ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2015
A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05119010 (A Pilot Study Evaluating a Ketogenic Diet Concomitant to Nivolumab and Ipilimumab in Patients With Metastatic Renal Cell Carcinoma), which is not on this map. Cited by 96 papers, 3 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.
A Pilot Study Evaluating a Ketogenic Diet Concomitant to Nivolumab and Ipilimumab in Patients With Metastatic Renal Cell Carcinoma
Who cites it
96 citing papers in PubMed, 3 syntheses or guidelines pooled it, 191 citations in OpenAlex.
- Ketogenic interventions in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease: A systematic review and critical appraisal.Frontiers in neurology · 2023Pooled 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
- Medium Chain Triglycerides induce mild ketosis and may improve cognition in Alzheimer's disease. A systematic review and meta-analysis of human studies.Ageing research reviews · 2020Pooled it
- Pharmacokinetic effects of a single dose nutritional ketone ester supplement on brain glucose and ketone metabolism in alcohol use disorder.Psychiatry research. Neuroimaging · 2026Trial
- Effectiveness of Exogenous Ketone Salts in Enhancing Circulating Acetoacetate Levels-A Pilot Study in Healthy Adults.Nutrients · 2025Trial
- Defining metabolic migraine with a distinct subgroup of patients with suboptimal inflammatory and metabolic markers.Scientific reports · 2023Trial
- KetoFLEX 12/3 Diet and Cognitive Health: A Precision-Nutrition Perspective on Mechanisms, Emerging Evidence, and Future Directions.Nutrients · 2026Review
- Article
- Ketosis as a Treatment for Severe Mental Illness: A Critical Review of Preclinical and Clinical Data.Current treatment options in psychiatry · 2026Review
- Exercise-induced β-hydroxybutyrate contributes to cognitive improvement in aging mice.Journal of sport and health science · 2025Article
- Providing alternative fuel for the brain in anorexia nervosa: a review of the literature on ketones and their effects on metabolism and the brain.Translational psychiatry · 2025Review
- The Ketogenic Diet Through a Metabolomic Lens: Biochemical Pathways, Therapeutic Applications, and Analytical Challenges.Nutrients · 2025Review
- Fueling Brain Inhibition: Integrating GABAergic Neurotransmission and Energy Metabolism.Neurochemical research · 2025Review
- β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.Cell chemical biology · 2025Article
- Ketogenic diet, adenosine, and dopamine in addiction and psychiatry.Frontiers in nutrition · 2025Review
- Perspectives on the ketogenic diet as a non-pharmacological intervention for major depressive disorder.Trends in psychiatry and psychotherapy · 2025Review
- Effect of sodium-glucose cotransporter 2 inhibitors on serum low-density lipoprotein cholesterol in Japanese patients with type 2 diabetes mellitus.Journal of diabetes investigation · 2024Article
- Ketosis prevents abdominal aortic aneurysm rupture through C-C chemokine receptor type 2 downregulation and enhanced extracellular matrix balance.Scientific reports · 2024Article
- Medium-Chain Triglycerides (MCTs) for the Symptomatic Treatment of Dementia-Related Diseases: A Systematic Review.Journal of nutrition and metabolism · 2024Review
- Ketogenic Diet: A Review of Composition Diversity, Mechanism of Action and Clinical Application.Journal of nutrition and metabolism · 2024Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundProviding ketone bodies to the brain can bypass metabolic blocks to glucose utilization and improve function in energy-starved neurons. For this, plasma ketones must be elevated well above the ≤ 0.2 mM default concentrations normally prevalent. Limitations of dietary methods currently used to produce therapeutic hyperketonemia have stimulated the search for better approaches.
methodDescribed herein is a new way to produce therapeutic hyperketonemia, entailing prolonged oral administration of a potent ketogenic agent--ketone monoester (KME)--to a patient with Alzheimer's disease dementia and a pretreatment Mini-Mental State Examination score of 12.
resultsThe patient improved markedly in mood, affect, self-care, and cognitive and daily activity performance. The KME was well tolerated throughout the 20-month treatment period. Cognitive performance tracked plasma β-hydroxybutyrate concentrations, with noticeable improvements in conversation and interaction at the higher levels, compared with predose levels.
conclusionKME-induced hyperketonemia is robust, convenient, and safe, and the ester can be taken as an oral supplement without changing the habitual diet.
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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.