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Update of doi: 10.1002/14651858.CD014353. RATIONALE: Enteral lipid formulations may offer benefits according to preclinical studies, but their effectiveness and safety in preventing and treating parenteral nutrition-associated liver disease (PNALD) in infants remains unknown. OBJECTIVES: To evaluate the benefits and harms of enteral lipid supplementation for the prevention and treatment of PNALD in infants. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and trial registers, together with reference checking and contact with study authors. The latest search was in December 2024. ELIGIBILITY CRITERIA: We included parallel, randomized control trials (RCTs) in infants comparing enteral lipid supplements with either a placebo or no intervention in infants who were either at risk or who had PNALD. We excluded studies involving infants receiving enteral feeds without the need for parenteral nutrition, as they were neither at risk for PNALD, nor diagnosed with PNALD, and infants with cholestasis secondary to primary liver disease, inborn errors of metabolism, or congenital infection. OUTCOMES: Our primary outcomes were the prevention of PNALD during hospital stay and the first year of life; and resolution of PNALD during hospital stay and the first year of life. Other outcomes included feeding intolerance during the hospital stay, time to full feeds measured in days during the hospital stay, length of hospital stay in days, need for liver transplantation in the first year of life and all-cause mortality up to hospital discharge and in the first year of life. RISK OF BIAS: We used the Cochrane risk of bias 1 (RoB 1) tool to assess bias in the RCTs. SYNTHESIS METHODS: We synthesized results for each outcome using meta-analyses where possible, using random-effect models to calculate risk ratios (RRs) and risk difference (RD) with 95% confidence intervals (CIs) for dichotomous outcomes. For continuous outcomes, we calculated mean differences (MDs). If combining the data was not feasible, we summarized data narratively using Synthesis without Metaanalysis (SWiM). We summarized the certainty of evidence according to GRADE methods. INCLUDED STUDIES: We included 11 studie

CONTEXT: In preclinical Alzheimer's disease (AD), the brain gradually becomes insulin resistant. As a result, brain glucose utilization is compromised, causing a cellular energy deficit that leads to the accumulation of free radicals, which increases inflammation and damages neurons. When glucose utilization is impaired, ketone bodies offer an alternative energy source. Ketone bodies are synthesized from fats, obtained from either the diet or adipose tissue. Dietary medium-chain fatty acids (MCFAs), which are preferentially metabolized into ketone bodies, have the potential to supply the insulin-resistant brain with energy. OBJECTIVE: This systematic review and meta-analysis aims to review the effect of MCFA supplements on circulating ketone bodies and cognition in individuals with subjective cognitive decline, mild cognitive impairment, and AD. DATA SOURCES: A comprehensive search of electronic databases was performed on August 12, 2019, to retrieve all publications meeting the inclusion criteria. Alerts were then set to identify any publications after the search date up until January 31, 2021. DATA EXTRACTION: Data were extracted by 2 authors and assessed by a third. In total, 410 publications were identified, of which 16 (n = 17 studies) met the inclusion criteria. DATA ANALYSIS: All studies assessing change in levels of blood ketone bodies due to MCFA supplementation (n = 12) reported a significant increase. Cognition outcomes (measured in 13 studies), however, varied, ranging from no improvement (n = 4 studies) to improvement (n = 8 studies) or improvement only in apolipoprotein E allele 4 (APOE ε4) noncarriers (n = 2 studies). One study reported an increase in regional cerebral blood flow in APOE ε4 noncarriers and another reported an increase in energy metabolism in the brain. CONCLUSION: MCFA supplementation increases circulating ketone body levels, resulting in increased brain energy metabolism. Further research is required to determine whether this MCFA-mediated increase in brain energy metabolism improves cognition. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42019146967. © The Author(s) 2023. Published by Oxford University Press

Chronic kidney disease (CKD) is closely associated with systemic inflammation. This randomized controlled trial aimed to evaluate the effects of omega-3 fatty acids supplementation on inflammatory markers in patients with CKD undergoing hemodialysis. Eligible participants with CKD receiving hemodialysis were randomly assigned to either an intervention group or a control group. The intervention group received three capsules of omega-3 fatty acids (3 g/day) for two months, while the control group received placebo capsules containing medium-chain triglyceride (MCT) oil. Inflammatory markers, including C-reactive protein (CRP) and interleukin-6 (IL-6), were measured both before and after the interventions. The results showed that CRP levels increased from 9.86 ± 12.64 to 11.46 ± 22.23 mg/L in the intervention group and from 5.24 ± 9.01 to 5.61 ± 7.93 mg/L in the control group (p = 0.11). Similarly, IL-6 levels increased from 17.84 ± 14.08 to 81.82 ± 66.22 pg/mL in the intervention group and from 14.96 ± 18.41 to 56.73 ± 115.45 pg/mL in the control group (p = 0.53). No statistically significant group differences were observed after adjusting for confounders such as age, sex, body mass index (BMI), smoking, dietary intake, and pre-existing diseases. The study findings showed that a two-month intake of omega-3 fatty acids supplements did not have a significant impact on reducing the levels of inflammatory markers in CKD patients undergoing hemodialysis. Larger trials with longer durations are warranted. Study Highlights What is the Current Knowledge on the Topic? ○ Omega-3 fatty acids have anti-inflammatory properties and are reported to be potentially beneficial in reducing inflammation associated with CKD, but the evidence regarding the effectiveness of omega-3 supplements in reducing inflammatory markers in this population remains inconsistent. What Question did this Study Address? ○ What is the effect of omega-3 fatty acids supplementation for 2 months on CRP and IL-6 levels in patients with CKD undergoing hemodialysis? What Does This Study Add to Our Knowledge? ○ Contrary to previous studies, this study found that omega-3 fatty acids supplementation did not signif

BackgroundBoth Mediterranean and ketogenic diets have been proposed as nutritional interventions in Parkinson's disease (PD). Combined approaches may offer maximal benefits.ObjectiveAssess the feasibility, safety and exploratory efficacy of two ketogenic interventions, using a Mediterranean diet base, in individuals with PD (PwP).MethodsIn this Phase II, random-order crossover study, PwP followed two 8-week dietary interventions, separated by an 8-week washout: 1) a high-fat, low-carbohydrate Mediterranean diet (MeDi-KD) and 2) a standard Mediterranean diet supplemented with medium chain triglycerides (MeDi-MCT).ResultsOf 52 participants randomized, 48 started the trial. Forty-one (79%) participants completed at least one, whereas only 33 (63%) completed both intervention phases. There were no intervention-related serious adverse events, nor any significant changes in plasma lipid profiles. Seventy-three percent and 92% of participants reported deviating from the MeDi-KD and MeDi-MCT no more than a few times per month, respectively. Moderate Mediterranean Diet Adherence Screener scores of 6.7 (SD: 1.6) and 7.2 (SD: 2.3) were achieved during the MeDi-KD and MeDi-MCT, respectively, out of a maximum of 14. Fifty percent of participants were in nutritional ketosis ([beta-hydroxybutyrate] ([BHB]) > 0.5 mM) at follow-up for the MeDi-KD, as compared with only 1 (3%) participant following the MeDi-MCT. MDS-UPDRS Part II and IV scores decreased by a mean of -1.4 (SD: 4.2; p = 0.039) and -1.0 (SD: 3.0; p = 0.044) points, respectively, following the MeDi-MCT.ConclusionsWhile both Mediterranean-ketogenic interventions appear safe in the short-term in PwP, their feasibility is called into question by a high study dropout rate (37%) and modest adherence. Preliminary benefits observed in patient-reported motor experiences were paradoxically limited to the MCT-supplemented MeDi, in which ketosis was not reliably achieved. Together, our findings indicate the need to refine behavioral strategies to optimize dietary awareness and adherence in future trials.Trial RegistrationThe trial was registered on ClinicalTrials.gov: NCT05469997. Plain Language Summary: Mediterranean-Ketogeni

Chronic kidney disease (CKD), characterized by progressive kidney failure, significantly increases mortality and comorbidity risks such as anemia. This study contrasts the impacts of omega-3 and medium-chain triglycerides (MCT) oil on levels of iron, ferritin, total iron-binding capacity (TIBC), hemoglobin (Hb), and transferrin saturation in patients with CKD undergoing dialysis. This interventional trial was conducted on 120 patients with CKD undergoing dialysis in Rasht, Iran. For 8 weeks, the omega-3 group was orally administered three 1000-mg capsules of omega-3 fatty acid supplement, and the MCT group was administered three 1000-mg capsules containing MCT oil daily. Serum concentrations of ferritin, iron, TIBC, Hb, and transferrin saturation were assessed pre-intervention and after the intervention. There was a significant increase in serum iron levels in the MCT group compared to the omega-3 group (103.72 ± 57.8 vs. 77.48±40.13; P = 0.031). No effect was found regarding other iron-related factors such as TIBC, Hb, transferrin saturation, and ferritin levels. The results of our study indicated that taking MCT oil increased serum iron levels compared to omega-3 supplementation in patients with CKD undergoing dialysis. Further research is needed to better understand the potential benefits of MCT oils in patients with CKD. © 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

INTRODUCTION: Postnatal inflammation is associated with increased mortality and adverse outcomes in preterm infants. The essential fatty acids arachidonic acid (ARA) and docosahexaenoic acid (DHA) are precursors of lipid mediators with a key role in resolving inflammation. Our aim was to investigate the effect of ARA and DHA supplementation on systemic inflammation in very preterm infants and to identify clinical factors associated with early inflammation. METHODS: Secondary analysis of data from a randomized clinical trial (ImNuT study). Infants with gestational age (GA) less than 29 weeks were randomized to receive a daily enteral supplement with ARA 100 mg/kg and DHA 50 mg/kg (ARA:DHA group) or MCT oil (control group) from the second day of life to 36 weeks postmenstrual age. ARA, DHA, and four proinflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were analyzed in repeated dried blood samples from birth to day 28 and the area under the curve (AUC) for each variable was calculated. RESULTS: The intention to treat population included 120 infants with mean (SD) GA 26.4 (1.7). The ARA:DHA group had significantly lower IL-6 levels from day 3 to day 28 compared to the control group, mean difference AUC log10 (95% CI): 0.16 (0.03-0.30) pg/mL, p = 0.018. There was no correlation between ARA or DHA blood concentrations and cytokine levels. Having a low gestational age was independently associated with increased levels of all cytokines during the first 4 weeks of life. CONCLUSIONS: Enhanced supplementation with ARA and DHA may modulate inflammation in very preterm infants. © 2023 The Author(s). Published by S. Karger AG, Basel.

BACKGROUND & AIMS: Studies have suggested that supplementation with docosahexaenoic acid (DHA) to preterm infants might be associated with an increased risk of bronchopulmonary dysplasia (BPD). Our aim was to investigate the effect of enteral supplementation with arachidonic acid (ARA) and DHA on short-term respiratory outcomes and neonatal morbidities in very preterm infants. METHODS: This is a secondary analysis of data from the ImNuT (Immature, Nutrition Therapy) study, a randomized double blind clinical trial. Infants with gestational age less than 29 weeks were randomized to receive a daily enteral supplement with ARA 100 mg/kg and DHA 50 mg/kg (intervention) or medium chain triglycerides (MCT) oil (control), from second day of life to 36 weeks postmenstrual age. Study outcomes included duration of respiratory support, incidence of BPD and other major morbidities associated with preterm birth. RESULTS: 120 infants with mean (SD) gestational age 26.4 (1.7) weeks were randomized and allocated to either the intervention or control group. Supplementation with ARA and DHA led to a significant reduction in number of days with respiratory support (mean (95% CI) 63.4 (56.6-71.3) vs 80.6 (72.4-88.8); p = 0.03) and a lower oxygen demand (FiO2) (mean (95% CI) 0.26 (0.25-0.28) vs 0.29 (0.27-0.30); p = 0.03) compared to control treatment. There were no clinically important differences in incidence of BPD and other major morbidities between the treatment groups. CONCLUSIONS: Supplementation with ARA and DHA to preterm infants was safe and might have a beneficial effect on respiratory outcomes. CLINICAL TRIAL REGISTRATION: The trial has been registered in www. CLINICALTRIALS: gov, ID: NCT03555019.

Background: An oral route of administration for tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) eliminates the harmful effects of smoking and has potential for efficacious cannabis delivery for therapeutic and recreational applications. We investigated the pharmacokinetics of CBD, Δ9-THC, 11-OH-THC, and 11-nor-9-carboxy-Δ9-THC (THC-COOH) in a novel oral delivery system, Solutech™, compared to medium-chain triglyceride-diluted cannabis oil (MCT-oil) in a healthy population. Materials and Methods: Thirty-two participants were randomized and divided into two study arms employing a comparator-controlled, parallel-study design. To evaluate the pharmacokinetics of Δ9-THC, CBD, 11-OH-THC, and THC-COOH, blood was collected at pre-dose (t=0) and 10, 20, 30, and 45, min and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48 h post-dose after a single dose of Solutech (10.0 mg Δ9-THC, 9.76 mg CBD) or MCT (10.0 mg Δ9-THC, 9.92 mg CBD). Heart rate and blood pressure were measured at 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 h. Relationships between cannabis use history, body mass index, sex, and pharmacokinetic parameters were investigated. Safety was assessed before and at 48 h post-acute dose. Results: Acute consumption of Solutech provided a significantly greater maximum concentration (Cmax), larger elimination and absorption rate constants, faster time to Cmax and lag time, and half-life for all analytes compared to MCT-oil (p<0.001). In addition, cannabis use history had a significant influence on the pharmacokinetic parameters of CBD, Δ9-THC, 11-OH-THC, and THC-COOH. On average, participants with later age of first use had higher Δ9-THC, CBD, and THC-COOH Cmax and later time-to-Cmax and half-life for Δ9-THC, CBD, THC-COOH, and 11-OH-THC than those with earlier age of first use (p≤0.032). Those with more years of recreational cannabis use had higher area under the curve for Δ9-THC and CBD, Cmax for CBD, and longer 11-OH-THC half-life than those with less (p≤0.048). Conclusion: This study demonstrated that consumption of Solutech enhanced most pharmacokinetics parameters measured compared to MCT-oil. Participant's cannabis use history, including their age of first use and number

Compared to term infants, the microbiota of preterm infants is less diverse and often enriched for potential pathogens (e.g., members of the family Enterobacteriaceae). Additionally, antibiotics are frequently given to preterm infants, further destabilizing the microbiota and increasing the risk of fungal infections. In a previous communication, our group showed that supplementation of the premature infant diet with medium-chain triglyceride (MCT) oil reduced the fungal burden of Candida spp. in the gastrointestinal tract. The objective of this study was to determine whether MCT supplementation impacts the bacterial component of the microbiome. Pre-term infants (n = 17) receiving enteral feedings of either infant formula (n = 12) or human milk (n = 5) were randomized to MCT supplementation (n = 9) or no supplementation (n = 8). Fecal samples were taken at randomization and prior to MCT supplementation (Week 0), on days 5-7 (Week 1) and day 21 (Week 3). After DNA extraction from samples, the QIIME2 pipeline was utilized to measure community diversity and composition (genera and phyla). Our findings show that MCT supplementation did not significantly alter microbiota diversity or composition in the gastrointestinal tract. Importantly, there were no significant changes in the family Enterobacteriaceae, suggesting that MCT supplementation did not enrich for potential pathogens. MCT holds promise as a therapeutic intervention for reducing fungal colonization without significant impact on the bacterial composition of the host gastrointestinal tract.

Nutritional supplementation with medium-chain triglycerides (MCTs) has the potential to increase memory function in elderly patients with frailty and dementia. Our aim was to investigate the effects of MCT on cognitive and gait functions and their relationships with focal brain metabolism and functional connectivity even in healthy older adults. Participants were blindly randomized and allocated to two groups: 18 g/day of MCT oil and matching placebo formula (control) administered as a jelly stick (6 g/pack, ingested three times a day). Gait analysis during the 6-m walk test, cognition, brain focal glucose metabolism quantified by 18F-fluorodeocyglucose positron emission tomography, and magnetic resonance imaging-based functional connectivity were assessed before and after a 3-month intervention. Sixty-three healthy, normal adults (females and males) were included. Compared with the control group, the MCT group showed better balance ability, as represented by the lower Lissajous index (23.1 ± 14.4 vs. 31.3 ± 18.9; P < 0.01), although no time × group interaction was observed in cognitive and other gait parameters. Moreover, MCT led to suppressed glucose metabolism in the right sensorimotor cortex compared with the control (P < 0.001), which was related to improved balance (r = 0.37; P = 0.04) along with increased functional connectivity from the ipsilateral cerebellar hemisphere. In conclusion, a 3-month MCT supplementation improves walking balance by suppressing glucose metabolism, which suggests the involvement of the cerebro-cerebellar network. This may reflect, at least in part, the inverse reaction of the ketogenic switch as a beneficial effect of long-term MCT dietary treatment. © 2022. The Author(s), under exclusive licence to American Aging Association.

OBJECTIVES: Supplementation with 6 g/day of medium-chain triglycerides (MCTs) at dinnertime increases muscle function and cognition in frail elderly adults relative to supplementation with long-chain triglycerides. However, suitable timing of MCT supplementation during the day is unknown. DESIGN: We enrolled 40 elderly nursing home residents (85.9 ± 7.7 years) in a 1.5-month randomized intervention trial. Participants were randomly allocated to two groups: one received 6 g/day of MCTs at breakfast (breakfast group) as a test group and the other at dinnertime (dinner group) as a positive control group. MEASUREMENTS: Muscle mass, strength, function, and cognition were monitored at baseline and 1.5 months after initiation of intervention. RESULTS: Thirty-seven participants completed the study and were included in the analysis. MCT supplementation in breakfast and dinner groups respectively increased right arm muscle area from baseline by 1.1 ± 0.8 cm2 (P<0.001) and 1.6 ± 2.5 cm2 (P<0.001), left arm muscle area by 1.1 ± 0.7 cm2 (P<0.001) and 0.9 ± 1.0 cm2 (P<0.01), right knee extension time by 39 ± 42 s (P<0.01) and 20 ± 32 s (P<0.05), leg open and close test time by 1.74 ± 2.00 n/10 s (P<0.01) and 1.67 ± 2.01 n/10 s (P<0.01), and Mini-Mental State Examination score by 1.5 ± 3.0 points (P=0.06) and 1.0 ± 2.1 points (P=0.06). These increases between two groups did not differ statistically significantly. CONCLUSION: Supplementation with 6 g MCTs/day for 1.5 months, irrespective of ingestion at breakfast or dinnertime, could increase muscle mass and function, and cognition in frail elderly adults.

BACKGROUND: Medium-chain triglyceride (MCT) oil consists of 8-12 carbons with higher absorption and provides better calories than long-chain triglyceride oil. This study was to explore the effect of MCT oil massage on growth in preterm infants. METHODS: A prospective, single-blind, randomized (two treatments and one control) study was conducted. Preterm infants weighing between 1500 and 2000 g were recruited and randomly assigned to three groups: the MCT oil massage, massage alone and no massage groups. The standardized massage intervention consisted of two 5-min phases, including tactile and kinesthetic stimulation, which were given three times a day for 7 consecutive days. Premature infants in the oil massage group received massage with 10 mL/kg/day of MCT oil divided equally into three applications. Weight, length and head circumference were measured in the three groups at birth and on study days 1 to 7. RESULTS: Forty-eight neonates were evaluated with 16 in each of three groups. The linear mixed effect model was adjusted for other factors, and results showed that weight gain on the 4th day in the oil massage group was greater than that in the no massage group (P < .05). From the 5th to 7th day, weight gain in the oil massage group was greater than that in the other two groups (P < .05). Regarding head circumference and height, this study found that the MCT oil massage group did not have better results than the other two groups. No adverse events were noted in the massage groups. CONCLUSION: The results indicate that preterm infant daily massage with MCT oil is an effective intervention for weight gain that should be recognized as part of low-birth-weight infant developmental care. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT04281563, Registered on 24 February 2020.

Chronic neuropathic pain (NP) is a growing clinical problem for which effective treatments, aside from non-steroidal anti-inflammatory drugs and opioids, are lacking. Cannabinoids are emerging as potentially promising agents to manage neuroimmune effects associated with nociception. In particular, Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination are being considered as therapeutic alternatives for treatment of NP. This study aimed to examine whether sex affects long-term outcomes on persistent mechanical hypersensitivity 7 weeks after ceasing cannabinoid administration. Clinically relevant low doses of THC, CBD, and a 1:1 combination of THC:CBD extracts, in medium chain triglyceride (MCT) oil, were orally gavaged for 14 consecutive days to age-matched groups of male and female sexually mature Sprague Dawley rats. Treatments commenced one day after surgically inducing a pro-nociceptive state using a peripheral sciatic nerve cuff. The analgesic efficacy of each phytocannabinoid was assessed relative to MCT oil using hind paw mechanical behavioural testing once a week for 9 weeks. In vivo intracellular electrophysiology was recorded at endpoint to characterize soma threshold changes in primary afferent sensory neurons within dorsal root ganglia (DRG) innervated by the affected sciatic nerve. The thymus, spleen, and DRG were collected post-sacrifice and analyzed for long-term effects on markers associated with T lymphocytes at the RNA level using qPCR. Administration of cannabinoids, particularly the 1:1 combination of THC, elicited a sustained mechanical anti-hypersensitive effect in males with persistent peripheral NP, which corresponded to beneficial changes in myelinated Aβ mechanoreceptive fibers. Specific immune cell markers associated with T cell differentiation and pro-inflammatory cytokines, previously implicated in repair processes, were differentially up-regulated by cannabinoids in males treated with cannabinoids, but not in females, warranting further investigation into sexual dimorphisms that may underlie treatment outcomes.

1. EFSA J. 2026 Sep 18;24(9):e10154. doi: 10.2903/j.efsa.2026.10154. eCollection 2026 Sep. Safety of synthetic cannabidiol as a novel food pursuant to regulation (EU) 2015/2283. EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA); Turck D, Bohn T, Cámara M, Castenmiller J, De Henauw S, Jos Á, Maciuk A, Mangelsdorf I, McNulty B, Naska A, Pentieva K, Siani A, Thies F, Cubadda F, McArdle HJ, Trezza V, Albert O, Beneventi E, Laganaro M, Nuin Garciarena I, Rossi A, Cruz SB, Seminati F, Magani M, Hirsch-Ernst KI. Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on cannabidiol (CBD) obtained by chemical synthesis as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of ≥ 98% (w/w) CBD and is intended to be marketed exclusively dissolved in medium-chain triglyceride (MCT) oil in food supplements at a maximum daily dose of 2 mg. The proposed target population is the general adult population over 25 years old and excluding pregnant and lactating women. The safety of CBD in individuals taking medications cannot be established. The information provided on the production process, composition and specifications of the NF does not raise safety concerns. The NF is not considered to be nutritionally disadvantageous, and no concerns were identified with respect to genotoxicity. The applicant submitted a 90-day subchronic oral toxicity study with the NF in which the liver was identified as the key target organ, with female rats being more sensitive than males. A BMDL10 of 10.5 mg/kg bw of CBD per day was derived for increased liver weight relative to body weight in female rats. In view of the remaining data gaps, including those related to reproductive and developmental toxicity, the uncertainty factor proposed in the Updated Statement on the safety of CBD published by EFSA in 2026 (i.e. 400) was applied to derive a safe intake level for cannabidiol of 0.026 mg/kg bw per day (2 mg/day for a 70-kg adult). The Panel concludes that the NF is safe under the proposed conditions of use, except for people taking medication, for wh

Chronic kidney disease (CKD) is characterized by inflammation and irreversible damage to the structure and function of kidneys. The kidneys require large amounts of energy to maintain their structural integrity and function, and in CKD there is a disruption of renal energy metabolism due to decreased oxidative phosphorylation and mitochondrial function. The canonical medium-chain fatty acids (MCFAs) are caproic (C6:0), caprylic (C8:0), and capric (C10:0) acids, while lauric acid (C12:0) is considered an intermediate fatty acid. The purpose of this study was to assess circulating markers of energy status and inflammation in felines with CKD when fed trioctanoin (C8 MCT), a medium-chain triglyceride (MCT), in the presence of fish oil. The C8 MCTs are hydrolyzed into MCFAs, which are more efficiently digested, transported to the liver, and absorbed into mitochondria than intermediate or long chain fatty acids. They also generate higher levels of ketone bodies such as beta-hydroxybutyrate (BHB), which is a preferred source of energy for kidneys. Various lipid metabolites and BHB contribute to energy metabolism and modulate inflammation. The subjects were cats with naturally occurring CKD (at least International Renal Interest Society (IRIS) stage one with symmetric dimethylarginine (SDMA) ≥14.0 μg/dL for at least 3 mo; n = 16) housed at Hill's Pet Nutrition Center. In a cross-over study, based on sex and age cats were assigned to the order of feeding of a control food (dry food for management of renal disease) and test food. On an as-fed basis, pork fat was decreased from 12.3% in the control food to 4.3% in the test food, allowing for the addition of 8% C8 MCTs. Fasting blood and urine were collected after feeding each food for 8 wk. Analyses included assessing plasma metabolomics, serum and urine biochemistries, and complete blood counts. Fasting levels of circulating BHB were increased by the test food and carnitine adducts showed a bidirectional effect, as compared to control food (P < 0.05). There were also decreases in inflammatory lipid mediators including dihydro- and hexosylceramides, lysophospholipids, and phosphatidylcholines with test food (P < 0.05 vs c

While medium-chain triglycerides (MCTs), medium- and long-chain triglycerides (MLCTs), and carotenoids individually possess anti-obesity properties, the synergistic metabolic regulatory effects of their combined intervention remain under-investigated. This study explored the effects of MCTs or structured MLCTs combined with natural carotenoids on high-fat diet (HFD)-induced obese mice. After establishing obesity in C57BL/6J mice using a 60% HFD, a ten-week intervention was conducted using 45% HFD containing 150 mg/kg carotenoids across three groups: MCT-C, MLCT-C, and a physical mixture of MCTs and long-chain triglycerides plus carotenoids (MCT+LCT-C), alongside a low-fat diet (LFD) control. Results showed that among the three HFD-fed intervention groups, the MCT-C group had the lowest body weight with significantly lower fat mass, fat pad coefficient, and adipocyte area, but higher liver coefficient and serum alanine aminotransferase levels compared to the LFD control group (p < 0.05). The MLCT-C and MCT+LCT-C groups exhibited higher body weight, white adipose tissue expansion, and adipocyte hypertrophy, with MCT+LCT-C showing the largest adipocyte volume and uniquely presenting hepatocyte necrosis, unlike other groups. Serum total cholesterol was lowest in MCT-C, while high-density lipoprotein cholesterol increased in MLCT-C and MCT+LCT-C. Notably, compared with the MCT+LCT-C group, MLCT-C demonstrated distinctly superior capabilities in maintaining gut microbiota homeostasis, as evidenced by enhanced community alpha diversity and significantly reduced the abundance of harmful Pseudomonadota, while preserving a highly comparable core functional profile. Collectively, these findings confirm that lipid structure differentially shapes gut microbiota and influences energy metabolism, providing a scientific basis for precision nutrition interventions.

BACKGROUND: Treatment strategies for intestinal failure associated liver disease (IFALD) include use of fish-oil lipid emulsion (FO-ILE) or mixed-oil emulsion containing soy, medium chain triglyceride, olive, and fish oils (SO,MCT,OO,FO-ILE). FO-ILE is limited to 1 g/kg/day, either limiting overall calorie provision or shifting calories toward carbohydrate predominance. The objective of this project was to compare the growth of neonates with IFALD receiving either SO,MCT,OO,FO-ILE or FO-ILE. MATERIAL AND METHODS: A retrospective chart review was conducted of neonates with IFALD receiving SO,MCT,OO,FO-ILE or FO-ILE. Growth metrics, nutritional data, and lab values were analyzed using the Mann-Whitney or t-test with a p-value < 0.05 used for significance. RESULTS: We included 46 patients (22 SO,MCT,OO,FO-ILE; 24 FO-ILE). Both groups had similar weight gain (SO,MCT,OO,FO-ILE 24.6 vs FO-ILE 31.6 g/day; p = 0.121), although the FO-ILE patients had increased weight z-scores over time (SO,MCT,OO,FO-ILE: -0.11 vs FO-ILE: 0.09 p = 0.032). The FO-ILE group received fewer calories (SO,MCT,OO,FO-ILE:112 vs FO-ILE:100.7 kcal/kg/day; p = 0.004), less lipid (SO,MCT,OO,FO-ILE: 2.1 vs FO-ILE 1.0 g/kg/day; p < 0.001), and more carbohydrate (SO,MCT,OO,FO-ILE: 9.6 vs FO-ILE: 12.8 mg/kg/min; p < 0.001). CONCLUSION: Neonates receiving FO-ILE had similar weight gain to those receiving SO,MCT,OO,FO-ILE while receiving fewer overall calories and parenteral lipid. The FO-ILE group did have increased weight z-score over time. Further investigation is needed to understand the influence of these differences on additional short-term and long-term outcomes. © 2026 The Authors.

BACKGROUND AND OBJECTIVES: Postprandial hyperglycemia is a modifiable determinant of type 2 diabetes risk and vascular complications. Japonica rice produces pronounced postprandial glucose excursions. Medium-chain triglycerides (MCTs), absorbed via the portal vein, are rapidly oxidized in the liver and can stimulate glucagon-like peptide-1 (GLP-1) secretion and increase ketone body production, mechanisms that may attenuate postprandial glycemia. METHODS AND STUDY DESIGN: This study aimed to determine whether mixing MCT oil into cooked rice reduces postprandial interstitial glucose responses in healthy adults under real-world consumption conditions. In a within-subject, two-condition meal test, 32 participants consumed on separate mornings either a rice-only meal (150 g packed Japonica rice plus 8 g fish miso paste) or the same meal with 12 g MCT oil mixed immediately before intake. Available carbohydrate was standardized at 56.8 g in both meals. Interstitial glucose was measured with Freestyle Libre (Abbott Laboratories, Abbott Park, IL, USA) at 15-minute intervals for 120 minutes. RESULTS: The primary outcome was incremental area under the curve (iAUC₀-₁₂₀). Secondary outcomes included time-point glucose, subjective satiety (100-mm Visual Analog Scale (VAS)), and palatability (5-point Likert scale). Compared with the rice-only meal, the MCT meal significantly reduced interstitial glucose concentrations at 45, 60, and 75 minutes and lowered iAUC₀-₆₀, iAUC₀-₉₀, and iAUC₀-₁₂₀. Palatability ratings were lower for the MCT meal, whereas satiety did not differ between conditions. CONCLUSIONS: Adding 12 g of MCT oil to 150 g of cooked rice attenuated postprandial glycemia without diminishing satiety. This simple, low-burden strategy may have practical utility for dietary glycemic management in everyday settings.

CLINICAL CHARACTERISTICS: Carnitine palmitoyltransferase (CPT) II deficiency is a disorder of long-chain fatty-acid oxidation. Three clinical phenotypes are typically described: lethal neonatal, severe infantile hepatocardiomuscular, and myopathic. However, a spectrum exists across these phenotypes, leading to a continuum of disease. Lethal neonatal and severe infantile hepatocardiomuscular phenotypes are severe multisystemic diseases characterized by liver failure with hypoketotic hypoglycemia, cardiomyopathy, seizures, and early death. The myopathic phenotype is usually mild and can manifest from infancy to adulthood with exercise-induced muscle pain and weakness, often progressing to episodic rhabdomyolysis and myoglobinuria. The CPT2-related myopathic phenotype is the most common disorder of lipid metabolism affecting skeletal muscle and the most frequent cause of hereditary myoglobinuria. Males are more likely to be symptomatic than females. DIAGNOSIS/TESTING: The diagnosis of CPT II deficiency is established in a proband with biallelic pathogenic variants in CPT2 identified by molecular genetic testing or reduced CPT enzyme activity in muscle or fibroblasts. MANAGEMENT: Targeted therapies: Low-fat/high-carbohydrate diet as prescribed by metabolic dietician; triheptanoin for one third of daily calories. Medium-chain triglyceride (MCT) oil can be substituted in areas where triheptanoin is not available. Supportive care: In addition to dietary management, frequent meals and avoidance of extended fasting, treatment of non-hypoglycemic seizures with anti-seizure medication, ongoing care coordination in planning for surgeries or procedures, education of caregivers and educators, and ensure a plan for transition to adult care. Emergency outpatient treatment includes oral feeds if not vomiting, carbohydrate and triheptanoin supplementation, antiemetics for occasional vomiting, antipyretics for fever, and treatment of underlying infections. Acute inpatient treatment includes D10-containing intravenous fluids with electrolytes, laboratory assessment for liver, kidney, and muscle disease, dietary management as tolerated, management of liver disease per hepatologist,

OBJECTIVE: Dietary medium-chain fatty acids (MCFAs) are absorbed in the intestine and transported to the liver via the portal vein. The rate-limiting enzyme for ketogenesis, 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), is expressed in both the liver and intestine. While the liver is well established as the primary site of ketogenesis during fasting, the intestine's role in nutritional hyperketonemia from dietary MCFAs is unclear. METHODS: To achieve nutritional hyperketonemia, we orally administered medium-chain (C8:0) triacylglycerol (MCT) oil to control and liver- and intestine-specific Hmgcs2 knockout mice and measured β-hydroxybutyrate (β-OHB) levels in the portal vein and systemic circulation. MCFA-driven β-OHB production was also assessed in primary murine hepatocytes and human and murine intestinal cell lines. Expression of enzymes involved in MCFA oxidation and ketogenesis was analyzed using publicly available bulk and single-cell RNA sequencing data from human and mouse tissues. RESULTS: In MCT-treated mice, β-OHB levels increased four-fold in systemic circulation and statistically more (six-fold) in the portal vein, the latter suggesting intestinal contribution to systemic hyperketonemia. However, circulating β-OHB increased similarly in control mice and those lacking intestinal Hmgcs2 . RNA sequencing data of human and mouse tissues showed that medium-chain acyl-CoA synthetases, enzymes required for MCFA activation, are scarcely expressed in intestinal cells. Consistently, cultured intestinal cells failed to produce β-OHB from MCFA (octanoic acid, C8:0), unlike hepatocytes, which produced substantial levels of β-OHB when treated with MCFA. Finally, MCT-induced nutritional hyperketonemia was completely abolished in mice lacking hepatic Hmgcs2 . CONCLUSION: Nutritional hyperketonemia from dietar

INTRODUCTION: Refractory and super-refractory status epilepticus (RSE and SRSE) are life-threatening neurological emergencies with significant morbidity and mortality. When conventional treatment strategies, including antiseizure medications (ASM) and anesthetic agents, fail, alternative metabolic approaches, such as the ketogenic diet (KD), have been considered. KD is a high-fat, low-carbohydrate, and adequate-protein diet that induces ketosis, exerting anticonvulsant effects. Different types of KD are available, including the classical KD and the modified Atkins diet (MAD). Most published evidence in RSE and SRSE stems from classical KD protocols with high fat-to-carbohydrate/protein ratios (e.g., 4:1), whereas evidence for MAD in this setting is limited, and outcome equivalence across KD types remains unclear. While emerging evidence suggests efficacy in RSE and SRSE, clinical application in adult intensive care unit (ICU) settings remains inconsistent. This standard operating procedure (SOP), developed collaboratively by neurologists, intensivists, anesthesiologists, and clinical nutrition experts, provides a structured framework for classical KD implementation in adult ICU patients with RSE and SRSE, covering indications, contraindications, initiation, monitoring, and safety considerations. DEFINITION: KD is a metabolic therapy that induces ketosis, providing an alternative energy source for the brain while modulating neurotransmitter activity and neuronal excitability. FIRST STEPS: KD should be considered in RSE persisting for > 72 h despite adequate antiseizure treatment or in SRSE early after ICU admission, preferably within 24 h. Before initiation, metabolic screening is required, including tests on liver and renal function, lipid profile, electrolyte balance, and glucose metabolism. Absolute contraindications, such as severe hepatic dysfunction, ileus, or severe hypertriglyceridemia, must be ruled out. Continuous EEG monitoring should be considered. The diet is typically initiated using a classical KD protocol with a 4:1 lipid-to-non-lipid ratio formula and stepwise fat increase, supplemented with medium-chain triglyceride (MCT) oil to enhance ketosis.

Chanarin-Dorfman syndrome (CDS) is an ultra-rare autosomal recessive subtype of neutral lipid storage disorder (NLSD); it is characterised by ichthyosis and intracytoplasmic accumulation of lipid droplets containing triglycerides, most commonly in granulocytes, muscle fibres, skin and liver. Several pathogenic variants in the ABHD5/CGI-58 gene have been described. Clinical manifestations include steatohepatitis, myopathy, ophthalmic disease, developmental delay. Liver involvement is an important cause of morbidity and mortality. We present a case of a 26-year-old male diagnosed with ichthyotic NLSD in childhood, who developed progressive myopathy and cardiac fibrosis in adulthood. He was treated with a combination of low-fat diet, MCT oil and co-enzyme Q10 which resulted in an initial improvement in muscle strength and stabilisation of muscle symptoms and well-being. Synopsis: Medical and dietetic management of liver and muscle complications in Chanarin-Dorfman syndrome. © 2025 The Authors.

Oral cannabidiol (CBD) product use is increasing despite suboptimal pharmacokinetics (PK) of currently available formulations. This study aimed to investigate the PK of CBD formulated using the drug delivery technology DehydraTECH™, which is hypothesized to increase absorption by bypassing first-pass liver metabolism due to enhanced lipophilic composition. Anticonvulsant activity of the leading formulation was investigated in the maximal electroshock seizure (MES) model. For the PK studies, Sprague Dawley rats were orally administered 25 mg/kg CBD in MCT oil or test formulations incorporating DehydraTECH™ (n = 10 per group). Plasma, brain tissue and urine and feces samples were collected to determine comparative absorption, distribution, and excretion by liquid chromatography with tandem mass spectrometry (LC-MS/MS). For the efficacy studies, a series of experiments was conducted using the lead formulation (CBDtech) from the PK trial. Effective dose (ED) of CBDtech in comparison to Epidiolex® (50-100 mg/kg), time of peak efficacy (TPE), and median ED (ED50) were assessed in the acute MES model. Clinical observations, presence/absence of hind limb extension (HLE), and maximum seizure severity (MSS) were recorded. No abnormal clinical signs were observed following dosing in any study. Area under the curve from dosing to the last measurable concentration (AUClast) was 391 to 2708% improved following treatment with DehydraTECH™ formulations as compared with the MCT control (all p < 0.01). CBD was detected in brain, urine, and feces samples following all DehydraTECH™ treatments. Treatment with the ED of CBDtech (75 mg/kg) resulted in full protection (absence of HLE) in 66.6% of test subjects following MES test compared to 50% in the Epidiolex® group. The one-hour timepoint was determined to be the TPE for CBDtech; HLE was absent in 75% of animals and partial in 12.5% of animals. In comparison, in the Epidiolex® group HLE was absent in 50% of animals and partial in 12.5% of animals. The calculated ED50 was 75 mg/kg. Formulation of CBD with DehydraTECH™ resulted in improved bioavailability and efficacy in an acute seizure model. These findings contribute to a deeper un

BACKGROUND: For parenteral nutrition (PN)-dependent neonates, soybean oil intravenous lipid emulsions (SO-ILEs) and mixed emulsions (SO, medium-chain triglyceride [MCT], olive oil [OO], and fish oil [FO] ILEs) are likely not providing adequate amounts of key fatty acids (FAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) and are devoid of choline. Current FO-containing ILEs provide excessive amounts of eicosapentaenoic acid (EPA). In neonatal piglets, we compared a novel lipid (NOV-C) with the addition of AA, DHA, and choline while sparing EPA with SO-ILE and SO,MCT,OO,FO-ILE. METHODS: We compared FA deposition in serum and tissues among groups of neonatal piglets fed exclusive PN based on SO-ILE (n = 7), SO,MCT,OO,FO-ILE (n = 7), or NOV-C (n = 8). On day 14, serum, liver, lung, brain, retina, and jejunum were collected and FAs in total phospholipid (PL) measured using gas liquid chromatography. RESULTS: In total PL, AA was higher for NOV-C compared with SO,MCT,OO,FO-ILE in serum (P = 0.003) and all tissues except brain (P = 0.08). DHA was higher for NOV-C and SO,MCT,OO,FO-ILE compared with SO-ILE in the liver (P = 0.001), jejunum (P < 0.001), and lung (P < 0.001). In the retina, DHA was higher for NOV-C compared with SO,MCT,OO,FO-ILE and SO-ILE (P = 0.004). EPA was higher for SO,MCT,OO,FO-ILE compared with SO-ILE and NOV-C in serum (P = 0.002) and all tissues except brain (P = 0.48). CONCLUSION: Compared with SO-ILE and SO,MCT,OO,FO-ILE, a novel lipid designed to deliver optimal AA, DHA, EPA, and choline for neonates resulted in higher AA and DHA in blood and tissues. The impact on neonatal immune development and key organ functions needs further exploration. © 2025 The Author(s). Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.

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.

BACKGROUND: Citrin deficiency (CD) is a pan-ethnic autosomal recessive inborn error of metabolism due to-pathogenic variants in the SLC25A13 gene which results in disruptions of multiple metabolic pathways including glycolysis, gluconeogenesis, lipogenesis, the urea cycle, and tricarboxylic cycle. METHODS: A retrospective observational study of CD patients managed according to standard clinical practice at a single centre in Singapore (KK Women's and Children's Hospital, KKH) was undertaken from August 2016-August 2024. We present the largest cohort of patients reported in Southeast Asia focusing on clinical, biochemical and imaging findings at diagnosis, and long-term outcomes/management (including drug therapy, food preferences/adherence, hospital admissions, growth, neurodevelopmental, biochemical, and imaging outcomes). We also explore the utility of newborn screening (NBS) as a means for early detection of CD. RESULTS: Eighteen CD patients (9 males; 2 sibling pairs) majority of Chinese ethnicity (n = 16) with a median duration of follow up 5 years 5 months, participated in this study. Median age at first presentation and at diagnosis was 50 days and 82 days, respectively. Fourteen patients presented with neonatal intrahepatic cholestasis caused by CD (NICCD), 2 asymptomatic from sibling screens, and two from abnormalities on NBS (one presenting with unconjugated hyperbilirubinaemia and the other with cholestasis and liver failure). Two patients had liver failure (one from NICCD group and another from NBS group). None required liver transplantation. All symptomatic patients had raised citrulline and threonine-serine ratios at presentation. None of the patients was prescribed any regular concomitant medications except for MCT oil. No genotype phenotype correlation was observed. At final assessment, all patients showed normalisation of liver parameter, galactose and plasma amino acids. Abnormalities in lipid profile in 9 patients (age 5-16 years) showed borderline high total cholesterol (median 5.4 mmol/L) and LDL (median 3.0 mmol/L) which was on the higher end of the normal range. Sixty-six percent of patients liver imaging findings were normal or showed stab

Biliary atresia, a rare pediatric liver condition, results in blocked bile ducts, impeding bile secretion and causing significant nutritional challenges. This perspective emphasizes the critical role of nutrition in supporting children with biliary atresia awaiting liver transplantation. The liver's multifaceted functions in energy metabolism, vitamin storage, and waste excretion emphasize the importance of tailored dietary interventions. Medium-chain triglyceride (MCT) oil serves as a crucial energy source, addressing fat malabsorption, while specialized water-soluble formulations deliver essential fat-soluble vitamins. Additionally, weaning strategies and developmental food practices are discussed to ensure optimal growth and development despite dietary restrictions. Feeding assistance through nasogastric or gastrostomy tubes is explored as a means to combat malnutrition and support liver function. The collective efforts of caregivers and healthcare providers are pivotal in preparing these children for successful liver transplantation, aiming to secure their future health and quality of life.

CLINICAL CHARACTERISTICS: Citrin deficiency can manifest in newborns or infants as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), in older children as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and in adults as recurrent hyperammonemia with neuropsychiatric symptoms in citrullinemia type II (CTLN2). Often citrin deficiency is characterized by strong preference for protein-rich and/or lipid-rich foods and aversion to carbohydrate-rich foods. NICCD: Children younger than age one year have a history of low birth weight with growth restriction and transient intrahepatic cholestasis, hepatomegaly, diffuse fatty liver, and parenchymal cellular infiltration associated with hepatic fibrosis, variable liver dysfunction, hypoproteinemia, decreased coagulation factors, anemia, and/or hypoglycemia. NICCD is generally not severe, and clinical manifestations are often resolved by age one year with appropriate treatment, although liver failure may still occur; liver transplantation has been required in rare instances. FTTDCD: Beyond age one year, many children with citrin deficiency develop a protein-rich and/or lipid-rich food preference and aversion to carbohydrate-rich foods. Clinical abnormalities may include poor weight gain, growth deficiency, severe fatigue, anorexia, and impaired quality of life. Laboratory changes are dyslipidemia, recurrent hypoglycemia, increased lactate-to-pyruvate ratio, higher levels of urinary oxidative stress markers, and considerable deviation in tricarboxylic acid cycle metabolites. One or more decades later, some adults with NICCD or FTTDCD may progress and develop features of CTLN2. CTLN2: Presentation is sudden and usually between ages 20 and 50 years. Clinical manifestations include recurrent hyperammonemia with neuropsychiatric (aggression, irritability, restlessness, hyperactivity, delusions, nocturnal delirium) and neurologic manifestations (flapping tremors, memory loss, disorientation, drowsiness, convulsive seizures, coma). Clinical manifestations are often caused by alcohol and sugar intake, medication, and/or surgery. Complications include severe liver steatosis and pancreatiti

CLINICAL CHARACTERISTICS: Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a disorder of long-chain fatty acid oxidation. Clinical manifestations usually occur in an individual with a concurrent febrile or gastrointestinal illness when energy demands are increased; onset of manifestations are usually rapid. The recognized presentations are: (1) out-of-range newborn screen (individual may be without features or with hepatic encephalopathy, hypoketotic hypoglycemia, and sudden onset of liver failure) and (2) later-onset manifestations (in the absence of newborn screening), including hepatic encephalopathy, hypoglycemia, absent or low levels of ketones, and elevated serum concentrations of liver transaminases, ammonia, and creatine kinase. Between episodes of hepatic encephalopathy, individuals appear developmentally and cognitively normal unless previous metabolic decompensation has resulted in neurologic damage. Acute fatty liver of pregnancy, in which the fetus has biallelic pathogenic variants in CPT1A, has been rarely associated with CPT1A deficiency. DIAGNOSIS/TESTING: The diagnosis of CPT1A deficiency is established in a proband with biallelic pathogenic variants in CPT1A identified by molecular genetic testing. Diminished carnitine palmitoyltransferase 1 (CPT1) enzyme activity on cultured skin fibroblasts when molecular genetic testing is not definitive may be an available option in some countries. Residual enzyme activity is 1%-5% in most individuals with CPT1A deficiency. MANAGEMENT: Prevention of primary manifestations: To prevent hypoglycemia, infants should eat frequently during the day, and cornstarch feedings may be considered continuously at night (typically after age one year); in older individuals fasting should not last more than 12 hours during illness, surgery, or medical procedures; adults need a high-carbohydrate, low-fat diet to provide a constant supply of carbohydrate energy and medium-chain triglycerides (MCT) to provide approximately one third of total calories. Prevention of hypoglycemia reduces the risk for related neurologic damage. Targeted therapies: Triheptanoin (an odd-carbon triglyceride) or MCT oil. Supportive care: Acute

Cardiovascular diseases (CVDs) persist as the primary cause of death worldwide, accounting for roughly 17.9 million fatalities each year. The prevalence of obesity, metabolic syndrome, and type 2 diabetes (key risk factors for CVD) continues to escalate at an alarming rate, necessitating novel therapeutic strategies to address this global health crisis. Nutritional ketosis, induced through ketogenic diets, modified fasting, intermittent fasting, and medium-chain triglyceride (MCT) oil consumption, has garnered attention for its potential cardioprotective effects. Ketosis is a metabolic state in which the body, due to a significantly reduced intake of carbohydrates, shifts its primary energy source from glucose to ketone bodies, i.e., beta-hydroxybutyrate (BHB), acetoacetate, and acetone, which are produced in the liver from fatty acids. This review examines the mechanisms by which ketone bodies, particularly BHB, mitigate cardiovascular risk. We focus mainly on the anti-inflammatory and antioxidative properties of BHB and summarize recent evidence to highlight the clinical relevance of ketosis in cardiometabolic health.

With the global epidemic trend of obesity, non-alcoholic fatty liver disease (NAFLD) has become a significant cause of chronic liver disease, seriously affecting human health. Medium-chain triglycerides (MCT) with a fatty acid chain length varying between 6 and 10 carbon atoms (most sources from coconut and palm kernel oils), which exhibited activities to improve lipid metabolism, prevent cardiovascular diseases, and enhance immunity. However, the efficacy differences and potential mechanisms between MCT and traditional long-chain vegetable oils (palm oil, PA; high oleic peanut oil, OA) in obesity-induced NAFLD were still unclear. The present study treated obesity-induced NAFLD mice with different dietary lipids for 16 weeks. The results showed that MCT supplements significantly improved abnormal elevation of weight gain and blood lipids and reduced hepatic lipid accumulation to a greater extent than PA and OA. Furthermore, bile acid profiling results indicated that MCT significantly changed the composition of bile acids in the liver, reduced the concentrations of cholic acid (CA), deoxycholic acid (DCA), β-muricholic acid (β-MCA), and ursodeoxycholic acid (UDCA) and increased the concentrations of chenodeoxycholic Acid (CDCA), taurochenodeoxycholic acid （TCDCA), hyodeoxycholic acid (HDCA), and taurohyodeoxycholic acid (THDCA). Mechanistically, MCT supplement upregulated FXR signal and inhibited the expression of key genes for triglyceride synthesis in the liver, thereby reducing hepatic lipid accumulation. In summary, MCT exerted a superior effect on PA and OA in improving obesity-induced NAFLD. These results provided new evidence for the application of MCT in treating NAFLD. © 2024 Institute of Food Technologists.

BACKGROUND AND AIMS: A limited number of randomized controlled trials (RCTs) have examined the use of lipid emulsions (LEs) of different compositions in home parenteral nutrition (HPN), and there are very few data on the long-term use of omega-3 (n-3) polyunsaturated fatty acids (PUFAs). The study's objective was to assess safety and tolerability of an n-3 PUFA-enriched LE in adult patients suffering from chronic intestinal failure (CIF) requiring long-term HPN. METHODS: In this prospective, randomized, controlled, double-blind, multicentre, international clinical trial, which was conducted at eleven sites, adult patients in need of HPN including lipids received either the investigational product, an n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) LE, or the reference product, a standard MCT/LCT LE, for an average duration of eight weeks. The primary outcome was the sum of changes of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives included fatty acid pattern in plasma and red blood cells (RBCs) and triene:tetraene ratio in plasma. RESULTS: 74 patients were enrolled up to premature study termination. Liver function parameters showed no clinically relevant differences between study groups and remained within normal ranges. The n-3 PUFAs EPA and DHA increased in plasma and RBCs in the Lipidem group and were higher in the Lipidem group than the reference group at the end of the study resulting in an increased n-3-index in RBCs with Lipidem. Average n-3-index was >8. The plasma triene:tetraene ratio decreased in both groups. CONCLUSION: This study is one of the largest comparing two LEs in the complex setting of HPN treatment of adult patients. Although it has been early terminated its results considerably contribute to the evidence on safety and efficacy of longer-term use of LEs in HPN treatment. The n-3 PUFA-enriched LE Lipidem was safe and well-tolerated, particularly in terms of liver function. Lipidem provided an additional supply of n-3 PUFAs and led to positive changes in fatty acid profiles of plasma and RBCs. The n-3-index was in the desirable range at

Glycogen storage diseases (GSDs) are a group of carbohydrate metabolism disorders, most of which are inherited in autosomal recessive patterns. GSDs are of two types: those that have to do with liver and hypoglycaemia (hepatic GSDs) and those that are linked to neuromuscular presentation. This study aims to assess the impact of dietary intervention, including medium-chain triglyceride (MCT) oil, on anthropometric measurements, body composition analysis and metabolic parameters among Jordanian children and is expected to be the first in the country. A sample of 38 children with glycogen storage disease type 1 (GSD-1) (median age = 6.4 years) were on a diet that included uncooked cornstarch therapy and a fructose-, sucrose- and lactose-restricted diet. Patients started to take MCT oil along with the prescribed diet after the first body composition test. Patients' nutritional status was re-evaluated three months later. The study results show that the percentage of patients who suffered from hypoglycaemia at the beginning of the study decreased significantly from 94.7% to 7.9% (p < 0.0001). The serum levels of triglycerides, cholesterol, uric acid and lactate decreased significantly after three months of intervention (100-71.1%, 73.7-21.1%, 97.4-52.6% and 94.7-18.4%, respectively). In contrast, there was no statistical difference in neutrophil count. Regarding clinical parameters, liver span was significantly reduced from (16.01 ± 2.65 cm) to (14.85 ± 2.26 cm) (p < 0.0001). There were significant improvements in growth parameters, including height-for-age and BMI-for-age for children aged ≥2 years (p = 0.034 and p = 0.074, respectively). Significant improvements in skeletal muscle mass and bone mineral content were also noticed at the end of the trial (p ≤ 0.05). In conclusion, medium-chain triglyceride therapy is found to improve biochemical and growth parameters in children with GSD-1 in Jordan.

Most studies on fat appetite have focused on long-chain triglycerides (LCTs) due to their obesogenic properties. Medium-chain triglycerides (MCTs), conversely, exhibit antiobesogenic effects; however, the regulation of MCT intake remains elusive. Here, we demonstrate that mice can distinguish between MCTs and LCTs, and the specific appetite for MCTs is governed by hepatic β-oxidation. We generated liver-specific medium-chain acyl-CoA dehydrogenase (MCAD)-deficient (MCADL-/-) mice and analyzed their preference for MCT and LCT solutions using glyceryl trioctanoate (C8-TG), glyceryl tridecanoate (C10-TG), corn oil, and lard oil in two-bottle choice tests conducted over 8 days. In addition, we used lick microstructure analyses to evaluate the palatability and appetite for MCT and LCT solutions. Finally, we measured the expression levels of genes associated with fat ingestion (Galanin, Qrfp, and Nmu) in the hypothalamus 2 h after oral gavage of fat. Compared with control mice, MCADL-/- mice exhibited a significantly reduced preference for MCT solutions, with no alteration in the preference for LCTs. Lick analysis revealed that MCADL-/- mice displayed a significantly decreased appetite for MCT solutions only while the palatability of both MCT and LCT solutions remained unaffected. Hypothalamic Galanin expression in control mice was elevated by oral gavage of C8-TG but not by LCTs, and this response was abrogated in MCADL-/- mice. In summary, our data suggest that hepatic β-oxidation is required for MCT-specific appetite but not for LCT-specific appetite. The induction of hypothalamic galanin upon MCT ingestion, dependent on hepatic β-oxidation, could be involved in the regulation of MCT-specific appetite.NEW & NOTEWORTHY Whether and how medium-chain triglyceride (MCT) intake is regulated remains unknown. Here, we showed that mice can discriminate between MCTs and LCTs. Hepatic β-oxidation participates in MCT-specific appetite, and hypothalamic galanin may be one of the factors that regulate MCT intake. Because of the antiobesity effects of MCTs, studying MCT-specific appetite may help combat obesity by promoting the intake of MCTs instead of LCTs.

Fat loss predicts adverse outcomes in advanced heart failure (HF). Disrupted circadian clocks are a primary cause of lipid metabolic issues, but it's unclear if this disruption affects fat expenditure in HF. To address this issue, we investigated the effects of disruption of the BMAL1/REV-ERBα circadian rhythmic loop on adipose tissue metabolism in HF.50 Wistar rats were initially divided into control (n = 10) and model (n = 40) groups. The model rats were induced with HF via monocrotaline (MCT) injections, while the control group received equivalent solvent injections. After establishing the HF model, the model group was further subdivided into four groups: normal rhythm (LD), inverted rhythm (DL), lentivirus vector carrying Bmal1 short hairpin RNA (LV-Bmal1 shRNA), and empty lentivirus vector control (LV-Control shRNA) groups, each with 10 rats. The DL subgroup was exposed to a reversed light-dark cycle of 8 h: 16 h (dark: light), while the rest adhered to normal light-dark conditions (light: dark 12 h: 12 h). Histological analyses were conducted using H&E, Oil Red O, and Picrosirius red stains to examine adipose and liver tissues. Immunohistochemical staining, RT-qPCR, and Western blotting were performed to detect markers of lipolysis, lipogenesis, and beiging of white adipose tissue (WAT), while thermogenesis indicators were detected in brown adipose tissue (BAT). The LD group rats exhibited decreased levels of BMAL1 protein, increased levels of REV-ERBα protein, and disrupted circadian circuits in adipose tissue compared to controls. Additionally, HF rats showed reduced adipose mass and increased ectopic lipid deposition, along with smaller adipocytes containing lower lipid content and fibrotic adipose tissue. In the LD group WAT, expression of ATGL, HSL, PKA, and p-PKA proteins increased, alongside elevated mRNA levels of lipase genes (Hsl, Atgl, Peripilin) and FFA β-oxidation genes (Cpt1, acyl-CoA). Conversely, lipogenic gene expression (Scd1, Fas, Mgat, Dgat2) decreased, while beige adipocyte markers (Cd137, Tbx-1, Ucp-1, Zic-1) and UCP-1 protein expression increased. In BAT, HF rats exhibited elevated levels of PKA, p-PKA, and UCP-1 proteins, along with

(Background) Esophagectomy (EPG) presents high morbidity and mortality. Omega-3 fatty acids (ω-3FA) are a pharmaconutrient with benefits for postoperative morbidity. Studies of ω-3FA administered parenterally after esophagectomy are scarce. This study proposes to investigate the effect of combining fish oil lipid emulsions (LE) administered parenterally with enteral nutrition support. (Methods) Randomization was 1:1:1 in three groups: Group A received a LE mixture of 0.4 g/kg/day of fish oil and 0.4 g/kg/day of LCT/MCT 50:50, Group B received 0.8 g/kg/day of fish oil LE, and Group C received 0.8 g/kg/day of LCT/MCT 50:50. Variables were measured at recruitment time and day +1, +3, and +5. Inflammatory variables studied were Interlukin-6, C-reactive protein (CRP), tumoral necrosis factor-α (TNF-α), IL-10, IL-8 and CD25s. Safety, nutritional parameters and complications were analyzed. (Results) Administration of ω-3LE in the immediate postoperative period did not modulate the earlier inflammatory response. Statistically significant differences were found in IL-6 and CRP overall temporal evolution but were not found when studying the type of LE administered or in patients needing critical care. Administration of ω-3 resulted in safe and improved hypertriglyceridemia, depending on the dose. (Conclusions) ω-3FA has no impact on the early inflammatory postoperative response assessed for a short period but was safe. More studies for longer periods are needed.

The health benefits of curcumin have been demonstrated by several clinical studies, but its low bioavailability compromises its functionality. In this regard, emulsions have proven to be effective encapsulation systems for curcumin. Nevertheless, emulsions with a high oil content (50%) may offer some advantages due to the large amount of compound they can incorporate. Therefore, the aim of this work was to study the pharmacokinetics and biodistribution of curcumin when carried in optimized emulsions containing 50% MCT oil and a plant-based emulsifier (soybean lecithin) at 2 h or 4 h post-oral administration to rats. The most stable emulsion was obtained using 50% of oil and a surfactant-oil-ratio 0.1, through a microfluidization process. After the oral administration of the systems (150 mg curcumin/kg body weight), curcumin glucuronide was the main compound present in plasma (AUC0-t = 1556.3 ng·h·ml-1), especially at 2-4 h post-administration. The total curcuminoid bioavailability was increased by 10.6-fold when rats were fed with the curcumin emulsion rather than with a control suspension. Moreover, rats fed with the emulsion showed the highest accumulation of free curcuminoids, which present the highest biological activity, in the liver (129 ng curcumin/g tissue) and brown adipose tissue (193 ng curcumin/g tissue). The obtained results are of great interest since the presence of curcumin in the brown adipose tissue has been shown to play a relevant role in the prevention of obesity and its related metabolic disorders.