Furthermore, isoflavones are able to inhibit aromatase activity, the enzyme that converts androgen to estrogen. Sirotkin A.V., Harrath A.H. Phytoestrogens and their effects. 2023 Scientific American, a Division of Springer Nature America, Inc. Lastly, the association between dietary isoflavone intake and the risk of developing gastric cancer has also been analyzed. "It's not. Yu Y., Jing X., Li H., Zhao X., Wang D. Soy isoflavone consumption and colorectal cancer risk: A systematic review and meta-analysis. ); sue.uhe@ollitrop.yupairam (M.P.P. Thanks for reading Scientific American. Franco et al. You J., Sun Y., Bo Y., Zhu Y., Duan D., Cui H., Lu Q. 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. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. (2016) also studied whether there was an association between different types of interventions and the reduction in hot flushes and night sweats [90]. Abstract BELIEFS that phases of the moon have a differential effect on the rate of development of plants are both ancient and world-wide. Arjmandi B.H., Smith B.J. Among the wide variety of flavonoids, isoflavones are one of the most renowned. However, a limitation in this field is that there is still a great heterogeneity among studies. (2016) included 17 studies (nine case-control studies and eight cohort studies) [80]. 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. Rienks et al. In the systematic review reported by Perna et al. Duffy C., Perez K., Partridge A. Hosoda K., Furuta T., Yokokawa A., Ishii K. Identification and quantification of daidzein-7-glucuronide-4-sulfate, genistein-7-glucuronide-4-sulfate and genistein-4,7-diglucuronide as major metabolites in human plasma after administration of kinako. In the same line, Yu et al. The authors observed that soy isoflavone consumption was inversely associated with cancer deaths. government site. The enzymes responsible for the hydrolysis of isoflavone glycosides are glucosidases, which can be produced by the intestinal mucosa or the microbiota [29]. A significant 19% reduction of the risk was found at high concentrations of daidzein, but not at genistein or equol concentrations. In their systematic revision, which included 1307 menopausal (n = 139) and post-menopausal (n = 1268) women, Perna et al. Ko K.P., Kim C.S., Ahn Y., Park S.J., Kim Y.J., Park J.K., Lim Y.K., Yoo K.Y., Kim S.S. Opposite effect in Asian women, Prospective studies (3) Case-control studies (5), Isoflavone consumption (>45 mg/day among the Asian population, and >1 mg/day among the non-Asian population), Potential reduction risk associated with isoflavone consumption, Prospective cohort study (5) Case-control study (7), Cohort prospective study (2 studies from Japan and 5 studies from Europe), 241 cases and 503 controls (from Japanese studies), and 2828 cases and 5593 controls (from European studies), Circulating isoflavone concentrations (nmol/L): Daidzein (Japanese: 115166; European: 2.843.96), Genistein, daidzein and equol did not affect prostate cancer risk in both Japanese and European men, Case-control study (15) Cohort study (8) Nested case-control study (7), 266,699 (21,612 patients with prostate cancer), Isoflavones were not associated with a reduction of prostate cancer risk, Daidzein, genistein, and equol (dose not defined), 19% reduction in prostate cancer risk was found at high concentrations of daidzein, but not with genistein or equol, Participants: 11,346 cases and 140,177 controls, Daidzein and genistein intakes were associated with a reduction of prostate cancer risk (no effect with equol), 559,486 (among them 16,917 colorectal cancer cases), Foods rich in isoflavones (dose not defined), Soy foods (30 mg/day170 g/day) and isoflavones (0.01460 mg/day). However, the authors pointed out several limitations of this study, such as the important source of heterogeneity in their study. Isoflavone content in soy-derived products is usually lower than in soybeans [17]. Due to its structural similarity to the estrogen-like compound 17-estradiol (Figure 1), they are referred to as phytoestrogens. Phenolic compounds are secondary metabolites, which are produced by plants as a defense mechanism against infection, water stress, cold stress, ultraviolet radiation and high visible light, among others [1,2]. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: A meta-analysis of prospective studies. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women. In this revision, three systematic reviews and five meta-analyses were included to explore the association of isoflavones and markers related to CVDs (Table 3). Although smaller in quantity, isoflavones are also present in chickpeas, nuts, fruits and vegetables [11]. Determination of total soy isoflavones in dietary supplements, supplement ingredients, and soy foods by high-performance liquid chromatography with ultraviolet detection: Collaborative study. 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. The conclusion was that isoflavones exerted little influence over bone mineral density and thus over bone health during menopause, although not all the studies observed the same effect. 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. Taken as a whole, all these results suggest that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Two of the studies also revealed that women who were able to produce equol or who had received equol supplementation could have had a greater benefit from isoflavones [53]. Yan Z., Zhang X., Li C., Jiao S., Dong W. Association between consumption of soy and risk of cardiovascular disease: A meta-analysis of observational studies. These positive effects were associated with 54 mg/day of genistein and 600 mg/day of synthetic isoflavone ipriflavone. 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). This difference could explain the slow effect of isoflavones in alleviating hot flushes. 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. Intestinal transport of quercetin glycosides in rats involves both deglycosylation and interaction with the hexose transport pathway. official website and that any information you provide is encrypted 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]. Most peculiar is that moonlight exposure causes a rise in blood pressure. Therefore, the authors concluded that the intake of dietary isoflavones paid a protective role against ovarian cancer. However, all the authors agree that further studies are necessary so as to confirm these results. (2018), 30 articles were included for analysis; 15 of them were case-control studies, eight cohort studies and seven nested case-control studies [76]. This result has implications for granivory and perhaps plant demography in invaded and restored coastal habitats. However, when a subgroup analysis by a class of flavonoids was carried out, they concluded that these inverse associations were significant for all categories of flavonoids except for isoflavones and flavonols. Isoflavones (high dose: 0.675.5 mg/day; and low dose: 0.0120.1 mg/day). Accessibility However, it is important to point out that the beneficial effects of soy isoflavone consumption have been exhibited by women with estrogen receptor-negative breast cancer, but not by women with receptor-positive breast cancer, who present a better prognosis [62]. Study duration ranged from four weeks to two years, with a median of 12 weeks. The difference for isoflavones required to find an effect can be due to variations in the amount of isoflavone intake between both populations. Circulating isoflavone and lignan concentrations and prostate cancer risk: A meta-analysis of individual participant data from seven prospective studies including 2,828 cases and 5,593 controls. Simental-Menda L.E., Gotto A.M., Atkin S.L., Banach M., Pirro M., Sahebkar A. Plants grow best when the moon is in the waxing phase, when its gravitational pull is strongest. 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. Abshirini M., Omidian M., Kord-Varkaneh H. Effect of soy protein containing isoflavones on endothelial and vascular function in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials. In: Thompson M.J., editor. In this sense, it has been described that both isoflavones and other estrogenic molecules could mediate their beneficial effects due to two different mechanisms: the classical estrogen receptor (ER)-mediated signaling pathway and the activation of intracellular pathways such as protein tyrosine kinase, phospholipase C and mitogen-activated protein kinase (MAPK) [5,6]. Chemical structure of 17-estradiol. In a more recent systematic review, including two meta-analyses, as well as one multicenter and randomized controlled trial, Chen and his team concluded that isoflavones reduced lumbar spine bone mineral density loss [53]. This is mainly due to their potential adverse effects, which range from increased coronary heart disease to stroke and cancer [53,85]. That aluminum may be harmful to plants as well as animals. Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin. 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]. It has been described that after the oral intake of isoflavones, their peak plasma concentration in humans occurs at around seven hours [33]. A systematic review and meta-analysis of the effects of isoflavone formulations against estrogen-deficient bone resorption in peri- and postmenopausal women. EFSA Pannel on Food Additives and Nutrient Sources Added to Food (ANS) Risk assessment for peri- and post-menopausal women taking food su pplements containing isola ted isoflavones. In fact, in 2015, in relation to the possible adverse effects on the mammary gland, uterus and thyroid, the European Food Safety Agency (EFSA) offered a scientific opinion with regards to the assessment of potential increased risk in peri- and postmenopausal women who took food supplements that contained isolated isoflavones. Gee J.M., DuPont M.S., Day A.J., Plumb G.W., Williamson G., Johnson I.T. Rienks J., Barbaresko J., Nthlings U. In general, evidence regarding the use of isoflavones on vasomotor symptoms suggests that they could be useful in reducing hot flushes. Effect of soy isoflavone supplementation on plasma lipoprotein(a) concentrations: A meta-analysis. 8600 Rockville Pike An official website of the United States government. 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. Neuroprotective effects of 17beta-estradiol and nonfeminizing estrogens against H. Endoh H., Sasaki H., Maruyama K., Takeyama K., Waga I., Shimizu T., Kato S., Kawashima H. Rapid activation of MAP kinase by estrogen in the bone cell line. In contrast, it seems that isoflavones do not act on central neurotransmitters directly. Discover world-changing science. 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]. aimed to compare the effects of animal and plant-sourced proteins on lipemia and blood pressure [60]. Abdi F., Alimoradi Z., Haqi P., Mahdizad F. Effects of phytoestrogens on bone mineral density during the menopause transition: A systematic review of randomized, controlled trials. Before The authors suggested that further studies grouping subjects by isoflavone intake or by the circulating isoflavone levels might enhance this association. Karr S.C., Lampe J.W., Hutchins A.M., Slavin J.L. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (, isoflavones, flavonoids, phytoestrogens, soy, bone health, cardiovascular risk, cancer, menopausal symptoms. Presence of four chemical forms of the three isoflavones found in soybeans. Indeed, Kim and Je (2017) indicated that a high intake of flavonoids is associated with a reduced risk of mortality from cardiovascular diseases in men and women [56]. Grosso G., Godos J., Lamuela-Raventos R., Ray S., Micek A., Pajak A., Sciacca S., DOrazio N., Del Rio D., Galvano F. A comprehensive meta-analysis on dietary flavonoid and lignan intake and cancer risk: Level of evidence and limitations. Moonlight sonata. Looking at a few examples of moonlight's. During menopause, there is a loss of bone density that can cause osteoporosis. However, some limitations were found in these prospective studies, such as the small sample size of the cohorts and the unspecific definition of high, moderate and low isoflavone intake. Diversely, Liu et al. Kelly G.E., Nelson C., Waring M.A., Joannou G.E., Reeder A.Y. In fact, all the body fluids, as the tides, were controlled by the lunar phases. Qiu S., Jiang C. Soy and isoflavones consumption and breast cancer survival and recurrence: A systematic review and meta-analysis. Franco O.H., Chowdhury R., Troup J., Voortman T., Kunutsor S., Kavousi M., Oliver-Williams C., Muka T. Use of Plant-Based Therapies and Menopausal Symptoms: A Systematic Review and Meta-analysis. Heterogeneity among studies furthermore, isoflavones are one of the effects of isoflavone intake between both populations distinct from of. 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