Search Results (64)

Background/Objectives: Ketone bodies are increasingly studied for their potential therapeutic effects, particularly through exogenous ketosis, in a variety of diseases. This systematic review aimed to rigorously assess the clinical efficacy of exogenous ketosis in adults with medical conditions. Methods: Following PRISMA guidelines, we systematically searched MEDLINE and Scopus databases. Our inclusion criteria were defined according to the PICOS framework, focusing on studies involving exogenous ketosis in adult patients with specific diseases. The study is registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42023492846). Results: After a stringent selection process, fifty-one studies were analyzed. Twenty-two studies focused on neurological disorders, one on psychiatric disorders, twenty-two on metabolic disorders, five on cardiovascular disorders, and one on an inflammatory disorder. Exogenous ketosis demonstrated potential benefits across multiple conditions, including Alzheimer’s disease, mild cognitive impairment, McArdle’s disease, various forms of heart failure, cardiogenic shock, pulmonary hypertension, and COVID-19-related acute respiratory distress syndrome, although evidence is mostly limited to surrogate endpoints with insufficient hard outcome data. Subtherapeutic ketone concentrations induced by medium-chain triglycerides and limited follow-up periods often precluded firm conclusions regarding clinically meaningful outcomes. Conclusions: Exogenous ketosis shows potential in neurological, metabolic, and cardiovascular disorders, while evidence in psychiatric and inflammatory conditions remains scarce and preliminary. Ketone esters appear preferable for effective and tolerable ketosis. Future research should focus on identifying responsive patient populations, optimizing treatment regimens, and conducting long-term clinical trials with hard endpoints to validate these findings. Full article

Tenbrio molitor (T. molitor) is a widely utilized feed ingredient, though it is deficient in long-chain omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). To address this, dietary supplements containing EPA and DHA in ethyl ester and triglyceride forms were administered to investigate the lipid metabolism and bioenhancement potential of T. molitor. The larvae exhibited normal growth across all treatment groups. EPA/DHA levels were significantly elevated in T. molitor-enriched diets, with newly identified phospholipid species including phosphatidylcholine 18:1_20:5 (PC 18:1_20:5) and phosphatidylethanolamine 18:0_20:5 (PE 18:0_20:5). KEGG pathway analysis revealed that glycerol phospholipid metabolism (ko00564), endogenous cannabinoid signaling (ko04723), and cell division (ko04148) were the core pathways that promoted phospholipid synthesis and oxidative lipid conversion (such as peroxide value-phosphatidylcholine, POV-PC). T. molitor activates glycerophospholipid metabolism, converting EPA/DHA into more bioavailable medium- and short-chain phospholipids, thereby enhancing its nutritional value and providing a new strategy for the development of functional foods/feeds. Full article

Background/Objectives: Exogenous ketone supplements elevate circulating ketones without carbohydrate restriction, but their long-term hepatic safety remains unclear. This study evaluated the formulation-dependent impact of chronic ketone supplementation on liver histopathology, inflammatory signaling, and systemic biomarkers in rats. Methods: Male Sprague-Dawley rats were orally administered 1,3-butanediol (BD), medium-chain triglycerides (MCTs), ketone ester (KE), ketone electrolytes/salts (KSs), or a ketone salt–MCT combination (KSMCT) for 4 weeks. In a separate arm, animals received standard diet (SD), or SD supplemented with low-dose KE (LKE) or high-dose KE (HKE), for 83 days. Liver structure was assessed by hematoxylin and eosin staining with quantification of red blood cell density and lipid accumulation. Inflammatory and metabolic responses were evaluated by TNF-α and arginase immunohistochemistry. Serum biochemistry included glucose, proteins, electrolytes, and liver and kidney function markers. Results: BD and KE induced macrovesicular steatosis, vascular congestion, and elevated TNF-α and arginase expression, consistent with hepatic stress. MCT caused moderate hepatocellular ballooning and lipid deposition, whereas KS preserved near-normal hepatic morphology. KSMCT produced intermediate effects, reducing lipid accumulation and TNF-α compared with MCT or KE alone. KE supplementation caused dose-dependent reductions in globulin and elevations in creatinine, while HKE reduced sodium and glucose levels. Conclusions: Chronic hepatic responses to exogenous ketones are highly formulation dependent. KS demonstrated the most favorable safety profile under the tested conditions, maintaining normal hepatic structure, while BD and KE elicited adverse changes. Formulation choice is critical for the safe long-term use of exogenous ketones. Full article

Background: The ketogenic diet (KD), a high-fat and low-carbohydrate dietary approach, has been used therapeutically in drug-resistant epilepsy and other neurological and metabolic disorders. Recent interest has shifted toward understanding its broader metabolic effects through metabolomics. This review aims to summarize current knowledge on the biochemical mechanisms and therapeutic implications of the KD, with a particular focus on metabolomic profiling and neurological health. Methods: This narrative review synthesizes findings from the last five years of metabolomic studies investigating the biochemical consequences of the KD and its variants, including the classical KD, modified Atkins diet (MAD), medium-chain triglyceride diet (MCT), and low glycemic index treatment (LGIT). The review integrates data on analytical techniques, such as liquid chromatography–mass spectrometry (LC-MS) and gas chromatography–mass spectrometry (GC-MS), and evaluates alterations in key metabolic pathways. Results: The KD significantly modulates energy metabolism, shifting adenosine triphosphate (ATP) production from glycolysis to fatty acid oxidation and ketone body utilization. It affects mitochondrial function, one-carbon metabolism, redox balance, neurotransmitter regulation, and gut–brain axis signaling. Metabolomic profiling has identified β-hydroxybutyrate (βHB) as a key regulatory metabolite influencing mitochondrial respiration. Long-term KD use may impact renal and hepatic function, necessitating clinical caution and individualized nutritional monitoring. Conclusions: Metabolomic analysis provides critical insights into the multifaceted effects of the KD, supporting its role as a targeted metabolic therapy in neurological diseases. However, potential risks linked to prolonged ketosis warrant further investigation. Future studies should focus on personalized applications and long-term safety profiles of KD variants across patient populations. Full article

Research on the effects of polyunsaturated fatty acids on children’s sleep has made significant advancements. This study explores the unique pathways through which polyunsaturated fatty acids, particularly docosahexaenoic acid and eicosapentaenoic acid from the n-3 series, influence sleep regulation in children. Neurobiologically, docosahexaenoic acid and eicosapentaenoic acid have been shown to bi-directionally modulate neurotransmitters and circadian rhythms via the gut–brain axis, reshaping gut microbiota and affecting brain signaling. In terms of inflammation and immune regulation, this study is the first to confirm that Maresin1, produced from n-3 fatty acids, can inhibit the activation of specific inflammasomes, thereby mitigating the disruptive effects of pro-inflammatory cytokines on sleep. The analysis of clinical applications indicates that newly developed medium- and long-chain triglyceride formulations rich in docosahexaenoic acid exhibit excellent digestive absorption in infants’ gastrointestinal systems, paving the way for new products designed to enhance infant sleep. However, current research has limitations concerning the precise dosing of docosahexaenoic acid, the representativeness of samples, and the overall rigor of study designs. Mechanistically, polyunsaturated fatty acids may exert their effects through various pathways, including neurobiology, inflammation, immune regulation, and endocrine modulation. In clinical studies, different formulations of fish oil show varying safety profiles and bioavailability. Future research should prioritize high-quality studies to clarify how different doses of polyunsaturated fatty acids affect children’s sleep, assess long-term safety, and investigate interactions with other factors, ultimately providing solid theoretical and practical guidance for improving children’s sleep. Full article

Chronic pancreatitis (CP) precipitates complex malnutrition through synergistic mechanisms: exocrine pancreatic insufficiency–driven maldigestion, duodenal or pancreatobiliary strictures limiting nutrient flow, cholestasis impairing micelle formation, alcohol-related anorexia, pain-induced hypophagia, proteolytic catabolism from type 3c diabetes, and a chronic inflammatory milieu that accelerates sarcopenia and bone demineralisation. Consequent calorie–protein depletion, micronutrient and fat-soluble vitamin deficits, and metabolic derangements markedly amplify morbidity. Pancreatic enzyme replacement therapy (PERT) with targeted micronutrient repletion is foundational; high-protein regimens co-administered with PERT curb muscle loss, and medium-chain triglycerides (MCTs) can augment caloric delivery by bypassing lipase dependence, although their benefit over personalised dietetic counselling is marginal. Optimal dietary fat thresholds and timing of escalation from oral to enteral or parenteral feeding remain unresolved. Comprehensive care also demands alcohol abstinence, effective analgesia and stringent glycaemic control. Serial monitoring—biochemical indices, densitometry, dual-energy X-ray absorptiometry and imaging-based body-composition metrics—permits early detection of high-risk patients and precision tailoring of interventions. Intensified multidisciplinary programmes already improve prognostic endpoints and are unveiling biomarkers of nutritional resilience. A structured, evidence-based strategy integrating PERT, macronutrient engineering, micronutrient repletion and metabolic surveillance is essential to mitigate nutrition-related morbidity, enhance long-term outcomes and optimise quality of life in CP. Full article

Background: The long-term clinical and laboratory results of a 33-year follow-up of a Greek family with abetalipoproteinemia (ABL) are described. Case Report: The patients (two brothers and their sister, aged 57, 49, and 62 years, respectively) are still alive, being under close surveillance. In two of the three patients, diarrhea appeared in early infancy, while in the third, it appeared during adolescence. CNS symptomatology worsened after the second decade of life. At the same time, night blindness appeared in the advanced stages of the disease, resulting in almost complete loss of vision in one of the male patients and severe impairment in the other. The diagnosis was based on the clinical picture, ophthalmological findings, serum lipid estimations, and presence of peripheral acanthocytosis. All patients exhibited typical serum lipidemic profile, ophthalmological findings, and acanthocytes in the peripheral blood. During the follow-up period, strict dietary modifications were applied, including the substitution of fat with medium-chain triglycerides (MCT oil). After 33 years since the initial diagnosis, all patients are alive without any sign of liver dysfunction despite continuous use of MCT oil. However, symptoms from the central nervous system and vision impairment worsened. Conclusion: The course of these patients suggests that the application of a modified diet, including MCT oil, along with close surveillance, could prolong the survival of patients without significant side effects from the liver. Full article

Background: Self-emulsifying drug delivery system (SEDDS) is widely used to improve the oral bioavailability of hydrophobic drugs. Emulsion droplet size was revealed to be a critical parameter that influences the thermodynamic stability, drug solubility, and drug absorption of the SEDDS. A high proportion of surfactant and/or co-surfactant was usually employed to reduce the particle size, which may lead the low drug loading and undesirable gastrointestinal toxicity. Methods: This manuscript proposed a novel strategy to reduce the particle size of emulsions using the hybrid of medium and long-chain triglyceride (MCT and LCT) SEDDS without promoting the concentration of surfactants and co-surfactants. The composition of SEDDS was selected based on the drug solubility. Particle size distribution and zeta potential of emulsion particles were determined using the dynamic light scattering technique. The bioavailability of formulations was evaluated in a mouse model. Results: The particle size of the emulsion was reduced from 113.50 ± 0.34 nm (MCT SEDDS) and 371.60 ± 6.90 nm (LCT SEDDS) to 21.23 ± 0.30 nm (MCT&LCT SEDDS). Progesterone, a poorly water-soluble drug, was selected as the model drug in the investigation of SEDDS. The hybrid of MCT&LCT progesterone SEDDS exhibited reduced particle size, enlarged self-emulsifying ranges, and increased drug content in the aqueous phase after lipolysis compared with the conventional mono-MCT or LCT SEDDS. In addition, the bioavailability of progesterone in the MCT&LCT SEDDS formulation was 3.82-fold higher than that of Utrogestan^® (a clinical oral administrated product) in a mouse model. Full article

Medium chain triglycerides (MCTs) are regarded as an important ingredient for functional foods and nutraceuticals. Cinnamomum camphora seed kernel oil (CCSKO) contains more than 95% medium chain fatty acids (MCFAs), which is a significantly higher level than palm kernel oil (62%) and coconut oil (55%). However, the safety assessment of CCSKO, as the only natural MCT oil rich in capric acid and lauric acid found so far in the world, has not been fully verified. The study aimed to investigate the 90-day sub-chronic oral toxicity and teratogenicity of CCSKO. In the sub-chronic oral toxicity study, no clinically significant adverse events occurred in male or female Sprague–Dawley (SD) rats with CCSKO daily administration for 13 weeks. Moreover, there were no dose–response relationships between CCSKO and body-weight gain, food intake and food utilization in male or female SD rats. No significant differences (p > 0.05) were found in the hematological properties or organ weights between the male and female SD rats. In the teratogenicity test, no toxicological signs were observed in either Wister pregnant rats or fetuses. The no-observed-adverse-effect level of CCSKO was determined to be more than 4 mL/kg body weight. These results suggested that CCSKO may be an excellent edible oil with high oral safety. 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/Objectives: Dietary supplementation with medium-chain triglycerides (MCTs) improves walking balance and cognitive function in healthy older adults. This study aimed to determine the biological effects of MCTs on gait-related skeletal muscles in healthy older adults by analyzing muscle density and glucose metabolism. Methods: ¹⁸F-FDG-PET/CT imaging data from 63 participants (18 g/day of MCTs and matching placebo in the form of a jelly stick [6 g each, ingested 3 times/day]) in a randomized clinical trial were analyzed. The three-dimensional regions of interest were set as muscles associated with walking balance (bilateral triceps, psoas, and vastus medialis). Each muscle’s mean standardized uptake value (SUV_mean) and Hounsfield units (HU) were calculated for relative quantitative measurements. Results: MCT supplementation for 3 months decreased the SUV_mean (p < 0.001) and increased the HU of the psoas (r = −0.61) and vastus medialis muscles (r = −0.59) (p < 0.001); no changes were apparent in participants supplemented with long-chain triglycerides. The changes in the SUV_mean for each muscle were correlated negatively with those of plasma β-hydroxybutyrate in MCT-supplemented participants (r = −0.57 [psoas] and −0.59 [vastus medialis]; p < 0.001). Conclusion: A 3-month MCT supplementation suppressed glucose metabolism and increased the muscle density in gait-related skeletal muscles, consistent with previous findings that MCT supplementation stabilizes balance functions during walking in healthy older adults. Full article

Background/Objectives: Structured medium- and long-chain triglycerides (sMLCT) may be a superior vehicle for medium-chain fatty acid delivery to peripheral tissues, such as skeletal muscle. Limited information is available concerning the effect of sMLCT on muscular performance or recovery after a muscle-damaging exercise protocol. The purpose of this study was to establish the effect of a novel formulation of sMLCT on muscular performance and recovery. Methods: Forty female adults (mean ± SD age = 22 ± 3 years; body mass index = 23.5 ± 3.4 kg/m²) were randomized into one of two study groups, placebo control [CON; n = 20] or sMLCT [n = 20], and completed five total visits to the laboratory. The baseline (i.e., pre-exercise) assessments of muscle performance, size, and soreness were compared to assessments immediately following exercise and 24, 48, and 72 h post-exercise. Results: No statistically significant condition × time interactions were noted for strength outcomes, although trends for condition × time interactions were present for torque over 25 ms (p = 0.06) and peak torque (p = 0.05). Similarly, no condition x time interactions were present for ultrasound echo intensity, the subjective ratings of soreness and pain, thigh circumference, leg volume, and vertical jump performance. Conclusions: Within the context of the current study, the ingestion of sMLCT did not significantly influence the rate of muscle strength recovery following muscle damaging resistance exercise. Full article

Background/Objectives: Sarcopenia and malnutrition are common in post-stroke patients, impairing recovery. Medium-chain triglycerides (MCT) may support muscle metabolism, while chair-stand exercises improve strength and mobility. However, their combined effects remain unclear. This study evaluated the synergistic effects of MCT supplementation and high-frequency chair-stand exercise on physical function and muscle health in post-stroke patients. Methods: A retrospective cohort study included 1080 post-stroke patients categorized into three groups: (1) MCT supplementation alone, (2) chair-stand exercise alone, and (3) both combined. MCT supplementation consisted of ~40 g/day MCT oil or powder. Functional outcomes were assessed using the Functional Independence Measure (FIM-motor), while muscle health was evaluated by handgrip strength (HGS) and skeletal muscle index (SMI). Multiple linear regression analyses were performed, adjusting for confounders. Results: The combined intervention group showed significantly greater improvements in FIM-motor scores at discharge (B = 8.79, 95% CI: 5.64–11.95, β = 0.32, p < 0.001) and FIM-motor gain (B = 6.02, 95% CI: 3.42–8.62, β = 0.29, p < 0.001) compared to the control. Increases in HGS (B = 2.441, 95% CI: 0.483–4.398, β = 0.18, p = 0.015) and SMI (B = 0.194, 95% CI: 0.102–0.419, β = 0.12, p = 0.039) were also observed. Chair-stand exercise was performed a median of 62 times/day and independently improved outcomes, while MCT alone had limited effects. Conclusions: MCT supplementation combined with chair-stand exercise enhances functional recovery and muscle health in post-stroke patients, supporting its role in rehabilitation. Further research is needed to evaluate long-term effects and to examine the pharmacokinetics of MCTs, including blood concentrations, in broader populations. Full article

Background: Nutraceuticals represent a strategy for maintaining health and constitute a brilliant market in Italy and across Europe. However, the absence of strict regulations regarding formulation requirements highlights a critical issue: their poor bioavailability. An example is coenzyme Q10 (CoQ10), a quinone known for its potential as a mitochondrial protective agent but characterized by low intestinal absorption. CoQ10 is a hydrophobic molecule with high molecular weight and poor water solubility, factors that significantly limit its intestinal bioaccessibility and, consequently, its oral bioavailability. Objectives: In this context, the present study describes a novel formulation designed to enhance CoQ10 bioaccessibility through in situ emulsification upon contact with gastroenteric fluids. This technology, termed Lipid-Based Auto-Emulsifying Drug Delivery System (LiBADDS), is unique because it combines a medium-chain triglyceride (MCT), a long-chain fatty acid, conjugated linoleic acid (CLA) with a high HLB solubilizer, Polysorbate 80 (PS80), and a sodium octenyl succinate starch derivative (SOS), which can create a nanometric emulsion simply by aqueous dispersion and upon contact with gastrointestinal fluids. This phenomenon promotes the prompt dispersion of CoQ10 and its rapid translocation into the serosal compartment of the intestinal epithelium. Methods: Its efficacy was evaluated in vitro through the Caco-2 cellular model and in vivo through a crossover study on healthy volunteers, measuring pharmacokinetic parameters such as AUC, C_max, T_max, ΔAUC, and ΔC_max. Results: Overall, LiBADDS demonstrated a significant improvement in both the bioaccessibility and bioavailability of CoQ10 compared to the unformulated substance. Conclusions: LiBADDS showed to be a promising tool to improve CoQ10 bioavailability by enhancing its bioaccessibility. Full article

Red yeast rice is a nutraceutical fermented product used worldwide for the symptomatic relief of dyslipidemia and cardiovascular disease. However, the fermentation-induced lipid transformation from rice to red yeast rice remains unclear. Herein, an ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry method was developed for the comprehensive lipid analysis during fermentation. A total of 246 lipids fall in 21 subclasses were annotated in rice and red yeast rice, including 37 lysophospholipids, 14 phospholipids, 29 diglycerides, 114 triglycerides and fatty acid (15 species), ceramide (12 species), hexosylceramide (3 species), sitosterol ester (2 species), monogalactosyldiacylglycerol (2 species), digalactosyldiacylglycerol (2 species), monogalactosylmonoacylglycerol (8 species), digalactosylmonoacylglycerol (5 species), coenzyme Q (1 species), acyl hexosyl campesterol ester (1 species), and acylcarnitine (1 species). Results showed that lipid profiles changed, and new lipid species emerged. Notably, 18 medium- and long-chain triacylglycerols and triacylglycerols with short-chains were tentatively identified. These triacylglycerols also show the effects of body fat accumulation reduction, and hypolipidemic and hypoglycemic activities. Furthermore, lipid species that were profoundly changed were quantified, and the dynamic changes were investigated. This study clarified the molecular species and compositional changes in fermented rice from lipid aspect. Full article