Effects Of Medium-chain Triglycerides Research Articles

Effect of medium-chain triglycerides and whey protein isolate preloads on glycaemia in type 2 diabetes: a randomized crossover study.

Small nutritional preloads can reduce postprandial glucose excursions in individuals with and without metabolic syndrome or type 2 diabetes (T2D). However, most studies have focused on preloads administered before single meals and have predominantly used protein-based preloads. To investigate the effects of sequential consumption of medium-chain triglycerides (MCT) and whey protein isolate (WPI) preloads before breakfast, lunch, and dinner on postprandial, diurnal, and 24-h glycaemia in individuals with T2D. Participants with T2D were studied over 3 randomized 24-h periods. They consumed either water before standardized breakfast, lunch, and dinner (CONTROL), 15 g MCT before breakfast and water before lunch and dinner (MCT), or 15 g MCT before breakfast and 10 g WPI before lunch and dinner (MCT + WPI). Diurnal (08:00-23:00 h) and 24 h (08:00-08:00 h) glycaemia (incremental AUC [Iauc]) and glycemic variability (%coefficient of variation [%CV]) were evaluated by continuous glucose monitoring. Postprandial glycaemia (PPG) after breakfast and lunch was assessed by arterialized blood glucose iAUC. In 21 enrolled patients (8 males/13 females, mean ± standard deviation age 55.1 ± 8.5 y, body mass index 31.7 ± 4.3 kg·m-2, glycated hemoglobin 59 ± 12 mmol·mol-1) diurnal and 24-h iAUC were similar across interventions, whereas 24-h %CV was lower in MCT (16.8 ± 0.8%, P = 0.033) and MCT + WPI (16.1 ± 0.9%, P = 0.0004) than CONTROL (18.7 ± 0.9%). PPG iAUC was ∼17% lower after breakfast in MCT and MCT + WPI compared with CONTROL, but only the MCT + WPI lowered glucose by 20% (P = 0.002) over the entire day (08:30-17:30 h). Gastric inhibitory polypeptide (GIP) (P = 0.00004), peptide YY (PYY) (P = 0.01), and β-hydroxybutyrate (P = 0.0001) were higher in MCT and MCT + WPI than CONTROL. Subjective appetite ratings were lower after breakfast and lunch in MCT + WPI (P = 0.001). Sequential consumption of MCT and WPI preloads did not affect diurnal or 24-h glycaemia but lowered PPG and 24-h glycemic variability in individuals with T2D. These effects were associated with increased circulating β-hydroxybutyrate, PYY, and GIP, and suppression of appetite. This trial was registered at clinicaltrials.gov as NCT04905589 (https://clinicaltrials.gov/study/NCT04905589).

Effect of Medium Chain Triglycerides on the Digestion and Quality Characteristics of Tea Polyphenols-Fortified Cooked Rice.

Nowadays, medium chain triglycerides (MCT) with special health benefits have been increasingly applied for fortifying food products. Therefore, the present work aimed to investigate the effects of MCT on traditional tea polyphenols-fortified cooked rice (TP-FCR). It was visualized by DSC, CLSM, XRD, FT-IR, and Raman spectroscopy. The higher content of starch-MCT complexes with an increase in the relative crystallinity and the generation of short-range ordered structures contributed to a more ordered and compact molecular arrangement, which can hinder the action of digestive enzymes on starch. SEM demonstrated that MCT transformed the microstructure of TP-FCR into a denser and firmer character, making it an essential component hindering the accessibility of digestive enzymes to starch granules and slowing the release of tea polyphenols in TP-FCR to attenuate starch digestion. Consequently, the addition of MCT reduced the polyphenol-regulated starch digestibility from 74.28% in cooked white rice to 64.43% in TP-FCR, and further down to 50.82%. Besides, MCT also reduced the adhesiveness and improved the whiteness of TP-FCR. The findings suggested that MCT incorporation could be a potential strategy in cooked rice production to achieve high sensory quality and low glycemic cooked rice.

Ketogenic effects of medium chain triglycerides containing formula and its correlation to breath acetone in healthy volunteers: a randomized, double-blinded, placebo-controlled, single dose-response study.

The efficacy of low-carbohydrate, high-fat diets, such as ketogenic diets, for cancer patients is of research interest. We previously demonstrated the efficacy of the ketogenic diet in a case study in which medium-chain triglycerides (MCTs) or MCT-containing formula (ketogenic formula) was used as a supplement to increase blood ketone bodies. However, little is known about the amounts needed to induce ketogenic effects and about the usefulness of monitoring of breath acetone. To investigate the pharmacokinetics of MCTs and their metabolites, blood ketone bodies and breath acetone, 24 healthy subjects received one of four single oral doses of the ketogenic formula (equivalent to 0, 10, 20, and 30 g of MCTs) under fasting conditions. Total blood ketone bodies, β-hydroxybutyrate, octanoic acid, and decanoic acid were increased in a dose-dependent manner. The ketogenic effect was considered to depend on octanoic and decanoic acids, because a positive correlation was observed between them. A strong positive correlation was also observed between total serum ketone bodies and breath acetone at each time points. Therefore, monitoring breath acetone levels seems a less invasive method to predict blood concentrations of ketone bodies during ketogenic diet therapy. Clinical trial registration:https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000032634, UMIN-CTR UMIN000032634.

Investigating the Effect of Medium Chain Triglycerides on the Elasticity of Pulmonary Surfactant

In recent years, vaping has increased in both popularity and ease of access. This has led to an outbreak of a relatively new condition known as e-cigarette/vaping-associated lung injury (EVALI). This injury can be caused by physical interactions between the pulmonary surfactant (PS) in the lungs and toxins typically found in vaping solutions, such as medium chain triglycerides (MCT). MCT has been largely used as a carrier agent within many cannabis products commercially available on the market. Pulmonary surfactant ensures proper respiration by maintaining low surface tensions and interface stability throughout each respiratory cycle. Therefore, any impediments to this system that negatively affect the efficacy of this function will have a strong hindrance on the individual's quality of life. Herein, neutron spin echo (NSE) and Langmuir trough rheology were used to probe the effects of MCT on the mechanical properties of pulmonary surfactant. Alongside a porcine surfactant extract, two lipid-only mimics of progressing complexity were used to study MCT effects in a range of systems that are representative of endogenous surfactant. MCT was shown to have a greater biophysical effect on bilayer systems compared to monolayers, which may align with biological data to propose a mechanism of surfactant inhibition by MCT oil.

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 5d. 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 (0.265μCi/μmol). Measurements were performed in the absence or presence of L-carnitine (1mM) or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase (L659699, 1.6μM) or acetoacetate-CoA deacylase (iodoacetamide, 50μM). 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). Invitro 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 β-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.

Effects of medium chain triglycerides with organic acids on growth performance, fecal score, blood profiles, intestinal morphology, and nutrient digestibility in weaning pigs.

ObjectiveThis study was conducted to evaluate the effects of medium chain triglycerides (MCT) with organic acids (OA) on growth performance, fecal score, blood profiles, intestinal morphology, and nutrient digestibility in weaning pigs.MethodsA total of 120 weaning pigs ([Yorkshire×Landrace]×Duroc) with an average body weight (BW) of 8.00±0.87 kg were assigned in five treatments considering sex and initial BW in 3 replications with 8 pigs per pen in a randomized complete block design. The experimental diets included a corn-soybean meal based basal diet with or without 0.1% or 0.2% MCT and 0.1% OA. The pigs were fed the diets for 5 weeks (phase 1, 0 to 2 weeks; phase 2, 3 to 5 weeks). A total of 15 barrows with an average BW of 12.48±0.37 kg were used to evaluate the nutrient digestibility by total collection method. The BW and feed intake were measured at the end of each phase. Blood samples and small intestine samples were collected at the end of each phase, too.ResultsSupplementing 0.1% MCT with 0.1% OA showed greater BW for week 5 and average daily gain (ADG) for overall period than control diet. Supplementing 0.1% MCT increased (p<0.05) ADG and improved (p<0.05) gain:feed ratio for phase 1. Dietary MCT and OA did not affect the fecal score and blood concentration of cortisol, immunoglobulin G, tumor necrosis factor-α, interleukin-1β (IL-1β), IL-6, and IL-10 in weaning pigs. Pigs fed the diets with 0.1% MCT had greater (p<0.05) villus height of duodenum and ileum for phase 1. Also, pigs fed the diet with 0.1% OA showed greater (p<0.05) villus height and villus height to crypt depth ratio of duodenum for phase 2. There was no significant difference in nutrient digestibility and nitrogen retention of pigs.ConclusionAddition of 0.1% MCT with 0.1% OA in weaning pig’s diet improved growth performance partly by enhancing intestinal morphology in weaning pigs.

Effects of medium chain triglycerides on lipid metabolism in high-fat diet induced obese rats.

This study aimed to compare the effects of three different medium chain triglycerides (MCTs) on lipid metabolism in obese rats. A high fat diet was fed to Sprague-Dawley rats to induce obesity, and then caprylic triglyceride (CYT), capric triglyceride (CT) and lauric triglyceride (LT) were synthesized and used to treat the obese rats for 12 weeks. The obesity phenotype and molecular changes related to lipid metabolism were determined. The results showed that all the three MCTs reduced the body weight (BW) and fat coefficient in obese rats, and the levels of plasma and liver lipids were also improved. Among the MCT groups, the LT group showed the lowest BW with the lowest food intake. Furthermore, three MCTs had different effects on the expression levels of lipid metabolism-related proteins (PPARs and SREBPs). The LT group performed the best among the three MCT groups in the protein expression levels. Interestingly, high-dose LT decreased the expression of the low density lipoprotein receptor (LDLR) in the liver, which impaired the transport of the very low density lipoprotein (VLDL)/low density lipoprotein (LDL) to the liver, resulting in high levels of total plasma cholesterol (TC) and LDL-c in the rats. We have for the first time found that different MCTs had different effects on the expression levels of triacylglycerol and cholesterol metabolism-related proteins in obese rats. These findings would help better understand the relationship between the health benefit and the type of MCT.

Protective effects of medium chain triglyceride diet in a mouse model of Dravet syndrome.

Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy with early childhood onset. Patients with DS do not respond well to antiepileptic drugs and have only a few treatment options available. Here, we evaluated the effect of medium chain triglyceride (MCT) diet therapy in a mouse model of DS. Scn1aR1407X/+ DS mice were given diets supplemented with MCTs with varying ratios of decanoic (C10) and octanoic (C8) acid or a control diet for 4weeks. Video monitoring was performed to evaluate spontaneous convulsive seizure frequency. Susceptibility to hyperthermia-induced seizures was also examined. Medium chain fatty acids, and mitochondrial and antioxidant markers were assessed in brain homogenate. Dietary intervention with MCTs significantly prolonged survival and reduced convulsive seizure frequency during the critical period of highest seizure occurrence in the Scn1aR1407X/+ DS mice. Moreover, MCT diet therapy showed protective effects against hyperthermia-induced seizures. We demonstrated that coadministration of C10/C8 was effective at reducing both seizures and mortality, whereas C10 alone only reduced mortality, suggesting that the ratio of C10 to C8 in the MCT is an important factor for efficacy. When C10 and C8 are supplemented at an 80:20 ratio in the diet, C10 accumulates in the brain in high enough concentrations to enhance brain energy metabolism by both stimulating mitochondrial enrichment and increasing its antioxidant status. The results from this study indicate that MCT diet therapy may provide therapeutic benefits in DS. Future clinical studies would elucidate whether these positive effects are mirrored in human patients.

The effects of medium chain triglyceride (MCT) supplementation using a C8:C10 ratio of 30:70 on cognitive performance in healthy young adults

PurposeThe brain can utilise medium chain triglycerides (MCTs) as an alternative fuel to glucose, and research has shown that MCT ingestion improves cognitive function in diseased and/or elderly individuals. The aim of this study is to determine if these improvements can also be observed in young, healthy adults. Furthermore, we aim to establish the ideal dosage and timeframe necessary for an effect. MethodsParticipants were divided equally into three groups of 10 (Placebo (0 g), 12 g and 18 g MCT/day) and were supplemented for 4 weeks. The supplement had a C8:C10 ratio of 30:70. Participants visited the laboratory once a week for 5 weeks (baseline, test weeks 1–4) to undergo a battery of cognitive tests; Trail Making, Digit Span, Spatial Span, Covert Shift of Attention, and Rapid Visual Information Processing. ResultsAfter 2–3 weeks of supplementation, MCT ingestion enhanced performance in cognitive tasks, including: Trail Making A/B and Digit Span Forwards/Backwards (ps<0.001) when compared to a placebo group taking a carbohydrate gel. In Spatial Span Backwards, there was a significant main effect of group (p = 0.002). Where significance was seen, there were main effects of time after 2–3 weeks (ps<0.05). There was minimal difference between the two MCT intervention groups in most measures (ps>0.05). There were also null results in tasks measuring attention and reaction time (ps>0.05). ConclusionsMCT ingestion improved cognitive performance after 2–3 weeks, with minimal difference between taking 12 g and 18 g MCT/day groups, suggesting a possible dose-response threshold at 12 g MCT/day when supplementing over a short period.

Reactivation of fatty acid oxidation by medium chain fatty acid prevents myocyte hypertrophy in H9c2 cell line.

Metabolic shift is an important contributory factor for progression of hypertension-induced left ventricular hypertrophy into cardiac failure. Under hypertrophic conditions, heart switches its substrate preference from fatty acid to glucose. Prolonged dependence on glucose for energy production has adverse cardiovascular consequences. It was reported earlier that reactivation of fatty acid metabolism with medium chain triglycerides ameliorated cardiac hypertrophy, oxidative stress and energy level in spontaneously hypertensive rat. However, the molecular mechanism mediating the beneficial effect of medium chain triglycerides remained elusive. It was hypothesized that reduction of cardiomyocyte hypertrophy by medium chain fatty acid (MCFA) is mediated by modulation of signaling pathways over expressed in cardiac hypertrophy. The protective effect of medium chain fatty acid (MCFA) was evaluated in cellular model of myocyte hypertrophy. H9c2 cells were stimulated with Arginine vasopressin (AVP) for the induction of hypertrophy. Cell volume and secretion of brain natriuretic peptide (BNP) were used for assessment of cardiomyocyte hypertrophy. Cells were pretreated with MCFA (Caprylic acid) and metabolic modulation was assessed from the expression of medium-chain acyl-CoA dehydrogenase (MCAD), cluster of differentiation-36 (CD36) and peroxisome proliferator-activated receptor (PPAR)-α mRNA. The signaling molecules modified by MCFA was evaluated from protein expression of mitogen activated protein kinases (MAPK: ERK1/2, p38 and JNK) and Calcineurin A. Pretreatment with MCFA stimulated fatty acid metabolism in hypertrophic H9c2, with concomitant reduction of cell volume and BNP secretion. MCFA reduced activated ERK1/2, JNK and calicineurin A expression mediated by AVP. In conclusion, the beneficial effect of MCFA is possibly mediated by stimulation of fatty acid metabolism and modulation of MAPK and Calcineurin A.

Effects of Medium Chain Triglycerides Intake on Lipid Metabolism and Intestinal Disaccharidase Activities in Rats

It has been reported that medium-chain triglyceride (MCT) have various physiological functions, such as anti-obesity and hypolipidemic effects. They can also elicit increased disaccharidase activity and intestinal cell proliferation. However, a meta-analysis of randomized controlled trials, comparing the effects of MCT on weight loss and body composition, detected commercial bias. Additional research on the physiological functions is needed in order to have conclusive evidence. Thus, we sought to evaluate the various functions of MCT by conducting a feeding study in rats. Rats fed a diet containing 15% (w/w) MCT, had significantly lower visceral fat weight, plasma and liver lipid concentrations; they had significantly higher intestinal maltase and glucoamylase activities; and they had a greater number of Ki-67 positive cells/crypt, compared to the rats fed a diet containing 15% (w/w) lard. The effects of a diet containing 5% (w/w) MCT was observed only for plasma cholesterol levels and the number of Ki-67 positive cells/crypt; in which some results were found to be inconsistent with previous reports. These results indicate that physiological functions of MCT are numerous and need to be confirmed by additional research.

Effect of Medium Chain Triglycerides Consumption on Running Performance in Long‐Distance Careers Recreational Runners

ObjectiveThe purpose of the study was to determine the effect of medium chain triglycerides (MCT) consumption on running performance in long‐distance careers recreational runners.MethodologyA double‐blind placebo controlled crossover study was conducted with 10 recreationally runners. Participants underwent two 21‐kilometers training sessions in random sequence, once with a commercial hydrating sport drink consumption as placebo and once with the same sport drink plus 30g of MCT that were divided and given in four doses of the same amount once before start and the rest at kilometers number 5, 10 and 15. Due to the physical requirements of the tests, a rest period of 45 days was indicated between both evaluations. Anthropometric measurements through ISAK methodology and dietary assessment by 24 hours dietary recalls and food frequency questionnaires were evaluated before both training sessions to analyze that there were no changes in these variables. Participants were encouraged to not change their training sessions or modify their diets.Results50% of participants finished both training sessions. No differences in weight and body composition or dietary intake were observed during the rest period. Gastrointestinal upsets were reported by 66.6% of runners with MCT consumption and there no reports when they consumed placebo. There were no differences in running time when participants consumed MCT, in fact time was a bit higher when compared to placebo (132.6±22.1 vs 128.4±28.1 minutes; P=0.8). No difference were observed when partial times were compared.Conclusion30 g of MCT consumption divided in 4 doses does not improve velocity or running performance during 21‐kilometers training sessions in recreationally runners. MCT consumption was associated with gastrointestinal discomfort, thus possible could affect sport performance.

Assessing the Impact of Factors that Influence the Ketogenic Response to Varying Doses of Medium Chain Triglyceride (MCT) Oil.

Healthy subjects without cognitive deficits <65years, similarly healthy subjects >=65years, and those with Alzheimer's Disease were assessed. Different doses (0g,14g, 28g, 42g) of MCT oil (99.3% C8:0) were administered, followed by fasting during the study period. BHB measured by finger prick sampling hourly for 5 hours after ingestion. Each subject attended four different days for each ascending dose. Data was also collected on body composition, BMI, waist/hip ratio, grip strength, gait speed, nutrient content of pre-study breakfast and side effects. Twenty-five participants: eight healthy; average age of 44yr (25-61), nine healthy; 79yr (65-90) and eight with AD; 78.6yr (57-86) respectively. Compiled data showed the expected linear dose response relationship. No group differences, with baseline corrected area under the blood vs. time curve (r2=0.98) and maximum concentrations (r2=0.97). However, there was notable individual variability in maximum BHB response (42g dose: 0.4 -2.1mM), and time to reach maximum BHB response both, within and between individuals. Variability was unrelated to age, sex, sarcopenic or AD status. Visceral fat, BMI, waist/hip ratio and pretest meal CHO and protein content all affected the BHB response (p<0.001). There was a large inter-individual variability, with phenotype effects identified. This highlights challenges in interpreting clinical responses to MCT intake.

Evaluation of effect of medium chain triglycerides on growth pattern of newborn in a tertiary care hospital

Evaluation of effect of medium chain triglycerides on growth pattern of newborn in a tertiary care hospital - IJMPO- Print ISSN No: - 2581-4699 Online ISSN No:- 2581-4702 Article DOI No:- 10.18231/2581-4702.2018.0034, IP International Journal of Medical Paediatrics and Oncology-IP Int J Med Paediatr Oncol

Medium-chain fatty acids decrease serum cholesterol via reduction of intestinal bile acid reabsorption in C57BL/6J mice

BackgroundBile acids play a pivotal role in cholesterol metabolism via the enterohepatic circulation. This study investigated the effects of medium-chain triglycerides (MCTs)/medium-chain fatty acids (MCFAs) on the reduction of bile acid absorption in the small intestine and the mechanisms of action in vivo and partially verified in vitro.MethodsThirty-six C57BL/6 J mice with hypercholesterolaemia were randomly divided into 3 groups: fed a cholesterol-rich diet (CR group), fed a cholesterol-rich and medium-chain triglyceride diet (CR-MCT group) and fed a cholesterol-rich and long-chain triglyceride diet (CR-LCT group). Body weights and blood lipid profiles were measured in all groups after 16 weeks of treatment. The concentrations of bile acids in bile and faeces were analysed using HPLC-MS (high-performance liquid chromatography-mass spectrometry). Gene transcription and the expression levels associated with bile acid absorption in the small intestines were determined using real-time PCR and Western blot. Ileal bile acid binding protein (I-BABP) was analysed using immunofluorescence. The effects of MCFAs on the permeability of bile acid (cholic acid, CA) in Caco-2 cell monolayers and I-BABP expression levels in Caco-2 cells treated with caprylic acid (C8:0), capric acid (C10:0), stearic acid (C18:0) and oleic acid (C18:1) were determined.ResultsMice in the CR-MCT group exhibited lower body weights and serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a higher HDL-C/LDL-C ratio than the CR-LCT group (P < 0.05). The concentrations of primary bile acids (primarily CA) and secondary bile acids in faeces and secondary bile acids in bile in the CR-MCT group were significantly higher than in the CR-LCT group (P < 0.05). C8:0 and C10:0 decreased the permeability of CA in Caco-2 cell monolayers. MCT/MCFAs (C8:0 and C10:0) inhibited I-BABP gene expression in the small intestines and Caco-2 cells (P < 0.05).ConclusionsMCT slowed the body weight increase and promoted the excretion of bile acids. MCT lowered serum cholesterol levels at least partially via reduction of bile acid absorption in the small intestine by inhibition of I-BABP expression. Our results provide the basis for clinical trials of MCT as a dietary supplement for lowering plasma cholesterol and reducing risk of CHD.

The lived experience of healthy adults following a ketogenic diet: A qualitative study

Background. Very-low-carbohydrate ketogenic diets (VLCKDs) promote benefits for a range of health conditions. However, there is little research elucidating the ‘lived experience’ of individuals undertaking these diets, and the effects of keto-induction, during adaptation to these diets. Objective. This study aimed to evaluate the subjective experiences of people following a very low carbohydrate, ketogenic diet. Design. This paper describes the qualitative experiences of twenty-eight non-obese, non-diabetic participants, (2 males, 26 females: age ± SD: 35 ± 4 y) in a randomised controlled trial to test the effects of medium chain triglyceride (MCT) supplementation in a VLCKD on time to nutritional ketosis (NK), symptoms of keto-induction, and mood. The experience provided by the diet was rated by a free-form daily diary entry and post-study focus group. Diary entries and focus group transcription were coded inductively and grouped into common themes. Results. Twenty-three participants completed the 3-week study. Physical effects accounted for over 28% of references. Other results were categorised as; mood, energy and cognition (23%), satiety and hunger (16%), cravings and temptation (11%), and sleep (8%). Overall, 49% of references were classified as ‘positive’ with 8% neutral, and 43% negative. Positive impressions were higher after participants had achieved nutritional ketosis and negative impressions higher during keto-induction. Negative impressions, both concerning physical symptoms and feelings of mood and well-being, tended towards improvement over the course of the study, and positive impressions improved. However, there was a large variation in responses, and several respondents reported adverse effects throughout the study. Conclusion. Despite challenges, especially gastrointestinal effects, the overall perception of the diet was positive, and it provided benefits for wellbeing, mood, sleep, and sugar cravings which tended towards improvement over the course of the study. Negative experiences decreased as participants adapted to the VLCKD. Most participants continued post-study, using a lower-carbohydrate diet, due to these perceived benefits. Our findings suggest that the experience of a VLCKD is positive but variable. Further research on individual tolerance and response to low carbohydrate diets is warranted.

The Effect of Medium Chain Triglycerides on Time to Nutritional Ketosis and Symptoms of Keto-Induction in Healthy Adults: A Randomised Controlled Clinical Trial.

Medium chain triglycerides (MCTs) are ketogenic and might reduce adverse effects of keto-induction and improve time to ketosis and the tolerability of very low carbohydrate diets. This study investigates whether MCT supplementation improves time to nutritional ketosis (NK), mood, and symptoms of keto-induction. We compared changes in beta-hydroxybutyrate (BOHB), blood glucose, symptoms of keto-induction, and mood disturbance, in 28 healthy adults prescribed a ketogenic diet, randomised to receive either 30 ml of MCT, or sunflower oil as a control, three times per day, for 20 days. The primary outcome measured was the achievement of NK (≥0.5 mmol·L−1 BOHB). Participants also completed a daily Profile of Mood States and keto-induction symptom questionnaire. MCT resulted in higher BOHB at all time points and faster time to NK, a result that failed to reach significance. Symptoms of keto-induction resulted from both diets, with a greater magnitude in the control group, except for abdominal pain, which occurred with greater frequency and severity in the MCT-supplemented diet. There was a possibly beneficial effect on symptoms by MCT, but the effect on mood was unclear. Based on these results, MCTs increase BOHB compared with LCT and reduce symptoms of keto-induction. It is unclear whether MCTs significantly improve mood or time to NK. The trial was registered by the Australia New Zealand Clinical Trial Registry ACTRN12616001099415.

Effect of Medium Chain Triglycerides on TCA and Ketogenic Capacity of Proximal Intestinal Fatty Acid Oxidation in Clofibrate Feed Newborn Pigs

Newborn pigs are much less efficient at utilizing milk fat as an energy source, than weaned pigs, due to a limited capacity of fatty acid oxidation. We have previously shown that clofibrate, a PPARα agonist, increases fatty acid oxidation levels in newborn pigs by increasing production of key metabolic enzymes. We hypothesize that feeding anaplerotic carbon sources or ketogenic fatty acids in conjunction with clofibrate will improve energy utilization in young pigs by increasing capacities of the TCA cycle or ketogenic activity. To test our hypothesis, suckling newborn pigs (N=48) from 6 litters, which received colostrum for 24 hours, from the North Carolina State University Swine Unit were randomly divided into a 2 (control vs clofibrate) × 4 (glycerol‐succinate, valerate, hexonoate, 2‐methylpentanoate) factorial design. All piglets were fed a standard milk replacer three times a day based on body weight (1.31±.2kg). All supplements, glycerol‐succinate (GS), triglycerides of valeric acid (triC5), hexanoic acid (triC6) or tri‐2‐methylpentanoate (2‐MPA), were fed at ~5% (w/w as fed to maintain an isocaloric diet). For the clofibrate treatment groups, clofibrate was included (.35%) only in the morning feedings. Milk was withheld on the sixth day when the mucosa was collected from the proximal small intestine. The mucosa (28.43±6.12 mg/mL protein) was homogenized and added to flasks that contained a buffer without (control) or with carnitine (1mM), L659699 (1.6 μM), or iodoacetamide (50 μM) and labeled [1–14C] palmitic acid (1mM) as the substrate. L659599 is an inhibitor of both mitochondria and cytosolic hydroxymethylglutaryl‐CoA synthase and iodoacetamide is an inhibitor of acetoacetate synthesis. After 30 mins, the reactions were terminated and 14C accumulation in CO2 and acid soluble products (ASP) was measured to determine fatty acid oxidation rates. The oxidation of palmitic acid (14C accumulations in CO2 +ASP; μmol/h.mg protein) was higher (P &lt; 0.0001) in the pigs that received triC5 (1.54) and triC6 (1.51) than those that received GS (1.27) or 2‐MPA (1.47). No differences were detected between pigs receiving triC5 and triC6 or between GS and 2‐MPA. Clofibrate had no effects on the palmitic acid oxidation from pigs fed GS or triC6, but the 14C accumulation in CO2 and ASP was increased by 40% and 26% in pigs receiving triC5 and 2‐MPA (P &lt;0.0003), respectively. Addition of carnitine with or without clofibrate increased palmitic acid oxidation by 44% as compared with the control (P &lt; 0.0001), while oxidation was reduced by 9% by L659699 (P &lt; 0.004). Oxidation rates in incubations with iodoacetamide were higher than with L659699 (P &lt; 0.03), but were not different from controls (P =0.92). The results indicate that fatty acid oxidation in the mucosa of the proximal small intestine of newborn pigs could be increased by enhancing ketogenic activity and TCA cycle capacity, thus demonstrating that dietary supplementation of ketogenic fatty acid and anaplerotic carbon would be favorable to improve milk fat utilization in pigs during the postnatal period.Support or Funding InformationSupported by the National Institute of Food and Agriculture, U.S. Department of Agriculture, under award number 2015‐67015‐23245.

Caffeine intake increases plasma ketones: an acute metabolic study in humans.

Brain glucose uptake declines during aging and is significantly impaired in Alzheimer's disease. Ketones are the main alternative brain fuel to glucose so they represent a potential approach to compensate for the brain glucose reduction. Caffeine is of interest as a potential ketogenic agent owing to its actions on lipolysis and lipid oxidation but whether it is ketogenic in humans is unknown. This study aimed to evaluate the acute ketogenic effect of 2 doses of caffeine (2.5; 5.0 mg/kg) in 10 healthy adults. Caffeine given at breakfast significantly stimulated ketone production in a dose-dependent manner (+88%; +116%) and also raised plasma free fatty acids. Whether caffeine has long-term ketogenic effects or could enhance the ketogenic effect of medium chain triglycerides remains to be determined.

Decreased Core Crystallinity Facilitated Drug Loading in Polymeric Micelles without Affecting Their Biological Performances.

Cargo-loading capacity of polymeric micelles could be improved by reducing the core crystallinity and the improvement in the amount of loaded cargo was cargo-polymer affinity dependent. The effect of medium chain triglyceride (MCT) in inhibiting PCL crystallization was confirmed by DSC and polarized microscope. When incorporating MCT into polymeric micelles, the maximum drug loading of disulfiram (DSF), cabazitaxel (CTX), and TM-2 (a taxane derivative) increased from 2.61 ± 0.100%, 13.5 ± 0.316%, and 20.9 ± 1.57% to 8.34 ± 0.197%, 21.7 ± 0.951%, and 28.0 ± 1.47%, respectively. Moreover, the prepared oil-containing micelles (OCMs) showed well-controlled particle size, good stability, and decreased drug release rate. MCT incorporation showed little influence on the performances of micelles in cell studies or pharmacokinetics. These results indicated that MCT incorporation could be a core construction module applied in the delivery of hydrophobic drugs.