Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering from some types of cancer, such as breast and endometrial cancer, although further studies are needed to confirm these results. Regarding breast cancer (Table 4), the same increase in soy isoflavone intake (10 mg/day) was related to a 9% lower risk of breast cancer mortality. Tamura A., Shiomi T., Hachiya S., Shigematsu N., Hara H. Low activities of intestinal lactase suppress the early phase absorption of soy isoflavones in Japanese adults. The results indicated that the isoflavone intake decreased the ovarian cancer risk by 33%. He X., Sun L.M. and J.T. Schmidt M., Arjomand-Wlkart K., Birkhuser M.H., Genazzani A.R., Gruber D.M., Huber J., Klbl H., Kreft S., Leodolter S., Linsberger D., et al. The two systematic reviews conclude that isoflavones have an important role in reducing hot flushes [52,53], although some observations need to be pointed out. Soy isoflavones osteoprotective role in postmenopausal women: Mechanism of action. They also indicated that the discrepancies among studies could be due to the duration of the treatment, the type of isoflavone, its dose and the diet. Isoflavone content in soy-derived products is usually lower than in soybeans [17]. As it has been stated in the Bioavailability section, microbiota composition in humans makes equol production very variable, which yields high interindividual differences. Sirotkin A.V., Harrath A.H. Phytoestrogens and their effects. Yu Y., Jing X., Li H., Zhao X., Wang D. Soy isoflavone consumption and colorectal cancer risk: A systematic review and meta-analysis. Metabolites of dietary (soya) isoflavones in human urine. Anywise, it has been observed that both isoflavones are demethylated by microbiota, formononetin to daidzein and biochanin A to genistein. Non-pharmacological treatments included isoflavones, which appeared to be better than placebo in the relief of vasomotor symptoms, although not significantly better than the treatment with estradiol and progesterone. Influence of cellular ERalpha/ERbeta ratio on the ERalpha-agonist induced proliferation of human T47D breast cancer cells. Indeed, some authors speculate that hepatic and lipoprotein lipase activity may have been altered after variable isoflavone intake from soybean, although no experimental data were provided [67]. Moreover, a higher intake of soy isoflavones was associated with a lower risk of mortality from gastric, colorectal, and lung cancers. Phenolic compounds, characterized by the presence of a hydroxyl group attached to at least one aromatic ring, can be classified as flavonoids and non-flavonoids. For this reason, the results should be interpreted with caution, and more randomized clinical trials are imperative. Possible mechanism of action of isoflavones for menopausal symptoms. Treutter D. Significance of flavonoids in plant resistance and enhancement of their biosynthesis. Global climate change is not a future problem. (2016), nine studies addressed to menopausal women and focused on bone health were analyzed [52]. In this sense, the authors suggested that the composition of the gut microflora may influence isoflavone absorption and metabolism and could affect the production of isoflavone metabolites, which, in turn, could mediate their biological activity. Metabolism of intraruminally administered [4-. (2016) published a meta-analysis of 13 case-control and four prospective cohort studies, where the results revealed that soy isoflavone consumption reduced the risk of developing colorectal cancer by 23% [79]. Phytoestrogen Metabolism by Adult Human Gut Microbiota. Zhao T.T., Jin F., Li J.G., Xu Y.Y., Dong H.T., Liu Q., Xing P., Zhu G.L., Xu H., Miao Z.F. Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. The enhanced bone formation is due to the stimulation of osteoblastic activity mainly through (a) the activation of estrogen receptors because they bind to nuclear estrogen receptors and exhibit estrogenic activity due to its similarity to 17-estradiol, and (b) the promotion of insulin-like growth factor-I (IGF-I) production [54,55] (Figure 4). With regard to prostate cancer, it has been proposed that it might be affected by isoflavone consumption due to its effect on hormone metabolism. The Sun ruled our heart, blood circulation and spine, while the Moon had influence on growth, fertility, breasts, stomach, uterus and menstrual flow. In some cases the purported effect may depend on external cues, such as the amount of moonlight. Careers, Unable to load your collection due to an error. Considering the isoflavone chemical structure, potential health adverse effects of these compounds related to their estrogenic activity have been postulated, despite the scientific opinion offered by EFSA indicating that isoflavone intake was safe. Due to the high prevalence of colorectal cancer, three meta-analyses addressing this issue are included in the present review. Santo A.S., Santo A.M., Browne R.W., Burton H., Leddy J.J., Horvath S.M., Horvath P.J. Grosso et al. The results showed no significant association between isoflavone consumption and gastric cancer risk, with the highest (0.675.5 mg/day) versus the lowest (0.0120.1 mg/day) categories of dietary isoflavone intake. Plasma isoflavone concentration is associated with decreased risk of type 2 diabetes in Korean women but not men: Results from the Korean Genome and Epidemiology Study. In miso and tempeh, the aglycone form is the most abundant one [9]. Among these, vasomotor symptoms comprising hot flushes and night sweats are the most common and bothersome, which, in turn, have a negative impact on womens quality of life. The enzymes responsible for the hydrolysis of isoflavone glycosides are glucosidases, which can be produced by the intestinal mucosa or the microbiota [29]. Gruber C.J., Tschugguel W., Schneeberger C., Huber J.C. Production and actions of estrogens. (2016) analyzed the effect of oral isoflavone supplementation on endometrial thickness in pre- and post-menopausal women, which is a biomarker for the proliferative effects of estrogens associated with an increased endometrial risk [72]. In general terms, it has been observed that in Asian countries where there is high consumption of soy and its derived foodstuffs, isoflavone intake is high, ranging from 15 to 60 mg/day [20,21], whereas, in western countries, it is notably lower, around 12 mg/day [22,23,24]. When a group receiving hormone replacement therapy was included in the study, significant differences between the effects of hormone replacement therapy and soy were found, being the effect of the former superior to that of isoflavones. The light of the moon also influences animals that are active in daytime. As in the case of other phenolic compounds, genistein and daidzein undergo phase II xenobiotic metabolism, mainly glucuronidation and sulfation reactions at 4and/or 7 positions of the isoflavone ring [34,35]. The light reflected off the moon has an effect on life on Earth, which isn't surprising, but not every lunar influence is heralded by a wolf's howl. In this sense, soy isoflavones have been proposed as beneficial because, in theory, they may contribute to the maintenance of good bone health (mass, mineral density and bone structure) in women who are at this stage in their life. Collison M.W. Others, however, consider such notions as prime examples of "New Age freakery". Moreover, even though the binding affinity of isoflavones to the ER receptors is less than that of 17-estradiol, they can also act as estrogenic compounds when the endogenous estradiol is not available [8]. This fact does not seem to be influenced by genetics since migrating from eastern to western countries appears to cause the loss of this protective effect. (2018) published a meta-analysis of seven prospective cohort studies (two studies from Japan with 241 cases and 503 controls, and five studies from Europe with 2828 cases and 5593 controls) [75]. They performed a separated meta-analysis for each of the interventions, including dietary soy isoflavones (including four studies), supplements and extracts of soy isoflavones (including six studies) and red clover isoflavones (including seven studies). Sarri G., Pedder H., Dias S., Guo Y., Lumsden M.A. Furthermore, among the four studies of breast cancer recurrence, three studies found that isoflavone intake decreased the risk of breast cancer recurrence, although further studies are required to confirm this finding [82]. Moreover, five studies reported side-effect data, and after the analysis, no significant differences were observed between the two groups. Hua X., Yu L., You R., Yang Y., Liao J., Chen D. Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis. This is mainly due to their potential adverse effects, which range from increased coronary heart disease to stroke and cancer [53,85]. Moreover, this association was more prominent among postmenopausal women than premenopausal women. Karr S.C., Lampe J.W., Hutchins A.M., Slavin J.L. Chen M.N., Lin C.C., Liu C.F. Kelly G.E., Nelson C., Waring M.A., Joannou G.E., Reeder A.Y. Sfakianos J., Coward L., Kirk M., Barnes S. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. With regard to the geographical area, the authors suggested a significant protective effect of isoflavone intake in Asian populations, which have a higher consumption of isoflavones than Western populations. An official website of the United States government. Although the mechanisms of action of isoflavones are not completely understood, it seems that isoflavones not only reduce the rate of bone resorption but also increase the rate of bone formation. Effect of soy isoflavone supplementation on plasma lipoprotein(a) concentrations: A meta-analysis. Sulfation of the isoflavones genistein and daidzein in human and rat liver and gastrointestinal tract. This meta-analysis included 266,699 participants (21,612 patients with prostate cancer among them). Messina M.J. Legumes and soybeans: Overview of their nutritional profiles and health effects. FOIA In addition, several studies have observed that the urine excretion of daidzein metabolites is notably higher than that of genistein metabolites [44,45,46]. After an extensive bibliographical review, the expert panel concluded that the results of observational studies do not support the hypothesis of an increased risk of breast cancer after isoflavone-rich food supplement intake [93]. Reduction of the endometrial thickness in North American women (for 0.23 mm). It is also important to mention that isoflavones could act as potential anticancer compounds due to their antioxidant role in malignant cell proliferation and differentiation (Figure 5). In this line, another meta-analysis, which included 52 controlled trials and 5313 patients, shows that soy isoflavones have beneficial effects on bone mineral density in the femur neck, lumbar spine, and hip, regardless of body weight or ethnicity [49]. Zhong et al. In some Asian countries, isoflavone intake, usually derived from soy consumption, can be associated with a lower prevalence of cardiovascular diseases (CVDs). Sotoca A.M., van den Berg H., Vervoort J., van der Saag P., Strm A., Gustafsson J.A., Rietjens I., Murk A.J. Regarding endometrial cancer, three prospective and five case-control studies were analyzed, which suggested a lower endometrial cancer risk associated with isoflavone consumption. The main isoflavones found in foodstuffs are daidzein, genistein and glycitein, as well as biochanin A and formononetin [9,12]. Urinary isoflavonoid excretion in humans is dose dependent at low to moderate levels of soy-protein consumption. In a study conducted by Karr et al., the authors analyzed the urinary excretion of genistein, daidzein, equol and O-DMA in fourteen young men and women [47]. Mace T.A., Ware M.B., King S.A., Loftus S., Farren M.R., McMichael E., Scoville S., Geraghty C., Young G., Carson W.E., et al. Plants grow best when the moon is in the waxing phase, when its gravitational pull is strongest. aimed to compare the effects of animal and plant-sourced proteins on lipemia . Similarly, Li et al. However, a limitation in this field is that there is still a great heterogeneity among studies. Thirty-seven articles presenting evidence of the physiological effects of viewing nature were selected. It supports the evidence that isoflavones can moderately attenuate bone resorption in women with low estrogen levels, primarily at the level of the lumbar spine and the femoral neck. They found that the use of dietary isoflavones or supplements and extracts was associated with an improvement in hot flushes, but not with a reduction in the frequency of night sweats. Their meta-analysis included five studies with a total of 728 menopausal women between 50.5 and 58.5 years old and concluded that women who are not able to produce equol could benefit from equol supplementation. In the same line, Yu et al. Bardin A., Boulle N., Lazennec G., Vignon F., Pujol P. Loss of ERbeta expression as a common step in estrogen-dependent tumor progression. The aglycone and conjugate forms of genistein represent up to 60% of total isoflavones, this being up to 30% in the case of daidzein. In addition, genistein and glycitein are transformed into dihydrogenistein and dihydroglycitein, respectively, before being further converted into other metabolites. Thanks for reading Scientific American. This fact was not taken into account in previous meta-analyses, and thus it may justify the discrepancies amongst them. Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin. This fact suggests that other components, such as fiber in the soy foods, may account for these negative associations. The most significant food source of isoflavones in humans is soy-derived products. The effect of the moon on planting times is stated as a matter of fact in such popular publications as The Old Farmer's Almanac and books such as Gardening and Planting by the Moon 2018, and, of course, calendars such as The Biodynamic Sowing and Planting Calendar 2018. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. You J., Sun Y., Bo Y., Zhu Y., Duan D., Cui H., Lu Q. Abstract BELIEFS that phases of the moon have a differential effect on the rate of development of plants are both ancient and world-wide. They also note that the effects of isoflavones are greater when administered as aglycones. Prez-Cornago et al. In this line, three meta-analyses were conducted to study isoflavone consumption and endometrial cancer risk. sharing sensitive information, make sure youre on a federal The authors suggested that further studies grouping subjects by isoflavone intake or by the circulating isoflavone levels might enhance this association. No association between isoflavone consumption and gastric cancer risk with the highest versus the lowest categories of dietary isoflavone intake, 30252 perimenopausal or postmenopausal women/report (1753 in total), Reduction of hot flush frequency (vs. placebo), Slight and slow attenuation of hot flushes (vs. estradiol), Slight and slow attenuation of hot flushes (vs. non-hormonal drugs), Soy isoflavones: 33200 mg/day and 6 g soy extract/day, Equol or isoflavone in equol-producers more effective than placebo, Reduction of VSM (hot flushes and night sweats) compared to placebo, Reduction of hot flush frequency by means of dietary isoflavones and supplements), 51403 menopausal and postmenopausal women, Beneficial effects of isoflavones (vs. placebo), 40403 menopausal and postmenopausal women. (2019) studied whether equol supplementation could benefit equol nonproducer subjects in lowering the incidence and severity of hot flushes [85]. The site is secure. Estimated Asian adult soy protein and isoflavone intakes. As with other phenolic compounds, isoflavones can be presented as free forms (aglycones) or conjugated with carbohydrates (glycosides). In this regard, it has been reported that isoflavones have a higher affinity to the -estrogen receptor [7], which, contrary to the -estrogen receptor, inhibits cell proliferation and stimulates apoptosis [84]. According to the results gathered in the present review, it can be stated that there is scientific evidence showing the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis on postmenopausal women, although the results do not seem entirely conclusive as there are discrepancies among the studies, probably related to their experimental designs. Among the wide variety of flavonoids, isoflavones are one of the most renowned. These two associations were significant for postmenopausal participants. Modified from Mace et al. However, the authors stated that they could not reach definitive conclusions due to, among other reasons, the lack of inclusion in the review of randomized controlled clinical trials focused on the treatment of osteoporosis in early menopause. Hormone replacement therapy has been proven to be effective in reducing vasomotor symptoms, although isoflavones have gained popularity as an alternative treatment to hormone replacement therapy to relieve menopausal symptoms. Thus, the EFSA scientific committees opinion agreed that isoflavone intake was safe, at least in the doses that the analyzed studies have used. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Li L., Xu L., Wu J., Dong L., Zhao S., Zheng Q. Kim Y., Je Y. Flavonoid intake and mortality from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies. 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