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Pleiotropic Effects of Isoflavones in Inflammation and Chronic Degenerative Diseases.
Bernatoniene, J, Kazlauskaite, JA, Kopustinskiene, DM
International journal of molecular sciences. 2021;(11)
Abstract
Isoflavones are phytoestrogens of plant origin, mostly found in the members of the Fabaceae family, that exert beneficial effects in various degenerative disorders. Having high similarity to 17-β-estradiol, isoflavones can bind estrogen receptors, scavenge reactive oxygen species, activate various cellular signal transduction pathways and modulate growth and transcription factors, activities of enzymes, cytokines, and genes regulating cell proliferation and apoptosis. Due to their pleiotropic activities isoflavones might be considered as a natural alternative for the treatment of estrogen decrease-related conditions during menopause. This review will focus on the effects of isoflavones on inflammation and chronic degenerative diseases including cancer, metabolic, cardiovascular, neurodegenerative diseases, rheumatoid arthritis and adverse postmenopausal symptoms.
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Naturally Occurring Flavonoids and Isoflavonoids and Their Microbial Transformation: A Review.
Wang, JF, Liu, SS, Song, ZQ, Xu, TC, Liu, CS, Hou, YG, Huang, R, Wu, SH
Molecules (Basel, Switzerland). 2020;(21)
Abstract
Flavonoids and isoflavonoids are polyphenolic secondary metabolites usually produced by plants adapting to changing ecological environments over a long period of time. Therefore, their biosynthesis pathways are considered as the most distinctive natural product pathway in plants. Seemingly, the flavonoids and isoflavones from fungi and actinomycetes have been relatively overlooked. In this review, we summarized and classified the isoflavones and flavonoids derived from fungi and actinomycetes and described their biological activities. Increasing attention has been paid to bioactive substances derived from microorganism whole-cell biotransformation. Additionally, we described the utilization of isoflavones and flavonoids as substrates by fungi and actinomycetes for biotransformation through hydroxylation, methylation, halogenation, glycosylation, dehydrogenation, cyclisation, and hydrogenation reactions to obtain rare and highly active biofunctional derivatives. Overall, among all microorganisms, actinomycetes are the main producers of flavonoids. In our review, we also summarized the functional genes involved in flavonoid biosynthesis.
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3.
Scientific Evidence Supporting the Beneficial Effects of Isoflavones on Human Health.
Gómez-Zorita, S, González-Arceo, M, Fernández-Quintela, A, Eseberri, I, Trepiana, J, Portillo, MP
Nutrients. 2020;(12)
Abstract
Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. The most significant food source of isoflavones in humans is soy-derived products. 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. 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. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. 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. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. However, a limitation in this field is that there is still a great heterogeneity among studies. 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.
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Effect of S-equol and Soy Isoflavones on Heart and Brain.
Sekikawa, A, Ihara, M, Lopez, O, Kakuta, C, Lopresti, B, Higashiyama, A, Aizenstein, H, Chang, YF, Mathis, C, Miyamoto, Y, et al
Current cardiology reviews. 2019;(2):114-135
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Abstract
BACKGROUND Observational studies in Asia show that dietary intake of soy isoflavones had a significant inverse association with coronary heart disease (CHD). A recent randomized controlled trial (RCT) of soy isoflavones on atherosclerosis in the US, however, failed to show their benefit. The discrepancy may be due to the much lower prevalence of S-equol producers in Westerners: Only 20-30% of Westerners produce S-equol in contrast to 50-70% in Asians. S-equol is a metabolite of dietary soy isoflavone daidzein by gut microbiome and possesses the most antiatherogenic properties among all isoflavones. Several short-duration RCTs documented that soy isoflavones improves arterial stiffness. Accumulating evidence shows that both atherosclerosis and arterial stiffness are positively associated with cognitive decline/dementia. Therefore, potentially, soy isoflavones, especially S-equol, are protective against cognitive decline/dementia. METHODS/RESULTS This narrative review of clinical and epidemiological studies provides an overview of the health benefits of soy isoflavones and introduces S-equol. Second, we review recent evidence on the association of soy isoflavones and S-equol with CHD, atherosclerosis, and arterial stiffness as well as the association of atherosclerosis and arterial stiffness with cognitive decline/ dementia. Third, we highlight recent studies that report the association of soy isoflavones and S-equol with cognitive decline/dementia. Lastly, we discuss the future directions of clinical and epidemiological research on the relationship of S-equol and CHD and dementia. CONCLUSIONS Evidence from observational studies and short-term RCTs suggests that S-equol is anti-atherogenic and improves arterial stiffness and may prevent CHD and cognitive impairment/ dementia. Well-designed long-term (≥ 2years) RCTs should be pursued.
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Dietary soybean isoflavones in Alzheimer's disease prevention.
Lu, Y, An, Y, Lv, C, Ma, W, Xi, Y, Xiao, R
Asia Pacific journal of clinical nutrition. 2018;(5):946-954
Abstract
Soybean isoflavone (SIF) is a type of polyphenol present extensively in legumes. Because of its unique chemical construction and the physiological activity of the phenolic hydroxyl group, SIF exhibits strong antioxidant activity in antioxidant and nonantioxidant enzyme systems. Genistein is the major isoflavone in soy foods, accounting for more than 50% of the isoflavone content. The health effects of soybean dietary isoflavones on humans have gained increased attention. Recent studies have suggested that SIF may alleviate neurodegenerative diseases such as Alzheimer's disease (AD). Despite the comprehensive research on AD, effective treatments for AD are yet to be established. The early diagnosis and prevention of mild cognitive impairment (MCI) have become crucial for delaying AD development. Several dietary polyphenols have exerted cognitive effects on AD, and the appropriate intake of dietary SIF helps reduce the risk of AD. This study reviews the possible mechanisms of AD pathogenesis and their relationships with SIF intake; the results provide useful insights for AD prevention in the future.
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Effects of a standardised extract of Trifolium pratense (Promensil) at a dosage of 80mg in the treatment of menopausal hot flushes: A systematic review and meta-analysis.
Myers, SP, Vigar, V
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2017;:141-147
Abstract
OBJECTIVE To critically assess the evidence for a specific standardised extract of Trifolium pratense isoflavones (Promensil) at a dosage of 80mg/day in the treatment of menopausal hot flushes. DATA SOURCES Systematic literature searches were performed in Medline, Scopus, CINAHL Plus, Cochrane, AMED and InforRMIT and citations obtained from 1996 to March 2016. Reference lists were checked; corresponding authors contacted and the grey literature searched for additional publications. REVIEW METHODS Studies were selected according to predefined inclusion and exclusion criteria. All randomised clinical trials of a specific standardised extract of Trifolium pratense isoflavones (Promensil) used as a mono-component at 80mg/day and measuring vasomotor symptoms were included. The data extraction and quality assessment were performed independently by one reviewer and validated by a second with any disagreements being settled by discussion. Weighted mean differences and 95% confidence intervals were calculated for continuous data using the fixed-effects model. RESULTS Twenty potentially relevant papers were identified, with only five studies meeting the inclusion criteria. The meta-analysis demonstrated a statistical and clinically relevant reduction in hot flush frequency in the active treatment group compared to placebo. Weighted mean difference 3.63 hot flushes per day: [95% CI 2.70-4.56]; p˂0.00001). Due to a lack of homogeneity a priori defined sub-group analyses were performed demonstrating a substantive difference between cross-over and parallel-arm clinical trial designs. CONCLUSION There is evidence for a statistical and clinically significant benefit for using a specific standardised extract of red clover isoflavones (Promensil) at 80mg/day for treating hot flushes in menopausal women across the 3 studies included in the meta-analysis. The preparation was safe over the short-term duration of the studies (3 months).
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Effect of Soy and Soy Isoflavones on Obesity-Related Anthropometric Measures: A Systematic Review and Meta-analysis of Randomized Controlled Clinical Trials.
Akhlaghi, M, Zare, M, Nouripour, F
Advances in nutrition (Bethesda, Md.). 2017;(5):705-717
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Soy may be a suitable food for anti-obesity efforts because of its high protein and isoflavone content. We conducted this meta-analysis to evaluate potential effects of soy and soy isoflavones on weight, waist circumference, and fat mass. PubMed, MEDLINE, Scopus, EMBASE, and Cochrane databases were searched. Twenty-four trials with soy and 17 trials with isoflavones passed the eligibility stage. According to the results, soy showed no overall statistically significant effect on weight, waist circumference, or fat mass, but a significant increasing effect on weight was observed in some circumstances: for instance, in obese subjects [mean difference (MD): 0.80 kg; 95% CI: 0.15, 1.45 kg; P = 0.02], with ingestions of ≥40 g soy protein/d (MD: 0.94 kg; 95% CI: 0.11, 1.77 kg; P = 0.03), with short-term applications (1-3 mo) (MD: 0.45 kg; 95% CI: 0.05, 0.86 kg; P = 0.03), and when soy was compared with meat (MD: 0.36 kg; 95% CI: 0.09, 0.64 kg; P = 0.03) and whey protein (MD: 1.53 kg; 95% CI: 0.10, 2.96 kg; P = 0.04). In contrast to the effects of soy on weight, soy significantly decreased waist circumference in older ages (MD: -0.36 cm; 95% CI: -0.71, -0.01 cm; P = 0.04), in women (MD: -0.32 cm; 95% CI: -0.57, -0.08 cm; P = 0.01), and at doses of <40 g soy protein/d (MD: -0.31 cm; 95% CI: -0.57, -0.05 cm; P = 0.02). Isoflavone studies, conducted only in women, showed that isoflavones may reduce body mass index (BMI; in kg/m2) (MD: -0.26; 95% CI: -0.55, 0.04; P = 0.085), especially in dosages <100 mg/d (MD: -0.48; 95% CI: -0.90, -0.06; P = 0.02) and in intervention periods of 2-6 mo (MD: -0.28; 95% CI: -0.56, 0.00; P = 0.053), but no effect was observed in higher doses or longer intervention periods. Also, a trend for reduced BMI after consumption of isoflavones was observed in Caucasians (MD: -0.35; 95% CI: -0.74, 0.04; P = 0.08). Overall, results showed that, although soy is the major source of isoflavones, soy and isoflavones may have different impacts on weight status.
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Evaluation of the potential antidepressant effects of soybean isoflavones.
Messina, M, Gleason, C
Menopause (New York, N.Y.). 2016;(12):1348-1360
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OBJECTIVE The aim of the study was to determine whether isoflavones affect depressive symptoms in women. METHODS Literature searches were conducted to identify clinical and epidemiologic studies that evaluated the impact of soy intake and isoflavone exposure on depressive symptoms. References from identified studies were also evaluated to identify eligible studies. RESULTS Only limited epidemiologic research has evaluated the impact of soy or isoflavone intake on depression although several studies from China and Japan did find soy product intake was inversely related to risk of depression. Often times, soy was, however, evaluated only as a component of a summative dietary pattern (eg, a "Japanese" or "Healthy" diet). Of the 20 intervention studies identified, roughly half found statistically significant reductions in depressive symptoms in response to isoflavones although several had design weakness. Of those studies reporting a lack of antidepressant effects of isoflavones, design limitations likely contributed to the lack of efficacy. In all but two trials, assessment of depression was, however, a secondary outcome. It is notable that both trials in which depression was a primary outcome found isoflavones significantly improved symptoms. CONCLUSIONS Although the data are inconsistent and limited, the clinical and epidemiologic evidence suggests that isoflavones may offer a safe, well-tolerated option for management of depression. Furthermore, the intervention doses used in the clinical studies fall well within the dietary range. The extant literature reveals key design features for future studies, which based upon the results of this review, are clearly warranted.
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Soy isoflavone consumption and colorectal cancer risk: a systematic review and meta-analysis.
Yu, Y, Jing, X, Li, H, Zhao, X, Wang, D
Scientific reports. 2016;:25939
Abstract
Colorectal cancer (CRC) is one of the most predominant solid carcinomas in Western countries. However, there is conflicting information on the effects of soy isoflavone on CRC risk. Therefore, we performed a meta-analysis to assess the association between soy isoflavone consumption and CRC risk in humans using PubMed, Embase, Web of Science, and Cochrane Library databases. A total of 17 epidemiologic studies, which consisted of thirteen case-control and four prospective cohort studies, met the inclusion criteria. Our research findings revealed that soy isoflavone consumption reduced CRC risk (relative risk, RR: 0.78, 95% CI: 0.72-0.85; I(2) = 34.1%, P = 0.024). Based on subgroup analyses, a significant protective effect was observed with soy foods/products (RR: 0.79; 95% CI: 0.69-0.89), in Asian populations (RR: 0.79; 95% CI: 0.72-0.87), and in case-control studies (RR: 0.76; 95% CI: 0.68-0.84). Therefore, soy isoflavone consumption was significantly associated with a reduced risk of CRC risk, particularly with soy foods/products, in Asian populations, and in case-control studies. However, due to the limited number of studies, other factors may affect this association.
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10.
Isoflavones and Prostate Cancer: A Review of Some Critical Issues.
Zhang, HY, Cui, J, Zhang, Y, Wang, ZL, Chong, T, Wang, ZM
Chinese medical journal. 2016;(3):341-7
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OBJECTIVE The purpose of this review is to discuss some critical issues of isoflavones protective against the development of prostate cancer (PCa). DATA SOURCES Data cited in this review were obtained primarily from PubMed and Embase from 1975 to 2015. STUDY SELECTION Articles were selected with the search terms "isoflavone", "Phytoestrogen", "soy", "genistin", and "PCa ". RESULTS Isoflavones do not play an important role on prostate-specific antigen levels reduction in PCa patients or healthy men. The effect of isoflavones on sex hormone levels and PCa risk may be determined by equol converting bacteria in the intestine, specific polymorphic variation and concentrations of isoflavones. The intake of various types of phytoestrogens with lower concentrations in the daily diet may produce synergistic effects against PCa. Moreover, prostate tissue may concentrate isoflavones to potentially anti-carcinogenic levels. In addition, it is noteworthy that isoflavones may act as an agonist in PCa. CONCLUSIONS Isoflavones play a protective role against the development of PCa. However, careful consideration should be given when isoflavones are used in the prevention and treatment of PCa.