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

Fortier, Mélanie; Castellano, Christian‐Alexandre; St-Pierre, Valérie; Myette-Côté, Étienne; Langlois, Francis; Roy, Maggie; Morin, Marie‐Christine; Bocti, Christian; Fülöp, Tamás; Godin, Jean‐Philippe; Delannoy, Carla; Cuenoud, Bernard; Cunnane, Stephen C.

doi:10.1002/alz.12206

Cited by 123 publications

(154 citation statements)

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“…Ketone salts, MCTs, and at least one ketone ester have been widely studied in humans and shown to be safe and largely well tolerated [ 30 , 31 , 32 ]. Depending on the specific compound, formulation, dose and dosing context, there are some mild-moderate, transient side effects associated with exogenous ketone ingestion; these typically include nausea, dizziness and stomach cramping [ 33 , 34 ], not unlike the transient side-effects sometimes reported by individuals on a ketogenic diet [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults

et al. 2021

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Nutritional ketosis is a state of mildly elevated blood ketone concentrations resulting from dietary changes (e.g., fasting or reduced carbohydrate intake) or exogenous ketone consumption. In this study, we determined the tolerability and safety of a novel exogenous ketone diester, bis-hexanoyl-(R)-1,3-butanediol (BH-BD), in a 28-day, randomized, double-blind, placebo-controlled, parallel trial (NCT04707989). Healthy adults (n = 59, mean (SD), age: 42.8 (13.4) y, body mass index: 27.8 (3.9) kg/m2) were randomized to consume a beverage containing 12.5 g (Days 0–7) and 25 g (Days 7–28) of BH-BD or a taste-matched placebo daily with breakfast. Tolerability, stimulation, and sedation were assessed daily by standardized questionnaires, and blood and urine samples were collected at Days 0, 7, 14, and 28 for safety assessment. There were no differences in at-home composite systemic and gastrointestinal tolerability scores between BH-BD and placebo at any time in the study, or in acute tolerability measured 1-h post-consumption in-clinic. Weekly at-home composite tolerability scores did not change when BH-BD servings were doubled. At-home scores for stimulation and sedation did not differ between groups. BH-BD significantly increased blood ketone concentrations 1-h post-consumption. No clinically meaningful changes in safety measures including vital signs and clinical laboratory measurements were detected within or between groups. These results support the overall tolerability and safety of consumption of up to 25 g/day BH-BD.

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Section: Introductionmentioning

confidence: 99%

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults

et al. 2021

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“…Blood lipids were also reported-total cholesterol increased by 6% in the kMCT group but remained within the clinical reference range (4.9-5.2 mM). [58]These results provide robust support for the concept that brain energy rescue with ketones can improve cognitive outcomes in both MCI and AD. While further investigations are required to determine the optimal dosage for maximum cognitive benefit of kMCTs, the results of the BENEFIC trial hold promise for future therapeutic treatment with BrainXpert Energy Complex for MCI.…”

Section: Oral Nutritional Supplements For Mild Cognitive Impairment (Benefic Trial)mentioning

confidence: 65%

Mild cognitive impairment: when nutrition helps brain energy rescue—a report from the EuGMS 2020 Congress

et al. 2021

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Background Mild cognitive impairment (MCI) is characterized by a decline in cognition and mainly affects older individuals above the age of 60. The global incidence of MCI varies, but it is often underdiagnosed and untreated. There is a distinct lack of approved pharmacologic options to treat MCI. There is, however, evidence to support the efficacy of nutritional interventions, such as ketogenic supplements/diets, which offer ketones as an alternative energy source to brain cells. This article explores the effect of ketones on metabolic activity in the brain and the mechanisms by which ketogenic medium-chain triglycerides (kMCTs) induce ketosis in patients with MCI. Key takeaways This article reviews the effect of ketogenic supplements/diets on brain metabolism, including evidence supporting the efficacy of ketones as an efficient fuel for the brain. It discusses the use of oral nutritional ketogenic supplements, with particular reference to the 6-month randomized controlled BENEFIC trial, which showed that consumption of a kMCT drink, BrainXpert Energy Complex, improved cognitive performance in individuals with MCI compared with placebo. Conclusion While there is a need for more long-term studies, results from the BENEFIC trial revealed the benefits of a brain-specific ketogenic supplement, as a nutritional intervention, on cognitive performance in individuals with MCI.

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“…An important part of the energy used by the brain is to maintain information processing speed through impulse propagation [8]. In the BENEFIC trial [13], positive correlations between plasma ketones and tests of episodic memory, executive function and language were found, but not with processing speed. This reinforces the essential role of WM in processing speed, where ketones may act as an important substrate.…”

Section: Discussionmentioning

confidence: 99%

“…Recent results show that WM metabolic deterioration in AD and MCI is specific to glucose and does not involve ketones [10]. Rescuing the brain energy deficit by providing ketones is an emerging therapeutic strategy for aging-associated cognitive decline [11] and has shown promise in several randomized trials [12, 13]. The Brain ENErgy Fitness, Imaging and Cognition (BENEFIC) trial conducted in MCI showed improved measures of episodic memory, language, executive function, and processing speed after the 6-month ketogenic intervention [14] as well as improved cortical energy metabolism.…”

Section: Introductionmentioning

confidence: 99%

A ketogenic supplement improves white matter energy supply and processing speed in mild cognitive impairment

Roy

Fortier

Rheault

et al. 2021

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INTRODUCTION: White matter (WM) energy supply is crucial for axonal function and myelin maintenance. Providing ketones, the brain s alternative fuel to glucose, is a therapeutic strategy to bypass the brain s glucose-specific energy deficit in mild cognitive impairment (MCI). How an additional supply of ketones affects glucose or ketone uptake in specific WM fascicles in MCI has not previously been described. METHODS: This 6-month interventional study included MCI participants randomized to a placebo (n = 16) or ketogenic medium chain triglyceride (kMCT; n = 17) drink. A neurocognitive battery and brain imaging were performed pre- and post-intervention. WM fascicle uptake of ketone and glucose and structural properties were assessed using positron emission tomography and diffusion imaging, respectively. RESULTS: Ketone uptake was increased by 2.5 to 3.2-fold in nine fascicles of interest (P < 0.001) only in the kMCT group, an effect seen both in deep WM and in fascicle cortical endpoints. Improvement in processing speed was associated with WM ketone uptake globally and in individual fascicles, most importantly the fornix (r = +0.61; P = 0.014). DISCUSSION: A 6-month ketogenic supplementation in MCI improved WM energy supply globally. The significant positive association with processing speed suggests that ketones may have a role in myelin integrity in MCI.

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

Cited by 123 publications

References 45 publications

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults

Mild cognitive impairment: when nutrition helps brain energy rescue—a report from the EuGMS 2020 Congress

A ketogenic supplement improves white matter energy supply and processing speed in mild cognitive impairment

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