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). ), 2CIBEROBN Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, 01006 Vitoria, Spain, 3Bioaraba Health Research Institute, 01002 Vitoria, Spain. Duffy C., Perez K., Partridge A. Efficacy of phytoestrogens for menopausal symptoms: A meta-analysis and systematic review. (2019), included 16 prospective cohort studies involving 11,169 breast cancer cases and 648,913 participants [70]. 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]. It is important to point out that the spine has a high proportion of trabecular bone and that this is probably the reason why the spine is thought to be more sensitive to isoflavones. They performed a separated meta-analysis for each of the interventions, including dietary soy isoflavones (including four studies), supplements and extracts of soy isoflavones (including six studies) and red clover isoflavones (including seven studies). and transmitted securely. 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. In this regard, it has been reported that isoflavones have a higher affinity to the -estrogen receptor [7], which, contrary to the -estrogen receptor, inhibits cell proliferation and stimulates apoptosis [84]. 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. 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). For the development of this section, the meta-analyses and systematic reviews published between 2015 and 2020 were taken into account. For this reason, the results should be interpreted with caution, and more randomized clinical trials are imperative. As in the previous study, the onset of soy isoflavones was very slow in comparison with other non-hormonal treatments. 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. In conclusion, this study reported some evidence that suggests the beneficial role that daidzein and genistein play in preventing breast cancer risk. Cheynier V., Sarni-Manchado P., Quideau S., editors. Soy products (0.05130 g/day) and total isoflavones (0.28 to 63 mg/day). Proof by rational experiment seems to have been. 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). 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. Isoflavones (high dose: 0.675.5 mg/day; and low dose: 0.0120.1 mg/day). 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]. However, the magnitude of risk reduction in Asian women was slightly larger than in non-Asian women (22% vs. 18%). Vlachopoulos C., Aznaouridis K., Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: A systematic review and meta-analysis. 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]. This difference could explain the slow effect of isoflavones in alleviating hot flushes. The four chemical forms of the three most abundant isoflavones. In like manner, a meta-analysis by Simental-Menda et al. Isoflavones are found in several vegetables, mainly in legumes (Fabaceae family) such as soy, white and red clover, alfalfa and beans [9,10]. It has been described that after the oral intake of isoflavones, their peak plasma concentration in humans occurs at around seven hours [33]. 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. These two associations were significant for postmenopausal participants. Bacterial metabolites of isoflavones forming in the gut. Lu D., Gigure V. Requirement of Ras-dependent pathways for activation of the transforming growth factor beta3 promoter by estradiol. Another meta-analysis, conducted by Zhao et al. Reduction of the endometrial thickness in North American women (for 0.23 mm). Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. A systematic review and meta-analysis of the effects of isoflavone formulations against estrogen-deficient bone resorption in peri- and postmenopausal women. Isoflavone excretion occurs mainly through urine and feces, primarily in the conjugate forms, and up to 95% takes place in 24 h [43]. Daily et al. 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. Thus, its consumption, according to epidemiological and clinical studies, has been postulated to be related to a decrease in the risk of different diseases. 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). 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). 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. Presence of four chemical forms of the three isoflavones found in soybeans. Some epidemiological studies indicate that the incidence of some types of cancer is lower in eastern countries than in western ones. National Library of Medicine Matulka R.A., Matsuura I., Uesugi T., Ueno T., Burdock G. Developmental and Reproductive Effects of SE5-OH: An Equol-Rich Soy-Based Ingredient. At high elevations, acidic fog and clouds might . Neuroprotective effects of 17beta-estradiol and nonfeminizing estrogens against H. Endoh H., Sasaki H., Maruyama K., Takeyama K., Waga I., Shimizu T., Kato S., Kawashima H. Rapid activation of MAP kinase by estrogen in the bone cell line. 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. Kov L., Dadkov K., Kaparovsk J., Kaparovsk T. Isoflavones. Future research in this field should quantify isoflavones as accurately as possible, analyzing larger cohorts and lengthening the follow-up stage. 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]. Nevertheless, it is important to consider this metabolite since it is key in the biological activity of isoflavones [13]. You J., Sun Y., Bo Y., Zhu Y., Duan D., Cui H., Lu Q. Lastly, Zhang et al. 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. A total of 16 studies were included in their meta-analysis with a range of 24 to 236 subjects. 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. 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. This meta-analysis included 266,699 participants (21,612 patients with prostate cancer among them). In the meta-analysis reported by Chen et al. This is mainly due to their potential adverse effects, which range from increased coronary heart disease to stroke and cancer [53,85]. 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. Jun S., Shin S., Joung H. Estimation of dietary flavonoid intake and major food sources of Korean adults. The authors indicated that no consensus was found regarding the protective effects of soy isoflavones (2080 mg) and equol (10 mg) on bone resorption. 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. (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]. Mace T.A., Ware M.B., King S.A., Loftus S., Farren M.R., McMichael E., Scoville S., Geraghty C., Young G., Carson W.E., et al. In this sense, the authors suggested that the composition of the gut microflora may influence isoflavone absorption and metabolism and could affect the production of isoflavone metabolites, which, in turn, could mediate their biological activity. 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]. 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. Murota K., Nakamura Y., Uehara M. Flavonoid metabolism: The interaction of metabolites and gut microbiota. 8600 Rockville Pike Perna et al. Others, however, consider such notions as prime examples of "New Age freakery". The authors reported that isoflavone intake from soy products and legumes was associated with a 19% reduction in endometrial cancer risk. Hence, plants grow faster and healthier. 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. 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. Thus, whereas Asian populations have an average isoflavone consumption of >30 mg/day, Western populations consume <1 mg/day [83]. Moreover, five studies reported side-effect data, and after the analysis, no significant differences were observed between the two groups. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. 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. (2017) included 26 trials with 2652 participants [48]. (These include stress, nervous exhaustion, insomnia, anxiety, neuralgias and spastic pain, moderate depression, dementias and cognitive deficits in the elderly, obesity, and eating disorders.) The authors concluded that evidence for the role of isoflavones and soy products in the prevention of cardiovascular diseases was scarce and inconclusive. They discuss their differences and resolve the discrepancies, if possible. 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