W. Yang, N. Pang and X. He (2025). Breaking the metabolic-inflammatory vicious cycle in polycystic ovary syndrome: a comparative review of ketogenic and high-fat diets. Lipids in health and disease, 24(1), 310. https://doi.org/10.1186/s12944-025-02693-5

PubMed 41053819

[Abstract]
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.