Evidence map›Paper›PMID 26766547›Full record

ReviewAnnals of the New York Academy of Sciences2016

Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease.

Stephen C Cunnane, Alexandre Courchesne-Loyer, Valérie St-Pierre, Camille Vandenberghe, Tyler Pierotti, Mélanie Fortier, Etienne Croteau, Christian-Alexandre Castellano

4 registry-linked trialsOpen access · bronzeAbstract readReview
PubMed Publisher
In one paragraph

Review in Annals of the New York Academy of Sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 128 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed, 8 pooled it
13.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05975528 phase4unknown statusstarted 2023, after this paper: background citation

Effect of Sodium-glucose Cotransporter-2 Inhibitor in Cellular Senescence in Patients With Cardiovascular Diseases or Advanced Type 2 Diabetes

Ran2023Enrolled92Registered outcomes14Posted comparisons0ConditionsCellular Senescence, Diabetes Mellitus, Sodium-Glucose Transporter 2 InhibitorsArmsGlimepiride, SGLT2 inhibitor
PMID 30907060PMID 31451866PMID 31542391PMID 31735593PMID 28577854PMID 26151266PMID 32269287PMID 34843980PMID 34638943PMID 32940423PMID 32604771PMID 30407726other papers from this trial
Open the trial in the graph
NCT03830268 nacompletednot on this mapstarted 2017, after this paper: background citation

Optimisation of Acute Medium Chain Triglycerides Intake Characteristics on Different Plasma Metabolites in Young and Older Participants

TypeinterventionalSponsorUniversité de SherbrookeRan2017 to 2019Enrolled20ConditionsKetonemiaArmsNo MCT intake with breakfast, no lunch, No MCT intake with lunch, no breakfast, 10g of Betaquik, 10g of Betaquik with low-carbs breakfast, 20g of Betaquik
NCT05732935 nacompletednot on this mapstarted 2023, after this paper: background citation

Fasting to Provide Energy Needed to Help Adults in Need of Cognitive Enhancement (FASTING ENHANCE)

TypeinterventionalSponsorUniversity of FloridaRan2023 to 2026Enrolled45ConditionsOverweight and Obesity, Time Restricted Feeding, Alzheimer DiseaseArmsTime Restricted Eating intervention, Successful Aging Comparison Group (LEARN)
NCT07364162 phase2recruitingnot on this mapstarted 2026, after this paper: background citation

Exogenous Ketone Ester Supplementation in ICU Delirium (KETONES ICU)

TypeinterventionalSponsorVanderbilt University Medical CenterRan2026 to 2027Enrolled40ConditionsICU Delirium, Critical IllnessArmsKetone monoester, Placebo
3 · Its place in the literature

Who cites it

128 citing papers in PubMed, 8 syntheses or guidelines pooled it, 226 citations in OpenAlex.

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  17. A scoping review of computational models on human glucose cerebral metabolism.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
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68 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Stephen C CunnaneResearch Center on Aging.
Alexandre Courchesne-LoyerResearch Center on Aging.
Valérie St-PierreResearch Center on Aging.
Camille VandenbergheResearch Center on Aging.
Tyler PierottiResearch Center on Aging.
Mélanie FortierResearch Center on Aging.
Etienne CroteauResearch Center on Aging.
Christian-Alexandre CastellanoResearch Center on Aging.
Institute on Aging · USUniversité de Sherbrooke · CA

Funding

CIHR
6 · The paper itself

Abstract

Brain glucose uptake is impaired in Alzheimer's disease (AD). A key question is whether cognitive decline can be delayed if this brain energy defect is at least partly corrected or bypassed early in the disease. The principal ketones (also called ketone bodies), β-hydroxybutyrate and acetoacetate, are the brain's main physiological alternative fuel to glucose. Three studies in mild-to-moderate AD have shown that, unlike with glucose, brain ketone uptake is not different from that in healthy age-matched controls. Published clinical trials demonstrate that increasing ketone availability to the brain via moderate nutritional ketosis has a modest beneficial effect on cognitive outcomes in mild-to-moderate AD and in mild cognitive impairment. Nutritional ketosis can be safely achieved by a high-fat ketogenic diet, by supplements providing 20-70 g/day of medium-chain triglycerides containing the eight- and ten-carbon fatty acids octanoate and decanoate, or by ketone esters. Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD mandates consideration of how the underlying problem of deteriorating brain fuel supply can be corrected or delayed.

Indexed as

AgingAlzheimer DiseaseAnimalsBrainDiet, KetogenicEnergy MetabolismGlucoseHumansKetonesRisk FactorsTreatment OutcomeGlucoseKetonesacetoacetate (AcAc)Alzheimer's diseasebeta-hydroxybutyrate (β-HB)glucoseketonesmedium-chain triglycerides (MCT)

Identifiers

PMID26766547
OpenAlexW2238829543

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.