ORIGINAL RESEARCH Preventive Effects of 10-Day Supplementation With Saffron and Indomethacin on the Delayed-Onset Muscle Soreness Abbas Meamarbashi, PhD and Ali Rajabi, MSc Objective: Delayed-onset muscle soreness (DOMS) often occurs after unaccustomed eccentric exercise and reduces exercise perfor- mance. We aimed to study the preventive effects of saffron and indomethacin on the biochemical and functional indicators of DOMS after 1-session eccentric exercise. Design: A 10-day, randomized, double-blind, placebo-controlled, pretest–posttest design. Setting: Controlled research laboratory. Participants: Thirty-nine nonactive male university students randomly divided into saffron (n = 12), indomethacin (n = 12), and control (n = 15) groups. Interventions: Saffron group received 1 capsule containing dried saffron powder (n = 12, 300 mg/d), indomethacin group received 75 mg indomethacin (n = 12, 25 mg thrice a day), and control group (n = 15) received placebo capsules, 1 week before and 3 days after eccentric exercise. Ten days before and 24, 48, and 72 hours after muscle soreness protocol, the maximum isometric and isotonic forces, plasma creatine kinase (CK), plasma lactate dehydrogenase (LDH), perceived pain, knee range of movement, and thigh circum- ference were measured. Muscle soreness protocol was performed with a weight load equal to 80% of the maximum isotonic force in 4 sessions with 20 repetitions and 3-minute rest in between. Main Outcome Measures: This study shows that 10-day supplementation with 300 mg saffron significantly decreased the CK and LDH concentrations (P , 0.0001). In the saffron group, there was no decline in maximum isometric and isotonic forces after eccentric exercise, but a significant decline in the isometric force was observed in the control group (P , 0.0001). No pain was reported in the saffron group, whereas the indomethacin group experienced pain before 72 hours (P , 0.001). Conclusions: Results obtained from the current novel research indicate a strong preventive effect of 10-day supplementation with saffron on the DOMS. Clinical Relevance: The saffron can be used to prevent DOMS and alleviate the DOMS symptoms. Key Words: saffron, indomethacin, delayed-onset muscle soreness, creatine kinase, lactate dehydrogenase, isometric and isotonic forces (Clin J Sport Med 2014;0:1–8) INTRODUCTION Delayed-onset muscle soreness (DOMS) is associated with pain and discomfort in the first few days after a strenuous exercise session. Eccentric muscular contractions in downhill running, hopping, plyometric exercise, squatting, and during the lowering phase of lifting weights can produce DOMS. 1 Athletes are concerned about muscular discomfort and pain phenomena because it can limit their exercise and training activity. 2 The main symptoms in DOMS are muscular stiff- ness, tenderness, and pain during active movements. 3,4 There are many symptoms related to the muscle inflammation and damage such as muscle fibre swelling, 5 elevated serum activ- ities of muscle specific enzymes such as the creatine kinase (CK) and lactate dehydrogenase (LDH), 6,7 reduced muscle strength, 1 and knee joint range of movement (ROM). 8 Eccentric exercise has series of effects in the cell membrane, causing an inflammatory response that leads to production of prostaglandin E 2 and leukotrienes. The muscle microscopic injury is instigated by a mechanical disruption to sarcomeres, 9 T-tubules, myofibrils, cytoskeletal protein, and the sarcoplasmic reticulum, 10–12 which leads to an inflamma- tory response. 13 After muscle injury, enzymatic reactions and inflammatory mediators such as thromboxanes, prostaglandins, and leukotrienes from the cyclooxygenase and lipoxygenase pathways correspond to increases in vascular permeability and pain perception by sensitizing the types III and IV afferent nerve fibres to both chemical and mechanical stimuli. 1 The magnitude of force loss after eccentric exercise has been claimed to be the best indirect marker of muscle soreness. 14 Mechanism of maximal force reduction in DOMS is thought to be secondary to sarcomere “popping” and disorganization, 15 as well as damage to components of the excitation–contraction coupling process. 16,17 Prevention and treatment strategies to alleviate the symptoms and signs of DOMS are numerous and varied, including pharmacological (eg, nonsteroidal anti-inflammatory medications), 18–20 exercise, 19,21–24 stretching, 19,21,22 whey pro- tein, 25 fish oil, isoflavones, 26 caffeine, 27 L-carnitine, 28 herbs, 29 antioxidant vitamins, 30 cryotherapy, 19,31–34 transcutaneous elec- trical nerve stimulation, 32 and ultrasound. 24,35 However, these Submitted for publication August 7, 2013; accepted March 5, 2014. From the Department of Physical Education and Sports Sciences, University of Mohaghegh Ardabili, Ardabil, Iran. Supported by the university postgraduate thesis grant M416. A. Meamarbashi was an employee of University of Mohaghegh Ardabili at the time of this study, and A. Rajabi was an MSc student during this study in the University of Mohaghegh Ardabili. Corresponding Author: Abbas Meamarbashi, PhD, Department of Physical Education and Sports Sciences, University of Mohaghegh Ardabili, Ardabil 56199-11367, Iran (a_meamarbashi@yahoo.com). Copyright © 2014 by Lippincott Williams & Wilkins Clin J Sport Med  Volume 0, Number 0, Month 2014 www.cjsportmed.com | 1 Copyright ª Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.