Dead or dying trees are a common sight in areas effected by acid rain. Regarding the mechanisms by which isoflavones act to alleviate vasomotor symptoms, is has been proposed that they bind to estrogen receptors and activate endothelial nitric oxide synthase (eNOS) transcription, leading to eNOS synthesis and nitric oxide production, the main mediator of vasodilatation, which allows cutaneous heat dissipation [91] (Figure 6). 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. 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]. There are a total of 15 3 = 3375 possible outcomes. Effects of isoflavones in menopausal symptoms. Association between Dietary Isoflavones in Soy and Legumes and Endometrial Cancer: A Systematic Review and Meta-Analysis. 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. 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. 8600 Rockville Pike Isoflavone Supplements for Menopausal Women: A Systematic Review. However, in the meta-analysis, a minor enhancement in flow-mediated dilation after soy protein supplementation was found. The results showed that a higher regular intake of foods rich in isoflavones might potentially decrease colorectal cancer incidence. Grosso 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. Importantly, the soy variety, environmental conditions of the culture and the processing of soybeans notably influence their isoflavone content [18]. Sansai et al. With regard to the published meta-analysis, the studies included were restricted to randomized controlled trials. 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. 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. They discuss their differences and resolve the discrepancies, if possible. Setchell K.D., Brown N.M., Lydeking-Olsen E. The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones. 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. (At least not real scientists.) Prez-Cornago et al. For their meta-analysis, Jiang et al. 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. Heinonen S., Whl K., Adlercreutz H. Identification of isoflavone metabolites dihydrodaidzein, dihydrogenistein, 6-OH-O-dma, and cis-4-OH-equol in human urine by gas chromatography-mass spectroscopy using authentic reference compounds. PV panels have been linked . For this reason, the results should be interpreted with caution, and more randomized clinical trials are imperative. Dong J.Y., Qin L.Q. Dietary isoflavones or isoflavone-rich food intake and breast cancer risk: A meta-analysis of prospective cohort studies. However, the moonlight decreases after the full moon. The four chemical forms of the three most abundant isoflavones. The results indicated that the isoflavone intake decreased the ovarian cancer risk by 33%. In contrast, it seems that isoflavones do not act on central neurotransmitters directly. In their systematic revision, which included 1307 menopausal (n = 139) and post-menopausal (n = 1268) women, Perna et al. (2015) concluded that soy isoflavones have both a slight and slow effect in attenuating menopausal hot flushes [87]. (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]. Sfakianos J., Coward L., Kirk M., Barnes S. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. Others, however, consider such notions as prime examples of "New Age freakery". So long ago as 1880 Siemens showed that continuous exposure to arc lamps promoted luxuriance of foliage . 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]. The aglycone and conjugate forms of genistein represent up to 60% of total isoflavones, this being up to 30% in the case of daidzein. Consequently, isoflavones can have estrogenic or anti-estrogenic effects [3]. In this study, five prospective cohort studies and seven case-control studies, with 6275 cases and 393,776 controls, were included. 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). 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]. The authors reported that neither soy food intake nor circulating isoflavones were associated with a reduced risk of prostate cancer. Moreover, a higher intake of soy isoflavones was associated with a lower risk of mortality from gastric, colorectal, and lung cancers. Ten studies reported a significant reduction in hot flush frequency in the phytoestrogen group when compared with the placebo group. Similarly, Li et al. Estimated Asian adult soy protein and isoflavone intakes. 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]. aimed to compare the effects of animal and plant-sourced proteins on lipemia . (2020) carried out their meta-analysis of 63 controlled trials, including 6427 postmenopausal women and concluded that isoflavones improve bone density at the lumbar spine, femoral neck and the distal radius in menopausal women [50]. The effect of soy isoflavones on arterial stiffness: A systematic review and meta-analysis of randomized controlled trials. This is mainly due to their potential adverse effects, which range from increased coronary heart disease to stroke and cancer [53,85]. Produced metabolites appear in plasma at variable concentrations and can enter enterohepatic circulation [28]. The gravitational attraction between the Earth and the Moon produces two bulges in the ocean on opposite sides of the Earth. and A.F.-Q. Thus, the EFSA scientific committees opinion agreed that isoflavone intake was safe, at least in the doses that the analyzed studies have used. Consensus: Soy isoflavones as a first-line approach to the treatment of menopausal vasomotor complaints. Zhong et al. The authors declare no conflict of interest. Possible mechanism of action of isoflavones for cancer prevention. Effects of isoflavones in different cancer types. This difference could explain the slow effect of isoflavones in alleviating hot flushes. Lund S., Holman G.D., Schmitz O., Pedersen O. 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. On the contrary, women who were already equol producers did not obtain any additional benefit from supplements of equol or isoflavones. Vlachopoulos C., Aznaouridis K., Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: A systematic review and meta-analysis. Isoflavone intake in four different European countries: The VENUS approach. Cheynier V., Sarni-Manchado P., Quideau S., editors. The difference for isoflavones required to find an effect can be due to variations in the amount of isoflavone intake between both populations. 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. 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. 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]. Soy isoflavones and their metabolites modulate cytokine-induced natural killer cell function. 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. Equol is produced from the isoflavone daidzein by intestinal bacteria, mainly in the large intestine. 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. He X., Sun L.M. 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]. Barnes S. The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products. 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 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. 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. government site. 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. Modified from Mace et al. Gut bacterial metabolism of the soy isoflavone daidzein: Exploring the relevance to human health. Received 2020 Nov 30; Accepted 2020 Dec 15. Bhathena S.J., Velasquez M.T. 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]. Looking at a few examples of moonlight's. 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. Federal government websites often end in .gov or .mil. Li L., Lv Y., Xu L., Zheng Q. Quantitative efficacy of soy isoflavones on menopausal hot flashes. Isoflavone content in soy-derived products is usually lower than in soybeans [17]. (2016), nine studies addressed to menopausal women and focused on bone health were analyzed [52]. 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 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. Murota K., Nakamura Y., Uehara M. Flavonoid metabolism: The interaction of metabolites and gut microbiota. Moreover, sodium-dependent glucose transporter 1 (SGLT1) allows phenolic compound-glycosylates to directly enter into epithelial cells, where they are hydrolyzed by cytosolic glucosidases [30,31]. The light of the moon also influences animals that are active in daytime. 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. In general, evidence regarding the use of isoflavones on vasomotor symptoms suggests that they could be useful in reducing hot flushes. Bustamante-Rangel M., Delgado-Zamarreo M.M., Perez-Martin L., Rodriguez-Gonzalo E., Dominguez-Alvarez J. Furthermore, the dose-response analysis revealed an 8% reduction in colorectal neoplasm risk for every 20 mg/day increase in isoflavone intake in Asian populations, and for every 0.1 mg/day increase in Western populations. 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]. Altogether, these results show that further studies are needed in order to find stronger conclusions. 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. However, some limitations were found in these prospective studies, such as the small sample size of the cohorts and the unspecific definition of high, moderate and low isoflavone intake. 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. (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]. Apparently, soy isoflavones modified adhesion molecules by binding to vascular endothelium and mimicking the effect of a modulator of estrogen receptors [64]. Study duration ranged from four weeks to two years, with a median of 12 weeks. 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. 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. 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. Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin. ); sue.uhe@ollitrop.yupairam (M.P.P. "It's not. Daidzein is first converted into dihydrodaidzein, which is the precursor of both equol and O-demethylangolensin (O-DMA) [37]. Careers, Unable to load your collection due to an error. Sotoca A.M., van den Berg H., Vervoort J., van der Saag P., Strm A., Gustafsson J.A., Rietjens I., Murk A.J. Arjmandi B.H., Smith B.J. 2023 Scientific American, a Division of Springer Nature America, Inc. Discover world-changing science. 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. 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. 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. 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]. Moreover, Rienks et al. 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. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. 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. Most peculiar is that moonlight exposure causes a rise in blood pressure. 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]. 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. The light reflected off the moon has an effect on life on Earth, which isn't surprising, but not every lunar influence is heralded by a wolf's howl. Man B., Cui C., Zhang X., Sugiyama D., Barinas-Mitchell E., Sekikawa A. 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. 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. In the systematic review reported by Perna et al. FOIA Thus, whereas Asian populations have an average isoflavone consumption of >30 mg/day, Western populations consume <1 mg/day [83]. Abdi et al. Endometrial cancer (Table 4), as well as breast cancer, is an estrogen-dependent cancer type related to high circulating estradiol concentrations. 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. Gaya P., Medina M., Snchez-Jimnez A., Landete J.M. 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 addition, Qiu 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. 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. However, it is important to mention that this connection has been established based on pre-clinical studies, whereas data derived from clinical trials have not demonstrated such association [92]. (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]. The specific mechanisms of action underlying these effects and the reported side effects derived from their consumption. 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. 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. Sulfation of the isoflavones genistein and daidzein in human and rat liver and gastrointestinal tract. Lambert M.N.T., Hu L.M., Jeppesen P.B. . ); sue.uhe@zednanref.oderfla (A.F.-Q. These two associations were significant for postmenopausal participants. The authors concluded that evidence for the role of isoflavones and soy products in the prevention of cardiovascular diseases was scarce and inconclusive. Therefore, it is necessary to support these results with additional studies. 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. A significant 19% reduction of the risk was found at high concentrations of daidzein, but not at genistein or equol concentrations. 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. In soybeans, the three most abundant isoflavones are present in four chemical forms: aglycone, glycoside, acetylglycoside and malonylglucoside (Table 1 and Figure 2). Morning 3: Temp 98.6 BP 124/83 Pulse 62 bpm. Thanks for reading Scientific American. 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. 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. An official website of the United States government. Liu J., Yuan F., Gao J., Shan B., Ren Y., Wang H., Gao Y. In like manner, a meta-analysis by Simental-Menda et al. Due to the high prevalence of colorectal cancer, three meta-analyses addressing this issue are included in the present review. In contrast, the effects on bone resorption biomarkers were more favorable in overweight or obese women than in women with a healthy weight. Isoflavone glycosides have to be hydrolyzed to the aglycone form prior to its absorption by passive diffusion in the upper small intestine [28]. Discrepancies, if possible a common sight in areas effected by acid rain O-demethylangolensin ( O-DMA ) [ 37.. 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scientific evidence regarding the effects of moonlight on plants
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