In this systematic review, 123 studies were included, with a total number of 516,330 participants. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. 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]. 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. Licensee MDPI, Basel, Switzerland. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women. 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]. (2017) also analyzed eight studies of prostate cancer, and they found an association between isoflavone intake and prostate cancer risk [61]. Murota K., Nakamura Y., Uehara M. Flavonoid metabolism: The interaction of metabolites and gut microbiota. 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. The main forms of conjugates in soybeans are the malonyl derivatives [14]. 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. Even though red clover has a greater amount of isoflavones, it is not an edible plant, and it is consumed as a food complement. The authors declare no conflict of interest. In this revision, three systematic reviews and five meta-analyses were included to explore the association of isoflavones and markers related to CVDs (Table 3). Furthermore, isoflavones are able to inhibit aromatase activity, the enzyme that converts androgen to estrogen. 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. 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. Plasma isoflavone concentration is associated with decreased risk of type 2 diabetes in Korean women but not men: Results from the Korean Genome and Epidemiology Study. 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. (2019) studied whether equol supplementation could benefit equol nonproducer subjects in lowering the incidence and severity of hot flushes [85]. The work reported by Lambert et al. 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]. Overall, evidence regarding the use of isoflavones in cancer prevention suggests that they may be useful in reducing the risk of suffering from some types of cancer, such as breast and endometrial cancer, two of the types for which the association between isoflavone intake and cancer risk has been studied more in-depth. The light of the moon also influences animals that are active in daytime. Sfakianos J., Coward L., Kirk M., Barnes S. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. ; WritingReview and Editing, M.P.P., S.G.-Z., I.E. The gravitational attraction between the Earth and the Moon produces two bulges in the ocean on opposite sides of the Earth. 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). Kim Y., Je Y. Flavonoid intake and mortality from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies. and A.F.-Q. Moonlight sonata. Scientists often disagree about certain things. U.S. Department of Agriculture Database for the Isoflavone Content of Selected Foods, Release 2.0. However, more studies are required to provide stronger evidence. 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. In the same line, in European men, isoflavone concentrations did not affect the risk of developing prostate cancer. Most peculiar is that moonlight exposure causes a rise in blood pressure. Xu B., Chibber R., Ruggiero D., Kohner E., Ritter J., Ferro A., Ruggerio D. Impairment of vascular endothelial nitric oxide synthase activity by advanced glycation end products. The six meta-analyses show a slight improvement in the frequency and intensity of hot flushes. Dietary polyphenol intake in Europe: The European Prospective Investigation into Cancer and Nutrition (EPIC) study. There are a total of 15 3 = 3375 possible outcomes. 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. While a moderate intake of soy isoflavones did not significantly affect breast cancer risk, a significant reduction was shown when the intake was high. 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. Lu D., Gigure V. Requirement of Ras-dependent pathways for activation of the transforming growth factor beta3 promoter by estradiol. 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]. Isoflavones (high dose: 0.675.5 mg/day; and low dose: 0.0120.1 mg/day). Kurzer M.S., Xu X. Dietary phytoestrogens. 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]. However, the authors stated that they could not reach definitive conclusions due to, among other reasons, the lack of inclusion in the review of randomized controlled clinical trials focused on the treatment of osteoporosis in early menopause. Perna et al. 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]. 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). 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. 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. Although results vary greatly, most of these applications are supported by at least a few clinical studies. Bethesda, MD 20894, Web Policies 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. As it has been stated in the Bioavailability section, microbiota composition in humans makes equol production very variable, which yields high interindividual differences. 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]. 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. Regarding endometrial cancer, three prospective and five case-control studies were analyzed, which suggested a lower endometrial cancer risk associated with isoflavone consumption. Isoflavone intake in four different European countries: The VENUS approach. Comparative efficacy of nonhormonal drugs on menopausal hot flashes. Effects of Acid Rain on Plants and Trees. (2016) also studied whether there was an association between different types of interventions and the reduction in hot flushes and night sweats [90]. 19% reduction in endometrial cancer risk. In miso and tempeh, the aglycone form is the most abundant one [9]. 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. Zhong et al. 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. The authors suggested that further studies grouping subjects by isoflavone intake or by the circulating isoflavone levels might enhance this association. Science is Knowledge Space & Physics The Effects of Moonlight May 22, 1858 Professor Piazza Smyth, the Astronomer Royal for Scotland, in his interesting account of a recent scientific. 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. Association of isoflavone biomarkers with risk of chronic disease and mortality: A systematic review and meta-analysis of observational studies. The authors indicated that high concentrations of daidzein and genistein (no specific values concerning these concentrations were available) were related to 34% and 28% reduction in breast cancer risk, respectively, whereas no association with equol was found. This result has implications for granivory and perhaps plant demography in invaded and restored coastal habitats. Dead or dying trees are a common sight in areas effected by acid rain. ), 2CIBEROBN Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, 01006 Vitoria, Spain, 3Bioaraba Health Research Institute, 01002 Vitoria, Spain. You et al. Applegate C.C., Rowles J.L., Ranard K.M., Jeon S., Erdman J.W. 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. Importantly, the soy variety, environmental conditions of the culture and the processing of soybeans notably influence their isoflavone content [18]. While equol production seems to be similar in animals, it is very variable in humans [41], and therefore, beneficial effects referred to equol have been observed only in individuals with a specific microbiota composition [38]. Focusing on the overall intake of isoflavones in humans, several studies have reported varied results. To address the link between lunar phases and agriculture from a scientic perspective, we conducted a review of textbooks and monographs used to teach agronomy, botany, horticulture and plant physiology; we also consider the physics that address the e ects of the Moon on our planet. 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. Morning 3: Temp 98.6 BP 124/83 Pulse 62 bpm. Furthermore, among the four studies of breast cancer recurrence, three studies found that isoflavone intake decreased the risk of breast cancer recurrence, although further studies are required to confirm this finding [82]. (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]. 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. Isoflavones have received attention due to their putative healthy properties. Sansai et al. (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]. 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. Possible mechanism of action of isoflavones for cancer prevention. 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]. Simental-Menda L.E., Gotto A.M., Atkin S.L., Banach M., Pirro M., Sahebkar A. . By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. sharing sensitive information, make sure youre on a federal Sotoca A.M., van den Berg H., Vervoort J., van der Saag P., Strm A., Gustafsson J.A., Rietjens I., Murk A.J. Consensus: Soy isoflavones as a first-line approach to the treatment of menopausal vasomotor complaints. (2015) concluded that soy isoflavones have both a slight and slow effect in attenuating menopausal hot flushes [87]. 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). Dietary intake of flavonoid subclasses and risk of colorectal cancer: Evidence from population studies. Reduction of the endometrial thickness in North American women (for 0.23 mm). In their systematic revision, which included 1307 menopausal (n = 139) and post-menopausal (n = 1268) women, Perna et al. It follows that additional high-quality, large-scale randomized controlled trials are needed. 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. Perna S., Peroni G., Miccono A., Riva A., Morazzoni P., Allegrini P., Preda S., Baldiraghi V., Guido D., Rondanelli M. Multidimensional Effects of Soy Isoflavone by Food or Supplements in Menopause Women: A Systematic Review and Bibliometric Analysis. Bacterial metabolites of isoflavones forming in the gut. For this reason, the results should be interpreted with caution, and more randomized clinical trials are imperative. government site. Gruber C.J., Tschugguel W., Schneeberger C., Huber J.C. Production and actions of estrogens. Therefore, the authors concluded that the intake of dietary isoflavones paid a protective role against ovarian cancer. ); sue.uhe@zelaznog.enatiam (M.G.-A. 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. Diversely, Liu et al. 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. On the contrary, a systematic review and meta-analysis reported by Man et al. THE effect of light on plant life has been the subject of many scientific investigations. However, the magnitude of risk reduction in Asian women was slightly larger than in non-Asian women (22% vs. 18%). The authors studied all possible correlations between isoflavone consumption and the risk of breast cancer. However, all the authors agree that further studies are necessary so as to confirm these results. (2017) conducted a meta-analysis with 21 case-control studies and two cohort studies, with a total number of 11,346 cases and 140,177 controls [77]. The authors suggested that this difference could be due to different genetic backgrounds and dietary patterns among Asian and Western populations. 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. Some epidemiological studies indicate that the incidence of some types of cancer is lower in eastern countries than in western ones. Chemical structure of 17-estradiol. Due to a decline in sunlight, the development of leaves . Collison M.W. 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. Some authors label equol as an isoflavone; however, since it is a daidzein-derived bacterial metabolite and not a naturally occurring isoflavone, this classification is not correct [10]. Gut bacterial metabolism of the soy isoflavone daidzein: Exploring the relevance to human health. 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. Thanks for reading Scientific American. Chadha R., Bhalla Y., Jain A., Chadha K., Karan M. Dietary Soy Isoflavone: A Mechanistic Insight. This finding suggests that bacterial deglycosylation contributes significantly to isoflavone absorption [32]. Thus, whereas Asian populations have an average isoflavone consumption of >30 mg/day, Western populations consume <1 mg/day [83]. 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]. Implications of phytoestrogen intake for breast cancer. Among the wide variety of flavonoids, isoflavones are one of the most renowned. In contrast, the effects on bone resorption biomarkers were more favorable in overweight or obese women than in women with a healthy weight. 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 another systematic review of three observational studies (including 68,748 participants), low evidence of isoflavones was shown in the prevention of cardiovascular diseases [61]. An official website of the United States government. Inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, but not in cohort studies. In view of the results gathered in the present review, we can conclude that there is scientific evidence that reveals the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis in postmenopausal women. (2018), 30 articles were included for analysis; 15 of them were case-control studies, eight cohort studies and seven nested case-control studies [76]. 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]. Metabolism of intraruminally administered [4-. Daidzein, genistein and glycitein occur naturally in the aglycone form, and thus their absorption is faster than that of others. 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 enzymes responsible for the hydrolysis of isoflavone glycosides are glucosidases, which can be produced by the intestinal mucosa or the microbiota [29]. Atkinson C., Frankenfeld C.L., Lampe J.W. In like manner, a meta-analysis by Simental-Menda et al. Oral isoflavone supplementation on endometrial thickness: A meta-analysis of randomized placebo-controlled trials. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. It supports the evidence that isoflavones can moderately attenuate bone resorption in women with low estrogen levels, primarily at the level of the lumbar spine and the femoral neck. and J.T. A systematic review and meta-analysis of the effects of isoflavone formulations against estrogen-deficient bone resorption in peri- and postmenopausal women. Modified from Mace et al. Hua et al. (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]. Produced metabolites appear in plasma at variable concentrations and can enter enterohepatic circulation [28]. Moreover, this association was more prominent among postmenopausal women than premenopausal women. In tropical climates meat which is exposed to the moonlight rapidly becomes putrid ; and in the Indies, the negroes who will lie sweltering and unoovered beneath the full glare of a tropical sun, carefully muffle their heads and faces when exposed to the moonbeams, which they believe will cause swelling and distortion of the features, and sometimes even blindness. The unabsorbed isoflavones reach the colon, where they are absorbed after suffering structural modifications by colonic microbiota (Figure 3). Arjmandi B.H., Smith B.J. (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, several studies have observed that the urine excretion of daidzein metabolites is notably higher than that of genistein metabolites [44,45,46]. 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