Investigating the Roles of SAA1, Insulin, and Lipid Profiles in Acne Pathogenesis and Severity

A recent prospective cohort study investigated the relationship between acne vulgaris and levels of serum amyloid A1 (SAA1) and insulin, with the goal of exploring their potential roles in disease pathogenesis, severity, and scar formation.¹ While hormonal and metabolic pathways are known contributors to acne development, growing attention has focused on inflammatory biomarkers that may help clarify systemic components of the disease.

Study Design and Demographics

The study enrolled 72 patients with acne and 66 age-matched healthy controls. Participants were between 18 and 45 years of age and had not received topical or systemic acne treatment for at least 3 months prior to enrollment. All patients underwent fasting blood sampling after a minimum 12-hour fast, and biochemical parameters—including lipid profiles, C-reactive protein (CRP), insulin, and SAA1—were measured. SAA1 and insulin levels were quantified using enzyme-linked immunosorbent assay (ELISA).

Clinical severity of acne was evaluated using the Global Acne Grading System (GAGS), while acne scarring was assessed using the Global Scale for Acne Scar Severity. The acne cohort had a mean GAGS score of 17.6 ± 7.7, reflecting a range of mild to moderate disease. Scar severity assessments showed that most patients had mild scarring: 22.2% were classified as almost clear, 51.4% had mild scars, 23.6% had moderate scars, and 2.8% had severe scars.

A total of 138 patients were included in the final analysis. The 2 groups were similar in age, with a median age of 22 years in both cohorts. However, the acne group had a significantly higher proportion of female participants compared with controls (82% vs 59%). BMI and several biochemical markers, including CRP and high-density lipoprotein (HDL), did not differ significantly between the groups.

SAA1 & Insulin Level Results

The primary finding was that SAA1 levels were significantly higher in patients with acne compared with healthy controls. SAA1 is an acute-phase reactant produced by the liver in response to proinflammatory cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor–α. It plays a role in systemic inflammatory responses and can promote recruitment of neutrophils and monocytes to sites of inflammation.² Elevated SAA1 levels in acne patients support the concept that acne involves not only local cutaneous inflammation but also measurable systemic inflammatory activity.

Despite the elevation in SAA1 levels among acne patients, no significant correlations were observed between SAA1 concentrations and either acne severity or scar severity. This suggests that SAA1 may reflect the presence of inflammation associated with acne but may not serve as a reliable indicator of disease intensity or clinical progression. According to the authors, the lack of correlation may also reflect the multifactorial nature of acne severity, which is influenced by hormonal, genetic, environmental, and microbial factors.

In contrast to SAA1, insulin levels did not differ significantly between the acne and control groups, and no association was observed between insulin levels and acne severity. Insulin has been proposed to contribute to acne development through mechanisms related to insulin resistance and hyperinsulinemia, which may increase sebaceous gland activity and promote follicular hyperkeratinization.³ However, the findings of this study suggest that insulin levels alone may not be a consistent biomarker for acne severity and that metabolic influences on acne likely involve more complex pathways.

Lipid Level Results

Interestingly, the study identified several differences in lipid parameters between the groups. Patients with acne had significantly lower levels of low-density lipoprotein (LDL), triglycerides, and total cholesterol compared with controls, although these values remained within normal reference ranges. Further analysis revealed weak but statistically significant negative correlations between both acne severity and scar severity and levels of LDL and total cholesterol.

The relationship between inflammation and lipid metabolism may partly explain these observations. SAA1 is known to interact with lipoproteins and can displace apolipoprotein A-I from HDL particles, potentially altering lipid metabolism during inflammatory states. Elevated SAA1 levels may also form complexes with LDL, which could contribute to the lower circulating LDL levels observed in the acne group.

These findings support the concept that inflammatory processes in acne may influence systemic metabolic pathways, although the clinical significance of these lipid changes remains uncertain. The authors note that behavioral factors may also contribute to differences in lipid profiles. For example, individuals with acne may modify their diets to avoid foods perceived to exacerbate acne, potentially reducing intake of dietary fats and cholesterol. However, the observed correlations between lipid levels and disease severity suggest that inflammatory mechanisms, rather than diet alone, may play a role.

Conclusion

Overall, the findings suggest that SAA1 may represent a novel biomarker reflecting inflammatory activity in patients with acne vulgaris. Although SAA1 levels were elevated in affected patients, the lack of correlation with disease severity indicates that its role may be limited to just indicating the presence of inflammation rather than predicting clinical outcomes. Larger, longitudinal studies incorporating detailed metabolic and inflammatory analyses will be necessary to further clarify.

References

1. Hizli P, İçöz Aytaç S, Baykan Ö, Öklü M, Kiliç FA. The Association of Acne Vulgaris and Disease Severity With Serum Amyloid A1 and Insulin Levels. J Cosmet Dermatol. 2026;25(3):e70720. doi:10.1111/jocd.70720

2. He R, Sang H, Ye RD. Serum amyloid A induces IL-8 secretion through a G protein-coupled receptor, FPRL1/LXA4R. Blood. 2003;101(4):1572-1581. doi:10.1182/blood-2002-05-1431

3. Emiroğlu N, Cengiz FP, Kemeriz F. Insulin resistance in severe acne vulgaris. Postepy Dermatol Alergol. 2015;32(4):281-285. doi:10.5114/pdia.2015.53047