Does MCT oil boost cognition in older adults with Alzheimer’s disease? Original paper

Alzheimer’s disease (AD) is the most common form of dementia, with an estimated worldwide prevalence of 50 million cases.^[1] Current pharmaceutical therapy provides symptomatic relief at best and does not affect disease progression.

In AD, the brain is unable to use glucose normally.^[2][3] Ketones, which are normally generated in fasting states or by the consumption of a very-low-carbohydrate high-fat diet, are an alternative source of fuel for the brain.^[4] Medium-chain triglyceride (MCT) oil is a nutritional source of ketone precursors and is therefore hypothesized to support cognition in people with AD.

In this 15-month trial, 20 participants (average age of 73) with mild to moderate AD were assigned to ingest either MCT oil (45 milliliters per day or the maximum dose tolerated; 30 milliliters per day was consumed on average) or a placebo for 4 months (phase 1). The participants then crossed over to the other condition for 4 months (phase 2). Finally, in an open-label extension, all of the participants ingested MCT oil daily for 7 months.

The primary outcomes assessed were changes in cognition measured using the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and Cognigram (a validated computer-based cognitive test that assesses psychomotor function, attention, visual learning, and working memory). The secondary outcomes were changes in cognition according to ApoE4 (a gene variant that increases the risk of AD) status, quality of life, beta-hydroxybutyrate level, blood lipids, glycemic control (i.e., HbA1c and fasting insulin), and adverse events.

In the participants who ingested MCT oil continuously (i.e., assigned to the placebo for 4 months, then MCT oil for 11 months), attention and psychomotor function were increased at the end of the study compared to the participants with interrupted ingestion of MCT oil (i.e., assigned to MCT oil for 4 months, then placebo for 4 months, then MCT oil for 7 months)). However, the participants who ingested MCT oil continuously for 11 months also had higher attention and psychomotor function at baseline.

Overall, MMSE and MoCA scores remained stable or improved in 80% of the participants, regardless of group assignment. Participants with a higher baseline MMSE score, higher baseline body mass index, or older age (> 73) were more likely to benefit from MCT oil. ApoE4 status did not affect the response to MCT oil. In participants who were assigned to interrupted ingestion of MCT oil, there was a borderline significant greater decline in MMSE scores compared to participants assigned to continuous ingestion of MCT oil.

There were 39 mild to moderate adverse events reported in 17 (85%) participants. Of these, 25 (64%) were gastrointestinal (e.g., diarrhea, abdominal cramping). There was no change in blood lipids, markers of glycemic control, or beta-hydroxybutyrate levels in either group.

The major limitation of this trial was the small sample size. Also, the researchers did not adjust for multiple comparisons, despite the inclusion of numerous outcomes, which increases the risk of false-positive results. Therefore, the results should be interpreted with caution.