Isoflavones Biosynthesis, Occurence and Health Effects. 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]. 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. 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]. 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. Due to the high prevalence of colorectal cancer, three meta-analyses addressing this issue are included in the present review. The authors found a statistical inverse association between isoflavone consumption and colorectal cancer risk in case-control studies, although not in cohort studies. . The dose of isoflavones ranged from 30 to 200 mg/day. Ronis M.J., Little J.M., Barone G.W., Chen G., Radominska-Pandya A., Badger T.M. (2019), included 16 prospective cohort studies involving 11,169 breast cancer cases and 648,913 participants [70]. 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. Analysis of isoflavones in Foods. Murota K., Nakamura Y., Uehara M. Flavonoid metabolism: The interaction of metabolites and gut microbiota. Future research in this field should quantify isoflavones as accurately as possible, analyzing larger cohorts and lengthening the follow-up stage. In soybeans, the three most abundant isoflavones are present in four chemical forms: aglycone, glycoside, acetylglycoside and malonylglucoside (Table 1 and Figure 2). and A.F.-Q. Estimated Asian adult soy protein and isoflavone intakes. Grosso et al. Lastly, Zhang et al. Scientists often disagree about certain things. 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]. U.S. Department of Agriculture Database for the Isoflavone Content of Selected Foods, Release 2.0. Conceptualization, S.G.-Z. 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]. They observed that daidzein and genistein intakes were associated with a significant reduction of prostate cancer risk. Abstract BELIEFS that phases of the moon have a differential effect on the rate of development of plants are both ancient and world-wide. 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. Kov L., Dadkov K., Kaparovsk J., Kaparovsk T. Isoflavones. 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]. 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]. Man B., Cui C., Zhang X., Sugiyama D., Barinas-Mitchell E., Sekikawa A. Potential health adverse effects in the intake of isoflavones have been postulated due to their estrogenic activity, especially in relation to breast cancer. (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 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). Of those, 35 have 4 / 3, which can be demonstrated by having a computer generate the 3375 combinations and count those that satisfy the criterion.Therefore, by chance alone, one would expect 35/3375 or about 1/96 studies to exhibit as good a coincidence with the full moon as that observed by the authors. 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. (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]. The results showed that a higher regular intake of foods rich in isoflavones might potentially decrease colorectal cancer incidence. In this line, another meta-analysis, which included 52 controlled trials and 5313 patients, shows that soy isoflavones have beneficial effects on bone mineral density in the femur neck, lumbar spine, and hip, regardless of body weight or ethnicity [49]. 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. Others, however, consider such notions as prime examples of "New Age freakery". A systematic review and meta-analysis of the effects of isoflavone formulations against estrogen-deficient bone resorption in peri- and postmenopausal women. Sfakianos J., Coward L., Kirk M., Barnes S. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. Due to its structural similarity to the estrogen-like compound 17-estradiol (Figure 1), they are referred to as phytoestrogens. Effect of soy isoflavone supplementation on plasma lipoprotein(a) concentrations: A meta-analysis. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. In some Asian countries, isoflavone intake, usually derived from soy consumption, can be associated with a lower prevalence of cardiovascular diseases (CVDs). Chemical structure of 17-estradiol. Isoflavone glycosides have to be hydrolyzed to the aglycone form prior to its absorption by passive diffusion in the upper small intestine [28]. However, all the authors agree that further studies are necessary so as to confirm these results. [(accessed on 21 September 2020)]; Messina M., Nagata C., Wu A.H. Karr S.C., Lampe J.W., Hutchins A.M., Slavin J.L. 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. However, a limitation in this field is that there is still a great heterogeneity among studies. (2019) conducted a meta-analysis where 23 prospective studies with a total of 330,826 participants were included. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. Modified from Wang et al., 2006 [4]. Franco et al. 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. Sulfation of the isoflavones genistein and daidzein in human and rat liver and gastrointestinal tract. Effects of isoflavones in different cancer types. 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]. Li L., Xu L., Wu J., Dong L., Zhao S., Zheng Q. Kurzer M.S., Xu X. Dietary phytoestrogens. Therefore, the authors concluded that the intake of dietary isoflavones paid a protective role against ovarian cancer. 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. 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]. and Rossi et al. Gee J.M., DuPont M.S., Day A.J., Plumb G.W., Williamson G., Johnson I.T. 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. With regard to prostate cancer, it has been proposed that it might be affected by isoflavone consumption due to its effect on hormone metabolism. In contrast, it seems that isoflavones do not act on central neurotransmitters directly. 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]. ); sue.uhe@zednanref.oderfla (A.F.-Q. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. 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]. 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. In Japanese men, pre-diagnostic circulating levels of genistein, daidzein and equol did not significantly affect prostate cancer risk. Although results vary greatly, most of these applications are supported by at least a few clinical studies. 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. ; WritingReview and Editing, M.P.P., S.G.-Z., I.E. Study duration ranged from four weeks to two years, with a median of 12 weeks. 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. Scientists not only seek supporting clues, but falsifying clues as well. Potential mechanism of action of isoflavones on bone metabolism. Focusing on the overall intake of isoflavones in humans, several studies have reported varied results. THE effect of light on plant life has been the subject of many scientific investigations. 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. 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. 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]. Furthermore, isoflavones are able to inhibit aromatase activity, the enzyme that converts androgen to estrogen. 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. Nevertheless, the results do not seem entirely conclusive, as there are discrepancies among the studies included in the systematic reviews and in the meta-analyses, probably related to their experimental designs. 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. Comparative efficacy of nonhormonal drugs on menopausal hot flashes. Lastly, the association between dietary isoflavone intake and the risk of developing gastric cancer has also been analyzed. The unabsorbed isoflavones reach the colon, where they are absorbed after suffering structural modifications by colonic microbiota (Figure 3). 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. Discover world-changing science. Proof by rational experiment seems to have been. 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. While a moderate intake of soy isoflavones did not significantly affect breast cancer risk, a significant reduction was shown when the intake was high. 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. Taken as a whole, all these results suggest that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Effects of isoflavones in menopausal symptoms. Two of the studies also revealed that women who were able to produce equol or who had received equol supplementation could have had a greater benefit from isoflavones [53]. Barnes S. The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products. After this, each metabolite undergoes its own metabolic pathway [40]. Duffy C., Perez K., Partridge A. Postprandial lipemia detects the effect of soy protein on cardiovascular disease risk compared with the fasting lipid profile. 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. Cheynier V., Sarni-Manchado P., Quideau S., editors. (2015) concluded that soy isoflavones have both a slight and slow effect in attenuating menopausal hot flushes [87]. You J., Sun Y., Bo Y., Zhu Y., Duan D., Cui H., Lu Q. Moreover, the authors suggested that ethnicity could have had influenced this association, but studies with larger sample sizes are needed to confirm this hypothesis. Oral isoflavone supplementation on endometrial thickness: A meta-analysis of randomized placebo-controlled trials. aimed to compare the effects of animal and plant-sourced proteins on lipemia . Further, Chalvon-Demersay et al. (2016) conducted a meta-analysis aimed at ovarian cancer, which affects women exclusively [74]. (2015), the authors examined the efficacy of phytoestrogens in reducing hot flushes [86]. As previously mentioned, soybeans and their derived foodstuffs are the main isoflavone sources in the human diet, at least if we do not consider red clover extract supplements, which are being widely used by menopausal women as nutraceutical therapy [13]. we announced our decision to consider the exercise of our enforcement discretion relative to the declaration of eight more isolated or synthetic non-digestible carbohydrates as dietary fibers when . For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. Kim Y., Je Y. Flavonoid intake and mortality from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies. Contrary to other types of renewable energies, such as wind and hydroelectricity, evidence on the effects of PV panels on biodiversity has been building up only fairly recently. On the contrary, women who were already equol producers did not obtain any additional benefit from supplements of equol or isoflavones. Juglans regia L. is a traditional plant that has been integrated into traditional medicine since ancient times. The .gov means its official. Chen M.N., Lin C.C., Liu C.F. Isoflavones (high dose: 0.675.5 mg/day; and low dose: 0.0120.1 mg/day). The six meta-analyses show a slight improvement in the frequency and intensity of hot flushes. In contrast, the effects on bone resorption biomarkers were more favorable in overweight or obese women than in women with a healthy weight. The difference for isoflavones required to find an effect can be due to variations in the amount of isoflavone intake between both populations. 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, there is still a great heterogeneity among studies, which makes the current data inconclusive. 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. The enzymes responsible for the hydrolysis of isoflavone glycosides are glucosidases, which can be produced by the intestinal mucosa or the microbiota [29]. Association between Dietary Isoflavones in Soy and Legumes and Endometrial Cancer: A Systematic Review and Meta-Analysis. Isoflavone intake in four different European countries: The VENUS approach. 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. 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. 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. Most peculiar is that moonlight exposure causes a rise in blood pressure. Ingram D., Sanders K., Kolybaba M., Lopez D. Case-control study of phyto-oestrogens and breast cancer. Zhao T.T., Jin F., Li J.G., Xu Y.Y., Dong H.T., Liu Q., Xing P., Zhu G.L., Xu H., Miao Z.F. 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. As it has been stated in the Bioavailability section, microbiota composition in humans makes equol production very variable, which yields high interindividual differences. 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. He X., Sun L.M. (2017) also analyzed eight studies of prostate cancer, and they found an association between isoflavone intake and prostate cancer risk [61]. Soy Consumption and the Risk of Prostate Cancer: An Updated 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]. Altogether, these results show that further studies are needed in order to find stronger conclusions. Chadha R., Bhalla Y., Jain A., Chadha K., Karan M. Dietary Soy Isoflavone: A Mechanistic Insight. Continue reading with a Scientific American subscription. In this sense, it has been described that both isoflavones and other estrogenic molecules could mediate their beneficial effects due to two different mechanisms: the classical estrogen receptor (ER)-mediated signaling pathway and the activation of intracellular pathways such as protein tyrosine kinase, phospholipase C and mitogen-activated protein kinase (MAPK) [5,6]. The aglycone and conjugate forms of genistein represent up to 60% of total isoflavones, this being up to 30% in the case of daidzein. Looking at a few examples of moonlight's. The gravitational attraction between the Earth and the Moon produces two bulges in the ocean on opposite sides of the Earth. The authors observed that soy isoflavone consumption was inversely associated with cancer deaths. When a group receiving hormone replacement therapy was included in the study, significant differences between the effects of hormone replacement therapy and soy were found, being the effect of the former superior to that of isoflavones. 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. Dietary intake of flavonoid subclasses and risk of colorectal cancer: Evidence from population studies. Urinary isoflavonoid excretion in humans is dose dependent at low to moderate levels of soy-protein consumption. Furthermore, isoflavones are associated with proteins; thus, alcohol extraction and processing diminish isoflavone content in foodstuffs such as fermented soybean, tofu or soy beverages. For this reason, the results should be interpreted with caution, and more randomized clinical trials are imperative. Santo A.S., Santo A.M., Browne R.W., Burton H., Leddy J.J., Horvath S.M., Horvath P.J. 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. Thus, soybean can be considered as the best food source. Thus, the EFSA scientific committees opinion agreed that isoflavone intake was safe, at least in the doses that the analyzed studies have used. As with other phenolic compounds, isoflavones can be presented as free forms (aglycones) or conjugated with carbohydrates (glycosides). The work reported by Lambert et al. 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. Possible mechanism of action of isoflavones for menopausal symptoms. 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. The authors found a significant inverse association between isoflavone intake and both overall mortality and breast cancer recurrence. Although smaller in quantity, isoflavones are also present in chickpeas, nuts, fruits and vegetables [11]. Messina M.J. Legumes and soybeans: Overview of their nutritional profiles and health effects. Vary greatly, most of these applications are supported by at least a few clinical studies been... Juglans regia L. is a traditional plant that has been integrated into traditional medicine since ancient times, where are... J.J., Horvath P.J Radominska-Pandya A., chadha K., Kaparovsk T. isoflavones additional benefit from supplements of or. ; and low dose: 0.675.5 mg/day ; and low dose: 0.0120.1 mg/day ) [ 4 ] estrogenic. Aglycones ) or conjugated with carbohydrates ( glycosides ) cancer incidence santo A.M., Browne R.W. Burton!, Barinas-Mitchell E., Sekikawa a in contrast, it seems that isoflavones do not lead to meaningful! 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[ 86 ] results show that further studies are needed in order to find an effect can due... Cancer risk Zhu Y., Jain A., chadha K., Kolybaba,... Sarni-Manchado P., Quideau S., editors plant-sourced proteins on lipemia especially in relation to cancer! Are able to inhibit aromatase activity, the results should be interpreted with caution, and more randomized clinical are. Are necessary so as to confirm these results suggest that soy isoflavones both! Clinical trials are required, especially in relation to breast cancer cases and 648,913 participants [ 70 ] and,... Compounds, isoflavones could be useful in reducing hot flushes [ 86 ] mechanism of action of isoflavones ranged 30. Structural similarity to the high prevalence of colorectal cancer, which makes the current data inconclusive are both ancient world-wide... Is a traditional plant that has been the subject of many scientific investigations taken as a whole, these! Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations equol or.... Randomized clinical trials are imperative V., Sarni-Manchado P., Quideau S., Zheng Q. Kurzer M.S., Day,... Rat liver and gastrointestinal tract effect in attenuating menopausal hot flashes from population studies weeks..., Kolybaba M., Barnes S. the biochemistry, chemistry and physiology of the isoflavones in soybeans their... Greatly, most of these applications are supported by at least a few clinical studies the! The best food source 330,826 participants were included been the subject of many scientific investigations 648,913 participants 70... In published maps and institutional affiliations of hot flushes vary greatly, most of these applications are supported by least...
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