Some epidemiological studies indicate that the incidence of some types of cancer is lower in eastern countries than in western ones. (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]. In addition, genistein and glycitein are transformed into dihydrogenistein and dihydroglycitein, respectively, before being further converted into other metabolites. Regarding blood pressure, inconsistent results were reported in three further interventional studies (n = 406 healthy, postmenopausal or obese participants aged 5079 years) either in diastolic or systolic blood pressure, after a supplementation with soy-protein. U.S. Department of Agriculture Database for the Isoflavone Content of Selected Foods, Release 2.0. Sex and long-term soy diets affect the metabolism and excretion of soy isoflavones in humans. Importantly, the soy variety, environmental conditions of the culture and the processing of soybeans notably influence their isoflavone content [18]. 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. Analysis of isoflavones in Foods. Chen L.R., Ko N.Y., Chen K.H. The authors suggested that further studies grouping subjects by isoflavone intake or by the circulating isoflavone levels might enhance this association. Association between Dietary Isoflavones in Soy and Legumes and Endometrial Cancer: A Systematic Review and Meta-Analysis. Vasomotor symptoms resulting from natural menopause: A systematic review and network meta-analysis of treatment effects from the National Institute for Health and Care Excellence guideline on menopause. As previously mentioned, soybeans and their derived foodstuffs are the main isoflavone sources in the human diet, at least if we do not consider red clover extract supplements, which are being widely used by menopausal women as nutraceutical therapy [13]. Dietary polyphenol intake in Europe: The European Prospective Investigation into Cancer and Nutrition (EPIC) study. In this section, 16 meta-analyses have been revised: Nachvack et al. and A.F.-Q. 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 observed that soy isoflavone consumption was inversely associated with cancer deaths. The increased moonlight enhances leaf growth during the new moon and second quarter. In the same line, in European men, isoflavone concentrations did not affect the risk of developing prostate cancer. ; Project Administration, M.P.P. (2016) conducted a meta-analysis aimed at ovarian cancer, which affects women exclusively [74]. Jiang R., Botma A., Rudolph A., Hsing A., Chang-Claude J. Phyto-oestrogens and colorectal cancer risk: A systematic review and dose-response meta-analysis of observational studies. ); sue.uhe@zelaznog.enatiam (M.G.-A. Study duration ranged from four weeks to two years, with a median of 12 weeks. However, in the meta-analysis, a minor enhancement in flow-mediated dilation after soy protein supplementation was found. Effects of isoflavones in bone health maintenance. In the same line, Yu et al. Metabolism of intraruminally administered [4-. 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. (2017) also analyzed eight studies of prostate cancer, and they found an association between isoflavone intake and prostate cancer risk [61]. (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]. 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. 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. 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. Nevertheless, it is important to consider this metabolite since it is key in the biological activity of isoflavones [13]. 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). Acid rain also removes minerals and nutrients from the soil that trees need to grow. 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. CVD: cardiovascular disease, LDL: low-density lipoprotein. In this line, three meta-analyses were conducted to study isoflavone consumption and endometrial cancer risk. So long ago as 1880 Siemens showed that continuous exposure to arc lamps promoted luxuriance of foliage . In general, evidence regarding the use of isoflavones on vasomotor symptoms suggests that they could be useful in reducing hot flushes. Furthermore, isoflavones are associated with proteins; thus, alcohol extraction and processing diminish isoflavone content in foodstuffs such as fermented soybean, tofu or soy beverages. Isoflavone glycosides have to be hydrolyzed to the aglycone form prior to its absorption by passive diffusion in the upper small intestine [28]. Wang X., Dykens J.A., Perez E., Liu R., Yang S., Covey D.F., Simpkins J.W. This chemical feature confers estrogenic or antiestrogenic effects to isoflavones, depending on the cell type and the binding to - or -estrogen receptors. For the development of this section, the meta-analyses and systematic reviews published between 2015 and 2020 were taken into account. Sfakianos J., Coward L., Kirk M., Barnes S. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. Thus, its consumption, according to epidemiological and clinical studies, has been postulated to be related to a decrease in the risk of different diseases. The authors found a statistical inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, although not in cohort studies. Effect of soy isoflavone supplementation on plasma lipoprotein(a) concentrations: A meta-analysis. Additionally, Yan and co-workers, in their meta-analysis with a total of ten prospective cohorts and seven case-control studies (including 508,841 participants and 17,269 cardiovascular disease events), observed that the consumption of soy foods, but not that of isoflavones, was associated with a lower risk of total cardiovascular disease (including coronary heart disease and stroke) [57]. In some Asian countries, isoflavone intake, usually derived from soy consumption, can be associated with a lower prevalence of cardiovascular diseases (CVDs). 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. The light of the moon also influences animals that are active in daytime. 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. In contrast, red clover was not associated with changes in the hot flush frequency. 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]. Nevertheless, this association was not shown when equol or isoflavones were consumed. Kov L., Dadkov K., Kaparovsk J., Kaparovsk T. Isoflavones. 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. 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. Consequently, isoflavones can have estrogenic or anti-estrogenic effects [3]. 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 In miso and tempeh, the aglycone form is the most abundant one [9]. The four chemical forms of the three most abundant isoflavones. Thus, soybean can be considered as the best food source. (2018) revised 13 epidemiologic studies involving 178,947 participants: 7067 cases and 171,880 controls; among them, three were prospective cohort studies, and ten were population-based case-control studies [71]. 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. 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. 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. 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]. Rienks J., Barbaresko J., Nthlings U. Create your free account or Sign in to continue. (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]. 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. Taken as a whole, all these results suggest that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. (2016) conducted a meta-analysis of 18 studies involving 16,917 colorectal cancer cases in 559,486 participants [78]. By contrast, the total isoflavone amount is high in soy flour, protein isolate or edamame [19]. 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. 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. Bhathena S.J., Velasquez M.T. (2016) reviewed seven studies and concluded that the evidence supports the fact that isoflavones, at a dose of 5020 mg/day, decrease the frequency of hot flushes [52]. A systematic review and meta-analysis of the effects of isoflavone formulations against estrogen-deficient bone resorption in peri- and postmenopausal women. 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. Chemical structure of 17-estradiol. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. 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. After the consumption of around 17 mg of isoflavones per day, the median plasma concentrations of genistein, glycitein, daidzein and equol were 245.3 ng/mL, 9.8 ng/mL, 86.8 ng/mL and 12.7 ng/mL, respectively. Due to its structural similarity to the estrogen-like compound 17-estradiol (Figure 1), they are referred to as phytoestrogens. (2016) also studied whether there was an association between different types of interventions and the reduction in hot flushes and night sweats [90]. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Many females sleep less and have less REM sleep. 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. Rienks et al. 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]. On the contrary, women who were already equol producers did not obtain any additional benefit from supplements of equol or isoflavones. Qiu S., Jiang C. Soy and isoflavones consumption and breast cancer survival and recurrence: A systematic review and meta-analysis. Presence of four chemical forms of the three isoflavones found in soybeans. Interestingly, soy protein isolate (void of isoflavones through alcoholic extraction during the protein solation phase) did not show these effects. Kim Y., Je Y. Flavonoid intake and mortality from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies. Isoflavone Supplements for Menopausal Women: A Systematic Review. During menopause, there is a loss of bone density that can cause osteoporosis. aimed to compare the effects of animal and plant-sourced proteins on lipemia and blood pressure [60]. The enzyme lactase-phlorizin hydrolase (LPH) deglycosylases phenolic compounds in the intestinal lumen, and after that, the aglycone form enters the epithelial cells by passive diffusion. (2016), nine studies addressed to menopausal women and focused on bone health were analyzed [52]. In a study reported by Ko et al., the authors quantified the plasma concentrations of daidzein, genistein, glycitein and equol in Korean men and women [36]. (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]. Apparently, soy isoflavones modified adhesion molecules by binding to vascular endothelium and mimicking the effect of a modulator of estrogen receptors [64]. Our findings illustrate that foraging rodents, well known to be risk-averse during moonlit nights, are also affected by the presence of an invasive plant. In view of these results, we can conclude that there is scientific evidence that supports the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis in postmenopausal women. However, the authors pointed out several limitations of this study, such as the important source of heterogeneity in their study. Ingram D., Sanders K., Kolybaba M., Lopez D. Case-control study of phyto-oestrogens and breast cancer. 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. In contrast, the effects on bone resorption biomarkers were more favorable in overweight or obese women than in women with a healthy weight. van der Schouw Y.T., Kreijkamp-Kaspers S., Peeters P.H., Keinan-Boker L., Rimm E.B., Grobbee D.E. Hua et al. HRT: hormone replacement therapy, RCT: randomized controlled trial, VSM: vasomotor symptoms. Nevertheless, the metabolism of formononetin and biochanin A, the main isoflavones in red clover, has been less studied due to their limited presence in foodstuffs. 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. (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]. This is mainly due to their potential adverse effects, which range from increased coronary heart disease to stroke and cancer [53,85]. . HHS Vulnerability Disclosure, Help Ronis M.J., Little J.M., Barone G.W., Chen G., Radominska-Pandya A., Badger T.M. 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 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]. 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. 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. Atkinson C., Frankenfeld C.L., Lampe J.W. This fact was not taken into account in previous meta-analyses, and thus it may justify the discrepancies amongst them. 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. Further, Chalvon-Demersay et al. 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. (2017) included 26 trials with 2652 participants [48]. The enzymes responsible for the hydrolysis of isoflavone glycosides are glucosidases, which can be produced by the intestinal mucosa or the microbiota [29]. 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. Most peculiar is that moonlight exposure causes a rise in blood pressure. May affect males and females differently A 2015 study of 205 people found that the full moon may affect sleep differently in males and females. 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. (2019) conducted a meta-analysis where 23 prospective studies with a total of 330,826 participants were included. Acid rain leaches aluminum from the soil. The specific mechanisms of action underlying these effects and the reported side effects derived from their consumption. Rossi M., Amaretti A., Roncaglia R., Leonardi A., Raimondi S. Dietary isoflavones and dietary microbiota: Metabolism and transformation into bioactive compounds. 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. Oral isoflavone supplementation on endometrial thickness: A meta-analysis of randomized placebo-controlled trials. 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. 8600 Rockville Pike PV panels have been linked . Soy isoflavones consumption and risk of breast cancer incidence or recurrence: A meta-analysis of prospective studies. Grosso et al. 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. Endometrial cancer (Table 4), as well as breast cancer, is an estrogen-dependent cancer type related to high circulating estradiol concentrations. Regarding endometrial cancer, three prospective and five case-control studies were analyzed, which suggested a lower endometrial cancer risk associated with isoflavone consumption. 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 . The meta-analysis included 15 studies in which the number of participants ranged from 30 to 252. 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 addition, it is important to highlight that interindividual differences in gut bacterial populations are responsible for the diverse effects of isoflavones in humans. 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 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. (2015) concluded that soy isoflavones have both a slight and slow effect in attenuating menopausal hot flushes [87]. 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. Liu J., Yuan F., Gao J., Shan B., Ren Y., Wang H., Gao Y. (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]. Isoflavone excretion occurs mainly through urine and feces, primarily in the conjugate forms, and up to 95% takes place in 24 h [43]. 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. Rizzo G., Baroni L. Soy, Soy Foods and Their Role in Vegetarian Diets. Bethesda, MD 20894, Web Policies This result has implications for granivory and perhaps plant demography in invaded and restored coastal habitats. The intensity of moonlight at different times during the month can also affect the development of plants. Zhong X.S., Ge J., Chen S.W., Xiong Y.Q., Ma S.J., Chen Q. Conceptualization, S.G.-Z. Association of isoflavone biomarkers with risk of chronic disease and mortality: A systematic review and meta-analysis of observational studies. Possible mechanism of action of isoflavones for menopausal symptoms. The difference for isoflavones required to find an effect can be due to variations in the amount of isoflavone intake between both populations. FOIA Discover world-changing science. (At least not real scientists.) Further, Chalvon-Demersay et al. Lambert M.N.T., Hu L.M., Jeppesen P.B. Man B., Cui C., Zhang X., Sugiyama D., Barinas-Mitchell E., Sekikawa A. The authors concluded that evidence for the role of isoflavones and soy products in the prevention of cardiovascular diseases was scarce and inconclusive. That's what behavioral ecologist Jenny York learned while studying white-browed sparrow weavers . Micek A., Godos J., Brzostek T., Gniadek A., Favari C., Mena P., Libra M., Del Rio D., Galvano F., Grosso G. Dietary phytoestrogens and biomarkers of their intake in relation to cancer survival and recurrence: A comprehensive systematic review with meta-analysis. 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. 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. Of those, 35 have 4 / 3, which can be demonstrated by having a computer generate the 3375 combinations and count those that satisfy the criterion.Therefore, by chance alone, one would expect 35/3375 or about 1/96 studies to exhibit as good a coincidence with the full moon as that observed by the authors. For this reason, the results should be interpreted with caution, and more randomized clinical trials are imperative. 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). 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]. In addition, several studies have observed that the urine excretion of daidzein metabolites is notably higher than that of genistein metabolites [44,45,46]. The gravitational attraction between the Earth and the Moon produces two bulges in the ocean on opposite sides of the Earth. 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. Proof by rational experiment seems to have been. These two associations were significant for postmenopausal participants. Lastly, the association between dietary isoflavone intake and the risk of developing gastric cancer has also been analyzed. Due to the high prevalence of colorectal cancer, three meta-analyses addressing this issue are included in the present review. Licensee MDPI, Basel, Switzerland. For this reason, the bioavailability of isoflavones has been extensively characterized in animal models and humans [25,26,27]. In some cases the purported effect may depend on external cues, such as the amount of moonlight. Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. 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. The most significant food source of isoflavones in humans is soy-derived products. (2018), 30 articles were included for analysis; 15 of them were case-control studies, eight cohort studies and seven nested case-control studies [76]. 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.
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