Severe obesity (SO), defined as a BMI ≥40 kg m-2 or ≥35 kg m-2 with comorbidities, is a complex chronic condition that poses major challenges to clinical management. Current evidence on the pathophysiological and environmental factors influencing outpatient care for people with SO (PSO) is synthesized and analyzed in this review. A literature search covering the past 10 years was conducted, including scientific articles and guidelines from scientific societies addressing these factors. The evidence suggests that conventional outpatient approaches are often insufficient for PSO, because they fail to address the complex biological, behavioral, and environmental mechanisms sustaining SO. Clinically meaningful weight loss often requires reductions of more than 10%, 15%, or even 20%; long-term success rates remain low among individuals treated with nonpharmacological or nonsurgical approaches alone. Genetic predisposition plays a central role, including rare monogenic and syndromic forms associated with early-onset obesity and poorer response to nontargeted therapies, as well as polygenic obesity. Dysfunctions in the leptin-melanocortin pathway also may impair appetite regulation and modify sensory, endocrine, and neural responses related to food intake. People with SO may also present with hedonic hunger and emotional or uncontrolled eating, in addition to higher rates of eating disorders, depression, and anxiety, which contribute to weight regain. The increasing prevalence of SO reinforces the need for a comprehensive, individualized, and multidisciplinary approach that incorporates pathophysiological and environmental determinants into care. Improving outcomes in SO depends not only on expanding therapeutic options but also on better training healthcare teams to recognize the multifactorial mechanisms underlying treatment resistance and weight regain. A structured, person-centered outpatient framework is proposed that integrates biological, psychosocial, and environmental determinants of SO, along with practical clinical tools to support individualized management and improve long-term care.

The potential of fermentation was evaluated as a technological strategy to enhance the nutritional quality and anabolic properties of plant proteins specifically for the prevention and management of sarcopenia. Sarcopenia involves a progressive loss of muscle mass and function linked to "inflammaging," digestive changes, and anabolic resistance. Although plant-based proteins are increasingly popular and important for planetary health, their anabolic potential is traditionally limited by lower digestibility and suboptimal essential amino acid profiles, particularly low leucine levels. This review synthesizes evidence from in vitro models, animal studies, and human clinical trials to examine how fermentation transforms plant-based foods and influences muscle metabolism pathways. Evidence suggests that fermentation reduces antinutritional factors, alters amino acid profiles, and improves protein digestibility, leading to increased bioavailability of essential amino acids, notably leucine. Mechanistically, fermented plant products stimulate anabolic cell signaling pathways (eg, Akt/mTORC1) and suppress the catabolic ubiquitin-proteasome pathway (eg, atrogin-1 and MuRF-1). Fermentation also generates bioactive isoflavone aglycones and angiotensin-converting enzyme-inhibitory and other peptides that may improve muscle perfusion and reduce oxidative stress. Furthermore, fermentation modulates the gut-muscle axis via short-chain fatty acid production, which may mitigate the systemic inflammation and oxidative stress associated with muscle loss. Human evidence translating these findings is currently limited. Fermentation offers a sustainable approach to optimizing plant-based nutrition to support muscle maintenance. Mechanistic findings are promising; however, further long-term human trials are required to translate this evidence into formal clinical recommendations for sarcopenia.

Mechanistic evidence was systematically reviewed on how major metabolites produced during fermentation of foods modulate obesity through gut microbiota remodeling and multiorgan metabolic regulation, with emphasis on the gut-brain axis, immunometabolic pathways, and epigenetic mechanisms. Obesity remains a major global public health challenge, and conventional management strategies are frequently limited by poor long-term efficacy, low adherence, and undesirable side effects. Increasing evidence positions the gut microbiome as a central metabolic organ that profoundly influences host energy homeostasis and adiposity. Individuals with obesity commonly have a disrupted intestinal microbial ecosystem characterized by reduced microbial diversity, depletion of health-promoting taxa, and enrichment of facultative pathogens, which compromise intestinal barrier function, promote chronic low-grade inflammation, and disturb systemic metabolic regulation. Fermented foods, integral to traditional diets, provide a rich source of live microorganisms and a diverse repertoire of bioactive metabolites produced through fermentation. A narrative review was conducted by synthesizing evidence from experimental, mechanistic, and preclinical studies on fermented foods, gut microbial ecology, fermentation-derived metabolites, and obesity-related metabolic pathways. Current evidence indicates that the anti-obesity effects of fermented foods are mediated not only by transient microbial colonization but, more importantly, by fermentation-derived metabolites such as short-chain fatty acids, conjugated linoleic acid, and indole derivatives (eg, indole-3-propionic acid). These metabolites exert multiorgan physiological effects through the gut-brain axis, immunometabolic pathways, and epigenetic regulation. Collectively, they modulate key processes, including enteroendocrine hormone secretion, hepatic glucose and lipid metabolism, browning of white adipose tissue, and central appetite control, ultimately contributing to metabolic restoration. This review provides a systematic and mechanistic evaluation of how major fermentation-derived metabolites counteract obesity by reshaping gut microbiota composition and functional activity across interconnected organ systems. The insights provide a strengthened conceptual framework for designing microbiota-directed nutritional strategies to sustain body-weight regulation.

This narrative review examines how artificial intelligence (AI) and omics are being integrated in food science and nutrition, with particular attention to current applications, practical limitations, and challenges that are specific to foods and dietary exposure. Foods are complex, multicomponent matrices whose composition and biological effects can change during processing, cooking, storage, and consumption. Dietary exposure also varies over time and across individuals. These features make food and nutrition fundamentally more difficult to model than many domains in which AI has advanced rapidly. Relevant literature was identified through searches of PubMed, Google Scholar, and Web of Science. For studies applying AI to foods, reports published in 2023 or later were preferentially selected unless suitable recent studies were unavailable. Selected publications were independently evaluated by the authors and subsequently discussed. The integration of AI and omics approaches are being applied to data integration, feature selection, predictive modeling, network analysis, clustering, interpretation, flavor and taste design, discovery of bioactive ingredients, functional food development, and prediction of dietary responses involving metabolites and the gut microbiome. Across these applications, food- and nutrition-specific difficulties emerged repeatedly, including the partial observability of food composition, changes caused by processing and cooking, mismatches between short-term measurements and long-term health outcomes, nonlinear dose-response relationships, and inter-individual variation. These challenges add to general issues such as data quality, multi-omics integration, model interpretability, and external validation. The integration of AI and omics is expanding the capacity to analyze complex data in food science and nutrition, but reliable translation will require methods adapted to the dynamic and partly observable nature of foods and diets. Improved standardization, exposure assessment, validation, study design, and interpretability will be essential for future research and practical application.

This narrative review synthesizes 5 decades of evidence on zinc deficiency-induced cyclic feeding in animal models, examines the underlying neurobiological mechanisms-with emphasis on recent advances in gut-brain axis signaling-and critically evaluates whether analogous periodic appetite fluctuations may occur in zinc-deficient humans. Zinc deficiency induces a distinctive cyclic feeding pattern in rodents, with food intake oscillating at an approximately 3.5-day period, as demonstrated by cosinor analysis, yet the mechanistic basis and potential human relevance of this phenomenon remain incompletely understood. PubMed was searched (through March 2026, with no date restrictions) using terms related to zinc, appetite-regulating neuropeptides and hormones, neuropsychiatric outcomes, and zinc-sensing receptors/transporters. A total of 41 references were selected on the basis of topical relevance, supplemented by citation chaining. The approximately 3.5-day cyclic feeding pattern has been reproducibly observed in several rat studies under controlled laboratory conditions, persisting at the individual-animal level and across dietary carbohydrate sources, though the evidence base is limited to predominantly male rats from a small number of research groups. Mechanistically, this periodicity involves paradoxical neuropeptide Y elevation with putatively impaired release, hypothalamic-pituitary-adrenocortical axis dysregulation, vagal zinc sensing, enteroendocrine cholecystokinin signaling, and intestinal and salivary functions mediated by the zinc-sensing receptor ZnR/GPR39. Clinical data-including zinc deficiency in anorexia nervosa and avoidant/restrictive food intake disorder patients, refeeding hypozincemia, and population-specific effects of zinc supplementation on body weight-provide circumstantial but not direct support for a human correlate. No direct evidence for cyclic feeding in zinc-deficient humans currently exists; however, conserved neurobiological substrates and emerging clinical findings warrant prospective studies employing continuous dietary monitoring and serial zinc assessment to test this hypothesis.

Flavonoids are widely consumed dietary polyphenols that have been extensively investigated for their antioxidant, anti-inflammatory, and anticancer properties. However, their role in oncology is more complex than is often assumed, as their biological effects may vary according to dose, bioavailability, metabolic transformation, tumour type, disease stage, and treatment context. This narrative review examines the dual and context-dependent nature of flavonoids in cancer biology, with emphasis on redox-dependent liabilities, genotoxicity, pharmacokinetic limitations, gut microbiota-mediated variability, and herb-drug interactions. The reviewed data indicate that flavonoids may exert protective, chemosensitizing, or regulatory effects under some conditions, while under others they may promote adaptive antioxidant responses, alter drug disposition, influence immune signaling, or produce adverse outcomes at supraphysiological exposure levels. Current evidence therefore does not support a uniformly beneficial interpretation of flavonoids in oncology. Rather, their significance lies in their biological duality and exposure-dependent behavior.

This narrative review aims to provide a vascular-oriented and nutrition-relevant synthesis of nicotinamide adenine dinucleotide+ (NAD+) metabolism in atherosclerosis and to clarify how dietary and lifestyle factors may modulate NAD+ homeostasis in vascular disease. Although NAD+ has emerged as a central regulator of vascular redox balance, mitochondrial function, inflammation, and DNA repair, its role in atherosclerosis remains conceptually fragmented and has not yet been fully examined within the context of nutrition-relevant research frameworks. We searched PubMed, Web of Science, Embase, and Google Scholar and synthesized evidence from mechanistic, preclinical, and clinical studies. Current evidence suggests that NAD+ network remodeling in atherosclerosis reflects the interplay of precursor availability, enzymatic consumption, and plaque microenvironment stressors. Nutritional modulation approaches can be broadly grouped into 4 domains: NAD+ precursor supplementation, flavonoid-related conservation strategies, gut microbiota-associated pathways, and lifestyle interventions. Human studies have consistently demonstrated systemic NAD-related metabolite engagement following precursor supplementation; however, convincing evidence for direct antiatherosclerotic benefit remains limited, and circulating NAD+ measures may not adequately represent vascular NAD+ status. By integrating vascular biology with nutrition-based modulation strategies, this review provides a practical conceptual framework for interpreting current evidence and guiding future research. Well-designed trials incorporating vascular-specific biomarkers and clinically meaningful cardiovascular endpoints are needed to determine the therapeutic relevance of NAD+-targeted nutritional interventions.