The role of lipid metabolism in acne risk: integrating blood metabolite and genetic insights
Authors: Liu Mingjuan , Diaz-Torres Santiago , Mitchell Brittany L , Toledo-Flores Deborah , Gharhakhani Puya , Simpson Michael A , Zhang Hanlin , Ong Jue-Sheng , Li Jun , Rentería Miguel E 
Published: February 2025

Abstract

Background
Acne vulgaris is a chronic inflammatory skin condition that significantly impacts an individual's quality of life, affecting social interactions, self-esteem and body image. It primarily targets the pilosebaceous unit, where inflammation occurs. Lipid metabolism is crucial in maintaining the skin barrier and modulating inflammatory responses, with specific fatty acids, such as ω-3 and sphingomyelin acid, playing key roles. Previous studies have highlighted associations between specific dietary habits and acne, yet the precise relationship between lipid profiles, particular fatty acids, dietary patterns and acne, remains inadequately understood. This gap in knowledge necessitates a deeper investigation into the mechanisms linking lipid metabolism with acne risk.

Objectives
To investigate the causal association between acne risk and 143 dietary habits alongside 229 blood metabolite markers, focusing on lipid metabolism.

Methods
Using a Mendelian randomization (MR) framework, we leveraged summary statistics data from genome-wide association studies to explore the associations between blood lipid metabolites, dietary factors and acne risk. We used statistical correction methods, including Bonferroni and false discovery rate (FDR) adjustments, to identify robust significant associations.

Results
Our MR analysis identified 10 lipid metabolites significantly associated with acne risk. After applying Bonferroni and FDR corrections, we pinpointed 10 and 27 serum indices or metabolites, respectively, as significantly linked to acne risk. The most prominent protective factors against acne included a higher ratio of polyunsaturated fatty acids to monounsaturated fatty acids (MUFAs) [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.65–0.83, P = 5.96×10−7]; a higher ratio of docosahexaenoic acid (DHA) to total fatty acids (OR 0.80, 95% CI 0.72–0.88, P = 6.64×10−6); and a higher ratio of ω-3 fatty acids to total fatty acids (OR 0.86, 95% CI 0.80–0.92, P = 7.54×10−6) and sphingomyelin acid (OR 0.80, 95% CI 0.72–0.88, P = 1.03×10−5). Conversely, the most significant risk factors for acne included elevated ratio of MUFAs to total fatty acids (OR 1.27, 95% CI 1.14–1.40, P = 6.21×10−6), higher ratio of triglycerides to total lipids in large high-density lipoprotein (OR 1.23, 95% CI 1.12–1.36, P = 1.36×10−5) and an increased ratio of ω-6 to ω-3 fatty acids (OR 1.16, 95% CI 1.08–1.24, P = 3.19×10−5).

Conclusion
Our study highlights the causal relationship between lipid markers and acne. Specifically, we identified 10 lipid traits, including monounsaturated and polyunsaturated fatty acids, ω-3/ω-6 and sphingomyelins, that influence acne development. These findings align with existing evidence on the role of lipids in skin health and comedogenesis. Further research is warranted to explore underlying mechanisms and assess the impact of dietary fats on acne, as well as to evaluate targeted interventions for diverse patient subgroups.