Abstract
BACKGROUND: Acne vulgaris (AV) is a chronic inflammatory dermatological condition, and its underlying pathogenesis may be associated with dyslipidemia. Omega-3 fatty acids regulates lipid metabolism and reduce inflammation. However, their effects on blood lipids in AV have not yet been reported. This study’s objective is to investigate the serum lipid metabolomic differences between patients and healthy individuals and explore the effects of isotretinoin combined with omega-3 fatty acids on serum lipid metabolism in AV. METHODS: Between July 2020 and June 2021, 46 patients with acne vulgaris and 20 healthy controls were recruited from the Affiliated Hospital of Southwest Medical University. Untreated patients were randomly allocated to receive oral isotretinoin combined with or without omega-3 fatty acids for 6 months. Serum lipid metabolomics was performed using liquid chromatography-tandem mass spectrometry (LC-MS). Statistical analysis of the lipid metabolites was conducted by partial least squares-discriminant analysis (PLS-DA). Correlations between differential lipid metabolites and disease severity indicators were tested by Spearman’s correlation analysis. Metabolic pathways in the isotretinoin and omega-3 combination treatment group were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. RESULTS: PLS-DA showed a clear separation of serum lipid metabolites between healthy controls and AV patients, with the combination treatment group showing a trend towards the healthy controls. The lipid metabolite composition of the combination treatment group showed significant changes, with 245 differential metabolites identified before and after treatment (P < 0.05). The Spearman’s coefficient showed a strong correlation between the serum level of StE (20:5) (6.44 ± 0.33 vs.7.18 ± 0.22, P < 0.001) and the Global Acne Grading System score (R = 0.73, P < 0.001). The KEGG analysis identified 18 different pathways before and after treatment in the combination treatment group. CONCLUSIONS: We found that omega-3 fatty acid supplementation improved the clinical responses in AV patients, correlating with improved lipid metabolism, thereby confirming its potential as a valuable adjunct therapeutic strategy. TRIAL REGISTRATION: The comprehensive clinical trial protocol has been retrospectively registered on the ISRCTN Registry of Clinical Trials website (NO. ISRCTN31758284) on 2022/07/09. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12944-026-02902-9.