Supplementation of Regular Diet With Medium-Chain Triglycerides for Procognitive Effects: A Narrative Review

Abstract

It is now widely accepted that ketosis (a physiological state characterized by elevated plasma ketone body levels) possesses a wide range of neuroprotective effects. There is a growing interest in the use of ketogenic supplements, including medium-chain triglycerides (MCT), to achieve intermittent ketosis without adhering to a strict ketogenic diet. MCT supplementation is an inexpensive and simple ketogenic intervention, proven to benefit both individuals with normal cognition and those suffering from mild cognitive impairment, Alzheimer's disease, and other cognitive disorders. The commonly accepted paradigm underlying MCT supplementation trials is that the benefits stem from ketogenesis and that MCT supplementation is safe. However, medium-chain fatty acids (MCFAs) may also exert effects in the brain directly. Moreover, MCFAs, long-chain fatty acids, and glucose participate in mutually intertwined metabolic pathways. Therefore, the metabolic effects must be considered if the desired procognitive effects require administering MCT in doses larger than 1 g/kg. This review summarizes currently available research on the procognitive effects of using MCTs as a supplement to regular feed/diet without concomitant reduction of carbohydrate intake and focuses on the revealed mechanisms linked to particular MCT metabolites (ketone bodies, MCFAs), highlighting open questions and potential considerations.

Keywords: capric acid (C10); caprylic acid (C8); cardiometabolic health; ketosis; medium-chain fatty acids; medium-chain triglycerides; neuroprotection; procognitive activity.

Figure 1

Medium-chain fatty acids, acetyl-CoA, and intersecting liver metabolic pathways. Long-chain fatty acids (LCFA) and medium-chain fatty acids (MCFA) are handled by the cells differently. MCFAs do not require transport proteins (TP) to cross membranes, get activated and undergo oxidation in mitochondria. Acetyl-CoA can feed TCA cycle, ketogenesis, lipogenesis, cholesterol synthesis. Excess LCFAs can be esterified to be stored in liver and excreted as VLDL particles. More details in text. AcAc, acetoacetate; Acetyl-CoA, acetyl-Coenzyme A; βHB, β-hydroxybutyrate; HMG-CoA, β-Hydroxy β-methylglutaryl-Coenzyme A; HMGCS-2, 3-hydroxy-3-methylglutaryl-CoA synthase 2; LCA-CoA, long-chain acyl-Coenzyme A; LCFA, long-chain fatty acids; MCA-CoA, medium-chain acyl-Coenzyme A; MCFA, medium-chain fatty acids; SCOT, Succinyl-CoA:3-ketoacid CoA transferase; TCA cycle, tricarboxylic acid cycle; TG, triglycerides; TP, transport proteins (see details in text); VLDL, very low density lipoprotein.

Figure 2

Known mechanisms of the neuroprotective effects of medium-chain triglyceride (MCT) metabolites – caprylic (C8) and capric (C10) medium-chain fatty acids and β-hydroxybutyrate. Details in text. A1R, A2R, adenosine receptors A1 and A2; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA receptor is a subtype of glutamate receptor); βHB, β-hydroxybutyrate; C10, capric acid; C8, caprylic acid; GABA, γ-aminobutyric acid; GPR109, G-protein-coupled receptor 109; GPR40, G-protein-coupled receptor 40; MCT, medium-chain triglycerides; PGC-1α, Peroxisome proliferator-activated receptor γ coactivator 1α; PPAR-γ, Peroxisome proliferator-activated receptor γ; UCP, uncoupling proteins.