Cell Biochem Biophys. 2025 Aug 29. doi: 10.1007/s12013-025-01878-0. Online ahead of print.

ABSTRACT

BACKGROUND: Obesity remains a leading global health challenge, driving a surge in dietary interventions aimed at effective weight loss and metabolic improvement. Low and very low carbohydrate diets, including the ketogenic diet (KD), have attracted renewed public and scientific interest for its reported rapid weight loss effects, though evidence for long-term benefits remains limited.

OBJECTIVE: This narrative review critically examines the role of low and very low carbohydrate diets, including the KD in obesity management, exploring their mechanistic basis, clinical efficacy, potential risks, and long-term sustainability, defined here as the ability of individuals to adhere to such diets safely and effectively over extended periods (≥ 12 months) without adverse health consequences.

METHODS: A comprehensive synthesis of peer-reviewed literature was performed utilizing sources including PubMed, Scopus, and Web of Science, focusing on human and animal studies that assessed the effects of KD on obesity, metabolic outcomes, and safety.

RESULTS: KD exerts anti-obesity effects through multiple pathways, including induction of nutritional ketosis, appetite suppression, enhanced fat oxidation, and improved insulin sensitivity. Clinical trials report significant short-term weight reduction and enhancements in glycemic control and lipid profiles. However, concerns persist regarding long-term adherence, cardiovascular risks, increased workload placed for the kidneys (renal strain), micronutrient deficiencies, and alterations in gut microbiota. Long-term benefits are debated, with evidence being limited and heterogeneous.

CONCLUSION: The ketogenic diet presents both promise and pitfalls in obesity management. While short-term benefits are evident, its safety and sustainability over extended periods require cautious evaluation. KD may be a useful short-term strategic tool for select individuals under clinical supervision, rather than a universal solution. Future study should focus on personalized ketogenic strategies integrated with broader lifestyle and nutritional frameworks.

PMID:40879882 | DOI:10.1007/s12013-025-01878-0

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