ORIGINAL RESEARCH Serum Zinc, Copper, Iron, and Magnesium Levels in Iranian Drug Users: A Case Control Study Ahmad Akbari, MD, Ghasem Mosayebi, MSc, PhD, Hassan Solhi, MD, Mohammad Rafiei, MSc, PhD, Azam Asadi, MD, and Ali Ghazavi, MSc, PhD Introduction: The changes in concentration of trace elements have effects on many organ systems, including the immune system. There have been conflicting reports on serum trace element levels in heroin users. This study was carried out to compare serum trace element concentrations in opium, heroin, and methamphetamine users. Methods: The study was done on 90 chronically illegal drug users (n = 30 per group) and 30 controls of the similar sex and age range (from 20 to 40 years). The control group was healthy subjects with no lifetime history of substance abuse or dependence. All of the sub- stance users were selected from among those who had a history of substance use, for a minimum of 1 year. Serum zinc (Zn), copper (Cu), iron (Fe), and magnesium (Mg) were measured spectrophoto- metrically using chemistry analyzer. Results: Serum Fe concentration was decreased in heroin (P = 0.026) and methamphetamine (P = 0.0001) users compared with healthy subjects, whereas serum Cu was higher in opium, heroin, and metham- phetamine users (P < 0.01). Copper was negatively and significantly correlated with Fe in all groups (P < 0.05). There was no statisti- cally significant difference between drug users and healthy subjects in serum concentrations of Zn and Mg. Conclusions: This study showed decreased in serum concentration of iron and increase in serum copper in drug users when compared with controls. Key Words: heroin, methamphetamine, opium, trace elements (J Addict Med 2015;9: 304–307) From the Arak University of Medical Sciences, Arak, Iran (A. Akbari and A. Asadi); Molecular and Medicine Research Center, Department of Im- munology, School of Medicine (GM), Department of Forensic Medicine & Toxicology (HS), Department of Biostatistics and Epidemiology (MR), and Tuberculosis and Pediatric Infectious Research Center (TPIRC), De- partment of Immunology, School of Medicine (AG), Arak University of Medical Sciences, Arak, Iran. Received for publication July 8, 2014; accepted April 7, 2015. The authors do not have any financial/commercial conflicts of interest in the study presented here. Send correspondence and reprint requests to Ali Ghazavi, MSc, PhD, Tubercu- losis and Pediatric Infectious Research Center, Department of Immunol- ogy, School of Medicine, Arak University of Medical Sciences, PO Box 3848176941, Arak, Iran. E-mail: ghazaviali@arakmu.ac.ir. Copyright C 2015 American Society of Addiction Medicine ISSN: 1932-0620/15/0904-0304 DOI: 10.1097/ADM.0000000000000134 I ncreasing rates of illegal drug use is one of the main chal- lenges in most countries (Drugs UNOo, 2010). Among il- legal drugs, opium, heroin, and methamphetamine have high rate of consumption in Iran (Ghazavi et al., 2013). There are several clinical reports showing an association between the use of illegal drugs and infectious diseases (Friedman et al., 2006; Drugs UNOo, 2010). Changes in trace element levels are one of the possible mechanisms involved in alterations of the immune system that increase susceptibility to infections. The concentrations of serum trace elements have been of inter- est to researchers for a number of years in many pathological conditions such as various infections and multiple sclerosis (El-Kholy et al., 1989; Ghazavi et al., 2011). The importance of appropriate levels of trace elements for protection against infections has been clearly established. Deficiencies of a number of trace elements alter the secretion of extracellular factors able to modulate the activities of im- mune cells and other cell types involved in the host response to infectious agents. However, it is also recognized that the needs of the host must be balanced against the possibility that exces- sive amounts of redox-active metals such as iron and copper can induce free radical mediated damage, and that infective agents also need the same trace elements for their survival and replication as the host (Failla, 2003). Zinc (Zn), copper (Cu), iron (Fe), and magnesium (Mg) are essential trace elements for the immune system. Various en- zymes that contribute to immune system responses require Zn and Cu as trace elements for their activity, which include cata- lase, superoxide dismutase, and glutathione peroxidase (Amini et al., 2009; Lal et al., 2013). Mechanisms by which immune cells kill microbes have been a subject of intense research in recent years. One of the mechanisms, the serum redistribu- tion of essential trace elements Zn, Cu, and Fe along with the increase in synthesis of acute-phase proteins, that takes part during most infections is now well established (Faryadi and Mohebali, 2003). Zinc deficiency has also been demonstrated to lead to a selective T helper type 1 deficiency in human subjects (Beck et al., 1997). Elevated Cu is thought to cause pathological changes induced in tissues by stimulating the production of free rad- icals, which damage multiple cells. Iron deficiency reduces total activity of protein kinase C (PKC) in activated T-cells, and therefore the carryover of PKC from the cytoplasm to the cis face of the cell membrane (Kuvibidila et al., 1999). Protein kinase C is crucial for phosphorylation of factors Copyright © 2015 American Society of Addiction Medicine. Unauthorized reproduction of this article is prohibited. 304 J Addict Med Volume 9, Number 4, July/August 2015