Influence of Carbohydrate Intake on Caprylic Acid (C8:0)-Induced Ketogenesis-A Systematic Review and Meta-Analysis.

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.

Carotenoid Bioaccessibility and Caco-2 Cell Uptake Following Novel Encapsulation Using Medium Chain Triglycerides.

Carotenoids are especially hydrophobic and dissolve poorly in water. Encapsulation is used to increase their solubility in water-based food products. However, it is not yet known whether encapsulation with a combination of lecithin and medium-chain triglycerides improves carotenoid bioaccessibility and intestinal cell uptake. The relative bioaccessibility and Caco-2 cell uptake of two water-soluble carotenoid (i.e. lutein and astaxanthin) dispersions in a liquid form (VitaSperse®) and a powdered form (VitaDry®) were compared to the carotenoid ingredient alone. An in vitro digestion model was used to assess bioaccessibility, measuring the micellarized fraction postdigestion. The micelle fraction was incubated with Caco-2 cells to assess intestinal uptake of carotenoids. Encapsulation (by either VitaDry® or Vitasperse®) increased total astaxanthin bioaccessibility 2-2.4× and cell uptake by ∼2× relative to control. Encapsulation also increased total lutein bioaccessibility by 3-5× and cell uptake 2.3× relative to control. There was no significant difference between VitaDry® and VitaSperse® products in regards to Caco-2 cell uptake. Increased bioaccessibility largely drove increased carotenoid cell uptake from the encapsulated formulations. These results suggest further study is warranted to determine if this encapsulation approach increases carotenoid bioavailability in human studies.

The therapeutic landscape of citrin deficiency.

Citrin deficiency (CD) is a recessive, liver disease caused by sequence variants in the SLC25A13 gene encoding a mitochondrial aspartate-glutamate transporter. CD manifests as different age-dependent phenotypes and affects crucial hepatic metabolic pathways including malate-aspartate-shuttle, glycolysis, gluconeogenesis, de novo lipogenesis and the tricarboxylic acid and urea cycles. Although the exact pathophysiology of CD remains unclear, impaired use of glucose and fatty acids as energy sources due to NADH shuttle defects and PPARα downregulation, respectively, indicates evident energy deficit in CD hepatocytes. The present review summarizes current trends on available and potential treatments for CD. Baseline recommendation for CD patients is dietary management, often already present as a self-selected food preference, that includes protein and fat-rich food, and avoidance of excess carbohydrates. At present, liver transplantation remains the sole curative option for severe CD cases. Our extensive literature review indicated medium-chain triglycerides (MCT) as the most widely used CD treatment in all age groups. MCT can effectively improve symptoms across disease phenotypes by rapidly supplying energy to the liver, restoring redox balance and inducing lipogenesis. In contrast, sodium pyruvate restored glycolysis and displayed initial preclinical promise, with however limited efficacy in adult CD patients. Ursodeoxycholic acid, nitrogen scavengers and L-arginine treatments effectively address specific pathophysiological aspects such as cholestasis and hyperammonemia and are commonly administered in combination with other drugs. Finally, future possibilities including restoring redox balance, amino acid supplementation, enhancing bioenergetics, improving ureagenesis and mRNA/DNA-based gene therapy are also discussed.

Efficacy and Safety of Exogenous Ketones in People with Mild Neurocognitive Disorder and Alzheimer's Disease: A Systematic Literature Review.

CONTEXT: Mild neurocognitive disorder (NCD), formally known as mild cognitive impairment, is usually the clinical stage preceding the development of Alzheimer's disease (AD), the most prevalent major NCD, and other causes of dementia. Glucose is a major source of energy for human brain metabolism and the uptake of glucose is reduced in patients with mild NCD, AD, and other NCDs. Unlike glucose, the uptake of ketones remains normal in people with mild NCD and AD, suggesting that the use of ketone bodies may compensate for glucose energy deficiency in patients with mild NCD and AD. OBJECTIVE: The aim of this systematic review was to summarize the efficacy and safety of exogenic ketones, including medium chain triglycerides (MCTs), on cognitive function in patients with mild NCD and AD. DATA SOURCES: The Embase, MEDLINE, MEDLINE In-Process, PubMed Ahead-of-Print, Cochrane Central Register of Controlled Trials, Europe PMC databases were searched from inception to April 2022. Studies reporting cognitive function efficacy and safety outcomes from randomized controlled trials of exogenic ketones in patients with mild NCD and AD were included. DATA EXTRACTION: Data were extracted by 1 reviewer and checked by a second reviewer. Risk of bias was assessed using the Cochrane risk of bias tool, version 2. DATA ANALYSIS: This review identified 13 individual trials investigating the efficacy and safety of MCT or coconut oil for patients with mild NCD or with AD. Because of the heterogeneity of the studies, a narrative synthesis was used. CONCLUSION: Overall, improvements associated with exogenic ketones were observed in multiple aspects of cognitive abilities, although the large heterogeneity between the included studies makes it difficult to draw firm conclusions from the current literature. Although some studies investigated the impact of the apolipoprotein E ε4 allele status on treatment efficacy, the current data are insufficient to conclude whether such an effect is present. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration No. CRD42022336664.

Medium-chain triglycerides combined with DHA improve cognitive function by inhibiting neurocyte apoptosis of the brain in SAMP8 mice.

Medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA, Cn-3, 22:6) are essential in improving cognitive function and protecting neurocytes. This study explored the effects of the combined intervention of MCTs and DHA on inhibiting neurocyte apoptosis of the brain and improving cognitive function in senescence-accelerated mouse-prone 8 (SAMP8). Four-month-old male SAMP8 mice were randomly divided into four treatment groups (12 mice/group): DHA, MCT, DHA + MCT, and control groups, which intervened for seven months. Twelve age-matched male senescence-accelerated mouse resistant 1 (SAMR1) was used as the natural aging group. TUNEL assay and HE staining were used to assess neurocyte apoptosis and damage in the brain of mice. Moreover, the cognitive function was analyzed using the Morris water maze (MWM) and open field (OF) tests. The results showed that the cognitive function of 11-month-old SAMP8 mice decreased with age, and further pathological examination revealed the damaged neurocyte structure, karyopyknosis, cell atrophy, and even apoptosis. MCTs combined with DHA supplementation could increase octanoic acid (C8:0), decanoic acid (C10:0), and DHA levels in the serum, inhibit neurocyte apoptosis, improve neurocyte damage, moreover delay age-related cognitive decline after seven-month treatment. Furthermore, combining MCTs and DHA was significantly more beneficial than MCTs or DHA alone. In conclusion, MCTs combined with DHA could delay cognitive decline by inhibiting neurocyte apoptosis of the brain in SAMP8 mice.

The impact of medium-chain triglycerides on weight loss and metabolic health in individuals with overweight or obesity: A systematic review and meta-analysis.

BACKGROUNDS: The efficacy of medium-chain triglycerides (MCTs) for weight management and mitigating metabolic disorders among individuals with overweight and obesity remains a topic of ongoing discussion. Notably, there is a gap in the distinction between pure MCTs and medium-long-chain triglycerides (MLCTs). METHODS: This meta-analysis investigates the efficacy of MCTs on weight loss and glucolipid metabolism in these populations, explicitly evaluating the differential effects of pure MCTs and MLCTs. We performed a random-effects meta-analysis on relevant studies examining weight loss and glucolipid parameters, incorporating a subgroup analysis conducted based on intervention types, pure MCTs versus MLCTs. RESULTS: Our findings revealed diets enriched with MCTs are more effective in achieving weight reduction (WMD: -1.53%; 95% CI: -2.44, -0.63; p < 0.01), particularly those containing pure MCTs (WMD: -1.62%; 95% CI: -2.78, -0.46; p < 0.01), compared to long-chain fatty acids (LCTs) enriched diets. However, our subgroup analysis indicates that an MLCTs-enriched diet did not significantly reduce weight loss. Additionally, MCTs-enriched diets were associated with significant reductions in blood triglyceride levels and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) scores, compared to LCTs-enriched diets. CONCLUSIONS: Hence, the authors recommend incorporating pure MCTs in dietary interventions for individuals with overweight and obesity, particularly those with comorbidities such as dyslipidemia and impaired glucose metabolism.

Mechanism of Ocular Penetration of Lipophilic Drugs from Lipophilic Vehicles.

Since eyedrops have conventionally been formulated in aqueous vehicles, ocular pharmacokinetic studies are generally performed using aqueous buffers to identify physicochemical properties of the drug and the vehicles that influence drug absorption. In recent years, biocompatible lipophilic vehicles are increasingly finding application in ocular drug delivery; however, the mechanism of drug penetration from these non-aqueous vehicles is poorly understood. This study aims to compare ocular penetration of the model lipophilic drug curcumin when incorporated into lipophilic vehicles. To elucidate whether intrinsic solubility in the lipophilic vehicle influences ocular penetration, a curcumin solution and suspension were prepared in medium chain triglycerides (MCT) and squalane, respectively. Ocular penetration and distribution of curcumin from both vehicles was compared and evaluated qualitatively and quantitatively ex vivo. Significantly greater and faster penetration was observed from the squalane suspension than from the MCT solution in all ocular tissues. Our results suggest that the ability of lipophilic drugs to partition out of lipophilic vehicles and into cell membranes, rather than their intrinsic solubility in the lipophilic vehicle, determines the rate and extent of their ocular penetration.

Comprehensive nutrition guidelines and management strategies for enteropathy in children.

Protein-losing enteropathy (PLE) describes a syndrome of excessive protein loss into the gastrointestinal tract, which may be due to a wide variety of etiologies. For children in whom the protein loss is associated with lymphangiectasia, medical nutrition therapy focused on restricting enteral long-chain triglycerides and thus intestinal chyle production is an integral component of treatment. This approach is based on the principle that reducing intestinal chyle production will concurrently decrease enteric protein losses of lymphatic origin. In patients with ongoing active PLE or those who are on a fat-restricted diet, particularly in infants and young children, supplemental calories may be provided with medium-chain triglycerides (MCT). MCT are absorbed directly into the bloodstream, bypassing intestinal lymphatics and not contributing to intestinal chyle production. Patients with active PLE or who are on dietary fat restriction should be monitored for associated micronutrient deficiencies. In this paper, we seek to formally present recommended nutrition interventions, principles of dietary education and patient counseling, and monitoring parameters in pediatric populations with PLE based on our experience in a busy clinical referral practice focused on this population.

Betanin combined with virgin coconut oil inhibits neuroinflammation in aluminum chloride-induced toxicity in rats by regulating NLRP3 inflammasome.

Background and aim: Activating NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) is crucial in the pathogenesis of Alzheimer's disease (AD). A multimodal treatment intervention is the most feasible way to alter the course of AD progression. Hence, the current study was conducted to study the combination of betanin (BET) and virgin coconut oil (VCO) on NLRP3 regulation in aluminum chloride-induced AD in Wistar rats. Experimental procedure: BET (100,200 mg/kg) and VCO (1, 5 g/kg) alone and in combination (BET 100 mg/kg + VCO 1 g/kg and BET 200 mg/kg + VCO 5 g/kg) were given orally for 42 days. On day 21 and 42nd, the behavioral test was performed to check the animal's cognition. Acetylcholinesterase (AChE) activity, oxidative stress markers, estimation of NLRP3 and IL-1ß, and histological examinations were conducted in the hippocampus (H) and cortex (C). Results and conclusion: Treatment with BET and VCO alone or combined improved behavioral characteristics (MWM and PA p < 0.0001; EPM p = 0.5184), inhibited AChE activity (C, p = 0.0101; H, p < 0.0001), and lowered oxidative stress in the brain. Also, combination treatment restored the levels of NLRP3 (C, p = 0.0062; H, p < 0.0001) and IL1ß (C, p = 0.0005; H, p = 0.0098). The combination treatment significantly reduced the degree of neuronal degeneration, amyloid deposition, and necrosis in the brain tissue. The current study revealed that the combination strategy effectively controlled neuroinflammation via modulation of the NLRP3 inflammasome pathway, paving the way for the new treatment.

Nutrition and Aging in Dogs and Cats.

Aging is often associated with chronic inflammation and declining health. Both veterinarians and owners of aging dogs and cats are interested in nutritional solutions and strategies to prevent signs of age-related disease, increase longevity, and improve quality of life. Physiological decreases in muscle mass, decreased immunity, and a decrease in sense acuity are some of the changes often seen in otherwise healthy senior pets; however, there may also be an increase in risk for pathologies such as renal, cardiovascular, musculoskeletal, and neoplastic diseases. Aging may also lead to cognitive decline and even cognitive dysfunction. Some nutritional strategies that may be helpful with the prevention and treatment of age-related diseases include supplementation with ω3 polyunsaturated fatty acids and antioxidant nutrients that can help modulate inflammation and benefit osteoarthritis, renal disease, cancer, and more. Supplementation with medium-chain triglycerides shows promise in the treatment of canine cognitive dysfunction as these may be metabolized to ketone bodies that are utilized as an alternative energy source for the central nervous system. Additionally, a high intake of dietary phosphorus in soluble and bioavailable forms can lead to renal disease, which is of greater concern in senior pets. There are no published guidelines for nutritional requirements specific to senior pets and as a result, products marketed for senior dogs and cats are highly variable.

Tolerance, adherence, and acceptability of a ketogenic 2.5:1 ratio, nutritionally complete, medium chain triglyceride-containing liquid feed in children and adults with drug-resistant epilepsy following a ketogenic diet.

OBJECTIVE: To investigate incorporating a ready-to-use 2.5:1 ratio liquid feed into a ketogenic diet (KD) in children and adults with drug-resistant epilepsy. METHODS: Following a three-day baseline, patients (n = 19; age: 19 years [SD 13], range: 8-46 years) followed a KD for 28 days (control period), then incorporated ≥200 mL/day of a ready-to-use liquid feed, made with a ratio of 2.5 g of fat to 1 g of protein plus carbohydrate and including medium chain triglycerides ([MCTs]; 25.6% of total fat/100 mL) for 28 days as part of their KD (intervention period). Outcome measures (control vs intervention period) included gastrointestinal (GI) tolerance, adherence to KD and intervention feed, dietary intake, blood ß-hydroxybutyrate (BHB) concentration, seizure outcomes, health-related quality of life (HRQoL), acceptability and safety. RESULTS: Compared to the control period, during the intervention period, the percentage of patients reporting no GI symptoms increased (+5% [SD 5], p = 0.02); adherence to the KD prescription was similar (p = 0.92) but higher in patients (n = 5) with poor adherence (<50%) to KD during the control period (+33% [SD 26], p = 0.049); total MCT intake increased (+12.1 g/day [SD 14.0], p = 0.002), driven by increases in octanoic (C8; +8.3 g/day [SD 6.4], p < 0.001) and decanoic acid (C10; +5.4 g/day [SD 5.4], p < 0.001); KD ratio decreased (p = 0.047), driven by a nonsignificant increase in protein intake (+11 g/day [SD 44], p = 0.29); seizure outcomes were similar (p ≥ 0.63) but improved in patients (n = 6) with the worst seizure outcomes during the control period (p = 0.04); and HRQoL outcomes were similar. The intervention feed was well adhered to (96% [SD 8]) and accepted (≥88% of patients confirmed). SIGNIFICANCE: These findings provide an evidence-base to support the effective management of children and adults with drug-resistant epilepsy following a KD with the use of a ready-to-use, nutritionally complete, 2.5:1 ratio feed including MCTs. PLAIN LANGUAGE SUMMARY: This study examined the use of a ready-to-use, nutritionally complete, 2.5:1 ratio (2.5 g of fat to 1 g of protein plus carbohydrate) liquid feed, including medium chain triglycerides (MCTs), into a ketogenic diet (KD) in children and adults with drug-resistant epilepsy. The results show that the 2.5:1 ratio feed was well tolerated, adhered to, and accepted in these patients. Increases in MCT intake (particularly C8 and C10) and improvements in seizure outcomes (reduced seizure burden and intensity) and KD adherence also occurred with the 2.5:1 ratio feed in patients with the worst seizures and adherence, respectively.

A high-fat diet supplemented with medium-chain triglycerides ameliorates hepatic steatosis by reducing ceramide and diacylglycerol accumulation in mice.

Non-alcoholic fatty liver disease (NAFLD) is projected to be the most common chronic liver disease worldwide and is closely linked to obesity, insulin resistance and type 2 diabetes. Currently, no pharmacological treatments are available to treat NAFLD, and lifestyle modification, including dietary interventions, is the only remedy. Therefore, we conducted a study to determine whether supplementation with medium-chain triglycerides (MCTs), containing a mixture of C8 and C10 (60/40), attenuates NAFLD in obese and insulin-resistant mice. To achieve that, we fed C57BL/6 male mice a high-fat diet (HFD) for 12 weeks to induce obesity and hepatic steatosis, after which obese mice were assigned randomly either to remain on the HFD or to transition to an HFD supplemented with MCTs (HFD + MCTs) or a low-fat diet (LFD) for 6 weeks as another dietary intervention model. Another group of mice was kept on an LFD throughout the study and used as a lean control group. Obese mice that transitioned to HFD + MCTs exhibited improvement in glucose and insulin tolerance tests, and the latter improvement was independent of changes in adiposity when compared with HFD-fed mice. Additionally, supplementation with MCTs significantly reduced hepatic steatosis, improved liver enzymes and decreased hepatic expression of inflammation-related genes to levels similar to those observed in obese mice transitioned to an LFD. Importantly, HFD + MCTs markedly lowered hepatic ceramide and diacylglycerol content and prevented protein kinase C-ε translocation to the plasma membrane. Our study demonstrated that supplementation with MCTs formulated mainly from C8 and C10 effectively ameliorated NAFLD in obese mice.

Effect of Different Medium-Chain Triglycerides on Glucose Metabolism in High-Fat-Diet Induced Obese Rats.

Obesity can be associated with significant metabolic disorders. Our previous study found that medium-chain triglycerides (MCTs) improved lipid metabolism in obese rats. However, scant attention has been given to exploring the impact of MCTs on glucose metabolism in obese rats. This study is designed to examine the effects and mechanisms of three distinct MCTs on glucose metabolism in obese rats. To induce obesity, Sprague-Dawley (SD) rats were fed a high-fat diet, followed by a 12-week treatment with caprylic triglyceride (CYT), capric triglyceride (CT), and lauric triglyceride (LT). The results showed that three types of MCT intervention reduced the levels of lipids (TC, TG, LDL-c, and HDL-c), hyperglycemia, insulin resistance (insulin, OGTT, HOMA-IR, and ISI), and inflammatory markers (IL-4, IL-1ß, and TNF-α) in obese rats (p < 0.01), The above parameters have been minimally improved in the high-fat restoring group (HR) group. MCTs can modulate the PI3K/AKT signaling pathways to alleviate insulin resistance and improve glucose metabolism in obese rats. Furthermore, MCTs can activate peroxisome proliferator-activated receptor (PPAR) γ and reduce the phosphorylation of PPARγser237 mediated by CDK5, which can improve insulin sensitivity without lipid deposition in obese rats. Among the MCT group, CT administration performed the best in the above pathways, with the lowest blood glucose level and insulin resistance. These findings contribute to a deeper understanding of the connection between health benefits and the specific type of MCT employed.

MCT Nanoemulsions for the Efficient Delivery of siRNA.

In this study, an oil-in-water (o/w) nanoemulsion is used to deliver siRNA targeting Twist1, a protein that contributes to tumor metastasis in a variety of cancers. The FDA-approved oil, medium chain triglycerides (MCT), is used as the hydrophobic phase for the nanoemulsion. The siRNA is paired with dioleoyl-3-trimethylammonium-propane (DOTAP) to form a hydrophobic salt that is soluble at high concentrations in MCT. The resulting MCT/siRNA-DOTAP solution is formulated into a nanoemulsion with an average particle size of 140 nm. The nanoemulsion displays long term stability over the course of 195 days. In an in vivo murine tumor model, the nanoemulsion facilitates a 46% decrease in Twist1 mRNA after 48 h.

Ketogenic diets: A systematic review of current scientific evidence and possible applicability in dogs and cats.

Ketogenic diets (KD) have been used in the treatment of epilepsy in humans for around a century and, more recently, they have been implanted for cancer patients, as well as in the treatment of obesity. This type of diet consists of high-fat levels, an adequate amount of protein and restricted carbohydrates, or high medium-chain triglycerides. Recently, the ketogenic diet has gained attention in veterinary medicine and studies were published evaluating the effects of KD in dogs with epilepsy. The objective of this review was to highlight recent studies about the application of KD in dogs and cats, to describe the neurobiochemical mechanisms through which KD improves epilepsy crisis, and their adverse effects. Studies were identified by a systematic review of literature available on PubMed, Embase, and Scopus. All cohort and case-control studies were included, and all articles were exported to Mendeley® citation manager, and duplicates were automatically removed. Seven articles and three conference abstracts conducted with dogs were included in the present study. There is evidence that the consumption of diets with medium-chain triglycerides increases the concentration of circulating ketone bodies and improves epilepsy signs, although these diets have higher carbohydrate and lower fat content when compared to the classic KD.

Effect of medium-chain triglycerides supplements and walking on health-related quality of life in sedentary, healthy middle-aged, and older adults with low BMIs: a randomized, double-blind, placebo-controlled, parallel-group trial.

Introduction: To extend individuals' healthy life expectancies, the improvement of subjective health and quality of life (QOL) has been increasingly prioritized, alongside the improvement of their physical functioning. Reports have indicated that intake of medium-chain triglycerides (MCTs) benefits the physical health of older individuals requiring nursing care, and athletes, and healthy individuals. But there are few studies investigating the effects of MCTs on subjective health and QOL. The present study sought to evaluate the combined effects of 12-week MCTs supplements and moderate-intensity walking exercise on the subjective health and QOL of middle-aged and older adults aged 60-74 with low BMIs (< 24 kg/m2) and who had no exercise habits. Methods: A placebo-controlled, double-blind, parallel-group trial was conducted. Three MCTs supplement groups with different doses and fatty acid compositions were compared with a control group. The study used the SF-36v2 questionnaire to assess subjective health and health-related QOL (HRQOL). Results: The result showed significant improvements in the scores on subscales of the physical QOL, such as Physical functioning and General health, and summary scores on the mental QOL, compared to the control. Conclusion: It is estimated that the combination of continuous intake of MCTs and walking exercise may affect HRQOL and improve subjective physical and mental health in sedentary, healthy, middle-aged and older adults. Clinical trial registration: https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000046861, UMIN000046861.

[Beneficial effects of ketogenic diet for Alzheimer's disease management]. / Intérêt du régime cétogène dans la prise en charge de la maladie d'Alzheimer.

Alzheimer's disease (AD) is a neurodegenerative disease that affects almost 1 million people in France and 55 million in the world. This pathology is a global health preoccupation because of the lack of efficient curative treatment and the increase of its prevalence. During the last decade, the comprehension of pathophysiological mechanisms involved in AD have been improved. Amyloid plaques and neurofibrillary tangles accumulation are characteristic of Alzheimer's brain patients, accompanied by increased brain inflammation and oxidative stress, impaired cerebral metabolism of glucose and mitochondrial function. Treatment of AD includes different approaches, as pharmacology, psychology support, physiotherapy, and speech therapy. However, these interventions do not have a curative effect, but only compensatory on the disease. Ketogenic diet (KD), a low-carbohydrates and high-fat diet, associated with a medium-chain triglycerides intake (MCTs) might induce benefices for Alzheimer disease patients. Carbohydrate restriction and MCTs promotes the production of ketone bodies from fatty acid degradation. These metabolites replacing glucose, serve the brain as energetic substrates, and induce neuroprotective effects. Such a nutritional support might slow down the disease progression and improve cognitive abilities of patients. This review aims to examine the neuroprotective mechanisms of KD in AD progression and describes the advantages and limitations of KD as a therapeutic strategy.

Title: Intérêt du régime cétogène dans la prise en charge de la maladie d'Alzheimer. Abstract: La maladie d'Alzheimer (MA), pathologie neurodégénérative en expansion, devient une préoccupation importante de santé publique, en raison d'une absence de traitement curatif efficace. Les mécanismes mis en œuvre dans la physiopathologie de la MA sont de mieux en mieux connus, et incluent l'accumulation de plaques amyloïdes et de dégénérescences neurofibrillaires. L'augmentation de l'inflammation et du stress oxydant et l'altération du métabolisme cérébral du glucose aggravent la pathologie en réduisant l'activité neuronale en perturbant la fonction mitochondriale. À l'heure actuelle, le traitement de cette pathologie regroupe différentes approches bien que ces interventions n'aient pas un effet curatif, mais uniquement compensatoire. L'alimentation cétogène, pauvre en glucides et enrichie en lipides, couplée à une prise de triglycérides à chaîne moyenne (MCT), favorise la production de corps cétoniques, substrats énergétiques qui pourraient présenter des effets neuroprotecteurs bénéfiques pour les personnes atteintes de la MA. Une telle prise en charge nutritionnelle pourrait limiter la progression de la maladie et améliorer les capacités cognitives des patients. Cette revue vise à examiner le rôle éventuel et les mécanismes neuroprotecteurs de l'alimentation cétogène dans la progression de la MA, et décrit les avantages et les limites de son utilisation comme stratégie thérapeutique.

Clinical Correlates of Cholestasis in Preterm Infants with Surgical Necrotizing Enterocolitis.

Background: We sought to investigate the clinical determinants and outcomes of cholestasis in preterm infants with surgical necrotizing enterocolitis (sNEC). Methods: Retrospective comparison of clinical information in preterm infants who developed cholestasis vs those who did not. Results: Sixty-two (62/91, 68.1%) infants with NEC developed cholestasis at any time following the onset of illness. Cholestasis was seen more frequently in those who had received ionotropic support at 24 hours following sNEC diagnosis (87.1% vs 58.6%; p = 0.002), had higher mean C-reactive protein levels 2 weeks after NEC diagnosis (p = 0.009), had blood culture-positive sepsis [25 (40.3%) vs 4 (13.8%); p = 0.011], received parenteral nutrition (PN) for longer durations (108.4 ± 56.63 days vs 97.56 ± 56.05 days; p = 0.007), had higher weight-for-length z scores at 36 weeks' postmenstrual age [-1.0 (-1.73, -0.12) vs -1.32 (-1.76, -0.76); p = 0.025], had a longer length of hospital stay (153.7 ± 77.57 days vs 112.51 ± 85.22 days; p = 0.024), had intestinal failure more often (61% vs 25.0%, p = 0.003), had more surgical complications (50% vs 27.6%; p = 0.044), and had >1 complication (21% vs 3.4%; p = 0.031). Using linear regression, the number of days after surgery when feeds could be started [OR 15.4; confidence interval (CI) 3.71, 27.13; p = 0.009] and the postoperative ileus duration (OR 11.9, CI 1.1, 22.8; p = 0.03) were independently associated with direct bilirubin between 2 and 5 mg/dL (mild-moderate cholestasis) at 2 months of age. The duration of PN was independently associated with direct bilirubin >5 mg/dL (severe cholestasis) at 2 months of age in these patients. Conclusion: Cholestasis was seen in 68% of infants following surgical NEC. The most likely contributive factors are intestinal failure and subsequent PN dependence for longer periods. Our data suggest that identification and prevention of risk factors such as sepsis and surgical complications and early feeds following NEC surgery may improve outcomes.

Pathogenesis and Management of Citrin Deficiency.

Citrin deficiency (CD) is a hereditary disorder caused by SLC25A13 mutations that manifests as neonatal intrahepatic cholestasis caused by CD (NICCD), failure to thrive and dyslipidemia caused by CD (FTTDCD), and adult-onset type 2 citrullinemia (CTLN2). Citrin, an aspartate-glutamate carrier primarily expressed in the liver, is a component of the malate-aspartate shuttle, which is essential for glycolysis. Citrin-deficient hepatocytes have primary defects in glycolysis and de novo lipogenesis and exhibit secondarily downregulated PPARα, leading to impaired ß-oxidation. They are unable to utilize glucose and free fatty acids as energy sources, resulting in energy deficiencies. Medium-chain triglyceride (MCT) supplements are effective for treating CD by providing energy to hepatocytes, increasing lipogenesis, and activating the malate-citrate shuttle. However, patients with CD often exhibit growth impairment and irreversible brain and/or liver damage. To improve the quality of life and prevent irreversible damage, MCT supplementation with a diet containing minimal carbohydrates is recommended promptly after the diagnosis.

Supplementation of Medium-Chain Triglycerides Combined with Docosahexaenoic Acid Inhibits Amyloid Beta Protein Deposition by Improving Brain Glucose Metabolism in APP/PS1 Mice.

The deterioration of brain glucose metabolism predates the clinical onset of Alzheimer's disease (AD). Medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA) positively improve brain glucose metabolism and decrease the expression of AD-related proteins. However, the effects of the combined intervention are unclear. The present study explored the effects of the supplementation of MCTs combined with DHA in improving brain glucose metabolism and decreasing AD-related protein expression levels in APP/PS1 mice. The mice were assigned into four dietary treatment groups: the control group, MCTs group, DHA group, and MCTs + DHA group. The corresponding diet of the respective groups was fed to mice from the age of 3 to 11 months. The results showed that the supplementation of MCTs combined with DHA could increase serum octanoic acid (C8:0), decanoic acid (C10:0), DHA, and ß-hydroxybutyrate (ß-HB) levels; improve glucose metabolism; and reduce nerve cell apoptosis in the brain. Moreover, it also aided with decreasing the expression levels of amyloid beta protein (Aß), amyloid precursor protein (APP), ß-site APP cleaving enzyme-1 (BACE1), and presenilin-1 (PS1) in the brain. Furthermore, the supplementation of MCTs + DHA was significantly more beneficial than that of MCTs or DHA alone. In conclusion, the supplementation of MCTs combined with DHA could improve energy metabolism in the brain of APP/PS1 mice, thus decreasing nerve cell apoptosis and inhibiting the expression of Aß.