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. Postprandial lipemia detects the effect of soy protein on cardiovascular disease risk compared with the fasting lipid profile. ); sue.uhe@zelaznog.enatiam (M.G.-A. This study was supported by Instituto de Salud Carlos III (CIBERobn) under Grant CB12/03/30007, Basque Government under Grant PA20/04 and the University of the Basque Country under Grant GIU18-173. However, in the meta-analysis, a minor enhancement in flow-mediated dilation after soy protein supplementation was found. 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]. The authors reported that isoflavone intake from soy products and legumes was associated with a 19% reduction in endometrial cancer risk. Efficacy of phytoestrogens for menopausal symptoms: A meta-analysis and systematic review. Sulfation of the isoflavones genistein and daidzein in human and rat liver and gastrointestinal tract. 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. (2015), the authors examined the efficacy of phytoestrogens in reducing hot flushes [86]. Apparently, soy isoflavones modified adhesion molecules by binding to vascular endothelium and mimicking the effect of a modulator of estrogen receptors [64]. 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. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. . However, the magnitude of risk reduction in Asian women was slightly larger than in non-Asian women (22% vs. 18%). and J.T. Effects of Acid Rain on Plants and Trees. Isoflavone intake in four different European countries: The VENUS approach. 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. 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). Intestinal transport of quercetin glycosides in rats involves both deglycosylation and interaction with the hexose transport pathway. Winkel-Shirley B. Biosynthesis of flavonoids and effects of stress. Prez-Cornago et al. Ingram D., Sanders K., Kolybaba M., Lopez D. Case-control study of phyto-oestrogens and breast cancer. 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. As in the previous study, the onset of soy isoflavones was very slow in comparison with other non-hormonal treatments. Therefore, the authors concluded that the intake of dietary isoflavones paid a protective role against ovarian cancer. However, more studies are required to provide stronger evidence. (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]. 19% reduction in endometrial cancer risk. Daidzein is first converted into dihydrodaidzein, which is the precursor of both equol and O-demethylangolensin (O-DMA) [37]. While a moderate intake of soy isoflavones did not significantly affect breast cancer risk, a significant reduction was shown when the intake was high. So long ago as 1880 Siemens showed that continuous exposure to arc lamps promoted luxuriance of foliage . Oral isoflavone supplementation on endometrial thickness: A meta-analysis of randomized placebo-controlled trials. The most significant food source of isoflavones in humans is soy-derived products, soybeans, soy flour, soy flakes, soy beverages and fermented soy products such as miso and tempeh, among others [9]. Saloniemi H., Whl K., Nyknen-Kurki P., Kallela K., Saastamoinen I. Phytoestrogen content and estrogenic effect of legume fodder. ; WritingOriginal Draft Preparation, S.G.-Z., M.G.-A., A.F.-Q., I.E. The light of the moon also influences animals that are active in daytime. Cheynier V., Sarni-Manchado P., Quideau S., editors. Inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, but not in cohort studies. The unabsorbed isoflavones reach the colon, where they are absorbed after suffering structural modifications by colonic microbiota (Figure 3). 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. Bardin A., Boulle N., Lazennec G., Vignon F., Pujol P. Loss of ERbeta expression as a common step in estrogen-dependent tumor progression. Thus, its consumption, according to epidemiological and clinical studies, has been postulated to be related to a decrease in the risk of different diseases. 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. Accessibility In contrast, it seems that isoflavones do not act on central neurotransmitters directly. However, the results do not seem entirely conclusive, for there are discrepancies among the studies, probably related to their experimental designs. Effects of isoflavones in menopausal symptoms. From laboratory experiments, it's known that light intensities as low as 0.1 lux (approximately 0.01 foot-candle) during the night can influence photoperiodic time measurement in some plants and animals. In miso and tempeh, the aglycone form is the most abundant one [9]. Produced metabolites appear in plasma at variable concentrations and can enter enterohepatic circulation [28]. During menopause, there is a loss of bone density that can cause osteoporosis. Bethesda, MD 20894, Web Policies 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. Bustamante-Rangel M., Delgado-Zamarreo M.M., Perez-Martin L., Rodriguez-Gonzalo E., Dominguez-Alvarez J. 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. [(accessed on 21 September 2020)]; Messina M., Nagata C., Wu A.H. That's what behavioral ecologist Jenny York learned while studying white-browed sparrow weavers . Beneficial role of dietary phytoestrogens in obesity and diabetes. Lu L.J., Anderson K.E. This fact was not taken into account in previous meta-analyses, and thus it may justify the discrepancies amongst them. Scientists often disagree about certain things. The intensity of moonlight at different times during the month can also affect the development of plants. Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. Li L., Lv Y., Xu L., Zheng Q. Quantitative efficacy of soy isoflavones on menopausal hot flashes. The aim of the present review is to gather the scientific evidence existing nowadays on the main beneficial effects of isoflavones on health: bone health, cardiovascular risk, cancer and menopausal symptoms. ); sue.uhe@ollitrop.yupairam (M.P.P. 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. The work reported by Lambert et al. The authors studied all possible correlations between isoflavone consumption and the risk of breast cancer. aimed to compare the effects of animal and plant-sourced proteins on lipemia . Rossi M., Amaretti A., Roncaglia R., Leonardi A., Raimondi S. Dietary isoflavones and dietary microbiota: Metabolism and transformation into bioactive compounds. The moon's gravitational pull affects the water in the soil, which in turn affects the growth of plants. Association between Dietary Isoflavones in Soy and Legumes and Endometrial Cancer: A Systematic Review and Meta-Analysis. The six meta-analyses show a slight improvement in the frequency and intensity of hot flushes. (2016) suggested that a daily intake of soy isoflavones, ranging from 20 to 100 mg/day, reduced total cholesterol and triglyceride plasma concentrations, as well as some markers of oxidative stress (nitric oxide and malonaldehyde), thus reducing cardiovascular risk [52]. 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. Careers, Unable to load your collection due to an error. 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). You 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.) 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. 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. Effects of isoflavones in cardiovascular disease-related markers. Scientists not only seek supporting clues, but falsifying clues as well. 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. Gruber C.J., Tschugguel W., Schneeberger C., Huber J.C. Production and actions of estrogens. 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. The authors suggested that further studies grouping subjects by isoflavone intake or by the circulating isoflavone levels might enhance this association. Proof by rational experiment seems to have been. Yu Y., Jing X., Li H., Zhao X., Wang D. Soy isoflavone consumption and colorectal cancer risk: A systematic review and meta-analysis. 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. Metabolism of intraruminally administered [4-. The authors concluded that evidence for the role of isoflavones and soy products in the prevention of cardiovascular diseases was scarce and inconclusive. Zhong et al. In fact, all the body fluids, as the tides, were controlled by the lunar phases. Dong J.Y., Qin L.Q. Metabolites of dietary (soya) isoflavones in human urine. In any case, it is important to bear in mind that a great number of expert scientists and doctors think that breast cancer survivors should not increase their isoflavone intake [94], although others consider that their consumption is safe and beneficial [95]. Importantly, the soy variety, environmental conditions of the culture and the processing of soybeans notably influence their isoflavone content [18]. Matulka R.A., Matsuura I., Uesugi T., Ueno T., Burdock G. Developmental and Reproductive Effects of SE5-OH: An Equol-Rich Soy-Based Ingredient. Ten studies reported a significant reduction in hot flush frequency in the phytoestrogen group when compared with the placebo group. Sarri G., Pedder H., Dias S., Guo Y., Lumsden M.A. Changes to Earth's climate driven by increased human emissions of heat-trapping greenhouse gases are already having widespread effects on the environment: glaciers and ice sheets are shrinking, river and lake ice is breaking up earlier, plant and animal geographic ranges are shifting, and plants and trees are blooming sooner. Moreover, an increase in thyroid hormone levels after isoflavone intake by food supplements has not been observed, and no side effects were confirmed with regard to the endometrial thickness or histopathological changes in the uterus. and A.F.-Q. 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. HHS Vulnerability Disclosure, Help The authors found a statistical inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, although not in cohort studies. 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. The association between dietary isoflavones intake and gastric cancer risk: A meta-analysis of epidemiological studies. 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]. However, the moonlight decreases after the full moon. 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. 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. (2016) published another systematic review of 23 randomized controlled trials to determine the effect of soy isoflavone extracts on bone mineral density in postmenopausal women [51]. 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 some Asian countries, isoflavone intake, usually derived from soy consumption, can be associated with a lower prevalence of cardiovascular diseases (CVDs). Thus, whereas Asian populations have an average isoflavone consumption of >30 mg/day, Western populations consume <1 mg/day [83]. Man B., Cui C., Zhang X., Sugiyama D., Barinas-Mitchell E., Sekikawa A. At high elevations, acidic fog and clouds might . He et al. As far as the mechanisms of action involved in the decrease in triglyceride concentration are concerned, it has been reported that hepatic lipase and/or lipoprotein lipase activity may be increased as a result of isoflavone presence. In this line, three meta-analyses were conducted to study isoflavone consumption and endometrial cancer risk. Gee J.M., DuPont M.S., Day A.J., Plumb G.W., Williamson G., Johnson I.T. Juglans regia L. is a traditional plant that has been integrated into traditional medicine since ancient times. In contrast, red clover was not associated with changes in the hot flush frequency. These two associations were significant for postmenopausal participants. 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. 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. Some gardening folklore suggests that planting crops according to the phases of the moon will give you a better harvest, but there is little scientific evidence to back this up. Possible mechanism of action of isoflavones for cancer prevention. Nevertheless, it is important to consider this metabolite since it is key in the biological activity of isoflavones [13]. 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. The Effects and Action Mechanisms of Phytoestrogens on Vasomotor Symptoms During Menopausal Transition: Thermoregulatory Mechanism. 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]. Plants grow best when the moon is in the waxing phase, when its gravitational pull is strongest. Comparative efficacy of nonhormonal drugs on menopausal hot flashes. However, all the authors agree that further studies are necessary so as to confirm these results. In addition, several studies have observed that the urine excretion of daidzein metabolites is notably higher than that of genistein metabolites [44,45,46]. HRT: hormone replacement therapy, RCT: randomized controlled trial, VSM: vasomotor symptoms. Isoflavones have received attention due to their putative healthy properties. He X., Sun L.M. Lambert M.N.T., Hu L.M., Jeppesen P.B. On the contrary, women who were already equol producers did not obtain any additional benefit from supplements of equol or isoflavones. 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. Isoflavone content in soy-derived products is usually lower than in soybeans [17]. However, a limitation in this field is that there is still a great heterogeneity among studies. 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. Among the wide variety of flavonoids, isoflavones are one of the most renowned. Batterham T.J., Shutt D.A., Braden A.W.H., Tweeddale H.J. Li L., Xu L., Wu J., Dong L., Zhao S., Zheng Q. Thanks for reading Scientific American. In general, evidence regarding the use of isoflavones on vasomotor symptoms suggests that they could be useful in reducing hot flushes. Interestingly, soy protein isolate (void of isoflavones through alcoholic extraction during the protein solation phase) did not show these effects. 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. Further, Chalvon-Demersay et al. 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. 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. For this reason, the results should be interpreted with caution, and more randomized clinical trials are imperative. 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