Search Results (500)

Deranged gut microbiota can release increased levels of uremic toxins leading to exacerbated kidney injury. In diabetic kidney disease (DKD), phenyl sulfate (PS) derived from tyrosine catabolism by gut microbiota has been demonstrated to be both an early diagnostic marker and a therapeutic target. In this perspective article, we summarize PS generation pathways and recent findings on PS and kidney injury in DKD. Increasing evidence has shown that the underlying mechanisms of PS-induced kidney injury mainly involve oxidative stress, redox imbalance, and mitochondrial dysfunction, which all may be targeted to attenuate PS-induced kidney injury. For future research directions, we think that a deeper understanding of the pathogenic role of PS in kidney injury using a variety of diabetic animal models should be investigated. Moreover, we also suggest beneficial approaches that could be used to mitigate the deleterious effect of PS on the kidney. These approaches include caloric restriction, tyrosine restriction, and administration of ketogenic drugs, ketogenic diets or natural products; all of which should be conducted under obese and diabetic conditions. Full article

This study examined the effect of a low-carbohydrate diet (LCD) and a low-carbohydrate ketogenic diet (LCKD) on diabetic retinopathy in high-fat diet-induced diabetes mellitus in rats and studied the mechanisms of action. Rats were divided into four groups: the Control group, which was fed a normal diet for 16 weeks; the HFD group, which was fed a high-fat diet (HFD) for the first 8 weeks and then switched to a normal diet for 8 weeks; the HFD+LCD group, fed a HFD for 8 weeks followed by an LCD for 8 weeks, and the HFD+LCKD group, which was fed a HFD for 8 weeks followed by an LCKD for 8 more weeks. Both the LCD and the LCKD effectively reduced the final body and total fat weights and decreased fasting serum levels of glucose, insulin, hemoglobin A1 (HbA1C), triglycerides, cholesterol, and LDL-c. They also reduced the levels of malondialdehyde (MDA), tumor necrosis factor-α, vascular endothelial factor, caspapse-3, and bax. In the HFD rats, we found increased serum levels of β-Hydroxybutyrate and upregulated expression of Bcl2, glutathione, superoxide dismutase, and hemeoxygenase-1. Moreover, the LCD and LCKD significantly reduced mRNA levels of Kelch-like ECH-associated protein 1 (Keap1) and enhanced mRNA and nuclear concentrations of nuclear factor erythroid factor 2 (Nrf2). All these effects were associated with improved layers of the retina in the HFD − LCD and HFD + LCKD rats but not in HFD animals. The impact of the LCKD was always more profound on all measured parameters and on improving the structure of the retina compared to the LCD. In conclusion, the LCKD is superior to the LCD in preventing diabetic retinopathy in HFD-fed rats. Mechanistically, our results suggest that the hypoglycemic and hypolipidemic conditions and the Nrf2-dependent antioxidant and anti-inflammatory effects may be involved in the preventative effects of the LCD and LCKD. Full article

Background: Exercise and dietary interventions are essential for maintaining weight and reducing fat accumulation. With the growing popularity of various dietary strategies, evidence suggests that combining exercise with dietary interventions offers greater benefits than either approach alone. Consequently, this combined strategy has become a preferred method for many individuals aiming to maintain health. Calorie restriction, 5/2 intermittent fasting, time-restricted feeding, and the ketogenic diet are among the most popular dietary interventions today. Aerobic exercise, resistance training, and mixed exercise are the most widely practiced forms of physical activity. Exploring the best combinations of these approaches to determine which yields the most effective results is both meaningful and valuable. Despite this trend, a comparative analysis of the effects of different exercise and diet combinations is lacking. This study uses network meta-analysis to evaluate the impact of various combined interventions on body composition and to compare their efficacy. Methods: We systematically reviewed literature from database inception through May 2024, searching PubMed, Web of Science, Embase, and the Cochrane Library. The study was registered in PROSPERO under the title: “Effects of Exercise Combined with Different Dietary Interventions on Body Composition: A Systematic Review and Network Meta-Analysis” (identifier: CRD42024542184). Studies were meticulously selected based on specific inclusion and exclusion criteria (The included studies must be randomized controlled trials involving healthy adults aged 18 to 65 years. Articles were rigorously screened according to the specified inclusion and exclusion criteria.), and their risk of bias was assessed using the Cochrane risk of bias tool. Data were aggregated and analyzed using network meta-analysis, with intervention efficacy ranked by Surface Under the Cumulative Ranking (SUCRA) curves. Results: The network meta-analysis included 78 randomized controlled trials with 5219 participants, comparing the effects of four combined interventions: exercise with calorie restriction (CR+EX), exercise with time-restricted eating (TRF+EX), exercise with 5/2 intermittent fasting (5/2F+EX), and exercise with a ketogenic diet (KD+EX) on body composition. Intervention efficacy ranking was as follows: (1) Weight Reduction: CR+EX > KD+EX > TRF+EX > 5/2F+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 2.94 (−3.64, 9.52); 2.37 (−0.40, 5.15); 1.80 (−1.75, 5.34)). (2) BMI: CR+EX > KD+EX > 5/2F+EX > TRF+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 1.95 (−0.49, 4.39); 2.20 (1.08, 3.32); 1.23 (−0.26, 2.71)). (3) Body Fat Percentage: CR+EX > 5/2F+EX > TRF+EX > KD+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 2.66 (−1.56, 6.89); 2.84 (0.56, 5.13); 3.14 (0.52, 5.75).). (4) Lean Body Mass in Male: CR+EX > TRF+EX > KD+EX (Relative to CR+EX, the effect sizes of TRF+EX and KD+EX are −1.60 (−6.98, 3.78); −2.76 (−7.93, 2.40)). (5) Lean Body Mass in Female: TRF+EX > CR+EX > 5/2F+EX > KD+EX (Relative to TRF+EX, the effect sizes of CR+EX, 5/2F+EX and KD+EX are −0.52 (−2.58, 1.55); −1.83 (−4.71, 1.04); −2.46 (−5.69,0.76).). Conclusion: Calorie restriction combined with exercise emerged as the most effective strategy for reducing weight and fat percentage while maintaining lean body mass. For women, combining exercise with time-restricted eating proved optimal for preserving muscle mass. While combining exercise with a ketogenic diet effectively reduces weight, it is comparatively less effective at decreasing fat percentage and preserving lean body mass. Hence, the ketogenic diet combined with exercise is considered suboptimal. Full article

Recent scientific research has shown that the ketogenic diet may have potential benefits in a variety of medical fields, which has led to the diet receiving a substantial amount of attention. Clinical and experimental research on brain tumors has shown that the ketogenic diet has a satisfactory safety profile. This safety profile has been established in a variety of applications, including the management of obesity and the treatment of drug-resistant epileptic cases. However, in human studies, the impact of ketogenic therapy on the growth of tumors and the life expectancy of patients has not provided results that are well characterized. Consequently, our purpose is to improve the comprehension of these features by succinctly presenting the developments and conclusions that have been gained from the most recent study that pertains to this non-pharmacological technique. According to the findings of our study, patients with brain tumors who stick to a ketogenic diet are more likely to experience improved survival rates. However, it is required to conduct additional research on humans in order to more accurately define the anti-tumor efficiency of this diet as well as the underlying processes that support the therapeutic effects of this dieting regimen. Full article

As the population ages, promoting healthy aging through targeted interventions becomes increasingly crucial. Growing evidence suggests that dietary interventions can significantly impact this process by modulating fundamental molecular pathways. This review focuses on the potential of targeted dietary strategies in promoting healthy aging and the mechanisms by which specific nutrients and dietary patterns influence key pathways involved in cellular repair, inflammation, and metabolic regulation. Caloric restriction, intermittent fasting, the Mediterranean diet, as well as the ketogenic diet showed promising effects on promoting healthy aging, possibly by modulating mTORC1 AMPK, an insulin signaling pathway. By understanding the intricate interplay between diet and molecular pathways, we can develop personalized dietary strategies that not only prevent age-related diseases, but also promote overall health and well-being throughout the aging process. Full article

Stress is a critical factor in the development of mental disorders such as addiction, underscoring the importance of stress resilience strategies. While the ketogenic diet (KD) has shown efficacy in reducing alcohol consumption in male mice without cognitive impairment, its impact on the stress response and addiction development, especially in females, remains unclear. This study examined the KD’s effect on increasing ethanol intake due to vicarious social defeat (VSD) in female mice. Sixty-four female OF1 mice were divided into two dietary groups: standard diet (n = 32) and KD (n = 32). These were further split based on exposure to four VSD or exploration sessions, creating four groups: EXP-STD (n = 16), VSD-STD (n = 16), EXP-KD (n = 16), and VSD-KD (n = 16). KD-fed mice maintained ketosis from adolescence until the fourth VSD/EXP session, after which they switched to a standard diet. The Social Interaction Test was performed 24 h after the last VSD session. Three weeks post-VSD, the Drinking in the Dark test and Oral Ethanol Self-Administration assessed ethanol consumption. The results showed that the KD blocked the increase in ethanol consumption induced by VSD in females. Moreover, among other changes, the KD increased the expression of the ADORA1 and CNR1 genes, which are associated with mechanisms modulating neurotransmission. Our results point to the KD as a useful tool to increase resilience to social stress in female mice. Full article

The prevalence of nonalcoholic fatty liver disease (NAFLD) is likely to be approaching 38% of the world’s population. It is predicted to become worse and is the main cause of morbidity and mortality due to hepatic pathologies. It is particularly worrying that NAFLD is increasingly diagnosed in children and is closely related, among other conditions, to insulin resistance and metabolic syndrome. Against this background is the concern that the awareness of patients with NAFLD is low; in one study, almost 96% of adult patients with NAFLD in the USA were not aware of their disease. Thus, studies on the therapeutic tools used to treat NAFLD are extremely important. One promising treatment is a well-formulated ketogenic diet (KD). The aim of this paper is to present a review of the available publications and the current state of knowledge of the effect of the KD on NAFLD. This paper includes characteristics of the key factors (from the point of view of NAFLD regression), on which ketogenic diet exerts its effects, i.e., reduction in insulin resistance and body weight, elimination of fructose and monosaccharides, limitation of the total carbohydrate intake, anti-inflammatory ketosis state, or modulation of gut microbiome and metabolome. In the context of the evidence for the effectiveness of the KD in the regression of NAFLD, this paper also suggests the important role of taking responsibility for one’s own health through increasing self-monitoring and self-education. Full article

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that results in the elevation of serum ketone bodies, known as ketosis. This metabolic consequence has been suggested as a method for treating neurological conditions, improving exercise performance, and facilitating weight loss for overweight individuals. However, since most research primarily uses male populations, little is known about the potential sex differences during the consumption of the KD. In addition, the effects of the KD on aging are relatively unexplored. Therefore, the purpose of this study was to explore sex- and age-specific differences in mice fed the KD. Male and female C57BL/6N mice at either 12 wks or 24 wks of age were randomly assigned to a KD (90% fat, 1% carbohydrate) or chow (13% fat, 60% carbohydrate) group for 6 wks. KD induced weight gain, increased adiposity, induced hyperlipidemia, caused lipid accumulation in the heart and liver, and led to glycogen depletion in the heart, liver, and muscle with varying degrees of changes depending on age and sex. While younger and older male mice on the KD were prone to glucose intolerance, the KD acutely improved rotarod performance in younger females. Overall, this study highlights potential sex and aging differences in the adaptation to the KD. Full article

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by the development and enlargement of multiple kidney cysts, leading to progressive kidney function decline. To date, Tolvaptan, the only approved treatment for this condition, is able to slow down the loss of annual kidney function without stopping the progression of the disease. Furthermore, this therapy is approved only for patients with rapid disease progression and its compliance is problematic because of the drug’s impact on quality of life. The recent literature suggests that cystic cells are subject to several metabolic dysregulations, particularly in the glucose pathway, and mitochondrial abnormalities, leading to decreased oxidative phosphorylation and impaired fatty acid oxidation. This finding paved the way for new lines of research targeting potential therapeutic interventions for ADPKD. In particular, this review highlights the latest studies on the use of ketosis, through ketogenic dietary interventions (daily calorie restriction, intermittent fasting, time-restricted feeding, ketogenic diets, and exogenous ketosis), as a potential strategy for patients with ADPKD, and the possible involvement of microbiota in the ketogenic interventions’ effect. Full article

Insulin resistance, induced by high fructose consumption, affects cognitive function negatively. Nifedipine may be suggested for neurological disorders. This study aimed to assess the effect of nifedipine with either a normal diet (ND) or a ketogenic diet (KD) in cognitive dysfunction. Male Wistar rats received 10% fructose in drinking water for 8 weeks to induce insulin resistance. Rats received nifedipine (5.2 mg/kg/day; p.o.) later with ND or KD for an additional five weeks. One and two-way ANOVAs were used in analyzing the data. Reversion to the ND improved insulin resistance and lipid profile, besides brain-derived neurotrophic factor (BDNF), glycogen synthase kinase-3 beta (GSK3β), and insulin-degrading enzyme (IDE) levels. Rats fed KD alone and those that received nifedipine with KD did not show similar improvement in the previously mentioned parameters as the ND group. However, nifedipine-ND rats showed improvement in cognitive behavior and insulin resistance. Treatment with nifedipine-KD ameliorated GSK3β, amyloid β (Aβ), and tau protein levels. As the nifedipine-KD combination succeeded in diminishing the accumulated Aβ and tau protein, KD may be used for a while due to its side effects, then nifedipine treatment could be continued with an ND. This conclusion is based on the finding that this combination mitigated insulin resistance with the associated improved behavior. Full article

Neurological disorders are increasing globally due to their complex nature, influenced by genetics and environmental factors. Effective treatments remain limited, and early diagnosis is challenging. Recent evidence indicates that metabolic activities play a crucial role in the onset of neural defects. Molecular changes offer new diagnostic markers and dietary targets for disease management. Diets such as MIND, DASH, omega-3 fatty acids, and polyphenols show promise in protecting brain metabolism through their anti-inflammatory properties. Personalized dietary interventions could mitigate neurodegenerative diseases. This review highlights the effects of various dietary interventions, including calorie restriction, fasting, and ketogenic diets, on neurological disorders. Additionally, it emphasizes the nutritional impacts on immunomodulation and the underlying mechanisms, including the influence of gut microbiota on brain function. Dietary interventions could serve as adjunctive therapies in disease management. Full article

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of renal failure. The pathogenesis of the disease encompasses several pathways and metabolic alterations, including the hyperactivation of mTOR and suppression of AMPK signaling pathways, as well as mitochondrial dysfunction. This metabolic reprogramming makes epithelial cyst-lining cells highly dependent on glucose for energy and unable to oxidize fatty acids. Evidence suggests that high-carbohydrate diets may worsen the progression of ADPKD, providing the rationale for treating ADPKD patients with calorie restriction and, in particular, with ketogenic dietary interventions, already used for other purposes such as in overweight/obese patients or in the treatment of refractory epilepsy in children. Preclinical studies have demonstrated that calorie restriction may prevent and/or slow disease progression by inducing ketosis, particularly through increased beta-hydroxybutyrate (BHB) levels, which may modulate the metabolic signaling pathways altered in ADKPK. In these patients, although limited, ketogenic intervention studies have shown promising beneficial effects. However, larger and longer randomized controlled trials are needed to confirm their tolerability and safety in long-term maintenance and their additive role in the therapy of polycystic kidney disease. Full article

There is emerging evidence to suggest that diet and dietary interventions can have an impact on heart failure (HF) outcomes. Currently, the restriction of salt intake is the only dietary advice that is consistently guideline-recommended for the management of HF despite conflicting evidence for its efficacy. Dietary components that have been investigated in people with HF include middle-chain triglyceride (MCT) oil, beta-hydroxybutyrate (BHB) salts, ketone esters and coenzyme Q10 (CoQ10). Supplementation with these components is thought to be cardioprotective possibly due to an increase in myocardial energy production. There have been research studies on the effectiveness of The Dietary Approaches to Stop Hypertension (DASH) diet and the Mediterranean Diet (MedDiet) in the treatment of HF, but with conflicting results. The ketogenic diet (KD) has come to the forefront of interest due to evidence indicating its effectiveness in addressing the metabolic shift that occurs in HF. However, there is a lack of randomised controlled trials (RCT) centred around the KD. In any dietary intervention, factors such as adherence and compliance affect the validity of the results. Malnutrition, sarcopenia and/or cardiac cachexia can be present in the more advanced stages of heart failure. Nutritional screening, assessment and support/intervention are important aspects of treatment in the advanced stages of heart failure. Furthermore, HF management through dietary intervention is further complicated by the presence of comorbidities, such as diabetes mellitus (DM) and coronary artery disease (CAD). Long-term studies on the use of dietary modifications in people with HF are warranted to ascertain their efficacy, safety and side effects. Full article

The ketogenic diet is used worldwide to treat various diseases, especially drug-resistant epilepsies. Medium-chain triglycerides or medium-chain fatty acids, primarily the major ketogenic compound caprylic acid (C8; C8:0), can significantly support ketogenesis. This review examines the effects of concurrent carbohydrate intake on C8-induced ketogenesis. A systematic literature search (PubMed and Web of Science) with subsequent data extraction was performed according to PRISMA guidelines and the Cochrane Handbook. Studies investigating the metabolic response to C8-containing MCT interventions with carbohydrate intake were included. The studies did not include a ketogenic diet. Three intervention groups were created. The quality of the studies was assessed using the RoB II tool, and the meta-analysis was performed using the Cochrane RevMan software. A total of 7 trials, including 4 RCTs, met the inclusion criteria. Ketone production was lower when C8 was combined with carbohydrates compared to MCT intake alone. The lower C8 dose group (11 g) did not show a significantly lower ketogenic effect than the higher dose group (19 g). Forest plot analysis showed heterogeneous data. The data suggest a non-linear relationship between C8, carbohydrate intake and ketone production. Further studies are needed to investigate the influence of different carbohydrates on C8-induced ketogenesis. Limitations include heterogeneous intervention conditions, such as different types of dispersions, caffeine intake, limited number of studies and variability in study design. Full article

High fat diets have been used as complementary treatments for seizure disorders for more than a century. Moreover, many fatty acids and derivatives, including the broad-spectrum antiseizure medication valproic acid, have been explored and used as pharmacological agents to treat epilepsy. In this work, we have explored the anticonvulsant potential of a large library of fatty acids and fatty acid derivatives, the LIPID MAPS Structure Database, using structure-based virtual screening to assess their ability to block the voltage-gated sodium channel 1.2 (NaV1.2), a validated target for antiseizure medications. Four of the resulting in silico hits were submitted for experimental confirmation using in vitro patch clamp experiments, and their protective role was evaluated in an acute mice seizure model, the Maximal Electroshock seizure model. These four compounds were found to protect mice against seizures. Two of them exhibited blocking effects on NaV1.2, CaV2.2, and CaV3.1. Full article