Search Results (73)

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

A psoriasis vulgaris flare is characterized by a rapid intensification of symptoms, which is often triggered by various factors that can worsen the condition. The risk factors for these exacerbations are numerous and include obesity, antihypertensive drugs, and psychological stress. Moreover, links have been documented between type II diabetes, hypertension, and psoriasis vulgaris. The present case report describes a 52-year-old female patient who presented at the clinic with disseminated erythematous-squamous plaques and patches covered by thick, white-pearly, easily detachable scales, along with stress, fatigue, anxiety, severe pruritus, irritability, insomnia, and decreased self-esteem. Her past medical regimen included various conventional topical options, including calcipotriol combined with betamethasone, clobetasol, betamethasone combined with salicylic acid, and betamethasone combined with gentamicin, yet the condition remained refractory, with periodic flare-ups. The integrated and personalized therapeutic approach aimed to target both the dermatological issues and the associated systemic and psychological factors contributing to the condition. The therapeutic strategy implemented in this case combined psychological counseling sessions, a very low-calorie ketogenic diet, oral supplementation with anti-inflammatory and antioxidant vitamins and minerals, topical treatments utilizing urea and Dead Sea-mineral-based formulations, and rosemary extract-based scalp care, without requiring additional conventional treatment. This comprehensive approach led to significant improvement, ultimately achieving complete remission of the patient’s psoriasis. The associated comorbidities were well controlled with the specified medication, without any further complications. Thus, the importance of alternative options was emphasized, particularly in the context of an incurable disease, along with the need for continued research to improve the ongoing therapeutic management of psoriasis vulgaris. Such approaches are essential to reducing the risk of flare-ups and to achieving better management of associated risk factors. Full article

Phytochemicals are a potential alternative to antibiotic growth promoters. This study evaluated the effects of phytochemicals (curcuminoids, trans-cinnamaldehyde, and piperine) and monensin on performance and ruminal fermentation during the transition period in grazing dairy cows. In a complete randomized design, 60 Holstein cows (36 multiparous, 24 primiparous; 9 fistulated) were assigned to (1) control (CTL), (2) monensin (MON, 0.30 g/cow/day), or (3) phytochemicals (PHY, 50 g/cow/day) treatment from 30 days prepartum to 60 days postpartum. Prepartum, cows received a total mixed ration (TMR); postpartum, they grazed between a.m. and p.m. milking and were supplemented with TMR. Ruminal fermentation was evaluated at −7, 30, and 60 days postpartum. Prepartum dry matter intake was lower in MON primiparous cows than in CTL and PHY. Additives increased milk yield and lactose percentage in primiparous cows. PHY cows had lower acetate, higher propionate, and reduced acetate-to-propionate and ketogenic-to-glucogenic ratios at 60 days postpartum. MON reduced prepartum protozoa, while PHY increased prepartum branched-chain volatile fatty acids (BCVFAs). Both additives decreased BCVFA and protozoa postpartum. Additives reduced ammonia at 30 days, but only PHY persisted at 60 days. MON and PHY improved primiparous performance, enhanced ruminal fermentation, and promoted glucogenic fermentation while reducing ammonia and protozoa. Full article

Psoriasis is a chronic inflammatory autoimmune disease that causes significant deterioration of the quality of life, and due to its multifactorial causes, it is often difficult to manage. Apart from genetic and environmental components, an important part of its pathophysiology comprises an oxidative stress induction that the standard antioxidative mechanisms of the human body cannot compensate for. Moreover, in many psoriatic patients, there is a documented imbalance between antioxidant and pro-oxidative factors. Usually, psoriasis is evaluated using the Psoriasis Area and Severity Index (PASI) score. It has been demonstrated that dietary choices can lead to significant modification of PASI scores. Hypocaloric diets that are rich in antioxidants are highly effective in this regard, especially when focusing on vegetables and restricting consumption of animal-derived protein. Specific dietary regimens, namely the Mediterranean diet and potentially the ketogenic diet, are very beneficial, in the former case owing in large part to the omega-three fatty acids it provides and its ability to alter gut microbiome, a factor which seems to play a notable role in the pathogenesis of the disease. Another option is the topical application of vitamin D and its analogues, combined with corticosteroids, which can ameliorate the manifestations of psoriasis at the level of the skin. Finally, oral vitamin D supplementation has a positive impact on psoriatic arthritis and can mitigate the risk of associated comorbidities. 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

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

Background: Developmental epileptic encephalopathies (DEEs) are often associated with variably severe cognitive and motor impairment and frequent refractory epilepsy, with many children not achieving adequate seizure control via standard antiepileptic medications. The classic ketogenic diet (KD) has proven effective in reducing seizure frequency and/or severity in a category of DEEs and in certain refractory epilepsies of infancy. However, its multifaceted mechanisms, e.g., epigenetic modulation, anti-inflammatory and antioxidative effects, and direct neuronal excitability changes, are balanced by a high burden and low long-term adherence. Medium-chain triglycerides (MCTs), particularly decanoic acid (C10:0), have gained attention in recent years for their potential direct inhibitory action on AMPA receptors, contributing to seizure reduction. Methods: A systematic review was conducted, including articles from January 2000 to January 2025, to explore the potential role of medium-chain triglyceride (MCT) add-on to classic KD and as MCT supplementation in free diets in the management of pediatric drug-resistant epilepsy (DRE). Results: Selected studies show how the action of MCTs, and decanoic acid in particular, is via negative modulation of AMPA receptors, with a positive impact on epileptic seizures. Conclusions: This review discusses the complexities of implementing and sustaining KD in children and presents recent pre-clinical and clinical evidence, including trials where MCTs (often enriched in decanoic acid) serve as an add-on therapy in both ketogenic and free/unrestricted diets. The summarized findings reinforce the therapeutic potential of MCTs, highlighting both the beneficial seizure outcomes and the hurdles that remain to be addressed through future research. 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

Background: The human brain relies on complex synaptic communication regulated by key genes such as SYNGAP1. SYNGAP1 encodes the GTPase-Activating Protein (SYNGAP), a critical synaptic plasticity and neuronal excitability regulator. Impaired SYNGAP1 function leads to neurodevelopmental disorders (NDDs) characterized by intellectual disability (ID), epilepsy, and behavioral abnormalities. These variants disrupt Ras signaling, altering AMPA receptor transport and synaptic plasticity and contributing to cognitive and motor difficulties. Despite advancements, challenges remain in defining genotype–phenotype correlations and distinguishing SYNGAP1-related disorders from other NDDs, which could improve underdiagnosis and misdiagnosis. Brain Gene Registry: The Brain Gene Registry (BGR) was established as a collaborative initiative, consolidating genomic and phenotypic data across multiple research centers. This database allows for extensive analyses, facilitating improved diagnostic accuracy, earlier interventions, and targeted therapeutic strategies. The BGR enhances our understanding of rare genetic conditions and is critical for advancing research on SYNGAP1-related disorders. Conclusions: While no FDA-approved treatments exist for SYNGAP1-related disorders, several therapeutic approaches are being investigated. These include taurine supplementation, ketogenic diets, and molecular strategies such as antisense oligonucleotide therapy to restore SYNGAP1 expression. Behavioral and rehabilitative interventions remain key for managing developmental and cognitive symptoms. Advancing research through initiatives like the BGR is crucial for refining genotype–phenotype associations and developing precision medicine approaches. A comprehensive understanding of SYNGAP1-related disorders will improve clinical outcomes and patient care, underscoring the need for continued interdisciplinary collaboration in neurodevelopmental genetics. Full article

Migraine is a prevalent neurological disorder characterized by significant disability and triggered by various factors, including dietary habits. This review explores the complex relationship between diet and migraine, highlighting both triggering and protective roles of dietary patterns and specific nutrients. Evidence suggests that certain foods, such as alcohol, caffeine, chocolate, MSG, nitrates, and tyramine, can trigger migraines in susceptible individuals. Conversely, dietary interventions, including carbohydrate-restricted diets, ketogenic diets, vitamin D3 supplementation, omega-3 fatty acids, Mediterranean dietary patterns, and increased water intake, have shown potential in reducing migraine frequency and severity. Observational studies also indicate that maintaining a healthy diet, rich in fruits and vegetables and low in processed foods, is associated with better migraine outcomes. The effectiveness of these interventions varies among individuals, underscoring the importance of personalized approaches. Future studies should further explore the role of diet in migraine management, focusing on randomized trials to establish causality and refine dietary recommendations for patients. Full article

Background: Recent findings have highlighted that abnormal energy metabolism is a key feature of autosomal-dominant polycystic kidney disease (ADPKD). Emerging evidence suggests that nutritional ketosis could offer therapeutic benefits, including potentially slowing or even reversing disease progression. This systematic review aims to synthesise the literature on ketogenic interventions to evaluate the impact in ADPKD. Methods: A systematic search was conducted in Medline, Embase, and Scopus using relevant Medical Subject Headings (MeSH) and keywords. Studies assessing ketogenic interventions in the management of ADPKD in both human and animal models were selected for data extraction and analysis. Results: Three animal reports and six human studies were identified. Ketogenic diets (KD) significantly slowed polycystic kidney disease (PKD) progression in rats with improved renal function and reduced cystic areas. There was reduced renal fibrosis and cell proliferation. The supplementation of beta-hydroxybutyrate (BHB) in rats also reduced PKD progression in a dose-dependent manner. Human studies (n = 129) on KD in ADPKD reported consistent body mass index (BMI) reduction across trials, with an average weight loss of ∼4 kg. Improvements in blood pressure were also noted. Ketosis was achieved in varying degrees. Effects on kidney function (eGFR) were beneficial. Results for kidney volume were mixed but most studies were underpowered for this outcome. Lipid profiles showed increases in total cholesterol (∼1 mmol/L) and LDL cholesterol (∼0.4 mmol/L) in most studies. Safety concerns such as “keto flu” symptoms, elevated uric acid levels, and occasional kidney stones were noted. Overall feasibility and adherence to the KD were rated positively by most participants. Conclusions: Human studies are promising; however, they have been limited by small sample sizes and short durations. Larger, long-term trials are needed to assess the efficacy, adherence, and safety of ketogenic diets in people with ADPKD. Full article

Background: The ketogenic diet (KD) is a widely used intervention for obesity and diabetes, effectively reducing body weight and blood glucose levels. However, the molecular mechanisms by which the KD influences body weight and glucose metabolism are not fully understood. While previous research has shown that the KD affects the gut microbiota, the exact role of microbiota in mediating its metabolic effects remains unclear. Methods: In this study, we used antibiotics to eliminate the gut microbiota, confirming its necessity for the KD’s impact on weight loss and glucose metabolism. We also demonstrated the significant role of FGF21 in these processes, through antibiotics intervention in Fgf21-deficient mice. Results: Furthermore, we revealed that the KD alters serum valine levels via the gut microbiota, which in turn regulates hepatic Fgf21 expression and circulating FGF21 levels through the GCN2-eIF2α-ATF5 signaling pathway. Additionally, we demonstrated that valine supplementation inhibits the elevated expression of FGF21, leading to the reduced body weight and improved glucose metabolism of the KD-fed mice. Overall, we found that the gut microbiota from the KD regulates Fgf21 transcription via the GCN2-eIF2α-ATF5 signaling pathway. ultimately affecting body weight and glucose metabolism. Conclusion: Our findings highlight a complex regulatory network linking the KD, Fgf21 expression, and gut microbiota, offering a theoretical foundation for targeted therapies to enhance the metabolic benefits of the KD. Full article

Background: Ketone body supplementation has emerged as a potential ergogenic aid in cycling. Exogenous ketones, primarily in the form of beta-hydroxybutyrate, offer an alternative fuel source, bypassing the need for strict ketogenic diets. However, the science surrounding their efficacy remains complex, with mixed field findings and unexplored mechanisms. Methods: A narrative review of the current literature was conducted, synthesizing studies on the metabolic and cognitive effects of ketone bodies in cycling. The review included an examination of human and mechanistic studies, along with emerging hypotheses on ketone bodies and their role in modulating red blood cell production and recovery processes. Results: Ketone body supplementation can theoretically spare glycogen, reduce muscle protein breakdown, enhance fat oxidation, and improve recovery by mitigating oxidative stress and inflammation. Additionally, ketone bodies may support cognitive function, reducing perceived mental fatigue. Preliminary evidence also suggests a potential role in modulating erythropoietin levels through histone acetylation, though further research is needed to establish its impact on oxygen delivery. Despite the theoretical potential, the practical assessment of field studies shows disappointing effects on performance from ketone body supplementation. Conclusions: While ketone bodies offer several potential benefits for cyclists, the variability in individual responses, lack of long-term data, and inconsistent findings in performance studies highlight the need for further research. Optimizing dosage, timing, and understanding the broader implications of ketone body supplementation will be crucial for their practical application in cycling. Full article

Reactive oxygen species (ROS) contribute to endothelial dysfunction, platelet activation, and coagulation abnormalities, promoting thrombus formation. Given the growing interest in non-pharmacological approaches to modulate oxidative stress, we examine the potential of various dietary interventions and antioxidant supplementation in reducing oxidative damage and preventing thrombotic events. Key dietary patterns, such as the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and ketogenic diets, as well as antioxidant-rich supplements like curcumin, selenium, and polyphenols, demonstrate promising effects in improving oxidative stress markers, lipid profiles, and inflammatory responses. This review highlights recent advances in the field, drawing from in vitro, ex vivo, and clinical studies, and underscores the importance of integrating dietary strategies into preventive and therapeutic approaches for managing thrombosis and cardiovascular health. Further research is needed to better understand long-term effects and personalize these interventions for optimizing patient outcomes. Full article

Background/Objectives: Elevating ketone levels with therapeutic nutritional ketosis can help to metabolically manage disease processes associated with epilepsy, diabetes, obesity, cancer, and neurodegenerative disease. Nutritional ketosis can be achieved with various dieting strategies such as the classical ketogenic diet, the modified Atkins diet, caloric restriction, periodic fasting, or the consumption of exogenous ketogenic supplements such as medium-chain triglycerides (MCTs). However, these various strategies can be unpleasant and difficult to follow, so that achieving and sustaining nutritional ketosis can be a major challenge. Thus, investigators continue to explore the science and applications of exogenous ketone supplementation as a means to further augment the therapeutic efficacy of this metabolic therapy. Methods: Here, we describe a structurally new synthetic triglyceride, glycerol tri-acetoacetate (Gly-3AcAc), that we prepared from glycerol and an acetoacetate precursor that produces hyperketonemia in the therapeutic range (2–3 mM) when administered to mice under both fasting and non-fasting conditions. Animal studies were undertaken to evaluate the potential effects of eliciting a ketogenic response systemically. Acute effects (24 h or less) were determined in male VM/Dk mice in both fasted and unfasted dietary states. Results: Concentration levels of β-hydroxybutyrate in blood were elevated (βHB; 2–3 mM) under both conditions. Levels of glucose were reduced only in the fasted state. No detrimental side effects were observed. Conclusions: Pending further study, this novel compound could potentially add to the repertoire of methods for inducing therapeutic nutritional ketosis. Full article