ArticleBiochimica et biophysica acta2015
Adaptive changes in amino acid metabolism permit normal longevity in mice consuming a low-carbohydrate ketogenic diet.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Relationship between Aging and Ketogenic Diet: A Bibliometric Analysis (1995-2025)Endocrine, metabolic & immune disorders drug targets · 2026Pooled it
- Very low-carbohydrate ketogenic diet in treatment-naïve women with endometrial cancer and overweight: a randomized feasibility study.Nature communications · 2026Trial
- Defining metabolic migraine with a distinct subgroup of patients with suboptimal inflammatory and metabolic markers.Scientific reports · 2023Trial
- Comparison of Ketogenic Diets with and without Ketone Salts versus a Low-Fat Diet: Liver Fat Responses in Overweight Adults.Nutrients · 2021Trial
- Ketogenic Diet and Brain Health: Cerebrovascular Mechanisms, Neuroprotection, and Translational Implications.Nutrients · 2026Review
- A long-term ketogenic diet causes hyperlipidemia, liver dysfunction, and glucose intolerance from impaired insulin secretion in mice.Science advances · 2025Article
- Hepatic toll of keto: unveiling the inflammatory and structural consequences of ketogenic diet in rats.BMC nutrition · 2025Article
- Impact of ketogenic diet on cardiovascular disease.Nutrition reviews · 2024Review
- Integrated Transcriptomic and Metabolomic Analysis Reveals Possible Molecular Mechanisms of Leaf Growth and Development inMetabolites · 2024Article
- Physiologic Adaptation to Macronutrient Change Distorts Findings from Short Dietary Trials: Reanalysis of a Metabolic Ward Study.The Journal of nutrition · 2024Article
- The impact of ketogenic diet on some metabolic and non-metabolic diseases: Evidence from human and animal model experiments.Food science & nutrition · 2024Review
- Targeting apoptosis and unfolded protein response: the impact of β-hydroxybutyrate in clear cell renal cell carcinoma under glucose-deprived conditions.Molecular biology reports · 2024Article
- Advances in Mass Spectrometry-Based Blood Metabolomics Profiling for Non-Cancer Diseases: A Comprehensive Review.Metabolites · 2024Review
- Effect of Ketogenic Diet on Obesity and Other Metabolic Disorders: Narrative Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Dietary restriction in senolysis and prevention and treatment of disease.Critical reviews in food science and nutrition · 2024Review
- Metabolic intervention by low carbohydrate diet suppresses the onset and progression of neuroendocrine tumors.Cell death & disease · 2023Article
- Article
- The Paradoxical Role of Circulating Ketone Bodies in Glycemic Control of Individuals with Type 2 Diabetes: High Risk, High Reward?Biomolecules · 2022Article
- Ketogenic diets slow melanoma growth in vivo regardless of tumor genetics and metabolic plasticity.Cancer & metabolism · 2022Article
- Short-Term Ketogenic Diet Induces a Molecular Response That Is Distinct From Dietary Protein Restriction.Frontiers in nutrition · 2022Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Ingestion of very low-carbohydrate ketogenic diets (KD) is associated with weight loss, lowering of glucose and insulin levels and improved systemic insulin sensitivity. However, the beneficial effects of long-term feeding have been the subject of debate. We therefore studied the effects of lifelong consumption of this diet in mice. Complete metabolic analyses were performed after 8 and 80weeks on the diet. In addition we performed a serum metabolomic analysis and examined hepatic gene expression. Lifelong consumption of KD had no effect on morbidity or mortality (KD vs. Chow, 676 vs. 630days) despite hepatic steatosis and inflammation in KD mice. The KD fed mice lost weight initially as previously reported (Kennnedy et al., 2007) and remained lighter and had less fat mass; KD consuming mice had higher levels of energy expenditure, improved glucose homeostasis and higher circulating levels of β-hydroxybutyrate and triglycerides than chow-fed controls. Hepatic expression of the critical metabolic regulators including fibroblast growth factor 21 were also higher in KD-fed mice while expression levels of lipogenic enzymes such as stearoyl-CoA desaturase-1 was reduced. Metabolomic analysis revealed compensatory changes in amino acid metabolism, primarily involving down-regulation of catabolic processes, demonstrating that mice eating KD can shift amino acid metabolism to conserve amino acid levels. Long-term KD feeding caused profound and persistent metabolic changes, the majority of which are seen as health promoting, and had no adverse effects on survival in mice.
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