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Pilot feasibility and safety study examining the effect of medium chain triglyceride supplementation in subjects with mild cognitive impairment: A randomized controlled trial.

ABSTRACT: BACKGROUND:Impaired brain glucose metabolism appears to be a potential pathogenic feature of mild cognitive impairment (MCI). This study examined the potential for increasing circulating ketone bodies through medium chain triglyceride (MCT) supplementation, as a means to beneficially modulate brain homeostasis in subjects with MCI. METHODS:Six participants with MCI were enrolled in a randomized placebo-controlled trial. Participants received 56 g/day of either medium chain triglycerides (MCTs) or placebo for 24 weeks. Serum ?-hydroxybutyrate concentrations, apolipoprotein-E4 status, and cognitive assessments were carried out. Due to the small number of participants only the raw scores were examined. RESULTS:Intake of MCT oil increased serum ketone bodies and improved memory, while intake of placebo did not show improvement in any of the cognitive measures tested. CONCLUSIONS:Consumption of 56 g/day of MCTs for 24 weeks increases serum ketone concentrations and appears to be a candidate for larger randomized control trials in the future that quantify the modulation of cognitive function through supplementation with ketone precursors, in patients with MCI.

SUBMITTER: Rebello CJ

PROVIDER: S-EPMC4669977 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Pilot feasibility and safety study examining the effect of medium chain triglyceride supplementation in subjects with mild cognitive impairment: A randomized controlled trial.

Rebello Candida J CJ Keller Jeffrey N JN Liu Ann G AG Johnson William D WD Greenway Frank L FL

BBA clinical 20150116

<h4>Background</h4>Impaired brain glucose metabolism appears to be a potential pathogenic feature of mild cognitive impairment (MCI). This study examined the potential for increasing circulating ketone bodies through medium chain triglyceride (MCT) supplementation, as a means to beneficially modulate brain homeostasis in subjects with MCI.<h4>Methods</h4>Six participants with MCI were enrolled in a randomized placebo-controlled trial. Participants received 56 g/day of either medium chain triglyc ...[more]

PMID: 26675661

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Project description:ObjectiveMedium chain triglycerides (MCT) have unique metabolic properties which may improve insulin sensitivity (Si) and beta cell function but data in humans are limited. We conducted a 6-week clinical trial of MCT oil supplementation.Methods22 subjects without diabetes (8 males, 14 females, mean ± standard error age 39±2.9 years, baseline BMI 27.0±1.4 kg/m2) were counseled to maintain their body weight and physical activity (PA) during the trial. Dietary intake, PA data, body composition, and resting energy expenditure (REE) were obtained through dietary recall, international PA questionnaire, dual x-ray absorptiometry, and indirect calorimetry, respectively. MCT prescriptions were given based on REE and PA to replace part of dietary fat with 30 grams of MCT per 2000 kcal daily. Insulin-modified frequently sampled intravenous glucose tolerance tests were performed before and after MCT to measure changes in Si, acute insulin response (AIR), disposition index (DI), and glucose effectiveness (Sg).ResultsMCT were well tolerated and weight remained stable (mean change 0.3 kg, p = 0.39). Fasting REE, respiratory quotient, and body composition were stable during the intervention. There were no significant changes in mean fasting glucose, insulin, insulin resistance, fasting total ketones, Si, AIR, DI, Sg, leptin, fructosamine, and proinsulin. The mean change in Si was 0.5 10-4 min-1 per mU/L (95% CI: -1.4, 2.4), corresponding to a 12% increase from baseline, and the range was -4.7 to 12.9 10-4 min-1 per mU/L. Mean total adiponectin decreased significantly from 22925 ng/mL at baseline to 17598 ng/mL at final visit (p = 0.02). The baseline clinical and laboratory parameters were not significantly associated with the change in Si.DiscussionThere were a wide range of changes in the minimal model parameters of glucose and insulin metabolism in subjects following 6 weeks of MCT as an isocaloric substitution for part of usual dietary fat intake. Since this was a single-arm non-randomized study without a control group, it cannot be certain whether these changes were due to MCT so further randomized controlled trials are warranted.

Project description:Reverse transcription followed by quantitative (real-time) polymerase chain reaction (RT-qPCR) has become the gold standard in mRNA expression analysis. However, it requires an accurate choice of reference genes for adequate normalization. The aim of this study was to validate the reference genes for qPCR experiments in the brain of rats in the model of mild ketosis established through supplementation with medium-chain triglycerides (MCT) and intermittent fasting. This approach allows to reproduce certain neuroprotective effects of the classical ketogenic diet while avoiding its adverse effects. Ketogenic treatment targets multiple metabolic pathways, which may affect the reference gene expression. The standard chow of adult Wistar rats was supplemented with MCT (2 ml/kg orogastrically, during 6 h of fasting) or water (equivolume) for 1 month. The mRNA expression of 9 housekeeping genes (Actb, B2m, Gapdh, Hprt1, Pgk1, Ppia, Rpl13a, Sdha, Ywhaz) in the medial prefrontal cortex, dorsal and ventral hippocampus was measured by RT-qPCR. Using the RefFinder® online tool, we have found that the reference gene stability ranking strongly depended on the analyzed brain region. The most stably expressed reference genes were found to be Ppia, Actb, and Rpl13a in the medial prefrontal cortex; Rpl13a, Ywhaz, and Pgk1 in the dorsal hippocampus; Ywhaz, Sdha, and Ppia in the ventral hippocampus. The B2m was identified as an invalid reference gene in the ventral hippocampus, while Sdha, Actb, and Gapdh were unstable in the dorsal hippocampus. The stabilities of the examined reference genes were lower in the dorsal hippocampus compared to the ventral hippocampus and the medial prefrontal cortex. When normalized to the three most stably expressed reference genes, the Gapdh mRNA was upregulated, while the Sdha mRNA was downregulated in the medial prefrontal cortex of MCT-fed animals. Thus, the expression stability of reference genes strongly depends on the examined brain regions. The dorsal and ventral hippocampal areas differ in reference genes stability rankings, which should be taken into account in the RT-qPCR experimental design.

Dataset Information

Pilot feasibility and safety study examining the effect of medium chain triglyceride supplementation in subjects with mild cognitive impairment: A randomized controlled trial.

Publications

Pilot feasibility and safety study examining the effect of medium chain triglyceride supplementation in subjects with mild cognitive impairment: A randomized controlled trial.

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