REVIEW OF: Fortier M et al, Alzheimer’s Dement 2021;17:543–552

STUDY TYPE: Randomized, placebo-­controlled trial

Ketogenic diets have been used in various health conditions, including weight loss, diabetes, and epilepsy. A ketogenic diet involves a substantial reduction in carbohydrates, replacing them with fat. The reduction in carbohydrates places the body into a state of ketosis, turning fat into ketones. Research is focusing on ketones as a major alternative energy source for the brain. Could ketones also improve cognition? Studies have shown that individuals at risk for Alzheimer’s disease demonstrate impairment in brain glucose uptake and energy metabolism prior to the onset of any cognitive symptoms, so ketones may be an alternative way to fuel the brain.

This six-month study examined whether adding a proprietary drink (an emulsion of Captex 355) supplying 30 grams/day of ketogenic medium-chain triglycerides (kMCTs) to participants’ usual food intake improved cognitive outcomes in mild cognitive impairment (MCI). The proprietary drink was compared to an indistinguishable vegetable oil placebo drink that was calorie-equivalent and nonketogenic. Researchers recruited 122 participants from the community and from memory clinics who were at least 55 years old and met criteria for MCI without medical comorbidities. They administered neurocognitive tests (which included episodic memory, executive function, and language domains) at baseline and during the last week of the study. During monthly visits, bottle counts and daily logs estimated compliance.

After six months, 39 patients completed the kMCT treatment and 44 completed the placebo treatment. The discontinuation rates were high, with an average 32% dropout rate (38% in the kMCT group compared to 26% in the placebo group). However, the overall compliance rate for those completing the study was 89%. Compared to placebo, there was clinically significant improvement in all three cognitive domains in the kMCT group, even after adjusting for age, sex, education, and APOE 4 status. Statistically significant improvements were found in episodic memory, verbal fluency, and the Boston Naming Test. Significantly fewer errors occurred under all conditions of the Trail Making and Stroop tests.

No serious adverse events were reported during the study; however, at least one adverse event occurred in 74% of the kMCT group and 40% of the placebo group. Gastrointestinal-related events accounted for 75% of the dropout rates in the kMCT group versus 50% in the placebo group.

CARLAT TAKE

This proprietary kMCT drink consumed for six months appears to improve cognition in MCI. Unanswered questions remain, including generalizability, length of treatment, and whether kMCTs delay progression to Alzheimer’s disease or modify the underlying disease process. Although there is not enough evidence to recommend this treatment at present, it is certainly food for thought.