Breaking the metabolic-inflammatory vicious cycle in polycystic ovary syndrome: a comparative review of ketogenic and high-fat diets.

Publisher: BioMed Central Country of Publication: England NLM ID: 101147696 Publication Model: Electronic Cited Medium: Internet ISSN: 1476-511X (Electronic) Linking ISSN: 1476511X NLM ISO Abbreviation: Lipids Health Dis Subsets: MEDLINE

Original Publication: [London] : BioMed Central, 2002-

Polycystic Ovary Syndrome*/diet therapy ; Polycystic Ovary Syndrome*/metabolism ; Polycystic Ovary Syndrome*/pathology ; Diet, High-Fat*/adverse effects ; Inflammation*/diet therapy ; Inflammation*/metabolism ; Inflammation*/pathology ; Diet, Ketogenic*; Adipose Tissue/metabolism ; Adipose Tissue/pathology ; Humans ; Female ; Insulin Resistance ; Lipid Metabolism ; Animals ; Gastrointestinal Microbiome

Polycystic ovary syndrome (PCOS) is a multifactorial metabolic-endocrine disorder in women of reproductive age in which lipid metabolism disorders and chronic low-grade inflammation reinforce and amplify each other. Recently, the ketogenic diet (KD), which is a high-fat, very-low-carbohydrate dietary intervention, has drawn attention because of its metabolic regulation and anti-inflammatory properties. This review integrates current evidence to elucidate how aberrant fatty acid turnover, adipose tissue dysfunction, and adipokine imbalance trigger convergent proinflammatory pathways, thus forming an "inflammatory hub" that links insulin resistance, hyperandrogenemia, impaired folliculogenesis, and heightened cardiovascular risk in PCOS. The mechanisms by which strict carbohydrate restriction promotes fatty acid β-oxidation and hepatic ketogenesis are delineated, thereby reprogramming cellular metabolism. The principal ketone body, β-hydroxybutyrate, directly suppresses the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 inflammasome, remodels the gut microbiota, and attenuates nuclear factor kappa-light-chain-enhancer of activated B cells signaling, thus yielding multitarget anti-inflammatory effects. Unlike isocaloric high-fat diets, which lead to obesity, inflammation, and insulin resistance, the KD lowers triacylglycerols and the proportion of small, dense low-density lipoprotein particles; enhances whole-body insulin sensitivity; and mitigates systemic inflammation. Collectively, the KD offers a multidimensional intervention that couples metabolic correction with immune modulation and holds promise for improving PCOS trajectories and long-term complications. Nevertheless, its long-term safety profile, lipid subclass optimization, and biomarker-driven personalization require further investigation.
(© 2025. The Author(s).)

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

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Keywords: Inflammation; Ketogenic diet; Lipid metabolism; Polycystic ovary syndrome

Date Created: 20251007 Date Completed: 20251007 Latest Revision: 20251009

20260130

PMC12502164

10.1186/s12944-025-02693-5

41053819