Perna et al. Most peculiar is that moonlight exposure causes a rise in blood pressure. Looking at a few examples of moonlight's. 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. It has been described that after the oral intake of isoflavones, their peak plasma concentration in humans occurs at around seven hours [33]. 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. 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. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women. (2017) carried out a meta-analysis of 143 case-control studies, where isoflavone intake was associated with endometrial, ovarian, and breast cancers [73]. Considering the isoflavone chemical structure, potential health adverse effects of these compounds related to their estrogenic activity have been postulated, despite the scientific opinion offered by EFSA indicating that isoflavone intake was safe. (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]. Moreover, five studies reported side-effect data, and after the analysis, no significant differences were observed between the two groups. 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. 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. official website and that any information you provide is encrypted However, in the meta-analysis, a minor enhancement in flow-mediated dilation after soy protein supplementation was found. 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. Metabolism of intraruminally administered [4-. 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. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. 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]. 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 general terms, caution should be exercised with the use of high doses of isoflavones in women with a family history of breast cancer [49]. The same results were reported in another meta-analysis published by the same authors a year later (Li et al., 2016), when they compared the efficacy of several non-hormonal drugs on hot flushes, including selective serotonin reuptake inhibitors (SSRIs), serotoninnorepinephrine reuptake inhibitors (SNRIs), gabapentin, clonidine and soy isoflavones [88]. In some cases the purported effect may depend on external cues, such as the amount of moonlight. The authors concluded that evidence for the role of isoflavones and soy products in the prevention of cardiovascular diseases was scarce and inconclusive. 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]. 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. Soy isoflavones and their metabolites modulate cytokine-induced natural killer cell function. (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]. U.S. Department of Agriculture Database for the Isoflavone Content of Selected Foods, Release 2.0. Nachvak S.M., Moradi S., Anjom-Shoae J., Rahmani J., Nasiri M., Maleki V., Sadeghi O. Soy, Soy Isoflavones, and Protein Intake in Relation to Mortality from All Causes, Cancers, and Cardiovascular Diseases: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies. 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. Qiu S., Jiang C. Soy and isoflavones consumption and breast cancer survival and recurrence: A systematic review and meta-analysis. Furthermore, isoflavones are associated with proteins; thus, alcohol extraction and processing diminish isoflavone content in foodstuffs such as fermented soybean, tofu or soy beverages. Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin. Nevertheless, this association was not shown when equol or isoflavones were consumed. ); [email protected] (M.P.P. Rienks J., Barbaresko J., Nthlings U. Diversely, Liu et al. Batterham T.J., Shutt D.A., Braden A.W.H., Tweeddale H.J. During menopause, there is a loss of bone density that can cause osteoporosis. In the same line, in European men, isoflavone concentrations did not affect the risk of developing prostate cancer. Thanks for reading Scientific American. In miso and tempeh, the aglycone form is the most abundant one [9]. The authors studied all possible correlations between isoflavone consumption and the risk of breast cancer. 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. 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). Importantly, the soy variety, environmental conditions of the culture and the processing of soybeans notably influence their isoflavone content [18]. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. 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. Isoflavones (high dose: 0.675.5 mg/day; and low dose: 0.0120.1 mg/day). However, the magnitude of risk reduction in Asian women was slightly larger than in non-Asian women (22% vs. 18%). National Library of Medicine Sex and long-term soy diets affect the metabolism and excretion of soy isoflavones in humans. For their meta-analysis, Jiang et al. With regard to the mechanisms by which isoflavones act to reduce cancer risk, it has been suggested that the effects are due to the similarity of the isoflavone molecule to estradiol. Focusing on the overall intake of isoflavones in humans, several studies have reported varied results. In the meta-analysis reported by Chen et al. Moreover, this association was more prominent among postmenopausal women than premenopausal women. Simental-Menda L.E., Gotto A.M., Atkin S.L., Banach M., Pirro M., Sahebkar A. 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. Possible mechanism of action of isoflavones for menopausal symptoms. Future research in this field should quantify isoflavones as accurately as possible, analyzing larger cohorts and lengthening the follow-up stage. 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. 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]. Liu J., Yuan F., Gao J., Shan B., Ren Y., Wang H., Gao Y. (2016) included 17 studies (nine case-control studies and eight cohort studies) [80]. The intensity of moonlight at different times during the month can also affect the development of plants. For this reason, the results should be interpreted with caution, and more randomized clinical trials are imperative. The two systematic reviews conclude that isoflavones have an important role in reducing hot flushes [52,53], although some observations need to be pointed out. 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. Inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, but not in cohort studies. CVD: cardiovascular disease, LDL: low-density lipoprotein. 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. However, the authors suggested that more prospective cohort studies are needed to further investigate this association and that the quantity of isoflavone intake should be accurately measured because flavonoid contents in food can vary significantly. This result has implications for granivory and perhaps plant demography in invaded and restored coastal habitats. 19% reduction in endometrial cancer risk. A systematic review and meta-analysis of the effects of isoflavone formulations against estrogen-deficient bone resorption in peri- and postmenopausal women. Winkel-Shirley B. Biosynthesis of flavonoids and effects of stress. After this, each metabolite undergoes its own metabolic pathway [40]. Association of isoflavone biomarkers with risk of chronic disease and mortality: A systematic review and meta-analysis of observational studies. The authors found, in a small number of studies (17 studies including 337 healthy, diabetic or hypercholesterolemic individuals), that a soy protein-based diet (rich in isoflavones) as compared to animal protein-based diets (meat, milk, casein, whey) resulted in reduced total cholesterol or LDL-cholesterol concentrations, increased HDL cholesterol concentrations, improved LDL:HDL cholesterol ratio, and decreased triglycerides. 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 authors declare no conflict of interest. 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. Lastly, Zhang et al. 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. Collison M.W. (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]. 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. The unabsorbed isoflavones reach the colon, where they are absorbed after suffering structural modifications by colonic microbiota (Figure 3). Prez-Cornago et al. The main forms of conjugates in soybeans are the malonyl derivatives [14]. Bustamante-Rangel M., Delgado-Zamarreo M.M., Perez-Martin L., Rodriguez-Gonzalo E., Dominguez-Alvarez J. Potential mechanism of action of isoflavones on bone metabolism. ), 2CIBEROBN Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, 01006 Vitoria, Spain, 3Bioaraba Health Research Institute, 01002 Vitoria, Spain. 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. 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. Ronis M.J., Little J.M., Barone G.W., Chen G., Radominska-Pandya A., Badger T.M. 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. He X., Sun L.M. These positive effects were associated with 54 mg/day of genistein and 600 mg/day of synthetic isoflavone ipriflavone. 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. Sansai et al. 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. The Effects and Action Mechanisms of Phytoestrogens on Vasomotor Symptoms During Menopausal Transition: Thermoregulatory Mechanism. The https:// ensures that you are connecting to the Endometrial cancer (Table 4), as well as breast cancer, is an estrogen-dependent cancer type related to high circulating estradiol concentrations. Moreover, the number of publications grouping women according to pre- or post-diagnosis intake criteria is small. Matulka R.A., Matsuura I., Uesugi T., Ueno T., Burdock G. Developmental and Reproductive Effects of SE5-OH: An Equol-Rich Soy-Based Ingredient. Isoflavones were the phytoestrogens used in most of the studies; therefore, the meta-analysis only included outcomes regarding isoflavones, while outcomes with other phytoestrogens were not included. 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. Therefore, it is necessary to support these results with additional studies. Kelly G.E., Nelson C., Waring M.A., Joannou G.E., Reeder A.Y. Li L., Xu L., Wu J., Dong L., Zhao S., Zheng Q. You J., Sun Y., Bo Y., Zhu Y., Duan D., Cui H., Lu Q. However, the results do not seem entirely conclusive, for there are discrepancies among the studies, probably related to their experimental designs. (At least not real scientists.) 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. 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. Murota K., Nakamura Y., Uehara M. Flavonoid metabolism: The interaction of metabolites and gut microbiota. The .gov means its official. Dong J.Y., Qin L.Q. Only one study examined the effects of red clover on night sweats, and a significant association was found, which showed a decreased frequency in 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]. Acid rain leaches aluminum from the soil. In their systematic revision, which included 1307 menopausal (n = 139) and post-menopausal (n = 1268) women, Perna et al. For this reason, the bioavailability of isoflavones has been extensively characterized in animal models and humans [25,26,27]. HHS Vulnerability Disclosure, Help Effects of isoflavones in different cancer types. 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. 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. For the development of this section, the meta-analyses and systematic reviews published between 2015 and 2020 were taken into account. 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. Daidzein is first converted into dihydrodaidzein, which is the precursor of both equol and O-demethylangolensin (O-DMA) [37]. This is mainly due to their potential adverse effects, which range from increased coronary heart disease to stroke and cancer [53,85]. The conclusion was that isoflavones exerted little influence over bone mineral density and thus over bone health during menopause, although not all the studies observed the same effect. 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]. (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]. With regard to isoflavone content in foodstuffs, it has been observed that in soybeans, the amount of these phenolic compounds ranges from 1.2 to 4.2 mg per g on dry weight, whereas in red clover, the amount varies between 10 and 25 mg per g on dry weight [15,16]. The authors found a significant inverse association between isoflavone intake and both overall mortality and breast cancer recurrence. (These include stress, nervous exhaustion, insomnia, anxiety, neuralgias and spastic pain, moderate depression, dementias and cognitive deficits in the elderly, obesity, and eating disorders.) van der Schouw Y.T., Kreijkamp-Kaspers S., Peeters P.H., Keinan-Boker L., Rimm E.B., Grobbee D.E. 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]. Effects of Acid Rain on Plants and Trees. Influence of cellular ERalpha/ERbeta ratio on the ERalpha-agonist induced proliferation of human T47D breast cancer cells. 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. [(accessed on 21 September 2020)]; Messina M., Nagata C., Wu A.H. 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. Man B., Cui C., Zhang X., Sugiyama D., Barinas-Mitchell E., Sekikawa A. aimed to compare the effects of animal and plant-sourced proteins on lipemia and blood pressure [60]. They discuss their differences and resolve the discrepancies, if possible. 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. Thus, the EFSA scientific committees opinion agreed that isoflavone intake was safe, at least in the doses that the analyzed studies have used. 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. . The authors reported that neither soy food intake nor circulating isoflavones were associated with a reduced risk of prostate cancer. 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]. 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