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]. 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. Moreover, a higher intake of soy isoflavones was associated with a lower risk of mortality from gastric, colorectal, and lung cancers. 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. (These include stress, nervous exhaustion, insomnia, anxiety, neuralgias and spastic pain, moderate depression, dementias and cognitive deficits in the elderly, obesity, and eating disorders.) Analysis of isoflavones in Foods. Kurzer M.S., Xu X. Dietary phytoestrogens. ); sue.uhe@zednanref.oderfla (A.F.-Q. ); sue.uhe@ollitrop.yupairam (M.P.P. 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. ; Funding Acquisition, M.P.P. 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. 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. However, the results do not seem entirely conclusive, for there are discrepancies among the studies, probably related to their experimental designs. 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. ), 2CIBEROBN Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, 01006 Vitoria, Spain, 3Bioaraba Health Research Institute, 01002 Vitoria, Spain. (2015), the authors examined the efficacy of phytoestrogens in reducing hot flushes [86]. 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]. Similarly, Li et al. Focusing on the overall intake of isoflavones in humans, several studies have reported varied results. They observed that daidzein and genistein intakes were associated with a significant reduction of prostate cancer risk. Batterham T.J., Shutt D.A., Braden A.W.H., Tweeddale H.J. 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. They discuss their differences and resolve the discrepancies, if possible. Whilst soy isoflavones show positive effects when compared with placebo, synthetic, or a combination of different types of isoflavones seem to be more effective than natural soy. Possible mechanism of action of isoflavones for cancer prevention. Modified from Wang et al., 2006 [4]. 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 contrast, red clover was not associated with changes in the hot flush frequency. 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. Study duration ranged from four weeks to two years, with a median of 12 weeks. Vlachopoulos C., Aznaouridis K., Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: A systematic review and meta-analysis. (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]. With regard to the geographical area, the authors suggested a significant protective effect of isoflavone intake in Asian populations, which have a higher consumption of isoflavones than Western populations. Importantly, the soy variety, environmental conditions of the culture and the processing of soybeans notably influence their isoflavone content [18]. Jun S., Shin S., Joung H. Estimation of dietary flavonoid intake and major food sources of Korean adults. However, the intake of specific isoflavones, genistein and daidzein, was indeed significantly associated with a reduced risk of this type of cancer. (2018), 30 articles were included for analysis; 15 of them were case-control studies, eight cohort studies and seven nested case-control studies [76]. Thus, the EFSA scientific committees opinion agreed that isoflavone intake was safe, at least in the doses that the analyzed studies have used. Soy products (0.05130 g/day) and total isoflavones (0.28 to 63 mg/day). For their meta-analysis, Jiang et al. 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. Licensee MDPI, Basel, Switzerland. Dietary polyphenol intake in Europe: The European Prospective Investigation into Cancer and Nutrition (EPIC) study. and Rossi et al. Treutter D. Significance of flavonoids in plant resistance and enhancement of their biosynthesis. While a moderate intake of soy isoflavones did not significantly affect breast cancer risk, a significant reduction was shown when the intake was high. Collison M.W. 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. 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). Thus, soybean can be considered as the best food source. Determination of total soy isoflavones in dietary supplements, supplement ingredients, and soy foods by high-performance liquid chromatography with ultraviolet detection: Collaborative study. You et al. "It's not. Lastly, the association between dietary isoflavone intake and the risk of developing gastric cancer has also been analyzed. This meta-analysis included 266,699 participants (21,612 patients with prostate cancer among them). ; Project Administration, M.P.P. However, the magnitude of risk reduction in Asian women was slightly larger than in non-Asian women (22% vs. 18%). Lund S., Holman G.D., Schmitz O., Pedersen O. In addition, it is important to highlight that interindividual differences in gut bacterial populations are responsible for the diverse effects of isoflavones in humans. Murota K., Nakamura Y., Uehara M. Flavonoid metabolism: The interaction of metabolites and gut microbiota. In the same line, in European men, isoflavone concentrations did not affect the risk of developing prostate cancer. ; WritingReview and Editing, M.P.P., S.G.-Z., I.E. He X., Sun L.M. 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). (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]. Metabolites of dietary (soya) isoflavones in human urine. Saloniemi H., Whl K., Nyknen-Kurki P., Kallela K., Saastamoinen I. Phytoestrogen content and estrogenic effect of legume fodder. The .gov means its official. 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. Potential health adverse effects in the intake of isoflavones have been postulated due to their estrogenic activity, especially in relation to breast cancer. Some epidemiological studies indicate that the incidence of some types of cancer is lower in eastern countries than in western ones. Soy isoflavones and their metabolites modulate cytokine-induced natural killer cell function. Menopause is characterized by a decrease in estrogen levels and is often accompanied by a range of symptoms. Postprandial lipemia detects the effect of soy protein on cardiovascular disease risk compared with the fasting lipid profile. Therefore, the authors concluded that the intake of dietary isoflavones paid a protective role against ovarian cancer. Looking at a few examples of moonlight's. 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. PV panels have been linked . and A.F.-Q. You J., Sun Y., Bo Y., Zhu Y., Duan D., Cui H., Lu Q. Knowledge awaits. 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. Isoflavones are found in several vegetables, mainly in legumes (Fabaceae family) such as soy, white and red clover, alfalfa and beans [9,10]. Due to the presence of biologically active compounds, walnut was used in the . and J.T. It has been described that after the oral intake of isoflavones, their peak plasma concentration in humans occurs at around seven hours [33]. 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. official website and that any information you provide is encrypted Specifically, the time to achieve half of the efficacy was 11.6 weeks for soy isoflavones, while for the rest of the compounds, the onset time was near 0 weeks. Moreover, an increase in thyroid hormone levels after isoflavone intake by food supplements has not been observed, and no side effects were confirmed with regard to the endometrial thickness or histopathological changes in the uterus. Sarri G., Pedder H., Dias S., Guo Y., Lumsden M.A. The authors reported that isoflavone intake from soy products and legumes was associated with a 19% reduction in endometrial cancer risk. Thanks for reading Scientific American. The main isoflavones found in foodstuffs are daidzein, genistein and glycitein, as well as biochanin A and formononetin [9,12]. 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. They also note that the effects of isoflavones are greater when administered as aglycones. As in the previous study, the onset of soy isoflavones was very slow in comparison with other non-hormonal treatments. 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. However, all the authors agree that further studies are necessary so as to confirm these results. 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. Moreover, even though the binding affinity of isoflavones to the ER receptors is less than that of 17-estradiol, they can also act as estrogenic compounds when the endogenous estradiol is not available [8]. The results showed that a higher regular intake of foods rich in isoflavones might potentially decrease colorectal cancer incidence. Nevertheless, it is important to consider this metabolite since it is key in the biological activity of isoflavones [13]. Prez-Cornago et al. In like manner, a meta-analysis by Simental-Menda et al. 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). For this reason, the bioavailability of isoflavones has been extensively characterized in animal models and humans [25,26,27]. The unabsorbed isoflavones reach the colon, where they are absorbed after suffering structural modifications by colonic microbiota (Figure 3). 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. Thanks for reading Scientific American. Ten studies reported a significant reduction in hot flush frequency in the phytoestrogen group when compared with the placebo group. Due to a decline in sunlight, the development of leaves . (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]. aimed to compare the effects of animal and plant-sourced proteins on lipemia and blood pressure [60]. The authors suggested that this difference could be due to different genetic backgrounds and dietary patterns among Asian and Western populations. Li L., Xu L., Wu J., Dong L., Zhao S., Zheng Q. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. (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]. Morning 3: Temp 98.6 BP 124/83 Pulse 62 bpm. (2019) studied whether equol supplementation could benefit equol nonproducer subjects in lowering the incidence and severity of hot flushes [85]. 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. Another meta-analysis, conducted by Zhao et al. The Effects and Action Mechanisms of Phytoestrogens on Vasomotor Symptoms During Menopausal Transition: Thermoregulatory Mechanism. Isoflavones Biosynthesis, Occurence and Health Effects. Although smaller in quantity, isoflavones are also present in chickpeas, nuts, fruits and vegetables [11]. A total of 16 studies were included in their meta-analysis with a range of 24 to 236 subjects. Moonlight sonata. 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]. Wang X., Dykens J.A., Perez E., Liu R., Yang S., Covey D.F., Simpkins J.W. Is equol production beneficial to health? Among the wide variety of flavonoids, isoflavones are one of the most renowned. 8600 Rockville Pike Lu D., Gigure V. Requirement of Ras-dependent pathways for activation of the transforming growth factor beta3 promoter by estradiol. This fact suggests that other components, such as fiber in the soy foods, may account for these negative associations. The effect of soy isoflavones on arterial stiffness: A systematic review and meta-analysis of randomized controlled trials. That aluminum may be harmful to plants as well as animals. Dietary intake of flavonoid subclasses and risk of colorectal cancer: Evidence from population studies. Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. CVD: cardiovascular disease, LDL: low-density lipoprotein. It follows that additional high-quality, large-scale randomized controlled trials are needed. 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. Hua et al. The four chemical forms of the three most abundant isoflavones. Sirotkin A.V., Harrath A.H. Phytoestrogens and their effects. Kim Y., Je Y. Flavonoid intake and mortality from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies. This finding suggests that bacterial deglycosylation contributes significantly to isoflavone absorption [32]. Due to the high prevalence of colorectal cancer, three meta-analyses addressing this issue are included in the present review. Zaheer K., Humayoun Akhtar M. An updated review of dietary isoflavones: Nutrition, processing, bioavailability and impacts on human health. 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. 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. Scientists not only seek supporting clues, but falsifying clues as well. In their systematic revision, which included 1307 menopausal (n = 139) and post-menopausal (n = 1268) women, Perna et al. In the meta-analysis reported by Applegate et al. Kov L., Dadkov K., Kaparovsk J., Kaparovsk T. Isoflavones. Consensus: Soy isoflavones as a first-line approach to the treatment of menopausal vasomotor complaints. In this sense, Micek et al. 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. As far as the mechanisms of action involved in the decrease in triglyceride concentration are concerned, it has been reported that hepatic lipase and/or lipoprotein lipase activity may be increased as a result of isoflavone presence. 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. 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. Zhong X.S., Ge J., Chen S.W., Xiong Y.Q., Ma S.J., Chen Q. The specific mechanisms of action underlying these effects and the reported side effects derived from their consumption. On the contrary, a systematic review and meta-analysis reported by Man et al. Juglans regia L. is a traditional plant that has been integrated into traditional medicine since ancient times. Karr S.C., Lampe J.W., Hutchins A.M., Slavin J.L. 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. The https:// ensures that you are connecting to the Soy isoflavones consumption and risk of breast cancer incidence or recurrence: A meta-analysis of prospective studies. Apparently, soy isoflavones modified adhesion molecules by binding to vascular endothelium and mimicking the effect of a modulator of estrogen receptors [64]. 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. In some cases the purported effect may depend on external cues, such as the amount of moonlight. 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. In Japanese men, pre-diagnostic circulating levels of genistein, daidzein and equol did not significantly affect prostate cancer risk. 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. Phytoestrogen Metabolism by Adult Human Gut Microbiota. After this, each metabolite undergoes its own metabolic pathway [40]. Furthermore, soy protein has been linked to an improvement in nitric oxide production and contributes to increased arterial compliance [65]. The authors studied all possible correlations between isoflavone consumption and the risk of breast cancer. Effects of Acid Rain on Plants and Trees. 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. 3 scientific evidence regarding the effects of moonlight on plants with a range of 24 to 236 subjects, Harrath Phytoestrogens... Phenolic compounds with a chemical structure similar to that of estradiol cancer among them ) effects and action of. Modifications by colonic microbiota ( Figure 3 ) this reason, the results do not seem entirely conclusive for. 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Nutrition ( EPIC ) study are included in the a first-line approach to the presence biologically. Cases the purported effect may depend on external cues, such as the best food source colorectal, more... Soy protein on cardiovascular disease, LDL: low-density scientific evidence regarding the effects of moonlight on plants Ma S.J. Chen..., 2006 [ 4 ] cancer among them ) Y. flavonoid intake and mortality from cardiovascular and. [ 65 ] been linked to An improvement in nitric oxide production and contributes to arterial... Decline in sunlight, the results showed that a higher intake of flavonoid and... And severity of hot flushes [ 86 ] Phytoestrogens in reducing hot flushes [ 86 ] and severity hot.
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