Keep Medium-Chain Triglycerides Top of Mind When Addressing Cognitive Impairment and Alzheimer’s Disease

Medium-chain triglycerides, or MCTs, have been popularized in the context of Bulletproof™ coffee or the ketogenic diet. MCTs and the keto diet have been investigated in the management of obesity,  insulin resistance, ,   epilepsy,  neurodegenerative conditions,  and others. 

What Are MCTs?

Commercially available MCTs are usually sourced from coconut oil or palm kernel oil. MCTs are fats made up of three saturated fatty acids of 6 to 12 carbons bound to one glycerol molecule. The main medium-chain fatty acids (MCFAs) are caproic acid, caprylic acid, capric acid, and lauric acid, which contain 6, 8, 10 and 12 carbons, respectively, hence their common designations as C6, C8, C10, and C12, respectively.

Ingested MCTs are rapidly and easily digested, and the liberated MCFAs are quickly absorbed in the intestinal lumen and transported to the liver. MCFAs in the liver can be used as an instant energy source or turned into ketones.

Alzheimer’s disease and mild cognitive impairment are characterized by the hypometabolism of glucose in affected brain regions.[i] Contrary to glucose, the metabolism of ketones by brain cells does not decline with normal aging.[ii], [iii] Ketones from ingested MCTs can permeate the blood-brain barrier to enter the brain where they could be used as an alternate energy source. Research also suggests that free C8 and C10 in blood can enter and be directly metabolized by the brain, thereby exerting an effect on brain energetics, and function without necessarily being first metabolized by the liver.[iv]

What Is the Evidence for MCTs in Cognitive Impairment and Alzheimer’s Disease?

A meta-analysis concluded that MCTs can induce mild ketosis and may improve cognition in patients experiencing mild cognitive impairment and Alzheimer’s disease.[i] This meta-analysis included 13 studies, which collectively enrolled a total of 422 patients. It found that MCT administration induced mild peripheral ketosis and improved cognition on a combined scale of the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Mini–Mental State Examination (MMSE).

Since the publication of this meta-analysis, several studies have validated the effect of MCTs on cognitive impairment and Alzheimer’s disease. The most recent study was a six-month randomized, placebo-controlled trial involving 83 participants with mild cognitive impairment.[i] The treatment group, consisting of 39 participants, ingested a ketogenic drink containing 15 g of MCTs (60% C8 and 40% C10) twice per day. After six months, free and cued recall (trial 1; p = 0.047), verbal fluency (categories; p = 0.024), Boston Naming Test (total correct answers; p = 0.033), and the Trail‐Making Test (total errors; p = 0.017) improved significantly in the MCT group compared to placebo. The MCT group improved in three domains: executive function, memory, and language. These improvements were directly and significantly correlated with plasma ketone levels and brain ketone uptake, suggesting a mechanistic link between mild ketosis, brain energy rescue by ketosis, and improved cognitive outcomes. The authors concluded that the use of a ketogenic MCT drink may be an effective, safe, and well-tolerated tool to delay the progression to Alzheimer’s disease.

Another study corroborated the benefit of MTCs in patients with mild to moderate Alzheimer’s disease.[i] This double-blind, randomized, placebo-controlled crossover study (placebo followed by MCTs or MCTs followed by placebo) examined the effect of 17.3 g of MCTs for 30 days per phase in 53 participants. The results showed a significant (p < 0.01) reduction in Alzheimer’s Disease Assessment Scale-Cognitive Subscale, Chinese version (ADAS‑Cog‑C) scores between the MCTs (2.62 points below baseline) and placebo interventions (2.57 points above baseline). The authors concluded that MCTs had positive effects on cognitive ability in mild to moderate Alzheimer’s disease patients with apolipoprotein E4 (apoE4), a prevalent genetic risk factor of Alzheimer’s disease.

A third study supports the positive effect of MCTs on cognitive function.[i] In this three-month randomized, controlled, single-blinded intervention trial, 64 elderly nursing-home residents were allocated to one of three groups: the first group received supplemental ʟ‑leucine and cholecalciferol (vitamin D) enriched with 6 g/d of MCTs (LD+MCT group) as a positive control, the second group received 6 g/d of MCTs (MCT group) as the test nutrient, and the third group received 6 g/d of long-chain triglycerides (LCT group) as a negative control. MCT supplementation was found to improve the Mini-Mental State Examination (MMSE) score by 3.5 points at the three-month intervention from baseline (p < 0.001; intention-to-treat adjusted means: baseline 17.5 points [95% CI: 14.9 to 20.2], three-month intervention 21.0 points [18.3 to 23.7]), whereas the LCT supplementation decreased the MMSE score by −0.7 points (baseline 17.0 points [95% CI: 14.4 to 19.6], three-month intervention 16.3 points [13.6 to 18.9]). At the three-month intervention, the difference in MMSE score between the MCT (21.0 points) and LCT (16.3 points) groups was significant (p < 0.05). The increase in MMSE score in response to MCTs was 2.1‑fold greater at 3 months than at 1.5 months and had returned to baseline value at the 4.5-months postintervention follow-up visit.

Conclusion

The results of studies on taking medium-chain triglyceride supplements and ketogenic diets are encouraging, and there are many medium-chain triglyceride supplements on the market. Medium-chain triglyceride supplements are available in powder and liquid form. It is convenient to add any of them to the diet, and there are few or few adverse reactions. To expand the clinical use of medium-chain triglycerides in the brain, it is definitely necessary to further study their effects on the brain.