Search Results (98)

A dietary supplement, trans-resveratrol and hesperetin (tRES+HESP)—also known as GlucoRegulate—induces increased expression of glyoxalase 1 (Glo1) by activation of transcription factor Nrf2, countering accumulation of the reactive dicarbonyl glycating agent, methylglyoxal. tRES+HESP corrected insulin resistance and decreased fasting and postprandial plasma glucose and low-grade inflammation in overweight and obese subjects in a clinical trial. The aim of this study was to explore, for the first time, health-beneficial gene expression other than Glo1 induced by tRES+HESP in human endothelial cells and fibroblasts in primary culture and HepG2 hepatoma cell line and activity of cis-resveratrol (cRES) as a Glo1 inducer. We measured antioxidant response element-linked gene expression in these cells in response to 5 µM tRES+HESP by the NanoString method. tRES+HESP increases gene expression linked to the prevention of dicarbonyl stress, lipid peroxidation, oxidative stress, proteotoxicity and hyperglycemia-linked glycolytic overload. Downstream benefits were improved regulation of glucose and lipid metabolism and decreased inflammation, extracellular matrix remodeling and senescence markers. The median effective concentration of tRES was ninefold lower than cRES in the Glo1 inducer luciferase reporter assay. The GlucoRegulate supplement provides a new treatment option for the prevention of type 2 diabetes and metabolic dysfunction–associated steatotic liver disease and supports healthy aging. Full article

Olive oil (OO) has longstanding significance in human history, particularly in the Mediterranean region, where it has been a cornerstone of diet, economy, and culture. This history adds to modern evidence-based knowledge. Background: The Mediterranean diet (MD), rich in plant-based foods and OO, has been extensively associated with improved cardiometabolic and cognitive health. Recent interest has emerged in understanding how intermittent fasting protocols may enhance these effects. Still, the quality of OO does not only lie in the extraction process; it is also dependent on the tree variety, the soil, and the agricultural practices, ending with the way in which the finished product is stored and consumed. Objectives: This review explores the synergistic potential between OO consumption and intermittent fasting, focusing on their combined impact on metabolic health, oxidative stress, and inflammatory pathways. Methods: A literature search was conducted using multiple databases to identify studies addressing the health effects of OO, fasting, and the MD. Both human and relevant preclinical studies were considered, with emphasis on those evaluating inflammatory markers, lipid metabolism, insulin sensitivity, and neuroprotective mechanisms. Results: Evidence suggests that the bioactive compounds in EVOO may potentiate the benefits of fasting by enhancing antioxidant capacity, reducing postprandial inflammation, and modulating gene expression related to cellular metabolism. Combined, these factors may support improved insulin sensitivity, reduced oxidative damage, and delayed onset of age-related diseases. Conclusions: Understanding the integrative role of OO and fasting within the MD framework could offer valuable insights for nutritional strategies aimed at preventing metabolic syndrome, type 2 diabetes, and neurodegeneration. These findings also support the need for future clinical trials exploring the timing, dosage, and dietary context in which these interventions are most effective. Full article

Sustainable health approaches promote functional food alternatives that support metabolic well-being while reducing reliance on added sugars and artificial sweeteners. Monk fruit extract (MFE), a natural, non-caloric sweetener, is gaining interest for its potential metabolic benefits, but its effects and regulatory status require further evaluation. Objective: This PRISMA-guided systematic review synthesizes findings from randomized controlled trials (RCTs) assessing the impact of MFE on metabolic health, lipid profiles, inflammation, and regulatory considerations. Methods: The literature search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library, covering studies published between 2015 and 2025. Inclusion criteria were human RCTs evaluating MFE’s metabolic effects, while animal studies, reviews, and mixed-intervention trials were excluded. Study quality was assessed using the Cochrane risk of bias tool and the Jadad scale. Results: Five randomized controlled trials met the inclusion criteria, demonstrating that monk fruit extract (MFE) reduces postprandial glucose levels by 10–18% and insulin responses by 12–22%. No severe adverse effects were observed. Regulatory analysis indicated that MFE is approved for use in the United States and China, while its status remains under review in the European Union. Conclusions: MFE shows potential as a functional food ingredient for metabolic health. However, long-term clinical trials and a harmonized regulatory framework must confirm its safety and efficacy within sustainable health strategies Full article

Type 2 diabetes is characterized by insulin resistance, which contributes to dysregulated glucose and lipid metabolism and is associated with chronic inflammation. While previous studies have examined the effects of myricitrin in streptozotocin-induced diabetic models, its impact on the db/db mouse, a model that better reflects insulin resistance-associated metabolic disturbances, remains unclear. In this study, mice were divided into three groups (db/+, db/db, and db/db + 0.02% myricitrin) and were fed their respective diets for five weeks. Myricitrin supplementation reduced fat mass, adipocyte size, and plasma leptin levels, which were elevated in db/db mice. Although myricitrin did not affect fasting blood glucose levels, it lowered plasma insulin, hemoglobin A1c, postprandial glucose levels, and the homeostasis model assessment of insulin resistance, suggesting improvements in insulin sensitivity and glucose homeostasis. Enhanced pancreatic insulin expression, along with reduced hepatic gluconeogenic enzyme activities and mRNA expression, contributed to the improved glucose homeostasis observed in myricitrin-supplemented mice. Additionally, myricitrin reduced hepatic triglyceride levels and lipid droplet accumulation by inhibiting hepatic fatty acid synthase activity. It also decreased plasma inflammatory marker levels and their mRNA expression in adipose tissue. These findings suggest that myricitrin may be a promising therapeutic candidate for type 2 diabetes. Full article

Inflammation is associated with the pathophysiology of type 2 diabetes and COVID-19. Phytochemicals have the potential to modulate inflammation, expression of SARS-CoV-2 viral entry receptors (angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2)) and glucose transport in the gut. This study assessed the impact of phytochemicals on these processes. We screened 12 phytochemicals alongside 10 pharmaceuticals and three plant extracts, selected for known or hypothesised effects on the SARS-CoV-2 receptors and COVID-19 risk, for their effects on the expression of ACE2 or TMPRSS2 in differentiated Caco-2/TC7 human intestinal epithelial cells. Genistein, apigenin, artemisinin and sulforaphane were the most promising ones, as assessed by the downregulation of TMPRSS2, and thus they were used in subsequent experiments. The cells were then co-stimulated with pro-inflammatory cytokines interleukin-1 beta (IL-1β) and tumour necrosis factor-alpha (TNF-α) for ≤168 h to induce inflammation, which are known to induce multiple pathways, including the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Target gene expression (ACE2, TMPRSS2, SGLT1 (sodium-dependent glucose transporter 1) and GLUT2 (glucose transporter 2)) was measured by droplet digital PCR, while interleukin-1 (IL-6), interleukin-1 (IL-8) and ACE2 proteins were assessed using ELISA in both normal and inflamed cells. IL-1β and TNF-α treatment upregulated ACE2, TMPRSS2 and SGLT1 gene expression. ACE2 increased with the duration of cytokine exposure, coupled with a significant decrease in IL-8, SGLT1 and TMPRSS2 over time. Pearson correlation analysis revealed that the increase in ACE2 was strongly associated with a decrease in IL-8 (r = −0.77, p < 0.01). The regulation of SGLT1 gene expression followed the same pattern as TMPRSS2, implying a common mechanism. Although none of the phytochemicals decreased inflammation-induced IL-8 secretion, genistein normalised inflammation-induced increases in SGLT1 and TMPRSS2. The association between TMPRSS2 and SGLT1 gene expression, which is particularly evident in inflammatory conditions, suggests a common regulatory pathway. Genistein downregulated the inflammation-induced increase in SGLT1 and TMPRSS2, which may help lower the postprandial glycaemic response and COVID-19 risk or severity in healthy individuals and those with metabolic disorders. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is correlated with an increased cardiovascular risk, independent of other traditional risk factors. The mechanisms underlying this pathogenic link are complex yet remain incompletely elucidated. Among these, the most significant are visceral adiposity, low-grade inflammation and oxidative stress, endothelial dysfunction, prothrombotic status, insulin resistance, dyslipidemia and postprandial hyperlipemia, gut dysbiosis, and genetic mutations. Cardiovascular diseases are the leading cause of death in patients with MASLD. These patients have an increased incidence of coronary artery disease, carotid artery disease, structural and functional cardiac abnormalities, and valvulopathies, as well as arrhythmias and cardiac conduction disorders. In this review, we present the latest data on the association between MASLD and cardiovascular risk, focusing on the pathogenic mechanisms that explain the correlation between these two pathologies. Given the high rates of cardiovascular morbidity and mortality among patients with MASLD, we consider it imperative to raise awareness of the risks associated with this condition within the general population. Further research is essential to clarify the mechanisms underlying the increased cardiovascular risk linked to MASLD. This understanding may facilitate the identification of new diagnostic and prognostic biomarkers for these patients, as well as novel therapeutic targets. Full article

Citrus fruits are widely distributed in East Asia, and tea made from citrus peels has demonstrated health benefits, such as a reduction in fever, inflammation, and high blood pressure. However, citrus leaves have not been evaluated extensively for their possible health benefits. In this study, the α-glucosidase-inhibitory activity of Jeju citrus hot-water (CW) and ethyl alcohol (CE) extracts, along with hesperidin (HP) (a bioactive compound in citrus leaf extracts), was investigated, and furthermore, their effect on postprandial blood glucose reduction in an animal model was determined. The hesperidin contents of CW and CE were 15.80 ± 0.18 and 39.17 ± 0.07 mg/g-extract, respectively. Hesperidin inhibited α-glucosidase (IC₅₀, 4.39), sucrase (0.50), and CE (2.62) and demonstrated higher α-glucosidase inhibitory activity when compared to CW (4.99 mg/mL). When using an SD rat model, during sucrose and starch loading tests with CE (p < 0.01) and HP (p < 0.01), a significant postprandial blood glucose reduction effect was observed when compared to the control. The maximum blood glucose levels (Cmax) of the CE administration group decreased by about 15% (from 229.3 ± 14.5 to 194.0 ± 7.4, p < 0.01) and 11% (from 225.1 ± 13.8 to 201.1 ± 7.2 hr·mg/dL, p < 0.05) in the sucrose and starch loading tests, respectively. Our findings suggest that citrus leaf extracts standardized to hesperidin may reduce postprandial blood glucose levels through the observed inhibitory effect against sucrase, which results in delayed carbohydrate absorption. Our findings provide a biochemical rationale for further evaluating the benefits of citrus leaves. Full article

The literature on the postprandial metabolic changes in individuals with Metabolic Syndrome (MetS) remains limited, despite the fact that postprandial states represent the most common physiological condition in Western societies. Background/Objectives: The objective of this study was to investigate the plasma metabolomics profile in both fasting and postprandial states following a high-fat challenge in individuals with MetS who consumed diets with varying quantities and qualities of dietary fat over 12 weeks. Methods: Seventy-five patients with MetS (28 males and 47 females) from the Spanish LIPGENE cohort were included in the study. MetS patients were randomly stratified to follow one of four dietary interventions (isoenergetic diets) for a 12-week long-term study. The four diets were high in saturated fatty acids and high in monounsaturated fatty acids (HSFA and HMUFA), low-fat high-complex carbohydrates (LFHCC), and LFHCC supplemented with n-3. The metabolomics analysis of plasma samples was carried out using Liquid Chromatography Time-of-Flight Mass Spectrometry (LC-TOF/MS). Results: We observed a decrease in inflammation biomarkers, including acetylcarnitine and L-carnitine during the fasting state and hexanoyl-L-carnitine and isobutyryl-L-carnitine during the postprandial period, mediated by the replacement of HSFA with HMUFA. Additionally, antioxidant compounds such as 4-hydroxybenzaldehyde and L-valine were expressed at higher levels after consumption of the HMUFA diet compared to the HSFA diet. HSFA also presented altered levels of phosphatidylcholine, a metabolite previously linked with insulin resistance. Conclusions: These findings suggest that replacing HSFA with HMUFA may reduce inflammation and improve antioxidant profiles, supporting the potential for tailored dietary interventions in individuals with MetS. Full article

Background/Objectives: Cattle-feeding systems may have health implications for consumers of beef products. Organic grass-fed (GRA) and conventional (CON) cattle-feeding systems may result in beef products with differing metabolite profiles and therefore could impact the postprandial metabolomic response of consumers. This study aims to measure whole beef metabolomics and postprandial metabolomic response of consumers between GRA and CON beef to elucidate potential health implications. Methods: This study followed a randomized double-blind crossover design with healthy male and female subjects (n = 10). Plasma samples were taken at fasting (0) and postprandially for four hours after consumption of a steak from each condition. Untargeted metabolomic analysis of whole beef and human plasma samples used LC/MS. Multivariate and pathway enrichment analysis in MetaboAnalyst was used to investigate metabolite and biochemical pathways that distinguished CON and GRA. Results: Cattle-feeding systems impacted both postprandial and whole beef steak metabolomic profiles. Metabolites that contributed to this variation included carnitine species (Proionylcarnitine), fatty acids, amino acids (L-valine), and Calamendiol. These metabolites have been associated with oxidative stress, inflammation, and cardiovascular health. Functional pathway enrichment analysis revealed numerous amino acid degradation pathways, especially branched-chain amino acids, and fatty acid degradation that changed throughout the postprandial time course. Conclusions: These findings suggest that CON and GRA cattle-feeding systems differentially impact whole beef metabolomics, as well as consumer postprandial metabolic responses and the associated health implications. Full article

The purpose of this study was to examine how green leaf juice drinking affect the postprandial blood glucose. Postprandial hyperglycemia causes vascular endothelial damage and chronic inflammation, promoting atherosclerosis, regardless of the presence of diabetes. Some ingredients in greenleaf juice have been reported to suppress blood glucose levels; however, the effect of greenleaf juice on reducing blood glucose levels in healthy individuals is unclear. We observed changes in postprandial blood glucose levels in 13 healthy young women who drank greenleaf juice before or concomitantly with rice. Compared to water, greenleaf juice consumption reduced blood glucose levels at 90 and 120 min after rice consumption, with no difference regardless of the time of greenleaf juice consumption. Greenleaf juice may be one of the most convenient and cost-effective methods for reducing postprandial blood glucose in healthy people. Full article

Polyphenol-rich Aronia fruits have great potential as a functional food with anti-inflammatory, hypolipidemic, and hypoglycemic biologic activities. However, clinical intervention trials investigating the impact of Aronia fruit consumption on human health are limited. A randomized, controlled, double-blinded, parallel intervention trial was conducted using 14 human subjects who ingested either 0 mL or 100 mL of Aronia juice daily for 30 days. Anthropometric measurements, fasting, and postprandial measures of glucose and lipid metabolism and inflammation, 16S rRNA fecal microbial composition data, and mass spectrometry-acquired serum and fecal metabolomic data were collected before and after the intervention period. Data were analyzed using general linear models, ANOVA, and t-tests. Daily consumption of Aronia prevented a rise in cholesterol levels (β = −0.50, p = 0.03) and reduced postprandial glucose (β = −3.03, p < 0.01). No difference in microbial community composition by condition was identified at any taxonomic level, but a decrease (β = −18.2, p = 0.04) in microbial richness with Aronia was detected. Serum and fecal metabolomic profiles indicated shifts associated with central carbon and lipid metabolism and decreases in pro-inflammatory metabolites. Our study further informs the development of polyphenol-based dietary strategies to lower metabolic disease risk. Full article

While the exercise-induced responses of circulated biomarkers related to inflammation and brain health are well documented in humans, little is known about the effect of menopausal status on these responses. This study compared the responses of inflammatory cytokines and brain-derived neurotrophic factor (BDNF) to high-intensity exercise between pre- and postmenopausal middle-aged females. Eight premenopausal (44 ± 3 years) and seven postmenopausal (57 ± 2 years) females performed a high-intensity interval training (HIIT) session consisting of 10 × 1 min running intervals (90% maximum heart rate) separated by 1 min passive recovery intervals. Blood samples were collected at baseline (fasted), pre-exercise (postprandial), and at 0, 30, and 90 min post-HIIT and analyzed for interleukin (IL-6) and 10 (IL-10), tumour necrosis factor-alpha (TNF-α), and BDNF. IL-6 significantly increased from pre-exercise to 0 min post-HIIT in postmenopausal (+40%, p = 0.01) and to 30 min post-HIIT in premenopausal females (+60%, p = 0.02). IL-6 remained elevated at 90 min post-HIIT in premenopausal (+104%, p = 0.05) and to a higher degree in postmenopausal females (+385%, p < 0.001). IL-10 showed no response. TNF-α increased from pre- to 0 min post-HIIT (+10%, p = 0.05), then decreased to below pre-exercise at 30 min (−10%, p = 0.02) and 90 min (−5%, p = 0.04) in both groups. BDNF increased immediately post-HIIT in premenopausal (+60%, p < 0.001) but not postmenopausal females. The differences in IL-6 and BDNF responses to HIIT between pre- and postmenopausal females provide evidence of the role of female reproductive hormones in the regulation of these exercise-induced responses. Full article

Undernutrition (UN) increases child vulnerability to illness and mortality. Caused by a low amount and/or poor quality of food intake, it impacts physical, cognitive, and social development. Modern types of food consumption have given highly processed food a higher cultural value compared to minimally processed food. Objective: The objective of this study was to evaluate the effect on growth, metabolism, physical activity (PA), memory, inflammation, and toxicity of an enriched black corn chip (BC) made with endemic ingredients on post-weaned UN mice. Methods: A chip was made with a mixture of black corn, fava beans, amaranth, and nopal cactus. To probe the effects of UN, UN was induced in 3wo post-weaned male C57Bl/6j mice through a low-protein diet (LPD—50% of the regular requirement of protein) for 3w. Then, the BC was introduced to the animals’ diet (17%) for 5w; murinometric parameters were measured, as were postprandial glucose response, PA, and short-term memory. Histological analysis was conducted on the liver and kidneys to measure toxicity. Gene expression related to energy balance, thermogenesis, and inflammation was measured in adipose and hypothalamic tissues. Results: Treatment with the BC significantly improved mouse growth, even with a low protein intake, as evidenced by a significant increase in body weight, tail length, cerebral growth, memory improvement, physical activation, normalized energy expenditure (thermogenesis), and orexigenic peptides (AGRP and NPY). It decreased anorexigenic peptides (POMC), and there was no tissue toxicity. Conclusions: BC treatment, even with persistent low protein intake, is a promising strategy against UN, as it showed efficacy in correcting growth deficiency, cognitive impairment, and metabolic problems linked to treatment by adjusting energy expenditure, which led to the promotion of energy intake and regulation of thermogenesis, all by using low-cost, accessible, and endemic ingredients. Full article

Consumption of a high-fat diet (HFD) has been suggested as a contributing factor behind increased intestinal permeability in obesity, leading to increased plasma levels of microbial endotoxins and, thereby, increased systemic inflammation. We and others have shown that HFD can induce jejunal expression of the ketogenic rate-limiting enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS). HMGCS is activated via the free fatty acid binding nuclear receptor PPAR-α, and it is a key enzyme in ketone body synthesis that was earlier believed to be expressed exclusively in the liver. The function of intestinal ketogenesis is unknown but has been described in suckling rats and mice pups, possibly in order to allow large molecules, such as immunoglobulins, to pass over the intestinal barrier. Therefore, we hypothesized that ketone bodies could regulate intestinal barrier function, e.g., via regulation of tight junction proteins. The primary aim was to compare the effects of HFD that can induce intestinal ketogenesis to an equicaloric carbohydrate diet on inflammatory responses, nutrition sensing, and intestinal permeability in human jejunal mucosa. Fifteen healthy volunteers receiving a 2-week HFD diet compared to a high-carbohydrate diet were compared. Blood samples and mixed meal tests were performed at the end of each dietary period to examine inflammation markers and postprandial endotoxemia. Jejunal biopsies were assessed for protein expression using Western blotting, immunohistochemistry, and morphometric characteristics of tight junctions by electron microscopy. Functional analyses of permeability and ketogenesis were performed in Caco-2 cells, mice, and human enteroids. Ussing chambers were used to analyze permeability. CRP and ALP values were within normal ranges and postprandial endotoxemia levels were low and did not differ between the two diets. The PPARα receptor was ketone body-dependently reduced after HFD. None of the tight junction proteins studied, nor the basal electrical parameters, were different between the two diets. However, the ketone body inhibitor hymeglusin increased resistance in mucosal biopsies. In addition, the tight junction protein claudin-3 was increased by ketone inhibition in human enteroids. The ketone body β-Hydroxybutyrate (βHB) did not, however, change the mucosal transition of the large-size molecular FD4-probe or LPS in Caco-2 and mouse experiments. We found that PPARα expression was inhibited by the ketone body βHB. As PPARα regulates HMGCS expression, the ketone bodies thus exert negative feedback signaling on their own production. Furthermore, ketone bodies were involved in the regulation of permeability on intestinal mucosal cells in vitro and ex vivo. We were not, however, able to reproduce these effects on intestinal permeability in vivo in humans when comparing two weeks of high-fat with high-carbohydrate diet in healthy volunteers. Further, neither the expression of inflammation markers nor the aggregate tight junction proteins were changed. Thus, it seems that not only HFD but also other factors are needed to permit increased intestinal permeability in vivo. This indicates that the healthy gut can adapt to extremes of macro-nutrients and increased levels of intestinally produced ketone bodies, at least during a shorter dietary challenge. Full article

Ageing changes the impact of nutrition, whereby inflammation has been suggested to play a role in age-related disabilities such as diabetes and cardiovascular disease. The aim of this study was to investigate differences in postprandial bile-acid response and its effect on energy metabolism between young and elderly people. Nine young, healthy men and nine elderly, healthy men underwent a liquid mixed-meal test. Postprandial bile-acid levels, insulin, glucose, GLP-1, C4, FGF19 and lipids were measured. Appetite, body composition, energy expenditure and gut microbiome were also measured. The elderly population showed lower glycine conjugated CDCA and UDCA levels and higher abundances of Ruminiclostridium, Marvinbryantia and Catenibacterium, but lower food intake, decreased fat free mass and increased cholesterol levels. Aging is associated with changes in postprandial bile-acid composition and microbiome, diminished hunger and changes in body composition and lipid levels. Further studies are needed to determine if these changes may contribute to malnutrition and sarcopenia in elderly. Full article