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Short‐term ketone monoester supplementation improves cerebral blood flow and cognitive function in adults with obesity: A randomized‐crossover trial

2021· article· en· W3172543148 on OpenAlexafffund
Jeremy J. Walsh, Hannah G. Caldwell, Helena Neudorf, Philip N. Ainslie, Jonathan P. Little

Bibliographic record

VenueThe FASEB Journal · 2021
Typearticle
Languageen
FieldMedicine
TopicDiet and metabolism studies
Canadian institutionsUniversity of British Columbia, Okanagan CampusKelowna General HospitalUniversity of British ColumbiaMcMaster University
FundersCanadian Institutes of Health ResearchMichael Smith Health Research BC
KeywordsCerebral blood flowMedicineCrossover studyPlaceboKetone bodiesDigit symbol substitution testInternal medicineTrail Making TestCardiologyAnesthesiaPathology

Abstract

fetched live from OpenAlex

Background/Objectives Adults with obesity are at increased risk of neurocognitive impairments, due in part to reductions in cerebral blood flow (CBF) and brain‐derived neurotrophic factor (BDNF). Ketone supplements containing β‐hydroxybutyrate (β‐OHB) are a purported therapeutic strategy for improving brain health in at‐risk populations. We tested the hypothesis that short‐term β‐OHB supplementation will elevate CBF and BDNF, and in turn improve cognitive function in individuals with obesity. Subjects/Methods In a placebo‐controlled double‐blind crossover design 14 adults with obesity (10F; age=56±12 yrs; BMI=33.8±6.9 kg/m 2 ) consumed 30 mL of either placebo or ketone supplement (12 g β‐OHB) thrice‐daily for 14 days. Participants were provided with all meals and snacks, which were matched between each 14‐day period. CBF, cerebrovascular conductance (CVC), and shear rate were measured in the common carotid (CCA), internal carotid (ICA), and vertebral (VA) arteries by duplex ultrasound. Plasma and serum BDNF were measured by ELISA. Cognitive function was assessed by the digit‐symbol substitution task (DSST), Stroop test, and task‐switching test. All measures were taken in the fasting, non‐supplemented state. Results CCA blood flow (25 mL×min ‐1 [12, 38], P =0.001), ICA shear rate (42 s ‐1 [15, 69], P =0.004), VA blood flow (18 mL×min ‐1 [10, 26], P <0.001), VA CVC (0.08 mL×min ‐1 ×mmHg ‐1 [0.01, 0.15], P =0.027), and VA shear rate (34 s ‐1 [10, 59], P =0.008) significantly increased following 14‐days of ketone supplementation. DSST performance (correct responses; CR) increased following ketone supplementation (+2.7 CR [1.3, 4.1], P <0.001) and this was positively associated with CCA blood flow (0.001 mL×min ‐1 ×CR ‐1 [0.001, 0.02], P =0.033) and CCA CVC (1.24 ml×min ‐1 ×mmHg ‐1 CR ‐1 [0.24, 2.24], P= 0.024), VA blood flow (0.034 mL×min ‐1 ×CR ‐1 [0.002, 0.066], P =0.039) and VA CVC (3.32 1.24 ml×min ‐1 ×mmHg ‐1 CR ‐1 [0.20, 6.43], P =0.04). There were no differences in serum (301.8 pg/mL [‐1033.4, 1637.2], P =0.65) and plasma BDNF (‐380.4 pg/mL [‐1023.9, 263.2], P =0.24) following ketone supplementation. Conclusions Short‐duration ketone supplementation improved aspects of cognitive function, which may have been facilitated by enhanced CBF in adults with obesity. Ketone supplementation was well‐tolerated and appears safe for cerebrovascular health, suggesting potential therapeutic benefits of β‐OHB for brain health in adults with obesity.

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How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.008
Threshold uncertainty score0.028

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0050.002
Bibliometrics0.0010.001
Science and technology studies0.0010.002
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0030.003
Insufficient payload (model declined to judge)0.0080.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.256
Teacher spread0.245 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2021
Admission routes2
Has abstractyes

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