Possible Extracellular Signals to Ameliorate Sarcopenia in Response to Medium-Chain Triglycerides (8:0 and 10:0) in Frail Older Adults.

In frail older adults (mean age 85 years old), a 3-month supplementation with a low dose (6 g/day) of medium-chain triglycerides (MCTs; C8:0 and C10:0) given at a meal increased muscle mass and function, relative to supplementation with long-chain triglycerides (LCTs), but it decreased fat mass. The reduction in fat mass was partly due to increased postprandial energy expenditure by stimulation of the sympathetic nervous system (SNS). However, the extracellular signals to ameliorate sarcopenia are unclear. The following three potential extracellular signals to increase muscle mass and function after MCT supplementation are discussed: (1) Activating SNS-the hypothesis for this is based on evidence that a beta2-adrenergic receptor agonist acutely (1-24 h) markedly upregulates isoforms of peroxisomal proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) mRNAs, promotes mitochondrial biogenesis, and chronically (~1 month) induces muscle hypertrophy. (2) An increased concentration of plasma acyl-ghrelin stimulates growth hormone secretion. (3) A nitrogen-sparing effect of ketone bodies, which fuel skeletal muscle, may promote muscle protein synthesis and prevent muscle protein breakdown. This review will help guide clinical trials of using MCTs to treat primary (age-related) sarcopenia.

[Influence of Postoperative Diet Type and Regimen on Hospital Comfort
and Rehabilitation of Lung Cancer Patients].

BACKGROUND: A reasonable and standardized dietary plan and procedure can help patients recovering quickly from lung cancer surgery. The aim of this study is to optimize the diet plan and procedure mainly based on medium chain triglyceride (MCT) diet and explore its clinical advantages for postoperative lung cancer patients. METHODS: From October 2023 to December 2023, a total of 156 patients were collected, who underwent lung cancer surgery in Lung Cancer Center, West China Hospital of Sichuan University. The patients were randomized into MCT group (76 cases) and routine diet (RD) group (80 cases). Clinical symptoms, biochemical index, postoperative hospitalization time and cost, dietary satisfaction and hospitalization comfort between the two groups were analyzed. RESULTS: The mean anus exhausting time in MCT group [24.00 (9.75, 36.97) h] was significantly shorter than that in RD group [28.50 (24.00, 48.00) h] (P<0.001). And the incidence of dizziness (18.42%), nausea and vomiting (6.58%) in MCT group were remarkably lower than those in RD group (51.25%, 31.25%) (P<0.001). Hospitalization comfort score in MCT group [(16.74±1.70)] was significantly higher than that in RD group [(14.83±2.34)] (P=0.016). Meanwhile, the average hospitalization cost in MCT group [(39,701.82±8105.47)¥] showed an obvious decrease compared with RD group [(44,511.79±9593.19)¥] (P=0.007). CONCLUSIONS: Optimizing the dietary plan and procedure mainly based on MCT diet for postoperative lung cancer patients can help the recovery of gastrointestinal function and improve hospitalization comfort, which promoted overall postoperative rehabilitation of patients with lung cancer surgery.

Major clinical events and healthcare resource use among patients with long-chain fatty acid oxidation disorders in the United States: Results from LC-FAOD Odyssey program.

Major clinical events (MCEs) related to long-chain fatty acid oxidation disorders (LC-FAOD) in triheptanoin clinical trials include inpatient or emergency room (ER) visits for three major clinical manifestations: rhabdomyolysis, hypoglycemia, and cardiomyopathy. However, outcomes data outside of LC-FAOD clinical trials are limited. The non-interventional cohort LC-FAOD Odyssey study examines data derived from US medical records and patient reported outcomes to quantify LC-FAOD burden according to management strategy including MCE frequency and healthcare resource utilization (HRU). Thirty-four patients were analyzed of which 21 and 29 patients had received triheptanoin and/or medium chain triglycerides (MCT), respectively. 36% experienced MCEs while receiving triheptanoin versus 54% on MCT. Total mean annualized MCE rates on triheptanoin and MCT were 0.1 and 0.7, respectively. Annualized disease-related inpatient and ER events were lower on triheptanoin (0.2, 0.3, respectively) than MCT (1.2, 1.0, respectively). Patients were managed more in an outpatient setting on triheptanoin (8.9 annualized outpatient visits) vs MCT (7.9). Overall, this shows that those with LC-FAOD in the Odyssey program experienced fewer MCEs and less HRU in inpatient and ER settings during triheptanoin-treated periods compared with the MCT-treated periods. The MCE rate was lower after initiation of triheptanoin, consistent with clinical trials.

Keto Clarity: A Comprehensive Systematic Review Exploring the Efficacy, Safety, and Mechanisms of Ketogenic Diet in Pediatric Epilepsy.

Epilepsy, a widespread neurological disorder characterized by recurrent seizures, affects millions globally, with a significant impact on the pediatric population. Antiepileptic drugs (AEDs) constitute the primary treatment; however, drug-resistant epilepsy (DRE), especially in children, poses a therapeutic challenge. Alternative interventions, such as surgery, vagus nerve stimulation, and the ketogenic diet (KD), have been explored. This systematic review aims to investigate various types of KDs, their distinctions, their effectiveness, and their safety concerning the reduction of seizure frequency, achieving seizure freedom, and the occurrence of adverse events. The study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive search was conducted using databases such as PubMed Central (PMC), MedLine, and Science Direct to identify relevant articles. Eligibility criteria and quality assessment tools were applied to evaluate the potential risk of bias and select 11 articles for inclusion in this review. The selected articles encompassed four randomized controlled trials (RCTs), two systematic reviews, and five narrative reviews. The data collected for this review was completed on October 2, 2023. Challenges, such as palatability, cultural factors, and adherence difficulties, were identified. Family or caregiver involvement plays a pivotal role in treatment success. Despite numerous RCTs and reviews, information gaps persist, hindering conclusive outcomes. Evaluating the risk-benefit ratio is crucial, considering potential side effects. The highly individualized nature of KD therapy, influenced by diverse seizure types and syndromes, necessitates a trial-and-error approach monitored by a multidisciplinary team. Long-term safety and efficacy demand continuous real-life patient data review. In summary, while KD presents a promising alternative for DRE, its success relies on meticulous planning, individualized implementation, and ongoing research to address existing challenges and information gaps.

Medium-chain triglycerides (8:0 and 10:0) increase muscle mass and function in frail older adults: a combined data analysis of clinical trials.

Background: Three clinical trials have examined the chronic effects of medium-chain triglycerides (MCTs) on muscle mass and function in frail older adults (mean age 85 years old). However, significant increases in muscle mass and some muscle function relative to long-chain triglycerides (LCTs) have yet to be shown, possibly due to the small number of participants in each trial. Objective: We re-analyzed these previous clinical trials to clarify whether MCT supplementation can increase muscle mass and function. Analysis: After adding post hoc tests to the original report, we compared changes in measurement between the MCT and LCT groups in the first 2 trials and conducted a combined data analysis. Methods: In a combined data analysis, changes from baseline in measurements at the 3 months intervention in the MCTs- and LCTs-containing groups were assessed by analysis of covariance adjusted for baseline values of each measurement, age, sex, BMI, allocation to trial, habitual intakes in energy, protein, leucine, octanoic acid, decanoic acid, and vitamin D during the baseline period. The Mann-Whitney U test was used to analyze data on right and left knee extension times. Results: MCT supplementation for 3 months increased muscle function relative to LCT supplementation with and without an L-leucine (1.2 g) and vitamin D (cholecalciferol, 20 µg)-enriched supplement. In a combined data analysis (n = 29 in MCTs, n = 27 in LCTs), relative to supplementation with 6 g LCTs/day, supplementation with 6 g MCTs/day at dinner for 3 months significantly increased body weight (adjusted mean change from baseline: MCTs 1.2 vs. LCTs 0.2 kg, p = 0.023), right arm muscle area (MCTs 1.4 vs. LCTs-0.7 cm2, p = 0.002), left calf circumference (p = 0.015), right-hand grip strength (MCTs 1.6 vs. LCTs 0.3 kg, p = 0.017), right knee extension time (p = 0.021), left knee extension time (p = 0.034), walking speed (p = 0.002), and number of iterations in leg open and close test (p < 0.001) and decreased right triceps skinfold thickness (p = 0.016). Conclusion: In frail older adults, supplementation for 3 months with a low dose (6 g/day) of MCTs (C8:0 and C10:0) increased muscle mass and function. These findings indicate the potential for the practical use of MCTs in daily life in treating sarcopenia.

Clinical profile, genetic spectrum and therapy evaluation of 19 Chinese pediatric patients with lipoprotein lipase deficiency.

BACKGROUND: Lipoprotein lipase (LPL) deficiency, the most common familial chylomicronemia syndrome (FCS), is a rare autosomal recessive disease characterized by chylomicronemia and severe hypertriglyceridemia (HTG), with limited clinical and genetic characterization. OBJECTIVE: To describe the manifestations and management of 19 pediatric patients with LPL-FCS. METHODS: LPL-FCS patients from 2014 to 2022 were divided into low-fat (LF), very-low-fat (VLF) and medium-chain-triglyceride (MCT) groups. Their clinical data were evaluated to investigate the effect of different diets. The genotype-phenotype relationship was assessed. Linear regression comparing long-chain triglyceride (LCT) intake and TG levels was analyzed. RESULTS: Nine novel LPL variants were identified in 19 LPL-FCS pediatric patients. At baseline, eruptive xanthomas occurred in 3/19 patients, acute pancreatitis in 2/19, splenomegaly in 6/19 and hepatomegaly in 3/19. The median triglyceride (TG) level (30.3 mmol/L) was markedly increased. The MCT group and VLF group with LCT intakes <20 en% (energy percentage) had considerably lower TG levels than the LF group (both p<0.05). The LF group presented with severe HTG and significantly decreased TG levels after restricting LCT intakes to <20 en% (p<0.05). Six infants decreased TG levels to <10 mmol/L by keeping LCT intake <10 en%. TG levels and LCT intake were positively correlated in both patients under 2 years (r=0.84) and those aged 2-9 years (r=0.89). No genotype-phenotype relationship was observed. CONCLUSIONS: This study broadens the clinical and genetic spectra of LPL-FCS. The primary therapy for LPL-FCS pediatric patients is restricting dietary LCTs to <10 en% or <20 en% depending on different ages. MCTs potentially provide extra energy.

Efficacy evaluation of a commercially available MCT enriched therapeutic diet on dogs with idiopathic epilepsy treated with zonisamide: a prospective, randomized, double-blinded, placebo-controlled, crossover dietary preliminary study.

BACKGROUND: Idiopathic epilepsy (IE) is a common, chronic brain dysfunction in dogs. Recently, the effect of feeding a diet enriched with medium-chain triglycerides (MCTs) on seizure frequency has been evaluated in several studies in dogs with IE. However, most dogs with IE in previous studies were treated with phenobarbital as the main antiseizure medication (ASM). In Japan, zonisamide (ZNS) is the most prescribed ASM for dogs with IE. The interaction between ZNS and various nutrients including MCTs and the potential effects on treatment efficacy resulting from combining these therapies have not been previously studied. A prospective, randomized, double-blinded, placebo-controlled, crossover dietary study was conducted. Dogs (n = 7) treated with ZNS were fed either a placebo diet (PL) or Purina ProPlan Veterinary Diet NeuroCare (NC) for 3 months, after which treatments were crossed over and continued for another 3 months. Seizure frequency (seizures/month; sz/m), blood tests including concentrations of ZNS and ß-hydroxybutyric acid, and owner's visual analogue scale score were collected from all dogs for both treatment periods. RESULTS: There was no significant difference in the seizure frequency between PL (2.95 ± 0.80 sz/m) and NC (1.90 ± 0.57 sz/m) during the 6 months of trial. Three of 7 dogs showed ≥ 50% seizure reduction, and 1 of those 3 dogs achieved seizure freedom in NC period. However, 2 of 7 dogs had no changes in epileptic seizure frequency, 2 of 7 dogs had a deterioration in seizure frequency in the NC period. Feeding the MCT diet concurrent with ZNS showed no apparent adverse effects and did not affect ZNS concentration. CONCLUSIONS: This study indicated that the commercially available MCT-enriched diet (NC) can be safely used concurrently with ZNS for dogs with IE.

Refueling the post COVID-19 brain: potential role of ketogenic medium chain triglyceride supplementation: an hypothesis.

COVID-19 infection causes cognitive changes in the acute phase, but also after apparent recovery. Over fifty post (long)-COVID symptoms are described, including cognitive dysfunction ("brain fog") precluding return to pre-COVID level of function, with rates twice as high in females. Additionally, the predominant demographic affected by these symptoms is younger and still in the workforce. Lack of ability to work, even for six months, has significant socio-economic consequences. This cognitive dysfunction is associated with impaired cerebral glucose metabolism, assessed using 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET), showing brain regions that are abnormal compared to age and sex matched controls. In other cognitive conditions such as Alzheimer's disease (AD), typical patterns of cerebral glucose hypometabolism, frontal hypometabolism and cerebellar hypermetabolism are common. Similar FDG-PET changes have also been observed in post-COVID-19, raising the possibility of a similar etiology. Ketone bodies (B-hydroxybutyrate, acetoacetate and acetone) are produced endogenously with very low carbohydrate intake or fasting. They improve brain energy metabolism in the face of cerebral glucose hypometabolism in other conditions [mild cognitive impairment (MCI) and AD]. Long-term low carbohydrate intake or prolonged fasting is not usually feasible. Medium chain triglyceride (MCT) is an exogenous route to nutritional ketosis. Research has supported their efficacy in managing intractable seizures, and cognitive impairment in MCI and AD. We hypothesize that cerebral glucose hypometabolism associated with post COVID-19 infection can be mitigated with MCT supplementation, with the prediction that cognitive function would also improve. Although there is some suggestion that post COVID-19 cognitive symptoms may diminish over time, in many individuals this may take more than six months. If MCT supplementation is able to speed the cognitive recovery, this will impact importantly on quality of life. MCT is readily available and, compared to pharmaceutical interventions, is cost-effective. Research shows general tolerability with dose titration. MCT is a component of enteral and parenteral nutrition supplements, including in pediatrics, so has a long record of safety in vulnerable populations. It is not associated with weight gain or adverse changes in lipid profiles. This hypothesis serves to encourage the development of clinical trials evaluating the impact of MCT supplementation on the duration and severity of post COVID-19 cognitive symptoms.

Medium-chain triglyceride-stabilized docetaxel-loaded HSA nanoparticles effectively inhibited metastatic non-small cell lung cancer.

Metastatic non-small cell lung cancer (NSCLC) is refractory with a very poor prognosis. Docetaxel (DTX) injection (Taxotere®) has been approved for the treatment of locally advanced or metastatic NSCLC. However, its clinical application is restricted by severe adverse effects and non-selective tissue distribution. In this study, we successfully developed DTX-loaded human serum albumin (HSA) nanoparticles (DNPs) with modified Nab technology, by introducing medium-chain triglyceride (MCT) as a stabilizer. The optimized formulation had a particle size of approximately 130 nm and a favorable stabilization time of more than 24 h. DNPs dissociated in circulation in a concentration-dependent manner and slowly released DTX. Compared with DTX injection, DNPs were more effectively taken up by NSCLC cells, thus exerting stronger inhibitory effects on their proliferation, adhesion, migration, and invasion. In addition, DNPs showed prolonged blood retention and increased tumor accumulation relative to DTX injection. Ultimately, DNPs produced more potent inhibitory effects on primary or metastatic tumor foci than DTX injections but caused markedly lower organ toxicity and hematotoxicity. Overall, these results support that DNPs hold great potential for the treatment of metastatic NSCLC in clinical.

A ketogenic diet containing medium-chain triglycerides reduces REM sleep duration without significant influence on mouse circadian phenotypes.

Ketogenic diets (KDs) affect the circadian rhythms of behavior and clock gene expression in experimental animals. However, these diets were designed to simulate a fasting state; thus, whether these effects are caused by diet-induced ketogenesis or persistent starvation is difficult to distinguish. The present study aimed to define the effects of a KD containing medium-chain triglycerides (MCT-KD) that increase blood ketone levels without inducing carbohydrate starvation, on circadian rhythms and sleep regulation. Mice were fed with a normal diet (CTRL) or MCT-KD for 2 weeks. Blood ß-hydroxybutyrate levels were significantly increased up to 2 mM by the MCT-KD, whereas body weight gain and blood glucose levels were identical between the groups, suggesting that ketosis accumulated without carbohydrate starvation in the MCT-KD mice. Circadian rhythms of wheel-running activity and core body temperature were almost identical, although wheel-running was slightly reduced in the MCT-KD mice. The circadian expression of the core clock genes, Per1, Per2, Bmal1, and Dbp in the hypothalamus, heart, liver, epididymal adipose tissues, and skeletal muscle were almost identical between the CTRL and MCT-KD mice, whereas the amplitude of hepatic Per2 and adipose Per1 expression was increased in MCT-KD mice. The MCT-KD reduced the duration of rapid-eye-movement (REM) sleep without affecting the duration of non-REM sleep and the duration of wakefulness. These findings suggested that the impact of ketone bodies on circadian systems are limited, although they might reduce locomotor activity and REM sleep duration.

The Effects of Medium Chain Triglyceride for Alzheimer's Disease Related Cognitive Impairment: A Systematic Review and Meta-Analysis.

BACKGROUND: The current lack of effective drug therapies for Alzheimer's disease (AD) has prompted researchers to seek alternative nutritional therapies, such as medium chain triglycerides (MCTs). However, results are inconclusive. OBJECTIVE: This systematic review and meta-analysis aims to summarize current evidence on the effect of MCT on cognitive function in patients with mild cognitive impairment (MCI) or AD. METHODS: A systematic search was conducted up until December 16, 2022, to identify human interventions reporting the effects of MCT on cognitive functioning of MCI or AD patients. 995 non-duplicated publications were identified, of which nine (n = 10 studies) met the inclusion criteria. RESULTS: Meta-analysis showed cognitive improvements in general (SMD = 0.64; 95% CI [0.05, 1.24]), but not in memory, language, and attention domains after oral MCT administration, compared to placebo. The effect of MCT was greater among APOEɛ4 (-) subjects than APOEɛ4 (+) subjects (SMD = 1.87; 95% CI [0.35, 3.40]). CONCLUSION: This review provides some evidence that treatment with MCT could improve general cognitive function in APOEɛ4 (-) cognitive impaired patients. Better characterized clinical studies are warranted before making a definitive conclusion on the use of MCT for MCI and AD management.

Effects of medium chain triglycerides on hepatic fatty acid oxidation in clofibrate-fed newborn piglets.

To investigate whether increasing tricarboxylic acid (TCA) cycle activity and ketogenic capacity would augment fatty acid (FA) oxidation induced by the peroxisome proliferator-activated receptor-alpha (PPARα) agonist clofibrate, suckling newborn piglets (n = 54) were assigned to 8 groups following a 2 ( ± clofibrate) × 4 (glycerol succinate [SUC], triglycerides of 2-methylpentanoic acid [T2M], valeric acid [TC5] and hexanoic acid [TC6]) factorial design. Each group was fed an isocaloric milk formula containing either 0% or 0.35% clofibrate (wt/wt, dry matter basis) with 5% SUC, T2M, TC5 or TC6 for 5 d. Another 6 pigs served as newborn controls. Fatty acid oxidation was examined in fresh homogenates of liver collected on d 6 using [1-14C] palmitic acid (1 mM) as a substrate (0.265 µCi/µmol). Measurements were performed in the absence or presence of L-carnitine (1 mM) or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase (L659699, 1.6 µM) or acetoacetate-CoA deacylase (iodoacetamide, 50 µM). Without clofibrate stimulation, 14C accumulation in CO2 was higher from piglets fed diets containing T2M and TC5 than SUC, but similar to those fed TC6. Under clofibrate stimulation, accumulation also was higher in homogenates from piglets fed TC5 than all other dietary treatments. Interactions between clofibrate and carnitine or the inhibitors were observed (P = 0.0004) for acid soluble products (ASP). In vitro addition of carnitine increased 14C-ASP (P < 0.0001) above all other treatments, regardless of clofibrate treatment. The percentage of 14C in CO2 was higher (P = 0.0023) in TC5 than in the control group. From these results we suggest that dietary supplementation of anaplerotic and ketogenic FA could impact FA oxidation and modify the metabolism of acetyl-CoA (product of ß-oxidation) via alteration of TCA cycle activity, but the modification has no significant impact on the hepatic FA oxidative capacity induced by PPARα. In addition, the availability of carnitine is a critical element to maintain FA oxidation during the neonatal period.

Triglycerides of medium-chain fatty acids: a concise review.

Medium-chain triglycerides contain medium-chain fatty acid esterified to the glycerol backbone. These MCFA have a shorter chain length and are quickly metabolized in the body serving as an immediate energy source. They are known to have good physiological as well as functional characteristics which help in treating various health disorders. Naturally, they are found in coconut oil, milk fat, and palm kernel oil, and they are synthetically produced by esterification and interesterification reactions. Due to their numerous health benefits, MCT is used as a functional or nutraceutical oil in various food and pharmaceutical formulations. To increase their nutraceutical benefits and food applications MCFA can be used along with polyunsaturated fatty acids in the synthesis of structured lipids. This review aims to provide information about triglycerides of MCFA, structure, metabolism, properties, synthetic routes, intensified synthesis approaches, health benefits, application, and safety of use of MCT in the diet.

Fabrication and characterization of nanoemulsions for encapsulation and delivery of vitexin: antioxidant activity, storage stability and in vitro digestibility.

BACKGROUND: Nanoemulsions were prepared as an encapsulation and delivery system for vitexin, a poorly water-soluble antioxidant. This study evaluated how the type and concentration of the dispersed oil phase and vitexin loading impacted droplet characteristics and nanoemulsion stability. The influences of storage temperature on antioxidant activity and in vitro gastrointestinal digestion on nanoemulsion stability were also investigated. RESULTS: Nanoemulsions prepared at different dispersed oil concentrations showed diverse characteristics and stability. Highest stability against droplet aggregation and phase separation with small oil droplets (< 150 nm) was observed for nanoemulsions prepared using 300 g kg-1 medium-chain triglyceride oil. These nanoemulsions are able to entrap and deliver vitexin with high encapsulation efficiency (88-90%) with no significant effect on emulsion stability. Vitexin-loaded nanoemulsions were stable during storage when refrigerated (4 °C) and at room temperature (25 °C) for up to 45 days with no effect on their antioxidant activity. Significantly delayed lipolysis rate and decreased extent of lipid digestion were observed in vitexin-loaded nanoemulsions. CONCLUSIONS: Stable vitexin-loaded nanoemulsions were successfully produced by high-pressure homogenization using a mixture of Tween 80 and lecithin as emulsifiers. Vitexin-loaded nanoemulsions stabilized with a mixture of these two emulsifiers were effective in retaining antioxidant activity during storage and protecting vitexin from changes during gastrointestinal digestion. Our results suggested that nanoemulsions were effective vitexin delivery systems for food applications. © 2022 Society of Chemical Industry.

Timing of Medium-Chain Triglyceride Consumption Modulates Effects in Mice with Obesity Induced by a High-Fat High-Sucrose Diet.

The prevalence of obesity is increasing worldwide, and obesity can cause type 2 diabetes, atherosclerosis, hypertension, cardiovascular disease, and cancer. Intake of medium-chain triglycerides (MCTs) containing medium-chain fatty acids reduces body fat and insulin resistance in rodents and humans. This study aimed to determine how the timing of MCT consumption affects obesity and metabolic dysfunction induced in mice by a high-fat high-sucrose diet (HFHSD). Mice received an HFHSD with or without MCT (M-HFHSD) during either the active or rest phase for 9 weeks. Significant reduction in body weight, white adipose tissue (WAT) weight, and adipocyte size in epididymal WAT (eWAT) and improved insulin sensitivity in mice fed with M-HFHSD during the active but not the rest phase were observed. The consumption of M-HFHSD during both active and rest phases increased glucose tolerance. Phosphorylated Akt was more abundant in the gastrocnemius muscles and eWAT of M-HFHSD-fed mice than in those fed HFHSD during the active phase. The mRNA and protein expression of lipogenic genes increased in the eWAT of mice fed M-HFHSD compared with those fed HFHSD. Feeding with M-HFHSD during the active phase significantly increased the abundance of phosphorylated Ser563 and 660 of hormone-sensitive lipase and its upstream protein kinase A in eWAT. These results indicated that the timing of consumption modulates the effects of MCT on eWAT hypertrophy and glucose and lipid metabolism in mice.

Metabolic fingerprinting of dogs with idiopathic epilepsy receiving a ketogenic medium-chain triglyceride (MCT) oil.

Consumption of medium-chain triglycerides (MCT) has been shown to improve seizure control, reduce behavioural comorbidities and improve cognitive function in epileptic dogs. However, the exact metabolic pathways affected by dietary MCT remain poorly understood. In this study, we aimed to identify changes in the metabolome and neurotransmitters levels relevant to epilepsy and behavioural comorbidities associated with the consuming of an MCT supplement (MCT-DS) in dogs with idiopathic epilepsy (IE). Metabolic alterations induced by a commercial MCT-DS in a population of 28 dogs with IE were evaluated in a 6-month multi-centre, prospective, randomised, double-blinded, controlled cross-over trial design. A metabolic energy requirement-based amount of 9% MCT or control oil was supplemented to the dogs' stable base diet for 3 months, followed by the alternative oil for another 3 months. A validated, quantitative nuclear magnetic resonance (NMR) spectroscopy platform was applied to pre- and postprandially collected serum samples to compare the metabolic profile between both DS and baseline. Furthermore, alterations in urinary neurotransmitter levels were explored. Five dogs (30%) had an overall reduction in seizure frequency of ≥50%, and were classified as MCT-responders, while 23 dogs showed a ≤50% reduction, and were defined as MCT non-responders. Amino-acid metabolism was significantly influenced by MCT consumption compared to the control oil. While the serum concentrations of total fatty acids appeared similar during both supplements, the relative concentrations of individual fatty acids differed. During MCT supplementation, the concentrations of polyunsaturated fatty acids and arachidonic acid were significantly higher than under the control oil. ß-Hydroxybutyric acid levels were significantly higher under MCT supplementation. In total, four out of nine neurotransmitters were significantly altered: a significantly increased γ-aminobutyric acid (GABA) concentration was detected during the MCT-phase accompanied by a significant shift of the GABA-glutamate balance. MCT-Responders had significantly lowered urinary concentrations of histamine, glutamate, and serotonin under MCT consumption. In conclusion, these novel data highlight metabolic changes in lipid, amino-acid and ketone metabolism due to MCT supplementation. Understanding the metabolic response to MCT provides new avenues to develop better nutritional management with improved anti-seizure and neuroprotective effects for dogs with epilepsy, and other behavioural disorders.

Fibrous and Spherical Aggregates of Ovotransferrin as Stabilizers for Oleogel-Based Pickering Emulsions: Preparation, Characteristics and Curcumin Delivery.

This study aimed to explore the effects and mechanisms of differently shaped aggregates of ovotransferrin (OVT) particles on oleogel-based Pickering emulsions (OPEs). Medium-chain triglyceride oil-based oleogels were constructed using beeswax, and their gel-sol melting temperatures were investigated. Atomic force microscopy confirmed that both OVT fibrils and OVT spheres were successfully prepared, and the three-phase contact angle measurements indicated that fibrous and spherical aggregates of OVT particles possessed great potential to stabilize the OPEs. Afterward, the oil-in-water OPEs were fabricated using oleogel as the oil phase and OVT fibrils/spheres as the emulsifiers. The results revealed that OPEs stabilized with OVT fibrils (FIB-OPEs) presented a higher degree of emulsification, smaller droplet size, better physical stability and stronger apparent viscosity compared with OPEs stabilized with OVT spheres (SPH-OPEs). The freeze-thaw stability test showed that the FIB-OPEs remained stable after three freeze-thaw cycles, while the SPH-OPEs could barely withstand one freeze-thaw cycle. An in vitro digestion study suggested that OVT fibrils conferred distinctly higher lipolysis (46.0%) and bioaccessibility (62.8%) of curcumin to OPEs.