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Randomized Controlled Trial
. 2021 Mar;17(3):543-552.
doi: 10.1002/alz.12206. Epub 2020 Oct 26.

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

Mélanie Fortier  1 , Christian-Alexandre Castellano  1 , Valérie St-Pierre  1 , Étienne Myette-Côté  1   2 , Francis Langlois  3 , Maggie Roy  1   2 , Marie-Christine Morin  1 , Christian Bocti  1   2 , Tamas Fulop  1   2 , Jean-Philippe Godin  4 , Carla Delannoy  5 , Bernard Cuenoud  5 , Stephen C Cunnane  1   2   6
Affiliations
Randomized Controlled Trial

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

Mélanie Fortier et al. Alzheimers Dement. 2021 Mar.

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.

Keywords: Alzheimer's disease; acetoacetate; beta-hydroxybutyrate; cognition; episodic memory; executive function; ketone; language; medium chain triglyceride; mild cognitive impairment.

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Conflict of interest statement

Stephen C. Cunnane has consulted for or received travel honoraria or test products for research from Nestlé Health Science, Bulletproof, Cerecin, and Abitec. Stephen C. Cunnane is the founder and director of the consulting company, Senotec Ltd. JPG is an employee of the Société des Produits Nestlé S.A. There are no other conflicts to report.

Figures

FIGURE 1
FIGURE 1
Change in cognitive scores. Change in raw scores from baseline (0) on the first trial of the RL/RI‐16 test (A) verbal fluency (categories) test (B) and Boston Naming Test (C‐ total correct responses), in the ketogenic medium chain triglyceride (kMCT) versus placebo group (P = .054, P = .005, P = .018, respectively)
FIGURE 2
FIGURE 2
Plasma ketones and cognitive outcomes. Correlation between the change in plasma beta‐hydroxybutyrate (BHB) or change in plasma total ketones (BHB + acetoacetate) and three cognitive outcomes on the placebo (○) or ketogenic medium chain triglyceride (kMCT) (●): trial 1 of the RL/RI‐16 test (A; r = +0.232, P = .039), verbal fluency (categories) test (B; r = +0.325, P = .013), and Boston Naming Test (total correct answers) (C; r = +0.229, P = .042)
FIGURE 3
FIGURE 3
Plasma free caprylic acid (C8) and capric acid (C10) (A) and total ketone response (B) throughout the 4‐hour metabolic study day. A dose of 15 g of ketogenic medium chain triglyceride (kMCT) (A, B) or placebo drink (B) was consumed (arrow) before (◇C8 kMCT; ∇C10 kMCT; ○ Placebo; □ kMCT) and 6 months after supplementation (◆ C8 kMCT; ▾ C10 kMCT; ⬤ Placebo; ■ kMCT). For clarity, placebo data are not shown for C8 and C10 (A) but did not exceed the baseline values shown at T0 for C8 (3.9 μM) or C10 (7.9 μM). Data are means ± standard deviation
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References

    1. Cunnane SC, Trushina E, Morland C, et al. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020;19(9):609‐633. - PMC - PubMed
    1. Morbelli S, Brugnolo A, Bossert I, et al. Visual versus semi‐quantitative analysis of 18F‐FDG‐PET in amnestic MCI: an European Alzheimer's Disease Consortium (EADC) project. J Alzheimers Dis. 2015;44:815‐826. - PubMed
    1. Ishibashi K, Onishi A, Wagatsuma K, Fujiwara Y, Ishii K. Longitudinal 18F‐FDG images in patients with Alzheimer disease over more than 9 years from a preclinical stage. Clin Nucl Med. 2020;45:e185‐e9. - PubMed
    1. Castellano CA, Baillargeon JP, Nugent S, et al. Regional brain glucose hypometabolism in young women with polycystic ovary syndrome: possible link to mild insulin resistance. PLoS One. 2015;10:e0144116. - PMC - PubMed
    1. Croteau E, Castellano CA, Richard MA, et al. Ketogenic medium chain triglycerides increase brain energy metabolism in Alzheimer's disease. J Alzheimers Dis. 2018;64:551‐561. - PubMed

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