In the meta-analysis reported by Applegate et al. In some Asian countries, isoflavone intake, usually derived from soy consumption, can be associated with a lower prevalence of cardiovascular diseases (CVDs). official website and that any information you provide is encrypted Dietary isoflavones or isoflavone-rich food intake and breast cancer risk: A meta-analysis of prospective cohort studies. Duffy C., Perez K., Partridge A. That aluminum may be harmful to plants as well as animals. Regarding the mechanisms by which isoflavones act to alleviate vasomotor symptoms, is has been proposed that they bind to estrogen receptors and activate endothelial nitric oxide synthase (eNOS) transcription, leading to eNOS synthesis and nitric oxide production, the main mediator of vasodilatation, which allows cutaneous heat dissipation [91] (Figure 6). Sex and long-term soy diets affect the metabolism and excretion of soy isoflavones in humans. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Hua et al. An official website of the United States government. Since hepatic lipase and lipoprotein lipase hydrolyze triglycerides into their constituents glycerol and fatty acids, their activation results in the delivery of the fatty acids to tissues such as muscle and adipose tissue. The authors found a significant inverse association between isoflavone intake and both overall mortality and breast cancer recurrence. In the same line, in European men, isoflavone concentrations did not affect the risk of developing prostate cancer. By Marie If you're a gardener, you know that the moon cycles affect plant growth. Reproductive and developmental toxicity studies have stated that 1 g and 2 g of equol per day is safe [96], although further studies are required [92]. Gut bacterial metabolism of the soy isoflavone daidzein: Exploring the relevance to human health. Interestingly, soy protein isolate (void of isoflavones through alcoholic extraction during the protein solation phase) did not show these effects. Oral isoflavone supplementation on endometrial thickness: A meta-analysis of randomized placebo-controlled trials. However, more studies are required to provide stronger evidence. Comparative efficacy of nonhormonal drugs on menopausal hot flashes. Despite the positive effect of isoflavones, the authors emphasized that the effects took a long time to appear. 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. (2017) conducted a meta-analysis with ten observational studies to assess the association between the isoflavone compounds daidzein, genistein and equol, and breast cancer [61]. Zamora-Ros R., Knaze V., Rothwell J.A., Hmon B., Moskal A., Overvad K., Tjnneland A., Kyr C., Fagherazzi G., Boutron-Ruault M.C., et al. Metabolism of intraruminally administered [4-. In addition, several studies have observed that the urine excretion of daidzein metabolites is notably higher than that of genistein metabolites [44,45,46]. In their systematic revision, which included 1307 menopausal (n = 139) and post-menopausal (n = 1268) women, Perna et al. 8600 Rockville Pike Metabolites of dietary (soya) isoflavones in human urine. THE effect of light on plant life has been the subject of many scientific investigations. At high elevations, acidic fog and clouds might . In the systematic review reported by Perna et al. Moreover, the authors suggested that ethnicity could have had influenced this association, but studies with larger sample sizes are needed to confirm this hypothesis. Nevertheless, this association was not shown when equol or isoflavones were consumed. Murota K., Nakamura Y., Uehara M. Flavonoid metabolism: The interaction of metabolites and gut microbiota. He X., Sun L.M. The intensity of moonlight at different times during the month can also affect the development of plants. However, the authors acknowledged several limitations to their study, such as the small sample size in the meta-analysis (middle-aged 276 women and 209 men), and recognized that a large number of subjects as well as a lengthier intervention are needed to investigate whether supplementation of soy isoflavones actually improves these outcomes. 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. As it has been stated in the Bioavailability section, microbiota composition in humans makes equol production very variable, which yields high interindividual differences. With regard to the published meta-analysis, the studies included were restricted to randomized controlled trials. Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering some types of cancer, such as breast and endometrial cancer, but further studies are needed to confirm these results. Zhang Q., Feng H., Qluwakemi B., Wang J., Yao S., Cheng G., Xu H., Qiu H., Zhu L., Yuan M. Phytoestrogens and risk of prostate cancer: An updated meta-analysis of epidemiologic studies. In the aforementioned mechanism, it has been reported that isoflavones bind to both ER and ER, although they present a higher affinity towards ER receptors [7]. Indeed, they reported that an increase of 10 mg/day of soy isoflavones consumption was associated with a 7% lower risk of cancer mortality [62]. Nevertheless, it is important to consider this metabolite since it is key in the biological activity of isoflavones [13]. 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]. 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 authors declare no conflict of interest. Jun S., Shin S., Joung H. Estimation of dietary flavonoid intake and major food sources of Korean adults. Arjmandi B.H., Smith B.J. Akhlaghi M., Ghasemi Nasab M., Riasatian M., Sadeghi F. Soy isoflavones prevent bone resorption and loss, a systematic review and meta-analysis of randomized controlled trials. 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. Daily J.W., Ko B.S., Ryuk J., Liu M., Zhang W., Park S. Equol Decreases Hot Flashes in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. The majority of the studies that used display stimuli, such as photos, 3D images, virtual reality, and videos of natural landscapes, confirmed that viewing natural scenery led to more relaxed body responses than viewing the control. This fact suggests that other components, such as fiber in the soy foods, may account for these negative associations. (2016), nine studies addressed to menopausal women and focused on bone health were analyzed [52]. Qiu S., Jiang C. Soy and isoflavones consumption and breast cancer survival and recurrence: A systematic review and meta-analysis. 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. Ronis M.J., Little J.M., Barone G.W., Chen G., Radominska-Pandya A., Badger T.M. Nachvak S.M., Moradi S., Anjom-Shoae J., Rahmani J., Nasiri M., Maleki V., Sadeghi O. Soy, Soy Isoflavones, and Protein Intake in Relation to Mortality from All Causes, Cancers, and Cardiovascular Diseases: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies. This article was originally published with the title "The Effects of Moonlight" in Scientific American 13, 37, 289 (May 1858), doi:10.1038/scientificamerican05221858-289, Daryl G. Kimball and Frank von Hippel | Opinion. DOI: 10.1093/OXFORDJOURNALS.AOB.A087491 Corpus ID: 89019113; Effects of Moonlight on Flower Induction in Pharbitis nil, Using a Single Dark Period @article{KadmanZahavi1987EffectsOM, title={Effects of Moonlight on Flower Induction in Pharbitis nil, Using a Single Dark Period}, author={Avishag Kadman-Zahavi and Dovrat Peiper}, journal={Annals of Botany}, year={1987}, volume={60}, pages={621-623} } Thus, the EFSA scientific committees opinion agreed that isoflavone intake was safe, at least in the doses that the analyzed studies have used. However, all the authors agree that further studies are necessary so as to confirm these results. Lastly, the association between dietary isoflavone intake and the risk of developing gastric cancer has also been analyzed. Yu Y., Jing X., Li H., Zhao X., Wang D. Soy isoflavone consumption and colorectal cancer risk: A systematic review and meta-analysis. This difference could explain the slow effect of isoflavones in alleviating hot flushes. Thanks for reading Scientific American. The authors suggested that further studies grouping subjects by isoflavone intake or by the circulating isoflavone levels might enhance this association. Perez-Cornago A., Appleby P.N., Boeing H., Gil L., Kyr C., Ricceri F., Murphy N., Trichopoulou A., Tsilidis K.K., Khaw K.T., et al. Zhong X.S., Ge J., Chen S.W., Xiong Y.Q., Ma S.J., Chen Q. ; Project Administration, M.P.P. Barnes S. The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products. (2017) included 26 trials with 2652 participants [48]. They also note that the effects of isoflavones are greater when administered as aglycones. This fact was not taken into account in previous meta-analyses, and thus it may justify the discrepancies amongst them. Potential health adverse effects in the intake of isoflavones have been postulated due to their estrogenic activity, especially in relation to breast cancer. With regard to isoflavone content in foodstuffs, it has been observed that in soybeans, the amount of these phenolic compounds ranges from 1.2 to 4.2 mg per g on dry weight, whereas in red clover, the amount varies between 10 and 25 mg per g on dry weight [15,16]. 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. Contrary to other types of renewable energies, such as wind and hydroelectricity, evidence on the effects of PV panels on biodiversity has been building up only fairly recently. Bethesda, MD 20894, Web Policies They observed that it was dose-dependent at low to moderate soybean consumption. Estradiol, which has proven efficacy on hot flushes, needs 3.09 weeks to achieve half of its peak activity, while isoflavones require 13.4 weeks, suggesting that 12 weeks of treatment is not enough for soy isoflavones to exert a beneficial effect. Soy products (0.05130 g/day) and total isoflavones (0.28 to 63 mg/day). Analysis of isoflavones in Foods. He Bays that his thermometrical instruments were sensibly affected by the moon's rays, even at the lowest of two stations occupied by him at different elevations. (2018) analyzed 12 studies with 37,275 women with breast cancer and reported that soy isoflavone consumption at a pre-diagnosis stage might have a small effect on the survival of postmenopausal women with breast cancer [69]. Explore our digital archive back to 1845, including articles by more than 150 Nobel Prize winners. Interestingly, in a study conducted by Tamura et al., the authors observed that in individuals without the LPH enzyme, the concentration of isoflavones and derived metabolites was similar to that found in individuals without an enzyme deficiency. Treutter D. Significance of flavonoids in plant resistance and enhancement of their biosynthesis. In general, evidence regarding the use of isoflavones on vasomotor symptoms suggests that they could be useful in reducing hot flushes. Urinary isoflavonoid excretion in humans is dose dependent at low to moderate levels of soy-protein consumption. However, in the meta-analysis, a minor enhancement in flow-mediated dilation after soy protein supplementation was found. 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. Before Furthermore, soy protein has been linked to an improvement in nitric oxide production and contributes to increased arterial compliance [65]. Beneficial role of dietary phytoestrogens in obesity and diabetes. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. By contrast, the total isoflavone amount is high in soy flour, protein isolate or edamame [19]. Sansai et al. Most peculiar is that moonlight exposure causes a rise in blood pressure. Modified from Wang et al., 2006 [4]. (At least not real scientists.) Possible mechanism of action of isoflavones for cancer prevention. Similarly, Li et al. Background Climate change and the current phase-out of fossil fuel-fired power generation are currently expanding the market of renewable energy and more especially photovoltaic (PV) panels. Focusing on the overall intake of isoflavones in humans, several studies have reported varied results. Rienks J., Barbaresko J., Nthlings U. 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. Further, Chalvon-Demersay et al. (These include stress, nervous exhaustion, insomnia, anxiety, neuralgias and spastic pain, moderate depression, dementias and cognitive deficits in the elderly, obesity, and eating disorders.) Isoflavones have received attention due to their putative healthy properties. Santo A.S., Santo A.M., Browne R.W., Burton H., Leddy J.J., Horvath S.M., Horvath P.J. Hence, plants grow faster and healthier. The authors studied all possible correlations between isoflavone consumption and the risk of breast cancer. Atkinson C., Frankenfeld C.L., Lampe J.W. After this, each metabolite undergoes its own metabolic pathway [40]. Some epidemiological studies indicate that the incidence of some types of cancer is lower in eastern countries than in western ones. As in the previous study, the onset of soy isoflavones was very slow in comparison with other non-hormonal treatments. Another meta-analysis explored the effects of several pharmacological and non-pharmacological treatments in the relief of vasomotor symptoms, taking into account not only hot flushes but also night sweats [89]. Lu D., Gigure V. Requirement of Ras-dependent pathways for activation of the transforming growth factor beta3 promoter by estradiol. Isoflavones Biosynthesis, Occurence and Health Effects. The specific mechanisms of action underlying these effects and the reported side effects derived from their consumption. Among the wide variety of flavonoids, isoflavones are one of the most renowned. The authors reported that neither soy food intake nor circulating isoflavones were associated with a reduced risk of prostate cancer. and J.T. Watanabe S., Yamaguchi M., Sobue T., Takahashi T., Miura T., Arai Y., Mazur W., Whl K., Adlercreutz H. Pharmacokinetics of soybean isoflavones in plasma, urine and feces of men after ingestion of 60 g baked soybean powder (kinako). That's what behavioral ecologist Jenny York learned while studying white-browed sparrow weavers . 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. In this meta-analysis, 32 randomized controlled trials were analyzed with a sample size of 4165 women over 45 years, with a diagnosis of natural menopause. You et al. 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]. Moreover, a higher intake of soy isoflavones was associated with a lower risk of mortality from gastric, colorectal, and lung cancers. 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. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. (2017) also analyzed eight studies of prostate cancer, and they found an association between isoflavone intake and prostate cancer risk [61]. In general terms, caution should be exercised with the use of high doses of isoflavones in women with a family history of breast cancer [49]. Although results vary greatly, most of these applications are supported by at least a few clinical studies. For this reason, the bioavailability of isoflavones has been extensively characterized in animal models and humans [25,26,27]. Phytoestrogen Metabolism by Adult Human Gut Microbiota. The authors observed that soy isoflavone consumption was inversely associated with cancer deaths. Isoflavone Supplements for Menopausal Women: A Systematic Review. Careers, Unable to load your collection due to an error. Day A.J., Caada F.J., Daz J.C., Kroon P.A., Mclauchlan R., Faulds C.B., Plumb G.W., Morgan M.R., Williamson G. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. Isoflavones were the phytoestrogens used in most of the studies; therefore, the meta-analysis only included outcomes regarding isoflavones, while outcomes with other phytoestrogens were not included. Concerning this issue, six meta-analyses and two systematic reviews are included in the present review (Table 5). Determination of total soy isoflavones in dietary supplements, supplement ingredients, and soy foods by high-performance liquid chromatography with ultraviolet detection: Collaborative study. Dietary intake of flavonoid subclasses and risk of colorectal cancer: Evidence from population studies. 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. It is important to point out that the spine has a high proportion of trabecular bone and that this is probably the reason why the spine is thought to be more sensitive to isoflavones. In addition, Qiu et al. The lunar effect is a purported unproven correlation between specific stages of the roughly 29.5-day lunar cycle and behavior and physiological changes in living beings on Earth, including humans. (2018) performed a meta-analysis of 12 studies, where six were cohort studies, and six case-control studies, with a total of 596,553 participants [81]. Chalvon-Demersay T., Azzout-Marniche D., Arfsten J., Egli L., Gaudichon C., Karagounis L.G., Tom D. A Systematic Review of the Effects of Plant Compared with Animal Protein Sources on Features of Metabolic Syndrome. Bustamante-Rangel M., Delgado-Zamarreo M.M., Perez-Martin L., Rodriguez-Gonzalo E., Dominguez-Alvarez J. 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. Chen L.R., Ko N.Y., Chen K.H. In this sense, Micek et al. (2019), included 16 prospective cohort studies involving 11,169 breast cancer cases and 648,913 participants [70]. Man B., Cui C., Zhang X., Sugiyama D., Barinas-Mitchell E., Sekikawa A. Chen M.N., Lin C.C., Liu C.F. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. 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]. Importantly, the soy variety, environmental conditions of the culture and the processing of soybeans notably influence their isoflavone content [18]. Li L., Lv Y., Xu L., Zheng Q. Quantitative efficacy of soy isoflavones on menopausal hot flashes. Thus, soybean can be considered as the best food source. These two associations were significant for postmenopausal participants. Lastly, Zhang et al. For this purpose, 23 studies with 2167 patients were included in this meta-analysis, which showed that a daily dose of more than 54 mg could decrease the endometrial thickness in North American women, whereas the contrary effect was observed in the Asian sample. In fact, all the body fluids, as the tides, were controlled by the lunar phases. Looking at a few examples of moonlight's. Vlachopoulos C., Aznaouridis K., Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: A systematic review and meta-analysis. However, the magnitude of risk reduction in Asian women was slightly larger than in non-Asian women (22% vs. 18%). However, the results do not seem entirely conclusive, for there are discrepancies among the studies, probably related to their experimental designs. Isoflavones are found in several vegetables, mainly in legumes (Fabaceae family) such as soy, white and red clover, alfalfa and beans [9,10]. However, it is important to mention that this connection has been established based on pre-clinical studies, whereas data derived from clinical trials have not demonstrated such association [92]. Abdi et al. The mean age of women ranged from 49 to 58.3 and 48 to 60.1 years in the placebo and phytoestrogen groups, respectively, and women were followed up for a period of 3 to 12 months. Ten studies reported a significant reduction in hot flush frequency in the phytoestrogen group when compared with the placebo group. sharing sensitive information, make sure youre on a federal Influence of cellular ERalpha/ERbeta ratio on the ERalpha-agonist induced proliferation of human T47D breast cancer cells. However, the intake of specific isoflavones, genistein and daidzein, was indeed significantly associated with a reduced risk of this type of cancer. Association of isoflavone biomarkers with risk of chronic disease and mortality: A systematic review and meta-analysis of observational studies. Even though red clover has a greater amount of isoflavones, it is not an edible plant, and it is consumed as a food complement. Kelly G.E., Nelson C., Waring M.A., Joannou G.E., Reeder A.Y. Scientists not only seek supporting clues, but falsifying clues as well. 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]. The enzymes responsible for the hydrolysis of isoflavone glycosides are glucosidases, which can be produced by the intestinal mucosa or the microbiota [29]. Therefore, the authors concluded that the intake of dietary isoflavones paid a protective role against ovarian cancer. The latter is the most common form in foodstuffs, with the exception of fermented soy products, such as miso and tempeh. Rienks et al. PV panels have been linked . (2016) also studied whether there was an association between different types of interventions and the reduction in hot flushes and night sweats [90]. Animal models and humans [ 25,26,27 ], Lv Y., Uehara M. flavonoid metabolism: the of. 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