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

Abstract

Objectives, Design, Setting: The ketogenic effect of medium chain triglyceride (MCT) oil offers potential for Alzheimer’s disease prevention and treatment. Limited literature suggests a linear B-hyroxybutyrate (BHB) response to increasing MCT doses. This pharmacokinetic study evaluates factors affecting BHB response in three subject groups. Participants: Healthy subjects without cognitive deficits <65years, similarly healthy subjects >=65years, and those with Alzheimer’s Disease were assessed. Intervention: Different doses (0g,14g, 28g, 42g) of MCT oil (99.3% C8:0) were administered, followed by fasting during the study period. Measurements: 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. Results: 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). Conclusion: There was a large inter-individual variability, with phenotype effects identified. This highlights challenges in interpreting clinical responses to MCT intake.

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

“…Their data also showed a marked individual variability in BHB response to their intervention. We also previously demonstrated 18 a marked individual response to BHB levels affected not only by amount of MCT consumed, but also by concomitant carbohydrate intake, and phenotypic percentage of visceral fat. These variables may be an added reason why, with similar interventions, there may be an individual response to cognitive outcomes, but not necessarily a group effect.…”

“…Hence, the potential advantage of nutritional ketone sources (MCT) over these restrictive diets. Our recent study showed a clear dose‐dependent effect on ketone (BHB) generation with varying doses of MCT supplementation, and was found to be equivalent in young, elderly, and AD subjects 18 .…”

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

“…MCT consumption, on the other hand, has the potential advantage of inducing nutritional ketosis without the need for a drastic change in dietary habits, especially during a time when a person is perhaps the least able to adjust (24- 28,30,39,[42][43][44][45][46]. Medium chain fatty acids (6-12C) from MCT are rapidly absorbed from the gastrointestinal tract, and unlike long chain fatty acids (13-22C), move directly into the liver via the portal vein and do not promote triglyceride synthesis (23).…”

“…Reducing simple sugar intake while providing MCT may improve insulin sensitivity and potentially help endogenous ketosis (54). Ketone response can also be easily assessed with finger-prick BHB testing (46). Long term safety with MCT consumption has been established in pediatric populations over the years with the use of MCT in pediatric supplements (55).…”

The Effects of Medium-Chain Triglyceride Oil Supplementation on Endurance Performance and Substrate Utilization in Healthy Populations: A Systematic Review

“…When consumed, MCTs are hydrolyzed in the intestines and transported directly to the liver via the hepatic portal venous system. 12,16,17 Unlike long-chain triglycerides (LCTs), MCTs can easily pass through the mitochondrial membrane without carnitine palmitoyl transferase or a shuttle system. [18][19][20][21] However, MCTs rapidly cross the mitochondrial membrane and enter metabolic pathways to be beta-oxidized, producing a larger amount of acetyl-CoA compared with carbohydrates (CHOs).…”