Isoflavone Supplementation Research Articles

Isoflavone Supplementation Does Not Potentiate the Effect of Combined Exercise Training on Resting and Ambulatory Blood Pressure in Non-Obese Postmenopausal Women: A Randomized Double-Blind Controlled Trial-A Pilot Study.

Physical exercise and isoflavone supplementation are potential strategies to prevent and treat cardiovascular diseases in postmenopausal women. The aim of this study was to investigate whether there are additive effects of isoflavone supplementation when associated with combined aerobic and resistance exercise on resting and ambulatory blood pressure monitoring (ABPM) and in blood pressure variability (BPV). Thirty-one non-obese postmenopausal women were randomly allocated into two groups: placebo and exercise (Placebo n = 19); and isoflavone supplementation (100 mg/day) and exercise (isoflavone n = 19). ABPM and BPV were evaluated before and after 10 weeks of moderate combined (aerobic and resistance) exercise training. Generalized Estimating Equation (GEE) with Bonferroni correction and intention-to-treat analysis was used to compare the effects of interventions on resting BP, ABPM and BPV. Combined exercise training decreased resting systolic (SBP) and diastolic blood pressure (DBP) and reduced 24 h and awake ambulatory SBP, DBP and mean blood pressure over time, with no additional effects of isoflavone supplementation. No changes were observed in sleep period, or in BPV indexes (Standard Deviation of 24 h (SD), daytime and nighttime interval (SDdn) and average real variability (ARV) in both groups. We conclude that isoflavone supplementation does not potentiate the effects of combined training on resting and ambulatorial systolic and diastolic blood pressure in non-obese postmenopausal women.

Isoflavone combined with exercise on bone mineral density in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials.

This meta-analysis of randomized control trials (RCTs) aimed to evaluate the effects of isoflavones supplementation combined with exercise training on bone mineral density (BMD) in postmenopausal women. Two reviewers did a complete search of two electronic database (Medline, PubMed) records up to January 31, 2019. Risk of bias was classified based on the Cochrane Collaboration tool. The pooled standard mean difference (SMD) combined with 95% confidence interval (CI) was used as the effect size of BMD values. A total of four RCTs with 609 participants were included for meta-analysis. The BMD did not differ significantly between isoflavone supplementation combined with exercise training group and placebo group (sub-whole body: SMD = 0.00, 95% CI, -0.23 to 0.24; lumbar spine: SMD = 0.15, 95% CI, -0.30 to 0.60; total hip: SMD = 0.05, 95% CI, -0.18 to 0.298; femoral neck: SMD = 0.10, 95% CI, -0.23 to 0.43; trochanter: SMD = 0.09, 95% CI, -0.14 to 0.33; ward's triangle: SMD = -0.03, 95% CI, -0.24 to 0.30). In addition, combined intervention did not provide additive effects on BMD improvements compared with exercise or isoflavone supplementation alone. The trials included in this meta-analysis were small and some had methodological limitations. The present meta-analysis reveals that isoflavone supplements combined with exercise training do not significantly increase BMD in postmenopausal women. In addition, combined intervention does not provide additive effects on BMD improvements compared with exercise or isoflavone supplementation alone.

The effect of soy isoflavones on arterial stiffness: a systematic review and meta-analysis of randomized controlled trials.

Some but not all randomized controlled trials (RCTs) of soy isoflavones showed their beneficial effect on arterial stiffness, a predictor of cardiovascular events, dementia, and all-cause mortality, independent of traditional risk factors. To test the hypothesis that supplementation of soy isoflavones reduces arterial stiffness, we performed a systematic review and meta-analysis of RCTs of soy isoflavones on arterial stiffness. The protocol of this systematic review was registered with PROSPERO (CRD42019126128) and written in accordance with PRISMA. The PubMed, Embase, and clinicaltrials.gov databases were searched using the following criteria: human subjects, soy isoflavones as intervention, and arterial stiffness as primary outcome. A random-effects meta-analysis was used to pool estimates across studies. Standardized mean difference (SMD) was used to synthesize quantitative results. Among 998 articles retrieved, 8 articles met our criteria. Duration of intervention was relatively short (maximum of 12weeks). Outcome measurements extracted were pulse wave velocity (PWV), systemic arterial compliance (SAC), augmentation index (AI), and cardio-ankle vascular index (CAVI). Soy isoflavones reduced arterial stiffness compared to placebo (standardized mean difference -0.33, 95% confidence interval -0.47, -0.19). Subgroup analyses showed no difference between treatment effects for intervention duration (< 6weeks vs. ≥ 6weeks) or gender (women only vs. men only vs. combined). Sensitivity analysis showed no difference in the effect of soy isoflavones between PWV, CAVI, SAC, and AI. Supplementation of soy isoflavones reduced arterial stiffness. Longer duration trials with larger number of participants are warranted.

Soy Isoflavone Supplementation Reduces RANKL/OPG Ratio on Postmenopausal Women with Osteopenia

Soy Isoflavone Supplementation Reduces RANKL/OPG Ratio on Postmenopausal Women with Osteopenia

Effects of isoflavones on bone turnover markers in peritoneal dialysis patients: a randomized controlled trial.

The aim of this study was to investigate the effects of soy isoflavones on serum markers of bone formation and resorption in peritoneal dialysis (PD) patients. In this randomized, double-blind, placebo-controlled trial, 40 PD patients were randomly assigned to either the soy isoflavone or the placebo group. The patients in the soy isoflavone group received 100mg soy isoflavones daily for 8weeks, whereas the placebo group received corresponding placebos. At baseline and the end of the 8th week, 7ml of blood was obtained from each patient after a 12- to 14-h fast and serum concentrations of bone formation markers (osteocalcin and bone alkaline phosphatase), bone resorption markers [N-telopeptide and receptor activator of nuclear factor kappa B ligand (RANKL)], and osteoprotegerin as an inhibitor of bone resorption were measured. Serum N-telopeptide concentration decreased significantly up to 27% in the soy isoflavone group at the end of week 8 compared to baseline (P = 0.003). Also, serum RANKL concentration reduced significantly up to 17% in the soy isoflavone group at the end of week 8 compared to baseline (P = 0.03). These bone resorption markers did not significantly change in the placebo group during the study. There were no significant differences between the two groups in mean changes of serum osteocalcin, bone alkaline phosphatase, and osteoprotegerin. This study indicates that daily administration of 100mg soy isoflavone supplement to PD patients reduces serum N-telopeptide and RANKL which are two bone resorption markers. CLINICALTRIALS.GOV: NCT03773029, 2018.

Effects of soy isoflavones on serum lipids and lipoprotein (a) in peritoneal dialysis patients

Background and aimLipid abnormalities are common in peritoneal dialysis (PD) patients and no effective treatment to decrease serum lipoprotein (a) [Lp(a)] in dialysis patients is known so far. Therefore, this research was designed to investigate the effects of soy isoflavone supplement on serum lipids and Lp(a) in PD patients. Methods & resultsIn this randomized, double-blind, placebo-controlled trial, 40 PD patients were randomly assigned to either the isoflavone or the placebo group. The patients in the isoflavone group received 100 mg soy isoflavone daily for 8 weeks, whereas the placebo group received corresponding placebos. At baseline and the end of the 8th week, 7 mL of blood was obtained from each patient and serum triglycerides, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and Lp(a) were measured. Serum Lp(a) reduced significantly up to 10% in the isoflavone group at the end of week 8 compared to baseline (P < 0.05), and the reduction was significant in comparison with the placebo group (P < 0.05). Serum HDL-C increased significantly up to 11.5% in the isoflavone group at the end of week 8 compared to baseline (P = 0.05), and the increment was significant in comparison with the placebo group (P < 0.05). There were no significant differences between the two groups in mean changes of serum triglycerides, total cholesterol, and LDL-C. ConclusionsThis study indicates that daily administration of 100 mg soy isoflavones reduces serum Lp(a) and increases HDL-C concentration which are two determinants of cardiovascular disease in PD patients. ClinicalTrials.govNCT03773029. Registration number and dateNCT03773029 - 2018.

A phase II randomized clinical trial using aglycone isoflavones to treat patients with localized prostate cancer in the pre-surgical period prior to radical prostatectomy.

Prostate cancer (PCa) is the most common cancer in American men. Additionally, African American Men (AAM) are 60% more likely to be diagnosed with PCa and 2.4 times more likely to die from this disease compared to Caucasian men (CM). To date, there are few strategies effective for chemoprevention for men with localized PCa. There is thus a need to continue to evaluate agents and strategies for chemoprevention of prostate cancer. Epidemiological, laboratory and early phase clinical trials have shown that the isoflavones modulates several biomarkers implicated in prostate carcinogenesis. The goal of this phase II randomized clinical trial was to explore the comparative effectiveness and safety of 40 mgs of aglycone isoflavones in AAM and CM with localized PCa in the pre-surgical period prior to radical prostatectomy. Thirty six participants (25 CM, 6AAM) were randomized to the isoflavone arm and 34 (25 CM, 7AAM) to the placebo arm, with 62 completing the intervention. Results indicated that isoflavones at a dose of 20 mgs BID for 3-6 weeks was well tolerated but did not reduce tissue markers of proliferation. A significant reduction in serum PSA was observed with isoflavone supplementation in CM compared to the placebo arm, but not observed in AAM. We observed no changes in serum steroid hormones with isoflavone supplementation. In AAM, a reduction in serum IGF-1 concentrations and IGF1: IGFBP-3 ratios were observed with isoflavone supplementation. Well-powered studies for longer duration of intervention may inform future trials with isoflavones, for chemoprevention of PCa.

Effect of porcine reproductive and respiratory syndrome virus infection and soy isoflavone supplementation on carcass cutability and meat quality of pigs

The objective was to evaluate the effects of porcine reproductive and respiratory syndrome virus (PRRSV) infection and dietary soy isoflavone (ISF) supplementation on carcass cutability and meat quality of commercial pigs. Barrows (21 d of age) were randomly allotted to experimental treatments that were maintained throughout the study: noninfected pigs received an ISF-devoid control diet (CON, n = 22) and infected pigs received either the control diet (PRRSV-CON, n = 20) or that supplemented with total ISF in excess of 1,500 mg/kg (PRRSV-ISF, n = 25). Pigs were penned by treatment, with six pigs within a pen. Following a 7-d adaptation, weanling pigs were inoculated once intranasally with either a sham-control (phosphate buffered saline [PBS]) or live PRRSV (1 × 105 tissue culture infective dose [TCID]50/mL, strain NADC20). Pigs were maintained on experimental diets for 166 d after inoculation and then slaughtered (192 or 194 d of age; approximately 120 kg body weight [BW]). At 1-d postmortem, left sides were separated between the 10th and 11th rib for the determination of loin eye area (LEA), backfat (BF) thickness, and loin quality (ultimate pH, instrumental color, drip loss, visual color, marbling, and firmness). Loin chops were aged 14 d postmortem prior to Warner-Bratzler shear force (WBSF) determination. Belly width, length, thickness, and flop distance were determined. Data were analyzed as a one-way ANOVA with pig as the experimental unit. Carcass yield, LEA, BF, and estimated lean percentage did not differ (P > 0.26) among treatments. Loins from CON pigs had increased ultimate pH (P = 0.01), reduced L* scores (P = 0.005) coupled with darker visual color scores (P = 0.004), were firmer (P < 0.0001), and exhibited reduced drip loss (P = 0.01) compared with PRRSV-CON and PRRSV-ISF pigs. However, WBSF did not differ (P = 0.51) among treatments after 14 d of aging. Bellies from CON pigs were more firm compared with bellies from PRRSV-CON and ISF pigs (P < 0.01). These data suggest PRRSV infection did not alter carcass characteristics but may have marginally reduced loin and belly quality. Supplementation with dietary soy isoflavones did nothing to mitigate the detrimental effects of PRRSV infection.

Isoflavone supplementation, via red clover hay, alters the rumen microbial community and promotes weight gain of steers grazing mixed grass pastures.

Biochanin A, an isoflavone present in the pasture legume red clover (Trifloium pratense L.), alters fermentation in the rumen of cattle and other ruminants. Biochanin A inhibits hyper-ammonia-producing bacteria and promotes cellulolytic bacteria and fiber catalysis in vitro and ex vivo. Consequently, biochanin A supplementation improves weight gain in grazing steers. Red clover contains biologically active isoflavones that may act synergistically. Therefore, the objective was to evaluate the effect of two levels of red clover hay on growth performance and the microbial community in growing steers grazing mixed grass pastures. A grazing experiment was conducted over 2 early growing seasons (2016 and 2017) with 36 cross-bred steers and twelve rumen-fistulated, growing Holstein steers for evaluation of average daily gain and rumen microbiota, respectively. Steers were blocked by body weight and assigned to pastures with one of four treatments: 1) pasture only, 2) pasture + dry distillers’ grains (DDG), 3) pasture + DDG + low level of red clover hay (~15% red clover diet), or 4) pasture + DDG + high level of red clover hay (~30% red clover diet). DDG were added to treatments to meet protein requirements and to balance total protein supplementation between treatments. All supplementation strategies (DDG ± red clover hay) increased average daily gains in comparison to pasture-only controls (P < 0.05), with a low level of red clover supplementation being the most effective (+0.17 kg d-1 > DDG only controls; P < 0.05). Similarly, hyper-ammonia-producing bacteria inhibition (10–100-fold; P < 0.05), fiber catalysis (+10–25%; P < 0.05) and short chain fatty acid concentrations were greatest with the low red clover supplement (+~25%; P < 0.05). These results provide evidence that lower levels or red clover supplementation may be optimal for maximizing overall microbial community function and animal performance in grazing steers.

Isoflavone Supplements for Menopausal Women: A Systematic Review.

Isoflavones have gained popularity as an alternative treatment for menopausal symptoms for people who cannot or are unwilling to take hormone replacement therapy. However, there is still no consensus on the effects of isoflavones despite over two decades of vigorous research. This systematic review aims to summarize the current literature on isoflavone supplements, focusing on the active ingredients daidzein, genistein, and S-equol, and provide a framework to guide future research. We performed a literature search in Ovid Medline using the search terms “isoflavone” and “menopause”, which yielded 95 abstracts and 68 full-text articles. We found that isoflavones reduce hot flashes even accounting for placebo effect, attenuate lumbar spine bone mineral density (BMD) loss, show beneficial effects on systolic blood pressure during early menopause, and improve glycemic control in vitro. There are currently no conclusive benefits of isoflavones on urogenital symptoms and cognition. Due to the lack of standardized research protocols including isoflavone component and dosage, outcomes, and trial duration, it is difficult to reach a conclusion at this point in time. Despite these limitations, the evidence thus far favors the use of isoflavones due to their safety profile and benefit to overall health.

The effects of isoflavone supplementation plus combined exercise on salivary markers of oxidative stress in postmenopausal women.

This study tested the effect of isoflavone supplementation in addition to combined exercise training in salivary oxidative stress markers in non-obese postmenopausal women. Thirty-two postmenopausal women without hormone therapy were randomly assigned to exercise + placebo (n = 15) or exercise + isoflavone supplementation (n = 17) groups. They performed 30 sessions of combined exercises (aerobic plus resistance) over ten weeks and consumed 100 mg of isoflavone supplementation or placebo. Saliva samples were collected after an overnight fast. Superoxide dismutase, total antioxidant capacity, thiobarbituric acid reactive substances, catalase, total protein and nitrite were determined before and after ten weeks of the intervention. The ANOVA two-way analysis of variance was applied with α of 5%. Both groups increase (p<0.05) superoxide dismutase activity and decrease catalase levels. There was interaction (time × group) in both nitrite and thiobarbituric acid reactive substances results, with increase (p<0.05) in placebo group and decrease (p<0.05) in isoflavone group. No difference was found for total antioxidant capacity or total protein. The combination of isoflavone supplementation and exercise training can promote an antioxidant effect through reduction of lipid peroxidation and concentrations of salivary nitrite.

Soy isoflavones and cholecalciferol reduce inflammation, and gut permeability, without any effect on antioxidant capacity in irritable bowel syndrome: A randomized clinical trial

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is more prevalent in women. Vitamin D deficiency and hormonal disorders are also prevalent in Iranian women, and may influence the severity of clinical outcomes mediated by microinflammation, oxidative stress and intestinal permeability pathways. Our objective was to investigate the effects of co-administration of soy and vitamin D on some inflammatory, antioxidant and gut permeability markers in women with IBS. In a randomized clinical trial, women (18-75 years of age) were randomly allocated into four groups to receive soy isoflavones (40mg/day), cholecalciferol (50,000 IU/15 days), both soy isoflavones and cholecalciferol, or placebo for six weeks. The outcomes were plasma inflammatory markers, antioxidant status and fecal protease activity at week 0 and week 6. After the intervention, plasma inflammatory markers and fecal protease activity were reduced significantly in all treatment groups compared to the placebo group; however, there was no significant effect on antioxidant status. This study suggests combined supplementation of soy isoflavones and active vitamin D can improve some biochemical parameters regarding inflammation and intestinal permeability of IBS in women. Clinical.Trials.govNCT02026518.

Isoflavone does not promote additional effects on heart rate variability of postmenopausal women performing combined exercise training: a clinical, controlled, randomized, double-blind study.

The aim of the study was to investigate the effects of ingesting isoflavones associated with combined aerobic and resistance exercise training on heart rate variability (HRV) indices in postmenopausal women. Twenty-eight healthy postmenopausal women performed 10 weeks of combined exercise training associated with isoflavone (n = 16) or placebo (n = 12) supplementation. The RR intervals (RRi) were collected for 20 min using a heart rate monitor. Analysis of HRV was performed in time (mean squared difference of successive RRi (RMSSD), standard deviation of all normal RRi (SDNN), and percentage of adjacent RRi differing by more than 50 ms (pNN50)), frequency (low-frequency percentage (LF%), high-frequency percentage (HF%), and low-/high-frequency ratio (LF/HF)), and nonlinear domains (standard deviation of the instantaneous variability of the beat-to-beat interval (SD1), long-term variability of the continuous RRi (SD2), and their ratio (SD2/SD1)). Student's t test did not show differences between groups in any general baseline characteristic variables. The results of the generalized estimating equation tests did not demonstrate interaction or group effects for any HRV indices. However, the results reported time effects for mean RR (p < 0.001), RMSSD (p = 0.044), and SD1 (p = 0.044), with increases in these indices in response to exercise training. There were no time effects for LF%, HF%, LF/HF, SDNN, pNN50, SD2, or SD2/SD1. In conclusion, isoflavone supplementation did not promote additional effects on HRV indices of postmenopausal women subjected to 10 weeks of combined exercise training. Novelty Combined training improves heart rate variability in postmenopausal women. Isoflavone supplementation did not promote additional effects on heart rate variability in postmenopausal women.

74 Effects of dietary soy isoflavone supplementation on carcass cutability and meat quality of pigs infected with porcine reproductive and respiratory virus

Abstract The objective was to evaluate the effects of porcine respiratory and reproductive syndrome virus (PRRSV) infection and dietary soy isoflavone supplementation on carcass cutability and meat quality of commercial pigs. Barrows were randomly allotted to experimental treatments that were maintained throughout the study: non-infected pigs received an isoflavone-devoid control diet (NC, n = 22), and infected pigs received either the control diet (PC, n = 20) or that supplemented with total ISF in excess of 1,600 mg/kg (ISF, n = 25). Following a 7-d adaptation, weanling pigs were inoculated intranasally with either a sham-control (PBS) or live PRRSV (1×105 TCID50/mL, strain NADC20). At 1 d postmortem (192–194 days of age; approximately 120kg BW), left sides were separated between the 10th and 11th rib for determination of loin eye area (LEA), backfat thickness (BF), and loin quality (ultimate pH, instrumental color, drip loss, visual color, marbling, and firmness). Loin chops were aged 14 d postmortem prior to Warner-Bratzler shear force (WBSF) determination. Belly width, length, thickness, and flop distance were determined. Data were analyzed as a one-way ANOVA with a model including effects of PRRSV status and dietary treatment, and also with single-df pre-determined contrasts to compare NC and PC (infection status) and PC and ISF (ISF effect within infected pigs). Carcass yield, LEA, BF, and estimated lean percentage did not differ (P &gt; 0.26) among treatments. Loins from NC pigs had increased ultimate pH (P = 0.01), reduced L* scores (P = 0.005) coupled with darker visual color scores (P = 0.004), were firmer (P &lt; 0.0001), and reduced drip loss (P = 0.01) compared with PC and ISF pigs. However, WBSF did not differ (P = 0.51) among treatments after 14 d of aging. Bellies from NC pigs were more firm compared with bellies from PC and ISF pigs (P &lt; 0.01). These data suggest PRRSV infection and soy isoflavone supplementation do not alter carcass characteristics but may marginally reduce loin and belly quality.

Acute Soy Supplementation Improves 20-km Time Trial Performance, Power, and Speed.

Isoflavones, a chemical class of phytoestrogens found in soybeans and soy products, may have biological functions similar to estradiol. After binding with ERβ or perhaps independently of estrogen receptors, isoflavones may augment vascular endothelial relaxation, contributing to improved limb blood flow. To determine if acute fermented soy extract supplementation influences 20-km time trial cycling performance and cardiac hemodynamics compared with a placebo. Subjects included 25 cyclists and triathletes (31 ± 8 yr, V˙O2peak: 55.1 ± 8.4 mL·kg·min). Each subject completed a V˙O2peak assessment, familiarization, and two 20-km time trials in randomized order after ingestion of a fermented soy extract supplement or placebo. The fermented soy extract consisted of 30 g powdered supplement in 16 fl. ounces of water. The placebo contained the same quantities of organic cocoa powder and water. Each trial consisted of 60 min of rest, 30 min at 55% Wpeak, and a self-paced 20-km time trial. Soy supplementation elicited a faster time to 20-km completion (-0.22 ± 0.51 min; -13 s), lower average HR (-5 ± 7 bpm), and significantly greater power (7 ± 3 W) and speed (0.42 ± 0.16 km·h) during the last 5 km of the time trial compared with placebo. Analysis of the results by relative fitness level (<57 vs ≥ 57 mL⋅kg⋅min) indicated that those with a higher level of fitness reaped the largest performance improvement alongside a reduced HR (-5 ± 7 bpm). Ingestion of a fermented soy extract supplement improved sprint-distance performance through improvements in both power and speed. For those with great aerobic fitness, soy supplementation may help to decrease cardiac demand alongside performance improvement.

Effects of dietary soy isoflavones and soy protein source on response of weanling pigs to porcine reproductive and respiratory syndrome viral infection.

Porcine reproductive and respiratory syndrome virus (PRRSV) is the most prevalent disease of swine globally. Infection of weanling pigs with PRRSV leads to a complex immune response resulting in significant disease and decreased growth performance. Previous experimental evidence suggests that increasing concentrations of soybean meal in the diet of young pigs confer benefits in terms of growth performance and immune parameters. The objective of this experiment was to identify potential modes of action for this benefit, specifically the ability for soy-derived isoflavones (ISF) to confer immunological benefits to young pigs infected with PRRSV. Four dietary treatments differing in soy protein source (soy protein concentrate vs. enzyme-treated soybean meal) and ISF supplementation (none vs. 1,500 mg total ISF/kg) were fed; the control diet (CON) contained soy protein concentrate and no supplemental ISF. Weanling pigs (60 barrows, 21 d of age, 5.71 ± 0.44 kg) from a naturally Mycoplasma hyopneumoniae (Mh)-infected source herd were individually housed in disease containment chambers and provided ad libitum access to experimental diets for 7 d before receiving either a sham inoculation or a 9.28 × 103 50% tissue culture infective dose of PRRSV at 28 d of age (0 d postinoculation). A total of 5 experimental treatments included an uninfected group receiving the CON diet, plus four infected groups each receiving a different dietary treatment. Growth performance and rectal temperatures were recorded throughout the study, and blood was collected for quantification of serum PRRSV load, presence of anti-PRRSV antibodies, differential complete blood counts, cytokine concentrations, and T-cell immunophenotyping. Data were analyzed as a 2-way or 3-way ANOVA for all treatments including PRRSV-infected pigs, in addition to a single degree of freedom contrast to compare uninfected and infected pigs receiving the CON diet. PRRSV-infection reduced growth rate and efficiency compared with noninfected controls with minimal influences by ISF. Supplemental ISF reduced PRRSV-induced band neutrophilia and improved cytotoxic-to-helper T-cell ratios. These results suggest that ISF contribute to activation of adaptive immune system pathways and could benefit recovery from and clearance of PRRSV infections.

Modulatory effect of inulin with soya isoflavones on plasma lipid profile and liver SCD-18 index in rats with induced type-2 diabetes mellitus.

Obesity and type-2 diabetes are often associated with nonalcoholic fatty liver disease (NAFLD). Soya isoflavones act as antidiabetic agents and protect against NAFLD. There are data suggesting that inulin may increase the plasma concentration and effect of soya isoflavones. The aim of the present study was to compare the effect of soya isoflavones, as opposed to the effect of soya isoflavones with inulin, on plasma lipid profile, liver morphology, and liver fatty acids in rats with induced type-2 diabetes mellitus. Data were collected on thirty-six male Sprague-Dawley rats divided into control and diabetic groups. Animals in the diabetic (DM) group were on a high-fat diet and were injected with low doses of streptozotocin. Animals in the control groups were fed a regular diet and were injected with a buffer. After the injections, the animals were divided into three groups of nondiabetic rats (nDM)-controls (c-nDM), rats treated with isoflavones (IS-nDM), and rats treated with isoflavones plus inulin (IS+IN-nDM)-and three parallel diabetic (DM) subgroups: controls (c-DM), rats treated with isoflavone (IS-DM), and rats treated with isoflavones plus inulin (IS+IN-DM). Hepatic steatosis and fibrosis were examined using hematoxylin-eosin staining and Mallory's trichrome methods respectively. Liver fatty acids were extracted and analyzed by gas chromatography. A lipid blood test was performed. The study showed significant changes in liver fatty acids, liver morphology, and plasma lipid profile. The estimated SCD-18 index significantly decreased in both the control and DM groups after isoflavone supplementation. The level of liver steatosis and fibrosis also decreased after isoflavone supplementation in the DM groups. The plasma lipid profile showed increased levels of HDL-C after isoflavone supplementation in the DM groups. These results support the protective use of isoflavones in liver steatosis and as beneficial to plasma lipid profile in individuals with diabetes. A novelty of this work is its comparison of supplementation using soya isoflavones with supplementation using both soya isoflavones and inulin. Surprisingly, additional supplementation with inulin modulates the positive effect of isoflavones.

Soy Isoflavone Supplementation Increases Long Interspersed Nucleotide Element-1 (LINE-1) Methylation in Head and Neck Squamous Cell Carcinoma

Aim: Soy isoflavones have been suggested as epigenetic modulating agents with effects that could be important in carcinogenesis. Hypomethylation of LINE-1 has been associated with head and neck squamous cell carcinoma (HNSCC) development from oral premalignant lesions and with poor prognosis. To determine if neoadjuvant soy isoflavone supplementation could modulate LINE-1 methylation in HNSCC, we undertook a clinical trial.Methods: Thirty-nine patients received 2–3 weeks of soy isoflavone supplements (300 mg/day) orally prior to surgery. Methylation of LINE-1, and 6 other genes was measured by pyrosequencing in biopsy, resection, and whole blood (WB) specimens. Changes in methylation were tested using paired t tests and ANOVA. Median follow up was 45 months.Results: LINE-1 methylation increased significantly after soy isoflavone (P < 0.005). Amount of change correlated positively with days of isoflavone taken (P = 0.04). Similar changes were not seen in corresponding WB samples. No significant changes in tumor or blood methylation levels were seen in the other candidate genes.Conclusion: This is the first demonstration of in vivo increases in tissue-specific global methylation associated with soy isoflavone intake in patients with HNSCC. Prior associations of LINE-1 hypomethylation with genetic instability, carcinogenesis, and prognosis suggest that soy isoflavones maybe potential chemopreventive agents in HNSCC.

Effects of Isoflavone Supplementation on Lipid Profiles and Antioxidant Enzyme Activities in Growing Rats Fed High Fat Diet.

The purpose of this study was to investigate the effects of isoflavone on serum lipids and antioxidant enzymes activities in growing rats fed high lard diet. Twenty four female Sprague-Dawley rats (body weight 50–60 g) were divided into three groups, control, high fat (HF, lard 200 g/kg diet) and high fat + isoflavone (HFI, lard 200 g/kg diet + isoflavone 310.9 mg/kg diet) for 4 weeks. The results of study indicated that body weight gain was not different by isoflavone diet. Mean intake was significantly lower in HF group and HFI group than control group. Food efficiency ratio was significantly higher in HF group and HFI group than control group. The level of serum triglyceride and total cholesterol were significantly lower in HFI group than control group and HF group. The level of high-density lipoprotein cholesterol, was significantly higher in control group than HF group and HFI group. The level of low-density lipoprotein cholesterol was not significantly different by experimental diets, but atherogenic index (AI) was significantly lower in control group and HFI group than HF group. Contents of total cholesterol and triglyceride in liver tissues were found to be insignificant. The concentration of lipid peroxidation, malondialdehyde was significantly lower in control groups and HFI group than HF group. And antioxidant enzymes in liver tissue were not significantly different by lard and isoflavone supplemented diets. In conclusion, it seems possible that isoflavone supplemented high fat diet may produce positive results on level of serum triglyceride, serum total cholesterol, AI and concentration of malondialdyhyde.

Isoflavones enhance the plasma cholesterol-lowering activity of 7S protein in hypercholesterolemic hamsters.

Previous studies have shown that 7S protein is the active ingredient responsible for the plasma cholesterol-lowering activity of soybean. It is hypothesized that isoflavones in soybean could enhance the blood cholesterol-lowering activity of 7S protein. Forty-eight hamsters were divided into six groups and fed a non-cholesterol diet or one of the five high-cholesterol diets containing 12.1% 7S protein with 0-15.62 mg g-1 isoflavones. The results showed that addition of isoflavones in diets dose-dependently enhanced the plasma total cholesterol-lowering activity of 7S protein. Addition of isoflavones in 7S protein-based diets significantly reduced hepatic cholesterol accumulation by 12.6-26.1%, compared with the high cholesterol control diet. Isoflavones could also facilitate excretion of neutral sterols in a dose-dependent manner. Supplementation of isoflavones in diets favourably modulated mRNA expression and the protein mass of HMG-CoA reductase. It was concluded that the enhancing effect of isoflavones on the blood cholesterol-lowering activity of 7S protein was mediated by inhibiting the cholesterol absorption and de novo cholesterol synthesis in hypercholesterolemic hamsters.