The June 2016 issue of the Journal of the American Medical Association (JAMA) includes a new meta-analysis of clinical trials on isoflavones and hot flashes.1 The study concluded that both “composite and specific phytoestrogen supplementations” were associated with modest reductions in the frequency of hot flashes and vaginal dryness.
Past analyses in medical journals haven’t been as supportive of this relationship. A meta-analysis published in the same journal in 2006 concluded that results were mixed for soy isoflavones and hot flashes.2 Even a 2015 position paper produced by the North American Menopause Society (NAMS) only hinted that soy isoflavones might alleviate hot flashes (although it came much closer to endorsing equol, a bacterially-derived metabolite of the isoflavone daidzein produced by about 25% of Westerners).3
One reason for the conflicting findings, however, has been a lack of appreciation for the fact that not all isoflavone supplements are biologically equivalent. As a result, the true impact of isoflavones on hot flashes has often been underestimated.
Two primary types of soy isoflavone supplements have been used in hot flash studies. One is derived from whole soybeans and has an isoflavone profile similar to that found in soybeans and soyfoods. In this supplement, genistein, daidzein and glycitein, the three isoflavones in soybeans, represent approximately 50, 40 and 10% of total isoflavone content, respectively. The other type of supplement is made from the hypocotyledon (or germ) portion of the soybean. In these supplements, genistein, daidzein and glycitein account for approximately 10, 40 and 50% of total isoflavone content, respectively.
Obviously, these two types of supplements are different chemical entities and should be treated as such. After all, although beta-carotene and lycopene are both carotenoids, they exert different physiological effects.
That the two isoflavone supplements have different effects was made clear in a 2012 meta-analysis which found that genistein-rich isoflavone supplements reduced hot flash frequency more than twice as much as low-genistein supplements.4 This study was published in the journal of the North American Menopause Society, which makes it all the more surprising that this same organization concluded only that isoflavones “might” have a small impact on hot flashes.
A recent Cochrane review also failed to differentiate between the two major types of soy isoflavone supplements.5 While they concluded that extracts comprised only of genistein could lower hot flash frequency, they didn’t determine whether isoflavone supplements containing all three isoflavones but differing amounts of genistein affected hot flashes differently. As a result, they were unable to conclude that isoflavone supplements have any effect on hot flashes.
There is no question that the new JAMA meta-analysis would have produced even stronger findings had the authors considered the different amounts of genistein in isoflavone supplements.
In conclusion, research on the effects of isoflavone supplements needs to take into account the genistein content of these supplements. When this doesn’t occur, the true effect of isoflavones on hot flashes is likely to be missed.
- Franco OH, Chowdhury R, Troup J, et al. Use of plant-based therapies and menopausal symptoms: A systematic review and meta-analysis. JAMA. 2016;315:2554-63.
- Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA. 2006;295:2057-71.
- Nonhormonal management of menopause-associated vasomotor symptoms: 2015 position statement of The North American Menopause Society. Menopause. 2015;22:1155-72; quiz 73-4.
- Taku K, Melby MK, Kronenberg F, Kurzer MS, Messina M. Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials. Menopause. 2012;19:776-90.
- Lethaby A, Marjoribanks J, Kronenberg F, Roberts H, Eden J, Brown J. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database Syst Rev. 2013;12:CD001395.