00204-016-1663-5.
Messina M. Soy and Health Update: Evaluation of the Clinical and Epidemiologic Literature. Nutrients. 2016 Nov 24;8(12). pii: E754.
Pawlowski JW, Martin BR, McCabe GP, McCabe L, Jackson GS, Peacock M, Barnes S, Weaver CM. Impact of equol-producing capacity and soy-isoflavone profiles ofsupplements on bone calcium retention in postmenopausal women: a randomized crossover trial. Am J Clin Nutr. 2015 Sep;102(3):695-703. doi: 10.3945/ajcn.114.093906.
Matthies A, Loh G, Blaut M, Braune A. Daidzein and genistein are converted to equol and 5-hydroxy-equol by human intestinal Slackia isoflavoniconvertens in gnotobiotic rats. J Nutr. 2012 Jan;142(1):40-6.
Bicíková V, Sosvorová L, Bradác O, Pán M, Bicíková M. Phytoestrogenes in menopause: working mechanisms and clinical results in 28 patients. Ceska Gynekol. 2012 Feb;77(1):10-4.
Benvenuti C, Setnikar I. Effect of Lactobacillus sporogenes on oral isoflavones bioavailability: single dose pharmacokinetic study in menopausal women. Arzneimittelforschung. 2011;61(11):605-9.
Tamura M, Hori S, Nakagawa H. Lactobacillus rhamnosus JCM 2771: impact on metabolism of isoflavonoids in the fecal flora from a male equol producer. Curr Microbiol. 2011 May;62(5):1632-7.
Nettleton JA, Greany KA, Thomas W, Wangen KE, Adlercreutz H, Kurzer MS. Plasma phytoestrogens are not altered by probiotic consumption in postmenopausal women with and without a history of breast cancer. J Nutr. 2004 Aug;134(8):1998-2003.
Jou HJ, Wu SC, Chang FW, Ling PY, Chu KS, Wu WH. Effect of intestinal production of equol on menopausal symptoms in women treated with soy isoflavones. Int J Gynaecol Obstet. 2008 Jul;102(1):44-9.