A total of 16 studies were included in their meta-analysis with a range of 24 to 236 subjects. Most would agree that the daily rising and falling of the moon, along with the monthly waxing and waning cycles, have effects on our oceans and seas. As in the previous study, the onset of soy isoflavones was very slow in comparison with other non-hormonal treatments. (2019), included 16 prospective cohort studies involving 11,169 breast cancer cases and 648,913 participants [70]. (2015), the authors examined the efficacy of phytoestrogens in reducing hot flushes [86]. Thirty-nine studies were included with a sample size of 200 women per trial, in which the intervention period ranged from two to 96 weeks (median 12 weeks). 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. (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]. Treutter D. Significance of flavonoids in plant resistance and enhancement of their biosynthesis. The most significant food source of isoflavones in humans is soy-derived products. Therefore, the authors concluded that the intake of dietary isoflavones paid a protective role against ovarian cancer. The authors declare no conflict of interest. Lastly, Abshirini et al. Nevertheless, the results do not seem entirely conclusive, as there are discrepancies among the studies included in the systematic reviews and in the meta-analyses, probably related to their experimental designs. Two meta-analyses, which covered prospective cohort studies, showed that soy isoflavone consumption was not associated significantly with mortality linked to cardiovascular events [56,62]. 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. and A.F.-Q. 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. ); sue.uhe@ollitrop.yupairam (M.P.P. The authors found a significant inverse association between isoflavone intake and both overall mortality and breast cancer recurrence. Produced metabolites appear in plasma at variable concentrations and can enter enterohepatic circulation [28]. 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]. Isoflavone glycosides have to be hydrolyzed to the aglycone form prior to its absorption by passive diffusion in the upper small intestine [28]. The water in the ocean on the side of the Earth closest to the moon experiences a larger gravitational attraction than the water on the opposite side. It is well-known that some of the most accurate BP readings occur right as someone wakes up and at that event, the BP will be shown for the most part to stay lower than that of a daily average. 8600 Rockville Pike Focusing on the overall intake of isoflavones in humans, several studies have reported varied results. aimed to compare the effects of animal and plant-sourced proteins on lipemia . (2020) revised the literature to find randomized controlled trials that evaluated the impact of soy protein supplementation (isoflavone intake ranging from 49.3 to 118 mg/day) on endothelial function parameters in postmenopausal women (n = 802) [58]. Dead or dying trees are a common sight in areas effected by acid rain. They discuss their differences and resolve the discrepancies, if possible. 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. They observed that daidzein and genistein intakes were associated with a significant reduction of prostate cancer risk. Due to the high prevalence of colorectal cancer, three meta-analyses addressing this issue are included in the present review. 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. Despite the positive effect of isoflavones, the authors emphasized that the effects took a long time to appear. Kim Y., Je Y. Flavonoid intake and mortality from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies. Saloniemi H., Whl K., Nyknen-Kurki P., Kallela K., Saastamoinen I. Phytoestrogen content and estrogenic effect of legume fodder. Many females sleep less and have less REM sleep. (2015) concluded that soy isoflavones have both a slight and slow effect in attenuating menopausal hot flushes [87]. Bardin A., Boulle N., Lazennec G., Vignon F., Pujol P. Loss of ERbeta expression as a common step in estrogen-dependent tumor progression. U.S. Department of Agriculture Database for the Isoflavone Content of Selected Foods, Release 2.0. As with other phenolic compounds, isoflavones can be presented as free forms (aglycones) or conjugated with carbohydrates (glycosides). Thirty-seven articles presenting evidence of the physiological effects of viewing nature were selected. 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]. Regarding the effect of specific isoflavones, they suggested that genistein, alone or in combination with daidzein, improved bone density and bone turnover in women after 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. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women. 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. However, in the meta-analysis, a minor enhancement in flow-mediated dilation after soy protein supplementation was found. (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]. Study duration ranged from four weeks to two years, with a median of 12 weeks. Altogether, these results show that further studies are needed in order to find stronger conclusions. 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. Ten studies reported a significant reduction in hot flush frequency in the phytoestrogen group when compared with the placebo group. Setchell K.D., Brown N.M., Lydeking-Olsen E. The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones. Specifically, the time to achieve half of the efficacy was 11.6 weeks for soy isoflavones, while for the rest of the compounds, the onset time was near 0 weeks. 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. The improvement was greater in treatments lasting more than one year and in subjects with normal weight, probably because subjects with excessive body weight have a lesser risk of bone loss. In the last few decades, scientific evidence has stressed the importance of plants in the prevention and/or supportive treatment of a plethora of diseases, many of them chronic, age-associated disorders. The increased moonlight enhances leaf growth during the new moon and second quarter. Effect of soy isoflavone supplementation on plasma lipoprotein(a) concentrations: A meta-analysis. Winkel-Shirley B. Biosynthesis of flavonoids and effects of stress. In this study, five prospective cohort studies and seven case-control studies, with 6275 cases and 393,776 controls, were included. The main forms of conjugates in soybeans are the malonyl derivatives [14]. Rienks J., Barbaresko J., Nthlings U. The site is secure. 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. Dong J.Y., Qin L.Q. Interestingly, soy protein isolate (void of isoflavones through alcoholic extraction during the protein solation phase) did not show these effects. 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. Isoflavones could be used as an alternative therapy for pathologies dependent on hormonal disorders such as breast and prostate cancer, cardiovascular diseases, as well as to minimize menopausal symptoms. The Effects and Action Mechanisms of Phytoestrogens on Vasomotor Symptoms During Menopausal Transition: Thermoregulatory Mechanism. Due to the presence of biologically active compounds, walnut was used in the . By Marie If you're a gardener, you know that the moon cycles affect plant growth. (2018) showed no effect of soy isoflavones on plasma concentrations of lipoprotein a (Lpa), a low-density lipoprotein associated with increased cardiovascular risk due to its pro-thrombotic and atherogenic properties [63]. A significant 19% reduction of the risk was found at high concentrations of daidzein, but not at genistein or equol concentrations. Effects of isoflavones in cardiovascular disease-related markers. Murota K., Nakamura Y., Uehara M. Flavonoid metabolism: The interaction of metabolites and gut microbiota. Future research in this field should quantify isoflavones as accurately as possible, analyzing larger cohorts and lengthening the follow-up stage. The authors found a statistical inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, although not in cohort studies. Cheynier V., Sarni-Manchado P., Quideau S., editors. 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. 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]. Valsta L.M., Kilkkinen A., Mazur W., Nurmi T., Lampi A.M., Ovaskainen M.L., Korhonen T., Adlercreutz H., Pietinen P. Phyto-oestrogen database of foods and average intake in Finland. 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. Phytoestrogen Metabolism by Adult Human Gut Microbiota. The physical stiffening of arteries has major health implications for its connection to various adverse cardiovascular and other health outcomes such as coronary heart disease, stroke, hypertension or heart failure [66]. Ingram D., Sanders K., Kolybaba M., Lopez D. Case-control study of phyto-oestrogens and breast cancer. The authors observed that soy isoflavone consumption was inversely associated with cancer deaths. 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. 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. Perna et al. 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. 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]. Lambert M.N.T., Hu L.M., Jeppesen P.B. Bacterial metabolites of isoflavones forming in the gut. official website and that any information you provide is encrypted (2016) included 17 studies (nine case-control studies and eight cohort studies) [80]. In miso and tempeh, the aglycone form is the most abundant one [9]. Menopause is characterized by a decrease in estrogen levels and is often accompanied by a range of symptoms. Finally, it is important to mention that despite the fact that potential isoflavone adverse effects have been widely studied, little is known about the side effect of the bacterial metabolite equol. Modified from Mace et al. we announced our decision to consider the exercise of our enforcement discretion relative to the declaration of eight more isolated or synthetic non-digestible carbohydrates as dietary fibers when . Gaya P., Medina M., Snchez-Jimnez A., Landete J.M. Sansai K., Na Takuathung M., Khatsri R., Teekachunhatean S., Hanprasertpong N., Koonrungsesomboon N. Effects of isoflavone interventions on bone mineral density in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials. Equol has been considered as the most interesting colonic metabolite due to its beneficial biological activity, which differs from that of its precursor, daidzein [13,38,39]. Vlachopoulos C., Aznaouridis K., Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: A systematic review and meta-analysis. In some cases the purported effect may depend on external cues, such as the amount of moonlight. Presence of four chemical forms of the three isoflavones found in soybeans. 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. In contrast, red clover was not associated with changes in the hot flush frequency. The work reported by Lambert et al. Effects of isoflavones in different cancer types. Consequently, isoflavones can have estrogenic or anti-estrogenic effects [3]. 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. Matulka R.A., Matsuura I., Uesugi T., Ueno T., Burdock G. Developmental and Reproductive Effects of SE5-OH: An Equol-Rich Soy-Based Ingredient. ; WritingOriginal Draft Preparation, S.G.-Z., M.G.-A., A.F.-Q., I.E. These two associations were significant for postmenopausal participants. Received 2020 Nov 30; Accepted 2020 Dec 15. 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]. Comparative efficacy of nonhormonal drugs on menopausal hot flashes. Zhong et al. Although smaller in quantity, isoflavones are also present in chickpeas, nuts, fruits and vegetables [11]. The six meta-analyses show a slight improvement in the frequency and intensity of hot flushes. The tides are crucial to life: tidal pools, sheltered and renewed in rhythm with these cycles, catalyzed some of the first stable ecologies and still represent unique niches. (2016) conducted a meta-analysis aimed at ovarian cancer, which affects women exclusively [74]. 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. Heinonen S., Whl K., Adlercreutz H. Identification of isoflavone metabolites dihydrodaidzein, dihydrogenistein, 6-OH-O-dma, and cis-4-OH-equol in human urine by gas chromatography-mass spectroscopy using authentic reference compounds. Kov L., Dadkov K., Kaparovsk J., Kaparovsk T. Isoflavones. . van der Schouw Y.T., Kreijkamp-Kaspers S., Peeters P.H., Keinan-Boker L., Rimm E.B., Grobbee D.E. Anywise, it has been observed that both isoflavones are demethylated by microbiota, formononetin to daidzein and biochanin A to genistein. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: A meta-analysis of prospective studies. Further, Chalvon-Demersay et al. and J.T. Lastly, with regard to isoflavone consumption safety, it seems that they are safe and that the most common adverse effect is mild and occurs at the gastrointestinal level. (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]. http://creativecommons.org/licenses/by/4.0/, https://data.nal.usda.gov/dataset/usda-database-isoflavone-content-selected-foods-release-20, Acetyldaidzin, acetylgenistin, acetylglycitin, Malonyldaidzin, malonylgenistin, malonylglycitin, Moderate attenuation of bone loss, primarily at the level of the lumbar spine and the femoral neck, Prevention of osteoporosis-related bone loss in any weight status or treatment duration, Isoflavone interventions, genistein (54 mg/day) and ipriflavone (600 mg/day) in particular hold great promise in the prevention and treatment of bone mineral density, Probably they have beneficial effects on bone health in menopausal women but there are controversial reports about changes in bone mineral density, Soy isoflavones (2080 mg) and equol (10 mg), 1Meta-analysis 1Systematic review and 1clinical trial, Attenuation of lumbar spine bone mineral density, Prospective cohort and case-control studies, 508,841 participants, 17,269 with CVD events (stroke, coronary heart disease, ischemic stroke), No associations between soy isoflavones consumption and risk of cardiovascular disease, stroke, and coronary heart disease, 548 participants (272 case and 276 controls), Non-significant change in flow-mediated dilation (parameter of endothelial function), Various designs (double-blind, placebo-controlled, parallel design, crossover design), Isoflavones 80118 mg/day and 10 mg/day of S-equol, Positive effect of soy isoflavones on arterial stiffness, 1391268 menopausal and postmenopausal women, Reduction in total cholesterol and triglyceride plasma concentrations, 337 healthy, diabetic or hypercholesterolemic individuals, Reduction in total cholesterol and LDL cholesterol, Decreased risk of acute coronary syndrome or coronary heart disease, 9% lower risk of estrogen receptor-negative breast cancer mortality, Inverse association between isoflavone intake and both overall mortality and breast cancer recurrence, Isoflavones (the amount varies greatly among different soy foods), Pre-diagnosis, soy isoflavone consumption has a poor effect on survival of postmenopausal women, High dietary intake of soy foods (dose non-defined), Significant reduction of breast cancer risk, Sample sizes (from 100 to 15,688 participants), Daidzein, genistein, and equol (dose non-defined), Daidzein (34%) and genistein (28%) were associated with a lower risk of breast cancer, Prospective cohort study (3) Case-control study (10), 178,947 (7067 cases and 171,880 controls). Possible mechanism of action of isoflavones for cancer prevention. The authors studied all possible correlations between isoflavone consumption and the risk of breast cancer. Knowledge awaits. CVD: cardiovascular disease, LDL: low-density lipoprotein. This meta-analysis included 266,699 participants (21,612 patients with prostate cancer among them). Prez-Cornago et al. Gee J.M., DuPont M.S., Day A.J., Plumb G.W., Williamson G., Johnson I.T. Barnes S. The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. The four chemical forms of the three most abundant isoflavones. 1Nutrition and Obesity Group, Department of Pharmacy and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Institute, 01006 Vitoria, Spain; sue.uhe@zemog.aoias (S.G.-Z. 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. 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. Thus, its consumption, according to epidemiological and clinical studies, has been postulated to be related to a decrease in the risk of different diseases. (2017) included 26 trials with 2652 participants [48]. Chang H.H., Robinson A.R., Common R.H. Excretion of radioactive diadzein and equol as monosulfates and disulfates in the urine of the laying hen. 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. Scientists often disagree about certain things. With regard to the published meta-analysis, the studies included were restricted to randomized controlled trials. In general, evidence regarding the use of isoflavones on vasomotor symptoms suggests that they could be useful in reducing hot flushes. Ronis M.J., Little J.M., Barone G.W., Chen G., Radominska-Pandya A., Badger T.M. An official website of the United States government. They also explained that the differences between isoflavones and the rest of the drugs might be because the latter act by modulating central neurotransmitters and, as a consequence, by regulating the central thermoregulatory centers in the hypothalamus. Jun S., Shin S., Joung H. Estimation of dietary flavonoid intake and major food sources of Korean adults. The authors concluded that evidence for the role of isoflavones and soy products in the prevention of cardiovascular diseases was scarce and inconclusive. 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. The authors reported that isoflavone intake from soy products and legumes was associated with a 19% reduction in endometrial cancer risk. 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. Morning 3: Temp 98.6 BP 124/83 Pulse 62 bpm. He X., Sun L.M. Yu Y., Jing X., Li H., Zhao X., Wang D. Soy isoflavone consumption and colorectal cancer risk: A systematic review and meta-analysis. Thus, soybean can be considered as the best food source. Nevertheless, it is important to consider this metabolite since it is key in the biological activity of isoflavones [13]. Abdi et al. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. Metabolites of dietary (soya) isoflavones in human urine. Gruber C.J., Tschugguel W., Schneeberger C., Huber J.C. Production and actions of estrogens. Santo A.S., Santo A.M., Browne R.W., Burton H., Leddy J.J., Horvath S.M., Horvath P.J. Atkinson C., Frankenfeld C.L., Lampe J.W. They observed that it was dose-dependent at low to moderate soybean consumption. (2016) also studied whether there was an association between different types of interventions and the reduction in hot flushes and night sweats [90]. However, the authors pointed out several limitations of this study, such as the important source of heterogeneity in their study. Moreover, five studies reported side-effect data, and after the analysis, no significant differences were observed between the two groups. 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scientific evidence regarding the effects of moonlight on plants