Article - A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT.

Expert Review

Reviewer: Marek Doyle

17th Mar 2023

Conflict of interest

None

Take home message

MCT supplementation is a promising strategy to rescue energy metabolism in the brain for those with MCIs by providing an alternative energy source
Improvements in cognition were associated with increased blood ketone levels from MCT supplementation
Practitioners should be mindful that higher intakes of MCTs (>30g/d) may lead to negative GI effects in some individuals.

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

This randomized controlled trial demonstrates that supplementation of a ketogenic drink containing medium-chain triglycerides (MCTs) is both safe and effective in improving cognitive outcomes in individuals with mild cognitive impairments (MCI), and does so through supporting energy metabolism in the brain.

Clinical practice applications

These findings might be useful for Nutritional Therapists and Clinical Practitioners as follows:

The results of this randomised controlled trial demonstrate that MCT supplementation (at 30g per day, split between two doses) is a viable strategy to support brain metabolism in individuals experiencing MCIs
There was a dose-dependant response on elevated ketones and selected cognitive improvements which may have pertinent applications to therapeutic practice (either dietary or supplemental)
The paper highlighted the involvement of energy metabolism in cognitive decline; this has potential therapeutic applications in terms of targeted nutritional support for mitochondrial function or energy signalling
Some individuals experienced negative gastrointestinal effects when consuming MCTs at 30g/d for prolonged periods; practitioners should be mindful of this.

Considerations for future research

Future research should consider:

Whether dietary-induced ketosis can therapeutically impact MCI and support patient well-being
Use of MCTs in those with severe cognitive impairments or those taking medication such as cholinesterase inhibitors

the role of glucose hypometabolism to determine alternative strategies for those who have GI issues with MCTs

Whether APOE4 status has any impact on therapeutic outcomes to MCT supplementation
Whether adjunct nutritional support for mitochondrial function alongside MCT could further impact on MCIs.

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Abstract

INTRODUCTION

Counteracting impaired brain glucose metabolism with ketones may improve cognition in mild cognitive impairment (MCI).

METHODS

Cognition, plasma ketone response, and metabolic profile were assessed before and 6 months after supplementation with a ketogenic drink containing medium chain triglyceride (ketogenic medium chain triglyceride [kMCT]; 15 g twice/day; n = 39) or placebo (n = 44).

RESULTS

Free and cued recall (Trial 1; P = .047), verbal fluency (categories; P = .024), Boston Naming Test (total correct answers; P = .033), and the Trail-Making Test (total errors; P = .017) improved significantly in the kMCT group compared to placebo (analysis of covariance; pre-intervention score, sex, age, education, and apolipoprotein E4 as covariates). Some cognitive outcomes also correlated positively with plasma ketones. Plasma metabolic profile and ketone response were unchanged.

CONCLUSIONS

This kMCT drink improved cognitive outcomes in MCI, at least in part by increasing blood ketone level. These data support further assessment of MCI progression to Alzheimer's disease.