Research report Lower serum zinc in Chronic Fatigue Syndrome (CFS): Relationships to immune dysfunctions and relevance for the oxidative stress status in CFS Michael Maes a,b,c, * , Ivana Mihaylova a,b , Marcel De Ruyter d a M-Care4U Outpatient Clinics, Olmenlaan 9, 2610 Antwerp-Wilrijk, Belgium b Clinical Research Center for Mental Health, Olmenlaan 9, Wilrijk, Belgium c Department of Psychiatry, Vanderbilt University, Nashville TN, USA d Salvator Ziekenhuis, Salvatorstraat, Hasselt, Belgium Received 28 August 2005; received in revised form 29 October 2005; accepted 1 November 2005 Available online 9 December 2005 Abstract The present study examines serum zinc concentrations in patients with chronic fatigue syndrome (CFS) versus normal volunteers. Serum zinc levels were determined by means of an atomic absorption method. We found that serum zinc was significantly lower in the CFS patients than in the normal controls. There was a trend toward a significant negative correlation between serum zinc and the severity of CFS and there was a significant and negative correlation between serum zinc and the subjective experience of infection. We found that serum zinc was significantly and negatively correlated to the increase in the alpha2 protein fraction and positively correlated to decreases in the expression of mitogen-induced CD69+ (a T cell activation marker) on CD3+ as well as CD3+CD8+ T cells. These results show that CFS is accompanied by a low serum zinc status and that the latter is related to signs of inflammation and defects in early T cell activation pathways. Since zinc is a strong anti-oxidant, the present results further support the findings that CFS is accompanied by increased oxidative stress. The results of these reports suggest that some patients with CFS should be treated with specific antioxidants, including zinc supplements. D 2005 Elsevier B.V. All rights reserved. Keywords: Chronic fatigue syndrome; Zinc; Inflammation; Oxidative stress; Immunity; Cytokines; Depression 1. Introduction Chronic fatigue syndrome (CFS) is defined as a debilitating fatigue lasting at least six months with the presence of four of the following symptoms: sore throat, tender cervical and axillary lymph nodes, dif- ficulties concentrating, muscle or joint pain, unrefresh- ing sleep, sleep disorders, headache, and post-exertion malaise (Fukuda et al., 1994; NIAID, 1996; Maes, 2005). The onset of CFS is associated with a number of trigger factors, such as viral or bacterial infections, stressful life events, type IV allergies, exposure to toxins (e.g. heavy metals), and the leaky gut syndrome (Maes, 2005). There are now some studies which indicate that the pathophysiology of CFS is related to disturbances in the 0165-0327/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2005.11.002 * Corresponding author. M-Care4U Outpatient Clinics, Olmenlaan 9, 2610 Antwerp-Wilrijk, Belgium. Tel.: +32 3 4809282; fax: +32 3 2889185. E-mail address: crc.mh@telenet.be (M. Maes). URLs: http://www.nfb.be, http://www.ediver.be, http://www.mcare4u.com, http://www.marquiswhoswho.net/MMAES/, http://hcr3.isiknowledge.com/author.cgi?&link1=Browse&link2= Results&id=5139 (M. Maes). Journal of Affective Disorders 90 (2006) 141 – 147 www.elsevier.com/locate/jad