ArticleFrontiers in molecular neuroscience2016
Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer's Disease.
Article in Frontiers in molecular neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 114 papers, 5 of them syntheses that pooled it.
What it found
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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.
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.
Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults >= 55 Years Old. A Double-Blinded Randomized Controlled Clinical Trial.
The Effect of Exogenous Β-OHB Supplementation on Cerebral Blood Flow and Functional Brain Characteristics in Adults with Subjective Cognitive Decline
Exogenous Ketone Ester Supplementation in ICU Delirium (KETONES ICU)
Who cites it
114 citing papers in PubMed, 5 syntheses or guidelines pooled it, 203 citations in OpenAlex.
- Influence of Carbohydrate Intake on Caprylic Acid (C8:0)-Induced Ketogenesis-A Systematic Review and Meta-Analysis.Nutrients · 2024Pooled it
- Ketogenic interventions in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease: A systematic review and critical appraisal.Frontiers in neurology · 2023Pooled it
- Toxic Effects of Glyphosate on the Nervous System: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- To Keto or Not to Keto? A Systematic Review of Randomized Controlled Trials Assessing the Effects of Ketogenic Therapy on Alzheimer Disease.Advances in nutrition (Bethesda, Md.) · 2020Pooled it
- Are ketogenic diets promising for Alzheimer's disease? A translational review.Alzheimer's research & therapy · 2020Pooled it
- Effect of glucose on medium chain triglyceride induced ketosis in healthy adults in a randomized, double-blind, controlled study.Scientific reports · 2026Trial
- Apabetalone Drives a Metabolic Shift Towards Ketogenesis and Reduces Liver Steatosis in Diet-Induced Obesity Mice.Biomedicines · 2026Article
- 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 · 2026Review
- Carbohydrate Ingestion on Exercise Metabolism and Physical Performance.Endocrine reviews · 2026Review
- Insulin Resistance as a Shared Pathophysiological Driver in Neurological Disorders: a Narrative Review.Current nutrition reports · 2026Review
- Article
- Review
- From plate to brain: role of mediators and moderators on the impact of diet on Alzheimer's disease.Frontiers in nutrition · 2026Review
- Intermittent fasting and neuroprotection in Alzheimer's disease: metabolic mechanisms, cellular signaling, and brain-peripheral crosstalk.Frontiers in nutrition · 2026Review
- Insulin resistance (TyG index) and body mass index as metabolic biomarker combined with ApoE genotype to diagnose Alzheimer's disease.Frontiers in aging neuroscience · 2026Article
- The metabolic engine of cognition: microglia-neuron interactions in health, ageing and disease.Nature metabolism · 2025Review
- Unraveling the Function of PPARα in Neurodegenerative Disorders: A Potential Pathway to Novel Therapies.Biomedicines · 2025Review
- Preferential lactate metabolism in the human brain during exogenous and endogenous hyperlactataemia.The Journal of physiology · 2025Article
- Potential therapeutic benefit of exogenous ketone ester administration in delirium: a narrative review.Critical care (London, England) · 2025Review
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer's disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults <40 years-old who have genetic or lifestyle risk factors for AD but in whom cognitive decline has not yet started. Examples include young adult carriers of presenilin-1 or apolipoprotein E4, and young adults with mild insulin resistance or with a maternal family history of AD. (iii) Regional brain glucose uptake is impaired in AD and mild cognitive impairment (MCI), but brain uptake of ketones (beta-hydroxybutyrate and acetoacetate), remains the same in AD and MCI as in cognitively healthy age-matched controls. These observations point to a brain fuel deficit which appears to be specific to glucose, precedes cognitive decline associated with AD, and becomes more severe as MCI progresses toward AD. Since glucose is the brain's main fuel, we suggest that gradual brain glucose exhaustion is contributing significantly to the onset or progression of AD. (iv) Interventions that raise ketone availability to the brain improve cognitive outcomes in both MCI and AD as well as in acute experimental hypoglycemia. Ketones are the brain's main alternative fuel to glucose and brain ketone uptake is still normal in MCI and in early AD, which would help explain why ketogenic interventions improve some cognitive outcomes in MCI and AD. We suggest that the brain energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD. At present, oral ketogenic supplements are the most promising means of achieving this goal.
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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.