Tabriz University of Medical Sciences Health Promotion Perspectives 2228-6497 16 3 2026 11 05 The Effects of Combination of Hydro Alcoholic Extracts of Nigella Sativa and Linum Usitatissimum on General Health, Fatigue and Its Contributing Factors in Relapsing-Remitting Multiple Sclerosis; a Pilot Randomized Double-blind Placebo-Controlled Clinical Trial 368 377 10.34172/hpp.44662 EN Amirreza Naseri https://orcid.org/0000-0001-9723-0109 Sarvin Sanaie https://orcid.org/0000-0003-2325-5631 Shahriar Parvaneh https://orcid.org/0000-0003-0709-5017 Danyal Salabat https://orcid.org/0009-0007-4256-1892 Hanie Karimi https://orcid.org/0000-0001-9941-0437 Anahita Najafi https://orcid.org/0000-0002-9191-9172 Reza Mosaddeghi-Heris https://orcid.org/0000-0002-3353-1102 Sanaz Hamedeyazdan https://orcid.org/0000-0002-8950-9879 Mirsobhan Mousavi https://orcid.org/0009-0008-5576-1225 Malihe Talebi Mahnaz Talebi https://orcid.org/0000-0002-7613-3913 Mostafa Araj-Khodaei https://orcid.org/0000-0002-2590-8467 Journal Article 10.34172/hpp.44662 2025 05 20 2026 01 31 Introduction: Fatigue is one of the most common and debilitating symptoms experienced by multiple sclerosis (MS) patients. This study aimed to evaluate the effects of combination of hydroalcoholic extracts of Nigella sativa and Linum Usitatissimum on general health, fatigue and its contributing factors in patients with relapsing-remitting MS (RRMS). Methods: In this parallel-group, randomized, double-blind, placebo-controlled pilot clinical trial, patients diagnosed with RRMS based on the 2017 McDonald criteria, with Expanded Disability Status Scale (EDSS)<4.5, and experiencing fatigue were enrolled. Participants were randomly assigned to receive the either the herbal supplement (n=25) or placebo (n=25). Capsules were administered twice daily over a period of three months. Fatigue and its contributing factors were assessed using the Comprehensive Fatigue Assessment Battery for Multiple Sclerosis (CFAB-MS) at baseline and at the end of the interventions. Result: A total of 35 patients completed the trial, 17 in the intervention group and 18 in the placebo group. Based on the visual analogue scale (VAS) for general health, the intervention group showed a statistically significant improvement in nutritional status (p-value:0.009). However, no significant differences were observed between the groups in terms of physical, mental, and social fatigue, pain, sleep disturbances, stress, mood, anxiety and worry, nutrition, environmental interactions, or fatigue management indices (P-values>0.05). Conclusion: Based on this preliminary research, three months of supplementation with a combination of hydroalcoholic extracts of N. sativa and L. Usitatissimum did not produce a significant improvement in fatigue and its associated factors among patients with RRMS.