Emulsification Increases the Acute Ketogenic Effect and Bioavailability of Medium-Chain Triglycerides in Humans: Protein, Carbohydrate, and Fat Metabolism

Alexandre Courchesne-Loyer, Carolyn-Mary Lowry, Valérie St-Pierre, Camille Vandenberghe, Mélanie Fortier, Christian-Alexandre Castellano, J Richard Wagner, Stephen C Cunnane, Alexandre Courchesne-Loyer, Carolyn-Mary Lowry, Valérie St-Pierre, Camille Vandenberghe, Mélanie Fortier, Christian-Alexandre Castellano, J Richard Wagner, Stephen C Cunnane

Abstract

Background: Lower-brain glucose uptake is commonly present before the onset of cognitive deterioration associated with aging and may increase the risk of Alzheimer disease. Ketones are the brain's main alternative energy substrate to glucose. Medium-chain triglycerides (MCTs) are rapidly β-oxidized and are ketogenic but also have gastrointestinal side effects. We assessed whether MCT emulsification into a lactose-free skim-milk matrix [emulsified MCTs (MCT-Es)] would improve ketogenesis, reduce side effects, or both compared with the same oral dose of MCTs consumed without emulsification [nonemulsified MCTs (MCT-NEs)]. Objectives: Our aims were to show that, in healthy adults, MCT-Es will induce higher ketonemia and have fewer side effects than MCT-NEs and the effects of MCT-NEs and MCT-Es on ketogenesis and plasma medium-chain fatty acids (MCFAs) will be dose-dependent. Methods: Using a metabolic study day protocol, 10 healthy adults were each given 3 separate doses (10, 20, or 30 g) of MCT-NEs or MCT-Es with a standard breakfast or no treatment [control (CTL)]. Blood samples were taken every 30 min for 4 h to measure plasma ketones (β-hydroxybutyrate and acetoacetate), octanoate, decanoate, and other metabolites. Participants completed a side-effects questionnaire at the end of each study day. Results: Compared with CTL, MCT-NEs increased ketogenesis by 2-fold with no significant differences between doses. MCT-Es increased total plasma ketones by 2- to 4-fold in a dose-dependent manner. Compared with MCT-NEs, MCT-Es increased plasma MCFA bioavailability (F) by 2- to 3-fold and decreased the number of side effects by ∼50%. Conclusions: Emulsification increased the ketogenic effect and decreased side effects in a dose-dependent manner for single doses of MCTs ≤30 g under matching conditions. Further investigation is needed to establish whether emulsification could sustain ketogenesis and minimize side effects and therefore be used as a treatment to change brain ketone availability over a prolonged period of time. This trial was registered at clinicaltrials.gov as NCT02409927.

Keywords: bioavailability; emulsification; ketogenesis; lipid metabolism; medium-chain triglycerides.

Figures

FIGURE 1
FIGURE 1
Changes in plasma octanoic acid (C8:0) (left panels) and decanoic acid (C10:0) (right panels) normalized to T0 during the metabolic test days with the CTL (○), MCT-NEs (▴), or MCT-Es (□) at the 10-g (A and D), 20-g (B and E), and 30-g (C and F) doses. aMCT-Es compared with MCT-NEs, bMCT-Es compared with CTL, cMCT-NEs compared with CTL (all P < 0.05). CTL, no-treatment control; MCFA, medium-chain FA; MCT-E, emulsified medium-chain TG; MCT-NE, nonemulsified medium-chain TG; T0, time 0; ↑, medium-chain TGs consumed.
FIGURE 2
FIGURE 2
Correlations between differences in plasma MCFAs octanoic acid (C8:0) (upper panel) and decanoic acid (C10:0) (lower panel) and differences in plasma ketones after consumption of MCT-NEs (dotted lines) at 10 g (● C8:0: r = 0.84, P = 0.0048; C10:0: r = 0.93, P = 0.0002), 20 g (▪ C8:0: r = 0.86, P = 0.0029; C10:0: r = 0.92, P = 0.0004), and 30 g (▴ C8:0: r = 0.98, P < 0.0001; C10:0: r = 0.89, P = 0.0012) or MCT-Es (solid lines) at 10 g (○ C8:0: r = −0.11, P = 0.7768; C10:0: r = −0.46, P = 0.2174), 20 g (□ C8:0: r = 0.72, P = 0.0291; C10:0: r = −0.15, P = 0.7005), and 30 g (△ C8:0: r = 0.80, P = 0.0091; C10:0: r = −0.04, P = 0.9274). MCFA, medium-chain FA; MCT-E, emulsified medium-chain TG; MCT-NE, nonemulsified medium-chain TG.
FIGURE 3
FIGURE 3
Changes in plasma ketones normalized to T0 during CTL (□ dotted lines) or metabolic tests with 10-g (A), 20-g (B), and 30-g (C) doses of MCT-NEs (▴ dashed lines) or MCT-Es (○ solid lines). aMCT-Es compared with MCT-NEs, bMCT-Es compared with CTL, cMCT-NEs compared with CTL (all P < 0.05). CTL, no-treatment control; MCT-E, emulsified medium-chain TG; MCT-NE, nonemulsified medium-chain TG; T0, time 0; ↑, medium-chain TGs consumed.
FIGURE 4
FIGURE 4
Normalized AUCs for plasma ketones (acetoacetate + β-hydroxybutyrate) during the 4-h metabolic test for the CTL (gray bar), MCT-NEs (black bars), or MCT-Es (white bars). Values are means ± SEMs; n = 10/group. *P < 0.05, **P < 0.01. CTL, no-treatment control; MCT-E, emulsified medium-chain TG; MCT-NE, nonemulsified medium-chain TG.

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