Menopause, defined as amenorrhea due to loss of ovarian function, is associated with osteoporosis, metabolic syndrome, vasomotor disturbances, and cardiovascular disease. While menopause hormone therapy (MHT) remains the gold standard for high-potency symptom management, biotic interventions offer a safe, alternative approach for those who cannot or choose not to use MHT. This review examines biotic interventions (probiotics, prebiotics, synbiotics, postbiotics) and their influence on the gut–menopause axis. Declining estrogen during menopause alters gastrointestinal physiology, including shifts in gut microbiota composition and impaired gut barrier function. Bibliometric analysis of the past two decades shows a sharp rise in publications after 2017, peaking in 2024. The intellectual landscape centers on “probiotics,” “menopause,” and “osteoporosis,” highlighting bone health as a key focus. Evidence indicates that biotic interventions, particularly Lactobacillus and Bifidobacterium species and selected fibers, can restore microbial balance, enhance short-chain fatty acid production, improve gut barrier integrity, modulate the estrobolome, reduce systemic inflammation, and support bone, metabolic, cardiovascular, and vasomotor health. Biotic strategies represent a multi-targeted, non-hormonal approach to managing menopausal health, addressing underlying physiological changes. These findings highlight emerging research trends while underscoring the need for long-term clinical trials, and support further exploration of personalized, microbiome-targeted interventions in menopause.
This review summarizes current evidence on the role of plant-based and sustainable dietary patterns in relation to metabolic syndrome (MetS) during childhood and adolescence and examines how sustainability-oriented nutrition indices can be used to assess both health and environmental outcomes in younger populations, highlighting their potential role in supporting long-term metabolic health. Childhood and adolescence are critical periods for establishing lifelong dietary behaviors and preventing metabolic and cardiovascular diseases. Well-planned plant-based diets, rich in fiber, antioxidants, and phytochemicals, are associated with improved glycemic control, lipid profiles, and body composition, thereby positively influencing key components of MetS. Beyond these metabolic benefits, plant-based diets are associated with lower environmental impacts, including reductions in greenhouse gas emissions and a decreased use of natural resources. Several dietary indices have been developed to evaluate these relationships in children and adolescents, including the Planetary Health Diet Index (PHDI and PHDI-C), the Mediterranean Diet Quality Index (KIDMED), the DASH diet index, and the Plant-Based Diet Index (PDI). However, most available studies are cross-sectional, and longitudinal or randomized controlled trials investigating causal associations between sustainable diets and metabolic health outcomes in youth remain limited. Current evidence suggests that plant-based, nutritionally adequate, and sustainable diets during childhood and adolescence may contribute to improved metabolic health, a lower risk of MetS, and healthy growth and development. Integrating sustainability concepts into nutrition policies, dietary guidelines, and educational programs may promote healthier dietary behaviors and increase awareness among children, adolescents, and their families. However, current evidence is largely based on cross-sectional studies, and well-designed longitudinal and intervention studies are needed to strengthen the evidence base and clarify causal relationships.
This review aims to provide a synthesized overview of dietary patterns and nutrition-related problems in individuals with neurodevelopmental disorders. The review focuses on studies addressing eating behaviors, nutritional difficulties, and intervention approaches in individuals diagnosed with Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), intellectual disability, and Down syndrome. Relevant studies were identified through systematic searches of PubMed, Scopus, and Web of Science for articles published after 2010. Selection criteria included peer-reviewed studies examining sensory, behavioral, physiological, and environmental factors affecting dietary patterns. The reviewed studies indicate that individuals with ASD frequently exhibit food selectivity and sensory sensitivities that limit dietary variety. In ADHD, impulsive eating behaviors and irregular dietary patterns are associated with an increased risk of obesity. Individuals with intellectual disabilities often experience poor diet quality, swallowing difficulties, and micronutrient deficiencies, frequently influenced by environmental and caregiver-related factors. In Down syndrome, both feeding difficulties and an elevated risk of obesity are observed, influenced by genetic and metabolic characteristics. Nutritional problems in neurodevelopmental disorders are multifactorial, involving biological, behavioral, sensory, cognitive, and environmental influences. These findings highlight the importance of early identification and the implementation of individualized, multidisciplinary intervention strategies, including active family involvement. Further research using more standardized and methodologically rigorous approaches is needed to strengthen the evidence base.
Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, and dietary modification represents one of the most important modifiable strategies for its prevention and management. Increasing evidence indicates that the cardiovascular effects of diet extend beyond direct effects of nutrients and are partly mediated by interactions between dietary substrates, the gut microbiota, and host metabolism. This review critically evaluates the role of diet–microbiota interactions in CVD pathogenesis and provides an integrated, metabolite-centered perspective on how major dietary patterns influence gut microbial metabolism and cardiovascular health. Particular attention is given to trimethylamine N-oxide (TMAO), lipopolysaccharides (LPS), short-chain fatty acids (SCFAs), bile acids (BAs), phenylacetylglutamine (PAGln), indolepropionic acid (IPA), and hydrogen sulfide (H₂S). Dietary patterns substantially influence microbial composition, substrate availability, intestinal barrier integrity, and the production or transformation of microbiota-associated metabolites. Western-style, animal-based, and high-fat dietary patterns, may promote proteolytic and sulfidogenic fermentation, dysbiosis, impaired intestinal barrier function, and increased production or availability of potentially harmful metabolites. TMAO and PAGln have been associated with atherosclerosis, endothelial dysfunction, platelet activation, thrombosis, and other cardiometabolic outcomes, although their associations with cardiovascular risk may depend on dietary source, renal function, host metabolism, and individual microbial characteristics. LPS provides an important link between intestinal permeability, metabolic endotoxemia, inflammation, and vascular dysfunction. In contrast, fiber-rich and plant-based dietary patterns promote saccharolytic fermentation and SCFA production, support microbial diversity and intestinal barrier integrity, and may reduce endotoxemia and the production of potentially adverse microbial metabolites. Mediterranean dietary patterns, characterized by high consumption of plant foods, whole grains, fiber, olive oil, polyphenols, and fish together with lower intake of red and processed meat and refined sugars, appear to favor a more beneficial microbial and metabolic profile. BAs have more complex and context-dependent effects through microbial transformation and host signaling pathways, particularly FXR and TGR5. Emerging evidence also suggests potentially important cardiovascular roles for IPA and H₂S; however, their dietary regulation and clinical relevance remain less well established. The gut microbiota represents an important metabolic interface linking dietary patterns with cardiovascular physiology and disease. The available evidence suggests that dietary patterns rich in plant foods, fiber, unsaturated fats, polyphenols, and other bioactive components may support beneficial microbial functions and metabolite profiles, whereas Western-style dietary patterns may favor microbial pathways associated with endotoxemia, inflammation, thrombosis, and atherogenesis. However, individual metabolites should not be interpreted in isolation because their cardiovascular effects may vary according to dietary source, microbial phenotype, host metabolism, renal function, and overall dietary context. Emerging evidence supports a biomarker-guided and individualized approach to nutritional modulation of the gut microbiota, including strategies targeting microbial metabolite production. Nevertheless, the clinical efficacy of microbiota-targeted interventions remains to be established. Future longitudinal and randomized interventional studies integrating dietary assessment, microbiome composition, metabolomics, host metabolic characteristics, and cardiovascular outcomes are needed to clarify causality and determine whether personalized nutrition and microbiota-targeted strategies can improve CVD prevention and reduce residual cardiovascular risk.
The United States delivers home parenteral nutrition (HPN) for chronic intestinal failure through a fragmented mix of hospitals, home-infusion companies, and individual clinicians, with no national accreditation pathway and no mandated standards for prescriber expertise or institutional capability. This review proposes a national framework for accountable, outcomes-driven HPN care and a phased path to its implementation. Claims-based analyses of approximately 24,000 U.S. adults on parenteral support show that most orders are written by clinicians managing very few patients over short intervals, with expertise concentrated in a small minority of providers and substantial travel burden in rural regions. A recently published international framework proposes principles for centralizing adult intestinal failure services but does not address implementation within the U.S. regulatory and payment architecture. Long-standing centralized systems in Denmark and the Czech Republic demonstrate what an organized system can achieve and what it can observe about its own performance. The fundamental problem is not that decentralized U.S. HPN care is demonstrably worse, but that the absence of national data makes the question unanswerable. There is no national registry, no standardized outcome reporting, and no national figure for infection, readmission, or weaning. We propose three pillars to centralize accountability rather than geography: tiered accreditation distinguishing Level I hubs from Level II regional spokes, with volume measured as network accountability; reimbursement reform funding longitudinal clinical management separately from supply; and a national registry with participation tied to payment.
The growing global demand for sustainable and nutritionally rich food sources has led to increased interest in legumes, owing to their high nutritional content and environmental benefits. Conventional processing techniques often pose constraints such as nutrient loss, flavour degradation, and energy inefficiency. Exploring and implementing non-conventional processing techniques may address these issues and open new opportunities for enhancing legume functionality. Several approaches for coupling conventional and non-conventional technologies have been explored to process legumes and achieve an optimal balance of enhanced nutritional and functional properties with reduced antinutritional components. The various categories of non-conventional techniques include thermal methods (microwave and ohmic heating), non-thermal methods (ultrasonication, high-pressure processing and pulsed electric field treatment), and emerging technologies (3D food printing, cold plasma processing and superheated steam processing). These techniques have been reviewed, with an emphasis on their principles and effects on compositional, antioxidative, and functional parameters when applied to various legumes. Non-conventional techniques, individually or in combination with conventional processes, exhibit significant potential to enhance the functionality of legumes. Their application can effectively improve the nutritional quality, functionality, and suitability of legumes for incorporation into various functional food formulations, thereby contributing to sustainable food innovation and global nutrition security.
Perimenopause is a period of hormonal volatility associated with clinically relevant changes in metabolism and cardiometabolic risk. In addition to vasomotor symptoms, sleep disruption, and changes in body composition, the transition from the late reproductive years to early postmenopause is characterized by physiologic alterations that may precede formal diagnostic thresholds for metabolic syndrome. However, screening and risk stratification are often anchored to postmenopausal benchmarks, potentially delaying identification of individuals at elevated risk. Accumulating evidence supports earlier attention to dynamic indices of cardiometabolic deterioration during perimenopause. Lifestyle interventions and, for selected individuals, menopausal hormone therapy may mitigate progression, although important uncertainties remain, including the long-term effectiveness of precision nutrition approaches and genotype-informed strategies. This narrative review summarizes physiologic changes across the menopausal transition and evaluates nutrition and lifestyle interventions that may attenuate adverse metabolic trajectories.
Gluten-free (GF) products are frequently characterized by reduced nutritional and sensory quality, as well as a higher glycemic index (GI) compared to conventional products. These attributes may pose challenges for individuals who adhere to a lifelong gluten-free diet (GFD). Sprouting has emerged as a promising strategy to enhance the nutritional profile of GF foods. This review evaluates the impact of sprouting on glycemic response and antioxidant activity in GF foods, with a particular focus on the underlying mechanisms. Recent studies indicate that sprouting enhances antioxidant activity, primarily by increasing endogenous enzyme activity and releasing bound phenolic compounds. However, its effects on glycemic response remain inconsistent. Sprouting may increase starch digestibility through enhanced α-amylase activity, yet it can also promote the formation of resistant starch and increase dietary fiber content, potentially contributing to lower glycemic responses. These changes are influenced by processing conditions such as time and temperature, as well as by factors related to the food system, including matrix characteristics and seed properties. Sprouting represents a promising approach to improving the functional properties of GF foods, particularly by enhancing antioxidant activity. However, its impact on glycemic response is variable and largely determined by the specific food system and processing context. Current evidence emphasizes the importance of considering formulation and matrix interactions when assessing glycemic outcomes. Future research should focus on well-controlled human studies and standardized formulations to clarify the independent effects of sprouting and to support the development of low-glycemic, nutritionally improved GF products.
Metabolic syndrome comprises insulin resistance, obesity, hypertension, and dyslipidaemia, increasing the risk of diabetes and cardiovascular diseases. It is a major contributor to global mortality. Approximately 28–31
Age-related cognitive decline is a major public health challenge and has a significant impact on a country’s economy and economic growth. Evidence suggests dietary patterns such as the Mediterranean Diet (MeDi), Dietary Approaches to Stop Hypertension (DASH), Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND), Alternative Health Eating Index (AHEI) and plant-based diets are associated with reduced cognitive decline and improved brain health. The main objective of this review is to summarize recent data and provide a literature-based evaluation of the effects of popular dietary patterns associated with cognitive health. An in-depth evaluation of the current literature suggests that adherence to healthy dietary patterns—including the MeDi, DASH, MIND, AHEI, and plant-based diets—can play an important role in preserving cognitive function and delaying cognitive aging. However, gaps remain in understanding the effects of long-term dietary adherence, specific food constituents, culturally diverse dietary practices, and the underlying molecular and neurophysiological mechanisms. These factors warrant further investigation to identify causal relationships between dietary patterns and beneficial effects on cognitive health. Literature-based evaluation offers a strong correlation between diet, nutrition, and age-related cognitive health. Despite these observations, studies affirm that new research incorporating well-powered longitudinal studies and culturally adaptable interventions are equally necessary. Furthermore, public health officials and global health entities should implement evidence-based and well-researched nutritional policies that are aimed at preserving cognitive health.
One way to reduce the health hazards of excess alcohol consumption and the subsequent health concerns is to include information on the label. While alcoholic beverages are characterised as food, they are exempt from some of the labelling information and requirements that apply to other food items, including not requiring total ingredient lists or nutrition information. A scoping review following a systematic process was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. This scoping review focuses on consumer preferences and attitudes relating to ingredient lists, nutrition information, and health warnings on alcohol labels. 56 papers were included in the review. We found that attitudes and preferences towards alcohol labels are mixed, and while consumers express interest in nutrition, ingredients and health warning information, their actual use of this information for decision-making remains limited. Those who are most likely to use information on labels, and think that the labels would influence their alcohol consumption are females, lighter drinkers and those who are more health conscious. Consumer attitudes and preferences towards alcohol labels are mixed. Consumer preferences influence and play an important role in determining acceptance of labels and what consumers want. This review has identified gaps in the literature around consumer preferences for nutrition and ingredients listings, while there is an abundance of evidence relating to health warnings on alcohol labels with mixed results.
Malnutrition, whether pre-existing or acquired in the ICU, is common in critically ill children. This narrative review synthesizes current evidence on nutritional assessment and therapy, highlighting how illness phase, underlying disease, and medical interventions influence energy expenditure and nutrient requirements. International guidelines recommend comprehensive nutritional assessment and early initiation of enteral nutrition (EN) for all patients admitted to the Pediatric ICU. However, EN is frequently underutilized or insufficient to meet metabolic demands and sometimes contraindicated. Barriers to delivery persist, and parenteral nutrition (PN) may be required when EN is not feasible or adequate. Nutrition plays a crucial yet complex role in the care of critically ill children. Optimizing individualized nutrition strategies, including timely EN and appropriate PN use, is essential to improve clinical outcomes, support recovery, and enhance long-term rehabilitation, while highlighting the need for improved implementation and future research.
Magnesium plays an indispensable role in human health and is intricately involved in many crucial physiological and metabolic pathways. True biochemical magnesium deficiency is rarely encountered in clinical practice but subclinical and functional deficiency of magnesium appears to be more common and is reported in many chronic health disorders. Estimating magnesium status is challenging and best evaluated by a combination of serum magnesium, urinary magnesium, and dietary magnesium intake. Many randomized controlled trials (RCTs) have demonstrated the efficacy of magnesium supplementation in various chronic disorders such as constipation, dyspepsia, mood disorders, metabolic diseases, and bone health. However, magnesium supplements are heavily advertised for several purported and hyped benefits, which require more high-quality evidence to support these claims. Caution should be exerted when supplementing magnesium to people who are predisposed to adverse effects, such as in renal insufficiency. Studies noted the significant role of magnesium in the acute management of eclampsia, asthma, and migraine. RCTs have noted a significant role of magnesium supplements in many chronic disorders, such as constipation, gastroesophageal reflux disease, metabolic dysfunction (diabetes, hypertension, dyslipidemia, and obesity), and mood disorders.
Vitamin D is a pleiotropic secosteroid with established skeletal functions and proposed extraskeletal effects; however, its clinical application remains contentious. Despite extensive observational evidence linking low 25(OH)D concentrations to chronic diseases, randomized controlled trials (RCTs) have largely failed to confirm many of these associations. This review focuses on the practical clinical management of vitamin D, integrating determinants of vitamin D status, assay-related limitations, targeted testing, evidence-based supplementation, and decision-making within a precision-nutrition context. The discordance between observational and interventional evidence is partly explained by the inclusion of vitamin D–replete populations in major trials, background supplementation, non-linear dose–response relationships, and assay variability. For skeletal outcomes, clinically meaningful effects are mainly observed in deficiency, whereas selected benefits have been reported in specific populations, including mortality reduction in adults aged ≥ 75 years, a modest reduction in cancer mortality, and reduced progression to diabetes in adults with high-risk prediabetes. The 2024 Endocrine Society guideline recommends empiric supplementation for selected groups and discourages routine screening in healthy adults. Daily or weekly dosing is preferred to intermittent high-dose regimens, which may increase falls and fractures. Standardization initiatives have improved 25(OH)D measurement accuracy, but inter-method variability persists, complicating thresholds and cross-study comparisons. Genetic polymorphisms in GC, CYP2R1, CYP24A1, and VDR contribute to variability in supplementation response, although precision-nutrition approaches remain investigational. Vitamin D should be viewed as a context-dependent, threshold-driven nutrient rather than a universal preventive therapy. Clinically, priority should be given to preventing and correcting severe deficiency (< 12 ng/mL [< 30 nmol/L]), a threshold below which adverse skeletal outcomes are well documented. Supplementation should target evidence-based indications, and laboratory testing should be reserved for situations in which results inform management. Bridging evidence and practice requires trials in deficient populations, improved assay harmonization, and integration of individualized risk factors into clinical decision-making.
The objective is to understand the bioactive compounds present in olive as functional natural histone deacetylase (HDAC) inhibitors and epigenetic modulators. This review focusses on oleuropein, hydroxytyrosol, and oleanolic acid analyzing their molecular targets, signaling pathways in major non communicable diseases. By integrating evidences from studies in cell lines, animals and preclinical studies, this review aims to identify research gaps, clarify mechanistic inconsistencies and propose future translational strategies for leveraging olive bioactives in precision epigenetic therapy. Oleuropein, hydroxytyrosol, and oleanolic acid exhibit epigenetic regulatory potential through modulation of HDAC activity. Oleuropein has been reported to promote histone acetylation leading to tumor suppressor genes and modulation of apoptosis signaling pathways. Whereas hydroxytyrosol exerts epigenetic effects by attenuating HDAC expression and oxidative stress mediated chromatin remodeling thereby influencing inflammatory metabolic gene regulation. Oleanolic acid demonstrates HDAC inhibitory potential and modulates acetylation dependent transcriptional pathways involved in cell cycle regulation, inflammation and cancer progression. Collectively they may serve as adjunct epigenetic modulators pending further validations. This review offers insights into the potential of oleuropein, hydroxytyrosol, and oleanolic acid as HDAC targeting agents for addressing metabolic disorders, cardiovascular protection, cancer prevention, and neurodegenerative disease therapy. These compounds also regulate glucose metabolism and glucose sensitivity, addressing metabolic disorders. They show encouraging preclinical evidence like HDAC inhibitors.
Maternal obesity is a major public health challenge that elevates pregnancy risks and predisposes offspring to lifelong metabolic disorders. Nutrition, as a modifiable determinant of the intrauterine environment, offers opportunities to interrupt this intergenerational cycle. This review synthesizes evidence on polyphenols, vitamins, omega-3 fatty acids, dietary fiber, probiotics, prebiotics, whole grains, and iron, highlighting underlying mechanisms and translational implications for maternal and offspring health. Preclinical studies demonstrate that these interventions improve maternal metabolism, modulate placental function, regulate gut microbiota, alter breast milk composition, and influence epigenetic programming. Clinical evidence is relatively strong for folic acid and vitamin D, whereas evidence for dietary fiber is emerging, with long-term offspring outcomes still insufficiently investigated. Polyphenols and omega-3 fatty acids exert antioxidant and anti-inflammatory effects, but translation is constrained by low bioavailability and limited safety data. Probiotics and prebiotics show potential in modulating maternal–infant gut health, yet trial outcomes are inconsistent and strain-specific. Whole grains and fortified foods may represent feasible options for population-level implementation, although robust longitudinal studies in obese pregnancies are still lacking. Dietary interventions hold promise for mitigating maternal obesity by improving metabolism, reducing inflammation, supporting placental function, and modulating gut microbiota, breast milk composition, and epigenetic programming. However, evidence is largely preclinical and long-term human data are limited. Future research should prioritize well-designed clinical trials and personalized approaches tailored to maternal phenotype and nutritional status to enable effective, scalable strategies for breaking the intergenerational cycle of obesity.
Obesity pharmacotherapy has become increasingly relevant in older adults due to challenges in lifestyle modification and the burden of non-communicable diseases. Despite the expanding use of anti-obesity medications (AOMs), sarcopenia and sarcopenic obesity (SO) remain major concerns in this population. This review synthesizes current evidence on glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a well-studied AOMs, focusing on their effects on sarcopenia through mechanistic insights and clinical considerations in older adults. GLP-1 RAs effectively induce weight loss; however, concomitant muscle mass loss is common, raising concerns about sarcopenia. Weight cycling introduces uncertainty regarding skeletal muscle health and SO risk. Although data on muscle mass indices and physical performance remain limited and inconsistent, evidence suggests favorable effects on muscle metabolism and composition. Mechanistically, these effects are linked to GLP-1 RA-mediated suppression of inflammatory pathways, modulation of skeletal muscle metabolism, and preservation of mitochondrial function, thereby influencing insulin resistance. The most common adverse events are mild to moderate gastrointestinal symptoms, which may be mitigated through dietary counseling during dose escalation. Integrating GLP-1 RA therapy with tailored resistance exercise and caloric restriction with dietary counseling, including adequate protein intake (1.2–1.6 g/kg/day), may help preserve muscle mass and function in older adults. Implementation of GLP-1 RA-specific medical nutrition therapy protocols, with dietitian involvement to optimize dietary recommendations and manage adverse events, is recommended. Studies addressing skeletal muscle quantity, quality, and functional capacity are needed to clarify the effects of GLP-1 RAs on sarcopenic obesity in older adults.
The Nova classification considers the purpose and degree of food processing to capture how recent changes in the food system may link with health. Its value for understanding diet-disease relationships is debated. However, reviews typically focus only on its value, or its limitations. Furthermore, by discussing the degree of processing only and not the purpose, or discussing processing in general, reviews of limitations do not address pitfalls of the Nova classification. This conflict and confusion stalls progress to improve public health. Therefore, this review aims to provide a balanced understanding, interpretation and utilisation of the Nova classification and purpose of food processing, with a critical evaluation of its potential value, of pitfalls largely overlooked to date with recommendations to avoid unintended consequences, and constructive reflections on a path forward. The Nova classification offers a framework linking upstream socioeconomic factors with downstream properties of available food, complementing existing food-based dietary guidance to improve access to healthy diets through food systems transformations. However, its practical application, narrative of intrinsic harm of ultra-processing, usage to guide diets in isolation, and overemphasis on mechanisms with weaker evidence are pitfalls that, whilst avoidable, can have unintended consequences. There is agreement on the need for food systems transformation to ensure access and affordability to healthy diets for all. For public health, the purpose behind food processing provides an understanding of systems drivers of food production and accessibility. This consideration can be reflected in policy to improve access to healthy diets, without necessarily explicit use of the Nova classification.
Aging is marked by progressive physiological decline driven by chronic inflammation, mitochondrial dysfunction, and impaired metabolic and musculoskeletal resilience. As the global population ages, dietary supplements have gained attention as potential tools to support healthy longevity. This review summarizes current evidence on nutritional compounds that target aging-related pathways, focusing on interventions that influence mitochondrial health, cognitive performance, immune function, metabolic regulation, and maintenance of muscle mass in older adults. Thirty-two human studies were identified through PubMed, Scopus, and Web of Science. Evidence indicates that several targeted nutrients, including protein, probiotics, antioxidants, and emerging mitochondrial-support compounds, may contribute to healthy aging. Protein and collagen supplementation, particularly when paired with resistance training, consistently improve muscle mass and physical function. Antioxidants, glycine, N-acetylcysteine, and NAD⁺ precursors show potential benefits for mitochondrial efficiency, cellular stress responses, and cognitive performance; however, findings vary across populations and dosing strategies. Heterogeneity in study designs, supplement formulations, and biomarker endpoints underscores the need for individualized and context-specific application. A personalized, evidence-informed supplementation strategy integrated with exercise and balanced nutrition may help optimize physiological function in aging adults. Future research should refine dosing protocols, evaluate synergistic nutrient combinations, and clarify the roles of antioxidants and mitochondrial-targeted compounds across diverse older populations.
Obesity is a complex metabolic disorder driven by factors such as chronic inflammation, insulin resistance, and significant alterations in the gut microbiota. Dipeptidyl peptidase-4 (DPP-4), an enzyme primarily known for inactivating incretin hormones like glucagon-like peptide-1 (GLP-1), is now recognized as a critical link between metabolic dysfunction and gut microbiome dysbiosis. This review aims to examine the mechanistic role of DPP-4 and its inhibitors in obesity, specifically focusing on how they modulate the gut microbiome to influence host energy balance and metabolic health. Recent experimental and clinical evidence indicates that DPP-4 activity contributes to obesity by influencing microbial composition, diversity, and function. Studies demonstrate that DPP-4 inhibitors can reshape the gut microbiota by reducing dysbiosis, decreasing the Firmicutes-to-Bacteroidetes ratio, and enhancing the production of short-chain fatty acids (SCFAs). Furthermore, these inhibitors improve gut barrier integrity and regulate bile acid metabolism, which helps attenuate systemic inflammation and restore insulin sensitivity. While DPP-4 inhibitors are often weight-neutral in clinical settings, they appear to assist in maintaining metabolic stability by enhancing central satiety signaling and reducing neuroinflammation. The gut microbiome acts as a key intermediary in the metabolic regulation managed by DPP-4. By restoring microbial balance and promoting beneficial metabolites, DPP-4 inhibitors offer therapeutic advantages that extend beyond traditional glycemic control to include improved energy equilibrium and reduced adiposity. Targeting the interactions between DPP-4 and the microbiota represents a promising future therapeutic strategy for managing obesity and its associated metabolic complications.
