Research Progress on the Effects of Immunonutrition on Oral Mucositis and Nutritional Status in Patients with Head and Neck Cancer Undergoing Radiotherapy

Patients with head and neck cancer (HNC) undergoing radiation therapy (RT) frequently face oral mucositis (OM), a challenging and highly prevalent acute toxic reaction. OM not only causes severe pain, dysphagia, and impaired nutritional intake but also intertwines with malnutrition to form a vicious cycle that is difficult to break, thereby significantly compromising treatment efficacy and patients’ quality of life. While traditional nutritional support can barely maintain basic energy supply, it proves inadequate in modulating the cytokine storm and immune response. In contrast, immunonutrition, as an emerging therapeutic paradigm, attempts to exert “pharmacological-level” regulatory effects by precisely incorporating specific components such as arginine, ω-3 polyunsaturated fatty acids (EPA, DHA), and nucleotides into standard formulas, aiming to suppress inflammation and oxidative stress while providing nutrients. In recent years, the academic community has focused on immunonutritional formulations represented by IMPACT®, deeply exploring their clinical value in the HNC radiotherapy population. This review aims to systematically organize and analyze relevant evidence to discuss how immunonutrition intervenes in the prevention and management of oral mucositis and improves patients’ nutritional status. Existing data suggest that immunonutritional intervention can not only effectively reduce the incidence of severe (grade ≥3) oral mucositis and alleviate its severity and progression but also demonstrate unique advantages in stabilizing patient body weight, lean body mass (muscle mass), and plasma protein levels (albumin, prealbumin), holding promise for breaking the causal chain between malnutrition and mucositis. Its underlying mechanisms may stem from recalibrating the balance of pro-inflammatory/anti-inflammatory cytokines (e.g., downregulating IL-6 and TNF-α while upregulating IL-10), reinforcing the body’s antioxidant defenses, and maintaining lymphocyte count and function. Certainly, existing research results still exhibit heterogeneity, often involving multiple variables such as timing of intervention, dosage range, duration of treatment, subject characteristics, and control settings. Looking ahead, there is an urgent need for more rigorously designed, large-sample multicenter randomized controlled trials, supplemented by in-depth mechanistic exploration and long-term follow-up, to clarify the optimal strategies, cost-effectiveness, and true impact on long-term prognosis of immunonutrition in supportive care for HNC radiotherapy.