Effects of a cow’s milk protein–free diet as an adjunct to standard therapy in juvenile idiopathic arthritis: a randomized controlled study

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disorder, characterized by chronic idiopathic joint inflammation in children under sixteen years of age. Emerging evidence suggests that food allergens- particularly cow's milk proteins may modulate inflammatory pathways, and that their elimination could potentially ameliorate disease activity. This study aimed to evaluate through a randomized controlled clinical trial whether eliminating cow's milk protein from the diet influences disease activity and symptom severity in children with JIA. METHODS: In this randomized controlled trial, 120 children with controlled juvenile idiopathic arthritis (JIA) receiving stable standard therapy were randomly allocated to either a cow's milk protein-free diet (intervention group, n = 60) or an unrestricted diet (control group, n = 60) for one month. Disease activity was assessed at baseline and post-intervention using subjective measures (patient- and physician-reported Visual Analog Scale [VAS]) and objective parameters, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), active joint count, morning stiffness duration, fever. RESULTS: Compared with baseline, the intervention group demonstrated statistically significant improvements in multiple outcomes, including patient VAS (2.9 ± 1.9 to 1.7 ± 1.4; P < 0.001), physician VAS (2.5 ± 1.8 to 1.6 ± 1.3; P < 0.001), ESR (14.6 ± 13.7 to 9.4 ± 7.3 mm/hr; P < 0.001), CRP (7.3 ± 13.7 to 2.5 ± 3.6 mg/dL; P = 0.011), morning stiffness duration (6.1 to 0.6 min; P = 0.002), active joint count (0.55 to 0.11; P < 0.001), and Disease Activity Score (5.53 ± 4.44 to 3.0 ± 2.6; P < 0.001). In contrast, the control group exhibited only minor or non-significant changes. CONCLUSION: In children with well-controlled JIA, a cow's milk protein-free diet was associated with modest short-term improvements in pain and disease activity. These findings suggest a potential adjunctive benefit alongside standard therapy, but the short duration, low baseline disease activity, and reliance on parental self-report warrant cautious interpretation. ETHICAL CONSIDERATION AND TRIAL REGISTRATION: The protocol of this clinical trial has been registered in the Iranian Clinical Trial Registration Center (registration code: IRCT20241230064216N1). Registered 28 April 2025, available from https://irct.behdasht.gov.ir/search/result?query=IRCT20241230064216N1, and ethical approval was obtained from the Ethics Committee of Shahid Beheshti University of Medical Sciences, registered 10 November 2024 (Ethics Code: IR.SBMU.MAP.REC.1403.531).