Isotretinoin-induced skin dryness and the therapeutic role of omega-3 fatty acids

The management of severe, recalcitrant nodulocystic acne has been revolutionized by the clinical deployment of isotretinoin, a first-generation systemic retinoid that remains the most potent therapeutic intervention. Despite its unparalleled capacity to induce long-term remission by targeting all major pathogenic factors of acne vulgaris, including sebaceous gland hyperactivity, follicular hyperkeratinization, microbial colonization by Cutibacterium acnes, and local inflammatory responses, isotretinoin is characterized by a predictable and often debilitating profile of adverse effects. Its potent sebum-suppressive mechanism simultaneously disrupts the epidermal barrier, resulting in dose-dependent xerosis, cheilitis, nasal dryness, and ocular dryness that compromise treatment adherence. This can significantly impair patient quality of life and treatment adherence. Omega-3 polyunsaturated fatty acids (PUFAs), principally eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have emerged as a promising adjunctive intervention, given their anti-inflammatory, immunomodulatory, and skin-barrier-enhancing properties. This review synthesizes evidence from randomized controlled trials, observational studies, and systematic reviews published predominantly between 2015 and 2026. The available data consistently indicate that concurrent oral omega-3 supplementation (1 g/day) significantly reduces the frequency and severity of isotretinoin-induced mucocutaneous side effects, including skin dryness, lip dryness, nasal dryness, and conjunctivitis. Proposed mechanisms include modulation of peroxisome proliferator-activated receptors (PPARs), suppression of pro-inflammatory cytokine pathways via nuclear factor-kappa B (NF-κB) inhibition, production of specialized pro-resolving mediators (SPMs), and reduction of trans-epidermal water loss (TEWL). Despite encouraging findings, the evidence base is limited by small sample sizes, heterogeneous dosing, and short follow-up durations. This review calls for larger, well-powered randomized trials and more nuanced mechanistic studies to establish standardized supplementation protocols.