Medium chain triglyceride (MCT) supplementation in rural aged care residents: Phase 2a clinical trial

The step-wedge trial will cover 3 phases over a 22-week period. The following phases include; 1) Routine Care, 2) Dose Optimisation, and 3) Stable Dose. This will be completed across 8 clusters, recruiting 5-6 participants per cluster. PHASE 1: Routine care During the routine care phase, the consented participants will be provided their usual care and will not be exposed to MCT supplementation. During this time all baseline measures will be collected the week prior to starting phase 2 (dose optimisation). The participant behaviour and stool chart history will be collected daily over the course of the routine care phase. Phase 1 duration will last between 1-8 weeks. PHASE 2: Dose optimisation Based on previous literature this phase will help optimise the MCT dose for every participant relative to their weight. All participants will complete a 10-week dose optimisation phase. The MCT supplement will be Bulletproof 360, Inc. Brain Octane C8 MCT Oil. It will be administered to participants twice a day, 50% with breakfast and 50% with dinner. The MCT is of a liquid oil consistency and will be administered separately, but at the same time as meals to minimise potential adverse events. The ml/kg value based on the standard molecular density of caprylic acid. – density 0.91 g/mL at 25 °C, which is the basis for all dosing calculations. This product has been approved for use in Canada and is registered in the Canadian Licenced Natural Health products Database; Natural Product Number: 80057199. This product has been used in a Canadian based randomised, double-blind, placebo-controlled crossover study for participants with probable Alzheimer’s Disease (1). Briefly, the dose will begin as a 0.05g/kg dose and will increase each week by 0.05g/kg as tolerated by the participant. Provided no symptoms have been reported dosage increases will be reviewed weekly and will be ordered through each participants online medication chart on LeeCare. Dosage alterations will be actioned based on each participants tolerance of the MCT supplement, as reported daily by clinical staff within the LeeCare reporting system, considering their tolerance of the MCT and daily stool chart documentation. Previously reported symptoms indicative of MCT supplementation intolerance include gastrointestinal irritation, loose stools, nausea, cramping and abdominal discomfort. These symptoms have previously been reported with large sudden increases in dosing. The gradual increase in dose can help minimise symptoms and any potential unknown adverse events. The additional symptoms of ketosis can include constipation, headache, halitosis, muscle cramps, diarrhea, and general weakness and rash. These occur greatest between days 1–4 of a fast or ketogenic diet (2). Only mild ketosis is reported with MCT supplementation, it is expected that symptoms of ketosis will also be mild. In MCT the aforementioned MCT trials, symptoms being reported are the adverse events associated with the supplement and not ketosis. Previous trials in older adults applied a dose range of 20-56 g per day (3). Therefore, no dose will exceed 56 g per day for participants with high body weight. Monitoring of adherence to the intervention will occur through access to the LeeCare digital health monitoring system. Reference 1. Juby, A. G., Blackburn, T. E., & Mager, D. R. (2022). Use of medium chain triglyceride (MCT) oil in subjects with Alzheimer’s disease: A randomized, double-blind, placebo-controlled, crossover study, with an open-label extension. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 8(1), e12259-n/a. https://doi.org/10.1002/trc2.12259 2. Harvey, C. J. D. C., Schofield, G. M., & Williden, M. (2018). The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review. PeerJ, 6, e4488. 3. Juby, A. G., Brocks, D. R., Jay, D. A., Davis, C. M. J., & Mager, D. R. (2021). Assessing the impact of factors that influence the ketogenic response to varying doses of medium chain triglyceride (MCT) oil. The Journal of Prevention of Alzheimer's Disease, 8, 19-28. PHASE 3: Stable dose Participants will continue to receive their individualised tolerable stable dose of MCT until the completion of the trial at 22 weeks. Participants will continue to be monitored of weight, capillary ketones, blood pressure, heart rate, stool, and behaviour charts. Participants will be reviewed on a case-to-case basis by the clinical staff if they start to develop symptoms over the course of Phase 2. This could include, for mild symptoms, reducing the MCT dose to the previous titration each day until symptoms reduce or removing the MCT supplement from the diet if more severe symptoms are experienced. All symptoms over the cause of the trial will be documented and reported as the primary outcome. Duration of phase 3 will vary from 4-11 weeks depending on which cluster participants are enrolled into.