Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome Jacopo Vecchiet a , Francesco Cipollone a , Katia Falasca a , Andrea Mezzetti a , Eligio Pizzigallo a , Tonino Bucciarelli b , Silvana De Laurentis a , Giannapia Affaitati a , Domenico De Cesare a , Maria Adele Giamberardino * a Department of Medicine and Science of Aging,‘G. D’Annunzio’ University of Chieti, Italy b Department of Biochemical Science,‘G. D’Annunzio’ University of Chieti, Italy Received 31 July 2002; received in revised form 12 September 2002; accepted 12 September 2002 Abstract In 21 patients with chronic fatigue syndrome (CFS) versus 20 normal subjects, we investigated the oxidant/antioxidant balance and its correlation with muscle symptoms. Patients versus controls showed significantly: lower Lag Phase and Vitamin E (Vit E) concentrations in plasma and low-density lipoproteins (LDL), higher LDL thiobarbituric acid reactive substances (TBARS), higher fatigue and lower muscle pain thresholds to electrical stimulation. A significant direct linear correlation was found between fatigue and TBARS, thresholds and Lag Phase, thresholds and Vit E in plasma and LDL. A significant inverse linear correlation was found between fatigue and Lag Phase, fatigue and Vit E, thresholds and TBARS. Increased oxidative stress and decreased antioxidant defenses are related to the extent of symptomatology in CFS, suggesting that antioxidant supplementation might relieve muscle symptoms in the syndrome. q 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Oxidative stress; Chronic fatigue syndrome; Vitamin E; Lag Phase; Thiobarbituric acid reactive substances; Muscle pain thresholds Chronic fatigue syndrome (CFS) is characterized by persistent and relapsing fatigue, lasting at least 6 months, not resolved by rest, causing a marked reduction of working activity and exacerbated by minimal physical exercise. Fati- gue is accompanied by secondary symptoms including sore throat, memory and concentration impairments, headache, sleep disorders, but most often muscle and joint pain. CFS diagnosis is performed according to standardized clinical criteria established by the Centers for Disease Control (CDC) [5]. The pathophysiology of the syndrome, whose onset often coincides with an acute viral illness, remains unclear, and this is reflected in a still empirical therapeutic approach [10,16,17]. A recent hypothesis claims that oxidative stress (OS) could play an important role in the etiology of CFS and suggests that the use of antioxidants might be useful in the treatment of the syndrome. Increased OS, resulting from an imbalance between oxidant attack due to free radical production and antioxidant defense [11], has indeed been documented in several studies in CFS patients, both in plasma and in muscle (oxidative damage to DNA and lipids in muscle specimens) [6,8,10]. It remains a matter of debate, however, whether and to what extent the oxidant/antioxi- dant imbalance directly accounts for all aspects of CFS symptomatology. Very few attempts, in fact, have so far been made to correlate the biochemical with the clinical parameters in standardized conditions [14]. In particular, no study has tried to relate OS indices to the change in pain sensitivity in muscles, i.e. the diffuse muscle hyperal- gesia (in contrast to subcutis and skin normosensitivity) that has proved a characteristic objective clinical marker of the syndrome [16]. Further experimental support is thus needed for a rationale for supplementation with antioxidants to control the clinical symptoms [10,14]. In the present study we therefore investigated CFS patients versus sex/age-matched controls for the potential impact of circulating OS on musculoskeletal complaints. Neuroscience Letters 335 (2003) 151–154 0304-3940/02/$ - see front matter q 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S0304-3940(02)01058-3 www.elsevier.com/locate/neulet * Corresponding author. Tel./fax: 139-0871-565286. E-mail address: mag@unich.it (M.A. Giamberardino).