Search Results (130)

Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and share key pathological features such as oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Recent research has highlighted the potential of ketogenic metabolism, particularly the use of ketone bodies like β-hydroxybutyrate, as a therapeutic approach targeting these shared mechanisms. This review provides a comprehensive synthesis of current knowledge on the neuroprotective effects of ketogenic interventions, including both dietary strategies and exogenous ketone supplementation. We discuss how ketone bodies improve mitochondrial function, reduce reactive oxygen species, modulate inflammatory pathways, and influence neurotransmission and synaptic plasticity. Additionally, we examine experimental and clinical evidence supporting the application of ketogenic therapies in neurodegenerative diseases, highlighting disease-specific findings, benefits, and limitations. While preclinical data are robust and suggest meaningful therapeutic potential, clinical studies remain limited and heterogeneous, with challenges related to adherence, safety, and patient selection. The review also addresses the translational relevance of ketogenic strategies, considering their feasibility, combination with other therapies, and the need for personalized approaches based on genetic and metabolic profiles. By critically evaluating existing data, this article aims to clarify the mechanisms through which ketogenic metabolism may exert neuroprotective effects and to outline future directions for research and clinical application in the context of neurodegenerative disorders. Full article

Background/Objectives: Diabetic kidney disease (DKD) is a major complication of type 2 diabetes mellitus (T2DM), and recent research highlights that amino acid composition—rather than total protein intake alone—may influence DKD risk. This study aimed to evaluate the associations between dietary protein intake, specific amino acid profiles, and the risk of DKD among adults with T2DM. Methods: A total of 378 T2DM patients were enrolled in this cross-sectional study. Dietary intake was assessed via a 24 h recall and a validated semi-quantitative food frequency questionnaire. Nutrient analysis was based on the Taiwanese Food Composition Database. Participants were categorized into three protein intake groups: Group 1 (≤0.8 g/kg), Group 2 (0.9–1.2 g/kg), and Group 3 (≥1.3 g/kg). Cox proportional hazards models were used to evaluate the associations of crude protein, branched-chain amino acids to aromatic amino acids (BCAA/AAA) ratio, and ketogenic amino acid intake with DKD risk. Adjustments were made for age, sex, diabetes duration, and blood pressure. Results: While crude protein intake showed no significant association with DKD risk, higher intake of ketogenic amino acids (e.g., leucine and lysine) was consistently and significantly associated with reduced DKD risk (adjusted HR range = 0.698–0.716, p < 0.01). Our findings highlight the protective potential of ketogenic amino acids such as leucine and lysine, which were significantly associated with lower DKD risk. The BCAA/AAA ratio also showed a downward trend in DKD risk, though not statistically significant. Kaplan–Meier analysis revealed that moderate protein intake (0.9–1.2 g/kg) corresponded to the most favorable DKD-free survival. Conclusions: Our findings suggest that, beyond total protein quantity, the intake of ketogenic amino acids may play a protective role in DKD prevention. Moderate protein consumption combined with higher leucine and lysine intake appears beneficial. These results support incorporating amino acid profiling in dietary strategies for DKD risk reduction. Further longitudinal and interventional studies are recommended to validate these associations. Full article

Background/Objectives: The educational needs of individuals with OA and obesity can drive personalized resources for effective dietary interventions that align patient interests with weight and disease management. Therefore, the purpose of the present study was to evaluate differences in nutritional education topics of interest between patients with OA who are characterized as having higher (≥30 kg/m²; HBMI) and lower BMI (<30 kg/m²; LBMI). Methods: Cross-sectional survey data (n = 296) were dichotomized into HBMI (n = 172; BMI: 38.67 ± 6.59 kg/m²) and LBMI (n = 124; BMI: 25.59 ± 3.00 kg/m²) groups. A mixed-method approach examined group differences across four primary domains: (i) strategies for weight management and healthy lifestyle, (ii) interest in vitamins and supplements, (iii) foods and nutrient with anti-inflammatory properties, and (iv) dietary patterns for weight loss. Logistic regression models compared topic interests between groups. Thematic analysis of open-ended responses captured additional insights. Results: Compared to LBMI participants, those in the HBMI group showed greater interest in weight loss strategies, emotional eating, and diets such as low-carbohydrate and ketogenic approaches, but less interest in general supplement information and plant-based diets. HBMI also had greater interest in practical strategies (e.g., feeling full, affordable foods) and reduced interest in certain anti-inflammatory foods. Both groups expressed a desire for evidence-based resources on foods that promote joint health. Conclusions: BMI-specific differences in nutritional education preferences highlight the need for tailored, patient-centered strategies in OA management. Addressing these differences may improve the effectiveness of education interventions and enhance patient–provider communication around diet and lifestyle in OA care. Full article

Background: Melanoma, one of the most aggressive forms of skin cancer, has seen significant therapeutic advances with immune checkpoint inhibitors (ICIs). However, many patients fail to respond or develop resistance, creating the need for adjunct strategies. Objective: The objective of this study is to critically evaluate how specific dietary patterns and nutrient-derived metabolites modulate melanoma metabolism and immunotherapy outcomes, emphasizing translational implications. Methods: We performed an integrative review of preclinical and clinical studies investigating dietary interventions in melanoma models and ICI-treated patients. Mechanistic insights were extracted from studies on nutrient transport, immunometabolism, and microbiome–immune interactions, including data from ongoing nutritional clinical trials. Results: Diets rich in fermentable fibers, plant polyphenols, and unsaturated lipids, such as Mediterranean and ketogenic diets, seem to contribute to the reprogramming of tumor metabolism and enhance CD8+ T-cell activity. Fasting-mimicking and methionine-restricted diets modulate T-cell fitness and tumor vulnerability via nutrient stress sensors (e.g., UPR, mTOR). High fiber intake correlates with favorable gut microbiota and improved ICI efficacy, while excess protein, methionine, or refined carbohydrates impair immune surveillance via lactate accumulation and immunosuppressive myeloid recruitment. Several dietary molecules act as network-level modulators of host and microbial proteins, with parallels to known drug scaffolds. Conclusions: Integrating dietary interventions into melanoma immunotherapy can significantly influence metabolic reprogramming by targeting metabolic vulnerabilities and reshaping the tumor–immune–microbiome axis. When combined with AI-driven nutrient–protein interaction mapping, this approach offers a precision nutrition paradigm that supports both physicians and patients, emerging as a novel layer to enhance and consolidate existing therapeutic strategies. Full article

Cardiovascular diseases (CVDs) remain the leading global cause of death, with obesity acting as a significant contributing factor through mechanisms such as chronic inflammation, insulin resistance, and endothelial dysfunction. Molecular pathways at the interface of obesity, diet, and CVDs reveal how altered lipid metabolism, oxidative stress, and inflammatory signaling contribute to CVD progression. Despite advancements in treatment, effective management of CVDs, particularly in the context of obesity, remains a challenge. This review addresses the gap in understanding the relationship between obesity, nutritional status, and CVD progression, evaluating the impact of dietary interventions such as low-carb, Mediterranean, ketogenic, and Dietary Approaches to Stop Hypertension diets on cardiovascular health. Key findings indicate that adipokines, interleukins, and tumor necrosis factor alpha play significant roles in inflammatory responses and insulin resistance, further exacerbating cardiovascular dysfunction. Furthermore, optimized dietary strategies have been shown to modulate several molecular pathways, improving cardiovascular risk factors and enhancing metabolic health. This review underscores the significance of understanding molecular metabolic pathways in the intricate relationship between obesity, diet, and CVDs. It highlights the role of personalized nutrition and comprehensive dietary patterns in the management of CVDs and advocates for further research to optimize dietary strategies for sustained cardiovascular health. Full article

Background/Objectives: Obesity remains a major public health concern, and effective dietary strategies for reducing cardiovascular risk are still under investigation. This interventional non-randomized study aimed to evaluate the short-term effects of the modified ketogenic diet (KD) and time-restricted eating (TRE) on cardiovascular risk, as assessed by the QRISK3 score. Methods: Forty-nine adults with obesity were assigned to either the KD (n = 23) or TRE (n = 26), based on voluntary presentation to a nutrition clinic. Interventions were monitored by a certified clinical nutritionist over 12 weeks. Anthropometric parameters, metabolic markers, and QRISK3 scores were measured at baseline and post-intervention. Results: Both dietary approaches led to significant reductions in body weight and QRISK3 scores. However, the KD resulted in more pronounced improvements in the lipid profile, systolic blood pressure, and glycemic control. Interaction analysis suggested that older participants and those with a higher baseline risk benefited more from the KD. Conclusions: Over 12 weeks, both diets improved cardiovascular risk and metabolic markers in individuals with obesity. The modified diet ketogenic dietary pattern showed more pronounced short-term benefits in the lipid profile, blood pressure, and glycemic control. These results suggest its potential utility in clinical practice, though long-term effectiveness and safety remain to be established. Full article

The 4Rs of sports nutrition were proposed in recent years as an evidence-based framework to optimize post-exercise recovery within the context of allostasis. Under this paradigm, it is important to consider that each R represents a factor with a tremendous influence on the allostatic response and improves individual components of the allostatic load (AL), which will positively impact the exercise-induced adaptations and the athlete’s recovery. The 4Rs correspond to the following. (i) Rehydration—This is necessary to guarantee the post-exercise consumption of at least 150% of the body mass lost during the exercise accompanied by sodium (if faster replacement is required). (ii) Refuel—Carbohydrate intake (~1.2 g/kg body mass per hour for up to 4 h post-exercise) is essential not only in restoring glycogen reserves but also in supporting the energy needs of the immune system and facilitating tissue repair. Despite changes in substrate utilization, a ketogenic diet generally has neutral or negative effects on athletic performance compared to carbohydrate-rich diets. (iii) Repair—The ingestion of high-quality protein stimulates post-exercise net muscle protein anabolism and might contribute to faster tissue growth and repair. The use of certain supplements, such as creatine monohydrate, might help to enhance recovery, while tart cherry, omega-3 fatty acids, and dietary nitrate (e.g., Beta vulgaris, Amaranthus L.), as well as other herbal extracts containing flavonoid-rich polyphenols, deserve further clinical research. (iv) Recuperate—Pre-sleep nutrition (casein- or protein-rich meal with slow digestion rate) has a restorative effect, facilitating the recovery of the musculoskeletal, endocrine, immune, and nervous systems. In this article, we update the 4Rs framework, delve deeper into the allostasis paradigm, and offer theoretical foundations and practical recommendations (the 4Rs app) for the assessment of AL in athletes. We cautiously propose an AL index (AL_index) for physique competitors and elite athletes to evaluate the cumulative physiological stress induced by exercise and, thereby, to adjust exercise and nutrition interventions. Full article

Alzheimer’s Disease (AD) is characterized by complex brain alterations leading to progressive cognitive decline and neuropsychiatric disturbances. This narrative review explores these changes and the potential of diet and exercise as modifiable lifestyle factors to mitigate AD’s impact. While some dietary components (e.g., B vitamins, ketogenic diet) and physical activity, particularly aerobic exercise, show promise for improving cognitive function and managing symptoms, evidence for consistent benefits remains limited and requires further investigation. Dietary and exercise research in AD faces significant limitations, including intervention complexity, study design challenges, disease heterogeneity, and difficulties in measuring long-term effects. Addressing these limitations is crucial to fully realize the therapeutic potential of these lifestyle interventions in combating AD. Full article

Background and Objective: Dietary interventions are the first-line treatment for overweight individuals (OW) and individuals with obesity (OB) with high-normal blood pressure (BP) or grade I hypertension, especially when at low-to-moderate cardiovascular risk (CVR). However, current guidelines do not specify the most effective dietary approach for optimising cardiovascular and metabolic outcomes in this population. This study aimed to compare the effects of a low-calorie, high-protein ketogenic diet (KD) vs. a low-calorie, low-sodium, and high-potassium Mediterranean diet (MD) on BP profiles assessed via ambulatory BP monitoring (ABPM), as well as on anthropometric measures, metabolic biomarkers, and body composition evaluated by bioelectrical impedance analysis (BIA). Methods: This prospective observational bicentric pilot study included 26 non-diabetic adult outpatients with central OW status or OB status (body mass index, BMI > 27 kg/m²) and high-normal BP (≥130/85 mmHg) or grade I hypertension (140–160/90–100 mmHg), based on office BP measurements. All participants had low-to-moderate CVR according to the second version of the systemic coronary risk estimation (SCORE2) and were selected and categorized as either KD (n = 15) or MD (n = 11). Comprehensive blood analysis, BIA, and ABPM were conducted at baseline and after three months. Results: At baseline, no significant differences were observed between the groups. Following three months of dietary intervention, both groups exhibited substantial reductions in body weight (KD: 98.6 ± 13.0 to 87.3 ± 13.4 kg; MD: 93.8 ± 17.7 to 86.1 ± 19.3 kg, p < 0.001) and waist circumference. Mean 24 h systolic BP (SBP) and diastolic BP (DBP) significantly declined in both groups (24 h mean SBP decreased from 125.0 ± 11.3 to 116.1 ± 8.5 mmHg (p = 0.003) and 24 h mean DBP decreased from 79.0 ± 8.4 to 73.7 ± 6.4 mmHg (p < 0.001)). Fat-free mass (FFM) increased, whereas fat mass (FM), blood lipid levels, and insulin concentrations decreased significantly. The ΔFM/ΔFFM correlates with ABP improvements. However, no significant between-group differences were detected at follow-up. Conclusions: The KD and the MD mediated weight loss and body composition changes, effectively improving bio-anthropometric and cardiovascular parameters in individuals with OW status or OB status and high BP. Although more extensive studies are warranted to elucidate potential long-term differences, our findings suggest the manner in which these two different popular dietary approaches may equally confer metabolic and cardiovascular benefits, emphasising the importance of weight and FM loss. Full article

Diet plays a crucial role in cancer development and progression, beyond traditional risk factors. This review aims to summarize current evidence on the role of diet and specific nutrients in cancer development and progression, focusing on molecular mechanisms. We also discuss the potential of personalized dietary interventions, based on tumor and patient characteristics, in enhancing cancer prevention and treatment strategies. The review covers the impact of calories, protein, sugar, and other dietary components on signaling pathways and growth factors involved in carcinogenesis. We examine the influence of obesity, insulin resistance, and other metabolic factors on cancer risk and outcomes. The article also explores current dietary strategies, including calorie restriction, ketogenic diets, and the role of the gut microbiome in modulating response to anticancer therapies. Finally, we highlight the need for further research to develop targeted, personalized dietary recommendations based on an individual’s tumor profile, stage of disease, and other clinical factors. Integrating such personalized dietary approaches into cancer prevention and treatment holds promise for improving patient outcomes and quality of life. Full article

Metabolic syndrome (MetS) is characterized by central obesity, insulin resistance, hypertension, dyslipidemia, and chronic inflammation, significantly increasing the risk of cardiovascular disease and type 2 diabetes. Effective management of MetS is critical, with exercise being a key intervention. This review analyzed the effects of different exercise intensities—low, moderate, and high-intensity interval training (HIIT)—on metabolic health, oxidative stress (OS), inflammation, and cardiovascular function. A search of Medline, PEDro, and EBSCO identified 2251 articles, with 159 studies published between 1999 and 2025 included after screening. Low-intensity exercise improved insulin sensitivity, reduced OS markers (e.g., MDA, 8-OHdG), and enhanced antioxidant enzyme activity. Moderate-intensity exercise showed similar benefits with notable reductions in inflammatory markers (e.g., IL-1β, TNF-α). HIIT promoted fat loss and improved metabolic markers but temporarily increased OS and inflammation. Dietary strategies also play a critical role. The Mediterranean diet and Dietary Approaches to Stop Hypertension (DASH) diets are well established, emphasizing nutrient-dense foods like unsaturated fats and fiber to reduce inflammation and manage weight. The ketogenic diet (KD), a high-fat, low-carbohydrate approach, has recently gained attention for its metabolic benefits. KD induces ketosis, improving insulin sensitivity, reducing triglycerides, and enhancing fat oxidation. Studies show KD effectively reduces body weight and glucose levels, though long-term adherence and nutrient deficiencies remain challenges. Intermittent fasting also showed potential benefits, though effects on glucose metabolism were inconsistent. This review underscores the need for tailored approaches combining exercise, diet, and fasting to optimize MetS outcomes, offering integrative strategies for prevention and management. Full article

Introduction: Migraine is a prevalent neurological disorder characterized by recurrent headaches with autonomic and neurological symptoms, significantly impacting quality of life globally. Its pathogenesis involves genetic, neurological, inflammatory, and metabolic factors, with insulin resistance and metabolic dysfunction increasingly recognized as important contributors. Historically, it has been known that certain foods can trigger migraine attacks, which led for many years to the recommendation of elimination diets—now understood to primarily target histamine-rich foods. Over the past two decades, attention has shifted toward underlying metabolic disturbances, leading to the development of dietary approaches specifically aimed at addressing these dysfunctions. Methods: A scoping literature review was conducted using PubMed and Embase to evaluate the relationships among migraine, insulin-related mechanisms, neurogenic inflammation, and dietary interventions. Initial searches focused on “MIGRAINE AND (neurogenic inflammation)” (2019–15 April 2025), followed by expanded searches from 1950 onward using terms such as “MIGRAINE AND (insulin, insulin resistance, hyperinsulinism)”, and “MIGRAINE AND (diet, dietary, nutrition, nutritional)”. A specific search also targeted “(INSULIN OR insulin resistance OR hyperinsulinism) AND (neurogenic inflammation)”. Abstracts were screened, full texts were retrieved, and duplicates or irrelevant publications were excluded. No filters were applied by article type or language. Systematic reviews and meta-analyses were prioritized when available. Results: Migraine pathogenesis involves trigeminovascular system activation, neurogenic inflammation mediated by CGRP and PACAP, immune dysregulation, mast cell activation, and cortical spreading depression (CSD). Emerging evidence highlights significant associations between migraine, insulin resistance, and hyperinsulinism. Hyperinsulinism contributes to migraine through TRPV1 sensitization, increased CGRP release, oxidative stress, mitochondrial dysfunction, and systemic inflammation. Metabolic dysfunction, including obesity and insulin resistance, exacerbates migraine severity and frequency. Dietary interventions, particularly anti-inflammatory, Mediterranean, and ketogenic diets, show promise in reducing migraine frequency and severity through mechanisms involving reduced inflammation, oxidative stress, improved mitochondrial function, and glucose metabolism stabilization. Conclusions: The interplay between insulin resistance, metabolic dysfunction, and neuroinflammation is crucial in migraine pathophysiology. Targeted dietary interventions, including ketogenic and Mediterranean diets, demonstrate significant potential in managing migraines, emphasizing the need for personalized nutritional strategies to optimize therapeutic outcomes. Full article

Background/Objectives: Ketogenic diets (KDs) have gained attention for their potential to promote weight loss and metabolic improvements. However, data on long-term body composition changes and adherence rates in real-world settings remain limited. Objective: This study aimed to assess the effects of a personalized ketogenic dietary program on anthropometric parameters over a 9-month period and to evaluate adherence across time. Methods: A total of 491 adults participated in a longitudinal intervention involving a structured ketogenic nutrition plan with follow-up at 3, 6, and 9 months. Body weight, fat mass (FM), skeletal muscle mass (SMM), and other composition metrics were measured at each visit. Results: Significant reductions in body weight (–12.6 kg) and fat mass (–10.3 kg) were observed after 3 months (p < 0.001), with minimal changes at 6 months and partial regain by Month 9. SMM remained relatively stable throughout the study. Retention dropped substantially after 3 months, dropping from 487 to 115 participants at Month 6 and 41 at Month 9. Despite this, participants who completed the program maintained significant anthropometric improvements. Conclusions: A well-formulated ketogenic diet may promote rapid fat loss while preserving lean mass in the short term. However, long-term adherence poses significant challenges. Strategies to enhance dietary sustainability and retention are essential for maximizing the benefits of KDs in clinical practice. Full article

Objective: Prolonged microgravity environments impair skeletal muscle homeostasis by triggering fiber-type transitions and metabolic dysregulation. Although exercise and nutritional interventions may alleviate disuse atrophy, their synergistic effects under microgravity conditions remain poorly characterized. This study investigated the effects of an 8-week ketogenic diet combined with aerobic exercise in hindlimb-unloaded mice on muscle fiber remodeling and metabolic adaptation. Methods: Seven-week-old male C57BL/6J mice were randomly divided into six groups: normal diet control (NC), normal diet with hindlimb unloading (NH), normal diet with hindlimb unloading and exercise (NHE), ketogenic diet control (KC), ketogenic diet with hindlimb unloading (KH), and ketogenic diet with hindlimb unloading and exercise (KHE). During the last two weeks of intervention, hindlimb unloading was applied to simulate microgravity. Aerobic exercise groups performed moderate-intensity treadmill running (12 m/min, 60 min/day, and 6 days/week) for 8 weeks. Body weight, blood ketone, and glucose levels were measured weekly. Post-intervention assessments included the respiratory exchange ratio (RER), exhaustive exercise performance tests, and biochemical analyses of blood metabolic parameters. The skeletal muscle fiber-type composition was evaluated via immunofluorescence staining, lipid deposition was assessed using Oil Red O staining, glycogen content was analyzed by Periodic Acid–Schiff (PAS) staining, and gene expression was quantified using quantitative real-time PCR (RT-qPCR). Results: Hindlimb unloading significantly decreased body weight, induced muscle atrophy, and reduced exercise endurance in mice. However, the combination of KD and aerobic exercise significantly attenuated these adverse effects, as evidenced by increased proportions of oxidative muscle fibers (MyHC-I) and decreased proportions of glycolytic fibers (MyHC-IIb). Additionally, this combined intervention upregulated the expression of lipid metabolism-associated genes, including CPT-1b, HADH, PGC-1α, and FGF21, enhancing lipid metabolism and ketone utilization. These metabolic adaptations corresponded with improved exercise performance, demonstrated by the increased time to exhaustion in the KHE group compared to other hindlimb unloading groups. Conclusions: The combination of a ketogenic diet and aerobic exercise effectively ameliorates simulated microgravity-induced skeletal muscle atrophy and endurance impairment, primarily by promoting a fiber-type transition from MyHC-IIb to MyHC-I and enhancing lipid metabolism gene expression (CPT-1b, HADH, and PGC-1α). These findings underscore the potential therapeutic value of combined dietary and exercise interventions for mitigating muscle atrophy under simulated microgravity conditions. Full article

Background: Trimethylamine N-oxide (TMAO) is a gut- and food-derived molecule. Elevated TMAO concentrations have been associated with an increased risk of cardiovascular disease (CVD) and all-cause mortality, highlighting its significance as a potential biomarker for adverse health outcomes. Given these associations, it is hypothesized that lifestyle interventions, such as healthy dietary patterns and exercise, could reduce TMAO concentrations. The aim of this systematic–narrative hybrid literature review was to evaluate the relationship between various lifestyle interventions and TMAO. Methods: MEDLINE (via PubMed^®), Scopus^®, and grey literature were searched until July 2024 for eligible clinical trials. Case reports, case series, case studies and observational studies were excluded, as well as studies that investigated food products, nutraceuticals, dietary supplements or have been conducted in the pediatric population. Results: In total, 27 studies were included in this review. While some dietary interventions, such as plant-based, high-dairy, very low-calorie ketogenic diet or the Mediterranean diet, were associated with lower TMAO concentrations, others—including high-protein and high-fat diets—were linked to an increase in TMAO concentrations. Studies that incorporated a combination of nutrition and exercise-based intervention presented neutral results. Conclusions: The relationship between dietary interventions and TMAO concentration remains controversial. While certain interventions show promise in reducing TMAO levels, others yield mixed or contradictory outcomes. Further research, including well-structured RCTs, is needed to investigate the aforementioned associations. Full article