Isoflavones and bone health in perimenopausal and postmenopausal women.

PURPOSE OF REVIEW: Isoflavones exert estrogenic activity distinct from estrogen, they have the potential to treat diseases and symptoms related to estrogen deficiency with minimal side effects and risks. Isoflavone supplementation, in general, is shown to exert beneficial effects against estrogen-deficient bone loss in women, however, some clinical trials still produce conflicting findings. The purpose of this review is to highlight and summarize the most recent and up-to-date research in the field and to bring attention to factors that play a major role in the outcomes of clinical trials that investigate phytoestrogens. Here, we also discuss the latest and most relevant data regarding the clinical safety of these substances. RECENT FINDINGS: Isoflavones are naturally occurring secondary metabolites found in the Fabacaea plant family. Clinical data from isoflavone interventions support that aglycones (abundant in fermented products) exert enhanced beneficial effects against estrogen-deficient bone loss in women compared with isoflavone glycosides. Studies that employ methods to determine isoflavone content and form of treatments are more likely detect beneficial effects on bone. EFSA have confirmed the safety of isoflavones for women in the most comprehensive report to date. SUMMARY: Isoflavone aglycones exert greater effects against bone loss than glycosides. Isoflavones show promise as a first-line prophylactic/treatment for bone loss in women.

Stevia Leaf to Stevia Sweetener: Exploring Its Science, Benefits, and Future Potential.

Steviol glycoside sweeteners are extracted and purified from the Stevia rebaudiana Bertoni plant, a member of the Asteraceae (Compositae) family that is native to South America, where it has been used for its sweet properties for hundreds of years. With continued increasing rates of obesity, diabetes, and other related comorbidities, in conjunction with global public policies calling for reductions in sugar intake as a means to help curb these issues, low- and no-calorie sweeteners (LNCSs, also known as high-potency sweeteners) such as stevia are gaining interest among consumers and food manufacturers. This appeal is related to stevia being plant-based, zero calorie and with a sweet taste that is 50-350 times sweeter than sugar, making it an excellent choice for use in sugar- and calorie-reduced food and beverage products. Despite the fact that the safety of stevia has been affirmed by several food regulatory and safety authorities around the world, insufficient education about stevia's safety and benefits, including continuing concern with regard to the safety of LNCSs in general, deters health professionals and consumers from recommending or using stevia. Therefore, the aim of this review and the stevia symposium that preceded this review at the ASN's annual conference in 2017 was to examine, in a comprehensive manner, the state of the science for stevia, its safety and potential health benefits, and future research and application. Topics covered included metabolism, safety and acceptable intake, dietary exposure, impact on blood glucose and insulin concentrations, energy intake and weight management, blood pressure, dental caries, naturality and processing, taste and sensory properties, regulatory status, consumer insights, and market trends. Data for stevia are limited in the case of energy intake and weight management as well as for the gut microbiome; therefore, the broader literature on LNCSs was reviewed at the symposium and therefore is also included in this review.

Phenolic Substances from Ocimum Species Enhance Glucose-Stimulated Insulin Secretion and Modulate the Expression of Key Insulin Regulatory Genes in Mice Pancreatic Islets.

Ocimum gratissimum and Ocimum basilicum are plants ethnopharmacologically used to treat diabetes mellitus, a life-threatening disease that affects millions of people worldwide. In order to further understand their antidiabetic potential, which has been previously demonstrated in animal models, we aimed to investigate the acute and chronic effects of major phenolic substances from both plants on insulin secretion and gene expression in pancreatic islets isolated from NMRI mice. Insulin secretion was measured after acute (1 h) and long-term (72 h) incubation of islets with one of four cinnamic acid derivatives (caftaric, caffeic, chicoric, and rosmarinic acids) or a C-glucosylated flavonoid (vicenin-2). All substances acutely enhanced glucose-stimulated insulin secretion (GSIS) from islets at concentrations from 10-10 to 10-6 M. They also increased GSIS after chronic incubation (10-8 M). None of them increased insulin secretion in the presence of low glucose concentration. Furthermore, these substances markedly changed the gene expression profile of key insulin regulatory genes INS1, INS2, PDX1, INSR, IRS1, and proliferative genes as well as glucose transporter 2 (GLUT2), in treated islets. Thus, they may play an important role in diabetes treatment. This is the first report on the insulin-secretory activity of caftaric acid, rosmarinic acid, and vicenin-2.

Cafestol, a Bioactive Substance in Coffee, Has Antidiabetic Properties in KKAy Mice.

Daily coffee consumption is inversely associated with risk of type-2 diabetes (T2D). Cafestol, a bioactive substance in coffee, increases glucose-stimulated insulin secretion in vitro and increases glucose uptake in human skeletal muscle cells. We hypothesized that cafestol can postpone development of T2D in KKAy mice. Forty-seven male KKAy mice were randomized to consume chow supplemented daily with either 1.1 (high), 0.4 (low), or 0 (control) mg of cafestol for 10 weeks. We collected blood samples for fasting glucose, glucagon, and insulin as well as liver, muscle, and fat tissues for gene expression analysis. We isolated islets of Langerhans and measured insulin secretory capacity. After 10 weeks of intervention, fasting plasma glucose was 28-30% lower in cafestol groups compared with the control group (p < 0.01). Fasting glucagon was 20% lower and insulin sensitivity improved by 42% in the high-cafestol group (p < 0.05). Cafestol increased insulin secretion from isolated islets by 75-87% compared to the control group (p < 0.001). Our results show that cafestol possesses antidiabetic properties in KKAy mice. Consequently, cafestol may contribute to the reduced risk of developing T2D in coffee consumers and has a potential role as an antidiabetic drug.

Cafestol, a Bioactive Substance in Coffee, Stimulates Insulin Secretion and Increases Glucose Uptake in Muscle Cells: Studies in Vitro.

Diet and exercise intervention can delay or prevent development of type-2-diabetes (T2D), and high habitual coffee consumption is associated with reduced risk of developing T2D. This study aimed to test whether selected bioactive substances in coffee acutely and/or chronically increase insulin secretion from ß-cells and improve insulin sensitivity in skeletal muscle cells. Insulin secretion from INS-1E rat insulinoma cells was measured after acute (1-h) and long-term (72-h) incubation with bioactive substances from coffee. Additionally, we measured uptake of radioactive glucose in human skeletal muscle cells (SkMC) after incubation with cafestol. Cafestol at 10(-8) and 10(-6) M acutely increased insulin secretion by 12% (p < 0.05) and 16% (p < 0.001), respectively. Long-term exposure to 10(-10) and 10(-8) M cafestol increased insulin secretion by 34% (p < 0.001) and 68% (p < 0.001), respectively. Caffeic acid also increased insulin secretion acutely and chronically. Chlorogenic acid, trigonelline, oxokahweol, and secoisolariciresinol did not significantly alter insulin secretion acutely. Glucose uptake in SkMC was significantly enhanced by 8% (p < 0.001) in the presence of 10(-8) M cafestol. This newly demonstrated dual action of cafestol suggests that cafestol may contribute to the preventive effects on T2D in coffee drinkers and be of therapeutic interest.

The Effect of Alginate Encapsulated Plant-Based Carbohydrate and Protein Supplementation on Recovery and Subsequent Performance in Athletes.

The main purpose of this study was to investigate the effect of a novel alginate-encapsulated carbohydrate-protein (CHO-PRO ratio 2:1) supplement (ALG) on cycling performance. The ALG, designed to control the release of nutrients, was compared to an isocaloric carbohydrate-only control (CON). Alginate encapsulation of CHOs has the potential to reduce the risk of carious lesions. METHODS: In a randomised cross-over clinical trial, 14 men completed a preliminary test over 2 experimental days separated by ~6 days. An experimental day consisted of an exercise bout (EX1) of cycling until exhaustion at W~73%, followed by 5 h of recovery and a subsequent time-to-exhaustion (TTE) performance test at W~65%. Subjects ingested either ALG (0.8 g CHO/kg/hr + 0.4 g PRO/kg/hr) or CON (1.2 g CHO/kg/hr) during the first 2 h of recovery. RESULTS: Participants cycled on average 75.2 ± 5.9 min during EX1. Levels of plasma branched-chain amino acids decreased significantly after EX1, and increased significantly with the intake of ALG during the recovery period. During recovery, a significantly higher plasma insulin and glucose response was observed after intake of CON compared to ALG. Intake of ALG increased plasma glucagon, free fatty acids, and glycerol significantly. No differences were found in the TTE between the supplements (p = 0.13) nor in the pH of the subjects' saliva. CONCLUSIONS: During the ALG supplement, plasma amino acids remained elevated during the recovery. Despite the 1/3 less CHO intake with ALG compared to CON, the TTE performance was similar after intake of either supplement.

Glucotoxicity and α cell dysfunction: involvement of the PI3K/Akt pathway in glucose-induced insulin resistance in rat islets and clonal αTC1-6 cells.

AIM/HYPOTHESIS: The objective of this study was to assess how long-term exposure to high glucose affects the α cell function and whether the increased glucagon secretion is mediated via insulin resistance. MATERIALS AND METHODS: We established a ß cell-depleted rat model to obtain pure primary α cells. Furthermore, isolated rat islets and TC1-6 cells (a clonal α cell line) were exposed to high glucose (25 or 30 mmol/L) and low glucose (5.5 mmol/L) for up to 5 days to evaluate the influence of chronic glucose toxicity on glucagon secretion and glucagon gene expression. Moreover, we added insulin and/or Wortmannin to examine if the inhibitory effect of insulin on glucagon secretion was impaired by high glucose via the phosphatidylinositol 3 kinase/PKB protein kinase B pathway. RESULTS: Both glucagon secretion and glucagon gene expression were increased in response to 5 days exposure to high glucose. While a moderate insulin concentration slightly inhibits glucagon secretion from rat islets and α TC1-6 cells at high glucose, a pronounced increase in glucagon secretion was observed at low glucose. We found that the insulin-mediated activity of the phosphatidylinositol 3 kinase/PKB protein kinase B pathway in the α cell was markedly impaired by chronic exposure to high glucose. CONCLUSION: The hypersecretion of glucagon induced by glucotoxicity may be secondary to insulin resistance of the α cell induced by impaired activity of the insulin signaling pathway.

Effects of Anthocyanin-rich Berries on the Risk of Metabolic Syndrome: A Systematic Review and Meta-analysis.

OBJECTIVE: Metabolic syndrome (MetS) can lead to fatal complications, including cardiovascular disease. Emerging evidence suggests has emerged that increased fruit and vegetable intake and decreased intake of saturated fats, simple sugars, and processed foods can improve cardiovascular health. Anthocyanins (color pigments) have anti-inflammatory and antioxidant capacities but are of low bioavailability. In this systematic review and metaanalysis, we investigate the possible beneficial effects of the intake of berries high in anthocyanins on MetS risk factors. We also investigate the influences of high-density lipoprotein (HDL), lowdensity lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC). METHODS: We identified 2,274 articles from PUBMED and EMBASE following a search input designed to include studies of interest of these, 21 met inclusion criteria. RESULTS: The studies showed an overall reduction in low-density lipoprotein (p=0.04). Increases in HDL were found with cranberry and freeze-dried berry intake during a 4-6-week intervention. No statistically significant findings were detected for fasting glucose, Hb1Ac, insulin levels, blood pressure, oxidized LDL (OX-LDL), BMI, and overall HDL. CONCLUSIONS: We conclude from this systematic review and meta-analysis that increased berry intake improves MetS key risk factors and reduces the risk of cardiovascular disease. Pronounced effects were apparent for concentrated berry products, such as freeze-dried strawberries.

Relation of Change or Substitution of Low- and No-Calorie Sweetened Beverages With Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Prospective Cohort Studies.

BACKGROUND: Adverse associations of low- and no-calorie sweetened beverages (LNCSB) with cardiometabolic outcomes in observational studies may be explained by reverse causality and residual confounding. PURPOSE: To address these limitations we used change analyses of repeated measures of intake and substitution analyses to synthesize the association of LNCSB with cardiometabolic outcomes. DATA SOURCES: MEDLINE, Embase, and the Cochrane Library were searched up to 10 June 2021 for prospective cohort studies with ≥1 year of follow-up duration in adults. STUDY SELECTION: Outcomes included changes in clinical measures of adiposity, risk of overweight/obesity, metabolic syndrome, type 2 diabetes (T2D), cardiovascular disease, and total mortality. DATA EXTRACTION: Two independent reviewers extracted data, assessed study quality, and assessed certainty of evidence using GRADE. Data were pooled with a random-effects model and expressed as mean difference (MD) or risk ratio (RR) and 95% CI. DATA SYNTHESIS: A total of 14 cohorts (416,830 participants) met the eligibility criteria. Increase in LNCSB intake was associated with lower weight (5 cohorts, 130,020 participants; MD -0.008 kg/year [95% CI -0.014, -0.002]). Substitution of LNCSB for sugar-sweetened beverages (SSB) was associated with lower weight (three cohorts, 165,579 participants; MD, -0.12 [-0.14, -0.10,] kg/y) and lower incidence of obesity (OB) (one cohort, 15,765 participants; RR 0.88 [95% CI 0.88, 0.89]), coronary heart disease (six cohorts, 233,676 participants; 0.89 [0.81, 0.98]), cardiovascular disease mortality (one cohort, 118,363 participants; 0.95 [0.90, 0.99]), and total mortality (one cohort, 118,363 participants; 0.96 [0.94, 0.98]) with no adverse associations across other outcomes. Substitution of water for SSB showed lower weight (three cohorts, 165,579 participants; MD -0.10 kg/year [-0.13, -0.06]), lower waist circumference (one cohort, 173 participants; -2.71 cm/year [-4.27, -1.15]) and percent body fat (one cohort, 173 participants; -1.51% per year [-2.61, -0.42]), and lower incidence of OB (one cohort, 15,765 participants; RR 0.85 [0.75, 0.97]) and T2D (three cohorts, 281,855 participants; 0.96 [0.94, 0.98]). Substitution of LNCSB for water showed no adverse associations. LIMITATIONS: The evidence was low to very low certainty owing to downgrades for imprecision, indirectness, and/or inconsistency. CONCLUSIONS: LNCSB were not associated with cardiometabolic harm in analyses that model the exposure as change or substitutions. The available evidence provides some indication that LNCSB in their intended substitution for SSB may be associated with cardiometabolic benefit, comparable with the standard of care, water.

Amino acid-induced gene expression profiling in clonal ß-cell line INS-1E cells.

BACKGROUND: There is abundant evidence that glucotoxicity and lipotoxicity contribute to impaired ß-cell function in type 2 diabetes. Interestingly, amino acid (AA) derangement is also a characteristic part of the diabetic state. The acute effects of AA on pancreatic ß-cell function have been widely explored; however, to our knowledge, the chronic effects of AA, e.g. proline (Pro), homocysteine (Hcy), and leucine (Leu), on pancreatic ß-cell function and integrity have not yet been studied. We aimed to investigate global alterations in ß-cell gene expression after long-term exposure of clonal INS-1E cells to elevated level of specific AA in vitro. METHODS: Global gene expression profiling was performed to characterize genes differently modified by Pro, Hcy, and Leu, respectively, in INS-1E cells. RESULTS: Gene expression profiling revealed significant changes in INS-1E cell mRNAs involved in the control of several aspects of ß-cell function, e.g. epigenetic regulation of gene expression, metabolism, innate and adaptive immune responses, cellular signalling, protein synthesis, apoptosis, and cellular stress response. After 72 h, INS-1E cells were differentially regulated (≥1.5- or ≤ -1.5-fold) by Pro (295 transcripts), Hcy (301 transcripts), and Leu (701 transcripts). It appears that Hcy effects changes opposite to those induced by Leu and/or Pro. CONCLUSIONS: AA appears to participate in and to influence many physiological processes including those involved in cholesterol metabolism, immune responses, and oxidative phosphorylation. Whether such events promote the ß-cell dysfunction and the ß-cell failure in diabetes remains to be elucidated. Our data strongly indicate that AA elevation may take part in the progressive development of type 2 diabetes.

Vitamin D Deficiency Is Inversely Associated with Homeostatic Model Assessment of Insulin Resistance.

The study was conducted to comprehensively assess the association of the concentration of vitamin D in the blood and insulin resistance in non-diabetic subjects. The objective was to pool the results from all observational studies from the beginning of 1980 to August 2021. PubMed, Medline and Embase were systematically searched for the observational studies. Filters were used for more focused results. A total of 2248 articles were found after raw search which were narrowed down to 32 articles by the systematic selection of related articles. Homeostatic Model Assessment of Insulin Resistance (HOMAIR) was used as the measure of insulin resistance and correlation coefficient was used as a measure of the relationship between vitamin D levels and the insulin resistance. Risk of bias tables and summary plots were built using Revman software version 5.3 while Comprehensive meta-analysis version 3 was used for the construction of forest plot. The results showed an inverse association between the status of vitamin D and insulin resistance (r = -0.217; 95% CI = -0.161 to -0.272; p = 0.000). A supplement of vitamin D can help reduce the risk of insulin resistance; however further studies, like randomized controlled trials are needed to confirm the results.

Insulin Resistance Is Inversely Associated with the Status of Vitamin D in Both Diabetic and Non-Diabetic Populations.

Vitamin D has been implicated in the regulation of glucose metabolism and insulin resistance. We designed this study to provide evidence that insulin resistance is dependent on the concentration of vitamin D in the body. Forty observational studies of both type 2 diabetes mellitus patients and healthy subjects were included in this meta-analysis. Related articles were searched from Embase, PubMed, and Medline through January 2021. Filters for search were used to obtain more focused results. We used Comprehensive Meta-Analysis Version 3 for the construction of forest plots. RevMan software version 5.3 was used to build the risk of bias tables and summary plots. The observational studies included in this systematic review and meta-analysis showed an inverse relationship of insulin resistance with the status of vitamin D both in non-diabetic (r = -0.188; 95% CI = -0.141 to -0.234; p = 0.000) and diabetic (r = -0.255; 95% CI = -0.392 to -0.107, p = 0.001) populations. From the meta-analysis we concluded that hypovitaminosis D is related to increased levels of insulin resistance in both type 2 diabetes patients and the healthy population all over the world.

Pancreatic ß Cells Inhibit Glucagon Secretion from α Cells: An In Vitro Demonstration of α-ß Cell Interaction.

Interactions between endocrine α and ß cells are critical to their secretory function in vivo. The interactions are highly regulated, although yet to be fully understood. In this study, we aim to assess the impact of α and ß cell co-culture on hormone secretion. Mouse clonal cell lines α-TC6-1 (α cell line) and MIN-6 (ß cell line) were cultured independently or in combination in a medium containing 5.5, 11.1, or 25 mM glucose, respectively. After 72 h, hormone release was measured using insulin and glucagon secretion assays, the cell distribution was visualized by inverted microscopy and an immunocytochemistry assay, and changes in gene expressions were assessed using the RT-PCR technique. The co-culture of the two cell lines caused a decrease in glucagon secretion from α-TC1-6 cells, while no effect on insulin secretion from MIN-6 cells was revealed. Both types of cells were randomly scattered throughout the culture flask, unlike in mice islets in vivo where ß cells cluster in the core and α cells are localized at the periphery. During the α-ß cell co-culture, the gene expression of glucagon (Gcg) decreased significantly. We conclude that islet ß cells suppress glucagon secretion from α cells, apparently via direct cell-to-cell contact, of which the molecular mechanism needs further verification.

Strong and Bitter Vegetables from Traditional Cultivars and Cropping Methods Improve the Health Status of Type 2 Diabetics: A Randomized Control Trial.

Vegetables rich in bitter-tasting phytochemicals may exert enhanced beneficial effects against key factors associated with type two diabetes (T2D). This study investigates whether selected cultivars of bitter and strong-tasting (BST) Brassica and root vegetables exert greater health benefits on T2D patients compared to equivalent modern mild and sweet tasting (MST) vegetables. A 12-week randomized, controlled, parallel intervention study involved 92 T2D patients, who were allocated three different diets: (1) 500 g daily of bitter and strong-tasting (BST) vegetables; (2) 500 g daily of mild and sweet-tasting (MST) vegetables; (3) 120 g daily MST normal diet (control). Both vegetable diets contained root vegetables and cabbages selected based on sensory differences and content of phytochemicals. Prior to and after the study, all participants underwent an oral glucose tolerance test (OGTT), 24 h blood pressure measurements, DEXA scans, and fasted blood samples. Both diets high in vegetables significantly reduced the participants' BMI, total body fat mass, and HbA1c levels compared to control, but in the BST group, significant differences were also found regarding incremental area under the curve glucose 240 min (OGTT) and fasting glucose levels. A high daily intake of root vegetables and cabbages showed significant health improvements in both vegetable groups. BST vegetables had the greatest impact on insulin sensitivity, body fat mass, and blood pressure compared to control; moreover, they further improved glycemic control compared to MST vegetables.

Decreasing Txnip mRNA and protein levels in pancreatic MIN6 cells reduces reactive oxygen species and restores glucose regulated insulin secretion.

BACKGROUND AND AIMS: Recently, thioredoxin-interacting protein (Txnip) expression has been implicated in a number of cellular events associated with diabetes, with increased Txnip levels associated with reduced glucose uptake into peripheral tissues, increased reactive oxygen species (ROS) in endothelial cells, beta cell glucotoxicity and apoptosis. The potential relevance of Txnip with regards to glucose-regulated insulin secretion (GSIS), a fundamentally important characteristic of beta cells and insulin-producing cells being considered as a possible cell therapy for diabetes, has not yet been investigated. METHODS: Here, studying glucose-responsive MIN6 B1(GSIS) and cells which had significantly reduced response to glucose after time in culture i.e. MIN6 B1(Non-GSIS), using ELISAs; qRT-PCR; immunoprecipitation and Western blotting; transient and stable (siRNA/shRNA and cDNA) approaches to achieve Txnip knock-down or over-expression, respectively,we established a direct association between Txnip expression and GSIS. RESULTS: Specifically, increasing Txnip levels correlate with increased intracellular ROS levels and with significant GSIS loss.Conversely, both transient and stable knock-down of Txnip expression was associated with GSIS recovery. CONCLUSION: This, we believe, is another reason in favour of targeting Txnip as a novel approach for diabetes-related therapy.

Identification of microRNAs with a role in glucose stimulated insulin secretion by expression profiling of MIN6 cells.

MicroRNAs (miRNAs) are a family of endogenous small non-coding RNAs which regulate mRNAs at the post-transcriptional level. MiRNAs have been identified in both normal physiological and pathological conditions. To date, a limited number of miRNAs have been shown to be involved in the regulation of insulin secretion. We have identified a panel of 10 miRNAs down-regulated in glucose non-responsive MIN6 cells compared to glucose responsive cells using TaqMan Low Density miRNA Arrays. Of these 10 miRNA targets, subsequent functional investigations involving knockdown of mir-200a, mir-130a and mir-410 levels suggested that they may decrease the capability of MIN6 cells to secrete insulin in response to stimulatory levels of glucose. Conversely, experiment with over-expression of mir-410 suggest that it may enhance levels of glucose stimulated insulin secretion. In this study, we have also identified 21 miRNAs not previously known to have a potential murine homologue.

The Effect of Plant Derived Bioactive Compounds on Inflammation: A Systematic Review and Meta-Analysis.

A growing number of people worldwide are changing their lifestyle leading to an increasing number of overweight and obese individuals with metabolic syndrome (MetS). With obesity and MetS come an elevated inflammatory state resulting in increased risk of Type 2 diabetes, cardiovascular disease, among other lifestyle diseases. Fruits and vegetables (FV) contain phytochemicals with health beneficial effects including anti-oxidative and anti-inflammatory properties. This systematic review and meta-analysis aims to investigate the effects of diets high in FV, and plant-based products on C-reactive protein (CRP). A systematic search in PUBMED and EMBASE gave rise to 883 articles, 16 of which are included in the meta-analysis. The effects of plant-based products and diets are investigated in subgroups including overweight, obese, and diabetes; as wells as the effect of plant-oils and anthocyanin on CRP. The analysis shows an overall significant reduction in CRP for all articles (p = 0.0006). A significant decrease in diabetic (p = 0.01), overweight (p = 0.005), and obese patients (p = 0.05) is observed, including significant effects of anthocyanins (p = 0.001) and plant-oils (p < 0.00001) on CRP. These findings strongly support the recommendation for diets high in FV and plant-oils to help attenuate elevated CRP.

[Isoflavones have therapeutic efficacy inoestrogen deficiency].

In this review, we discuss isoflavones, which are bioactive selective estrogen receptor modulators shown to have therapeutic efficacy in reducing bone resorption and improving menopause symptoms in women with estrogen deficiency. The European Food Safety Authority reached consensus that there "is no evidence of harm" of isoflavone supplements for peri- and post-menopausal women. Bioavailable isoflavone aglycones being rich in fermented sources are shown to have enhanced effects compared to glycosides, and isoflavones represent an effective and safe new treatment for oestrogen deficient bone loss and climacteric symptoms.

The Effect of Ingesting Carbohydrate and Proteins on Athletic Performance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Endurance athletes participating in sporting events may be required to complete multiple training sessions a day or on successive days with a limited recovery time. Nutritional interventions that enhance the restoration of endogenous fuel stores (e.g., liver and muscle glycogen) and improve muscle damage repair have received a lot of attention. The purpose of this review is to investigate the effect of ingesting carbohydrate (CHO) and protein (PRO) on athletic performance. Studies were identified by searching the electronic databases PubMed and EMBASE. Random-effects meta-analyses were conducted to examine the intervention efficacy. A total of 30 randomized controlled trials (RCT), comprising 43 trials and 326 participants in total, were included in this review. The meta-analysis showed an overall significant effect in Time-To-Exhaustion (TTE) and Time-Trial (TT) performance, when ingesting carbohydrates and proteins (CHO-PRO) compared to CHO-only (p = 0.03 and p = 0.0007, respectively). A subgroup analysis demonstrated a significant effect in TTE by ingesting CHO-PRO compared to CHO, when supplements were provided during and/or following an exercise bout. CHO-PRO significantly improved TTE compared to CHO-only, when a long-term recovery (i.e., ≥8 h) was implemented (p = 0.001). However, no effect was found when the recovery time was short-term (i.e., ≤8 h). No significant effect was observed when CHO-PRO and CHO-only supplements were isocaloric. However, a significant improved TTE was evident with CHO-PRO compared to CHO-only, when the supplements were matched for carbohydrate content (p < 0.00001). In conclusion, co-ingesting carbohydrates and proteins appears to enhance TTE and TT performance compared to CHO-only and presents a compelling alternate feeding strategy for athletes.

Endothelial dysfunction in small arteries and early signs of atherosclerosis in ApoE knockout rats.

Endothelial dysfunction is recognized as a major contributor to atherosclerosis and has been suggested to be evident far before plaque formation. Endothelial dysfunction in small resistance arteries has been suggested to initiate long before changes in conduit arteries. In this study, we address early changes in endothelial function of atherosclerosis prone rats. Male ApoE knockout (KO) rats (11- to 13-weeks-old) were subjected to either a Western or standard diet. The diet intervention continued for a period of 20-24 weeks. Endothelial function of pulmonary and mesenteric arteries was examined in vitro using an isometric myograph. We found that Western diet decreased the contribution of cyclooxygenase (COX) to control the vascular tone of both pulmonary and mesenteric arteries. These changes were associated with early stage atherosclerosis and elevated level of plasma total cholesterol, LDL and triglyceride in ApoE KO rats. Chondroid-transformed smooth muscle cells, calcifications, macrophages accumulation and foam cells were also observed in the aortic arch from ApoE KO rats fed Western diet. The ApoE KO rats are a new model to study endothelial dysfunction during the earlier stages of atherosclerosis and could help us improve preclinical drug development.