Oral myo-inositol plus D-chiro-inositol (3.6:1) reduces insulin resistance pathway biomarkers in acne-involved skin among subjects with metabolic comorbidities: A gene expression study.

BACKGROUND: Hyperinsulinemia and insulin resistance promote acne pathogenesis through reduced Forkhead box protein O1 (FOXO1) signaling and increased mechanistic target of rapamycin (MTOR) and insulin-like growth factor-1 (IGF1) activity. While oral myo-inositol (MI) and D-chiro-inositol (DCI) supplementation may improve insulin sensitivity, evidence regarding direct pathway modulation in acne-involved skin remains limited. In this exploratory, single-arm, uncontrolled study, we sought to investigate the effects of oral MI/DCI (3.6:1 ratio) on cutaneous expression of these biomarkers in adults with acne and metabolic comorbidities (polycystic ovary syndrome or metabolic syndrome). METHODS: Forty-five adults with active inflammatory acne on the back were enrolled across three subgroups of 15 - including women with polycystic ovary syndrome (PCOS), women with metabolic syndrome (MetS), and men with MetS. All participants received oral MI/DCI (1100 mg + 300 mg daily) for 12 weeks in a single-arm, open-label, pre-post biopsy study. Paired punch biopsies of acne-involved skin were obtained before and after supplementation, and FOXO1, MTOR, and IGF1 mRNA expression was quantified by qRT-PCR. Clinical response was assessed by Investigator Global Improvement rating. RESULTS: Following the 12-week supplementation, FOXO1 expression increased (Cohen's d = +1.13; p < 0.001), whereas MTOR (Cohen's d = -3.46; p < 0.001) and IGF1 (Cohen's d = -1.62; p < 0.001) decreased significantly compared with baseline. Changes were directionally consistent across all subgroups. Clinical improvements were observed in 82.2% of participants. Plasma testosterone in men remained stable (p = 0.638). CONCLUSIONS: In this exploratory, uncontrolled study, 12 weeks of oral MI/DCI supplementation (3.6:1 ratio) was associated with significant changes in insulin resistance pathway gene expression in acne-involved skin. These findings provide preliminary mechanistic support for further randomized, controlled trials evaluating MI/DCI as a potential adjunctive strategy in acne associated with metabolic comorbidities.