Rheumatol Int (2008) 28:1117–1121 DOI 10.1007/s00296-008-0593-9
O R I G I N A L A R T I CL E
The relationship between serum trace element levels and clinical parameters in patients with Wbromyalgia Omer Faruk Sendur · Engin Tastaban · Yasemin Turan · Cevval Ulman
Received: 31 December 2007 / Accepted: 29 April 2008 / Published online: 22 May 2008 © Springer-Verlag 2008
Abstract We examined the association between serum trace elements and clinical Wndings such as number of sensitive tender points, severity of fatigue and functional status in patients with Wbromyalgia (FM). Thirty-two patients diagnosed as having FM according to the ACR 1990 criteria and 32 normal healthy controls (NHC) were included in this study. The demographic data, disease duration, number of tender points and accompanying symptoms (fatigue, sleep disorders, headache, paresthesia, irritable bowel syndrome, sicca symptoms, Raynaud’s phenomena) of the patients were noted. Visual analog scale (10 cm) was implemented to estimate daily severity of pain and fatigue. Fibromyalgia impact questionnaire was used for functional assessment. Serum selenium (g/dL) and serum zinc (g/dL) levels were measured by atomic absorption spectrometer. Serum magnesium (mmol/L) level was measured by the original kits of Abbott Aeroset auto-analyzer. The mean age of patients in FM group and NHC were calculated as 42.9 (SD = 7.7) years and 41.3 (SD = 9.7) years, respectively. Serum levels of zinc (P = 0.001) and magnesium (P = 0.002) were signiWcantly decreased
O. F. Sendur · E. Tastaban · Y. Turan Department of Physical Medicine and Rehabilitation, Adnan Menderes University Medicine School Hospital, Aydin, Turkey C. Ulman Department of Biochemistry, Celal Bayar University Medicine School Hospital, Manisa, Turkey Y. Turan (&) 240 sk No: 2/1 D:4, Bornova, 35040 Izmir, Turkey e-mail:
[email protected]
by FM groups, whereas there was no considerable diVerence with selenium levels of both groups (P > 0.05). Association between serum zinc level and number of tender points (P = 0.008) and that between fatigue and magnesium level (P = 0.003) was found as meaningful. According to the results of this study, it was asserted that serum magnesium and zinc levels may play an important role in the pathophysiology of FM. Keywords Fibromyalgia · Selenium · Zinc · Magnesium · Clinical Wndings
Introduction Fibromyalgia (FM) is a rheumatic disorder characterized by musculoskeletal pain, stiVness and tenderness of speciWc anatomic sites that are called tender points [1]. FM is a chronic pain disorder that often leads to widespread functional impairment and constraints the quality of life of many patients. The etiology of FM is still unknown and also it is associated with many factors and predictors [2, 3]. Trace elements such as selenium and zinc are essential for many antioxidant enzymes as cofactor [4–7]. Magnesium is a trace element, which plays a considerable role in ATP synthesis and it is important for adequate muscle metabolism. Reduction of blood Xow and ATP beneath the tender points and local hypoxia are important factors in progress of patients with FM [8]. DeWciency in trace elements may take part in pathophysiologia of Wbromyalgia and it contributes to clinical symptoms [9]. Within this study, it is fundamentally aimed to investigate serum magnesium, selenium, zinc levels and their correlation between clinical Wndings and functional status in patients with FM.
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Materials and methods Thirty-two patients diagnosed as having FM according to the ACR 1990 criteria [10] and 32 normal healthy individuals (NHC) were included in this study after receiving approval of the local ethics committee and informed consent of the patients. Patients who had other severe disease and undesired habits (e.g., smoking, alcohol, etc.) were excluded from this study. The demographic features, disease duration and accompanying symptoms (e.g., fatigue, morning stiVness, depression, sleep disturbances, paresthesias, headache, irritable bowel syndrome, Raynoud’s-like symptoms and restless leg syndrome) of the patients were documented. The patients were examined in terms of widespread chronic pain, number of tender points and functional capacity. Severity of fatigue and pain (in resting, in activity) were determined by visual analogue scale (VAS; 10 cm) [11]. The tender points deWned by ACR were determined by applying a 4 kg pressure by thumb on the speciWc points of body and the number of sensitive points was recorded. Fibromyalgia impact questionnaire (FIQ) was used for functional assessment [12, 13]. In the laboratory investigation, serum selenium (g/dL) and serum zinc (g/dL) levels were measured with atomic absorption spectrometer. Serum magnesium (mmol/L) level was measured with the original kits of Abbott Aeroset autoanaylzer (Abbott Laboratories, Abbott Park, IL, USA). The concentrations of selenium and zinc were determined by a periodically validated atomic absorption spectrometer (Perkin Elmer AAS 700 system) with deuterium background correction as follows: wavelength 213.9 nm (Zn); slit 0.7 nm; acetylene/air oxidizing Xame; energy 70; duplicate reading with integration time of 2 s. Selenium levels were measured with hydride generation atomic absorption spectroscopy, by SE-FÃAS MHS system. A hollow cathode lamp for selenium operating at 9 mA intensity was employed. Reduction of the selenium compounds present on the samples was carried out using a 0.2% NaBH4 in 0.05% NaOH dissolution. Atomization was performed using an air–acetylene Xame and absorbance was measured using a 196.0-nm wavelength and 0.7-nm slit width. Stock solutions of 1,000 mg/L (Certipur OC333013 for Zn and Certipur OC309307 for selenium, Merck, Germany) were used for standard preparation. The accuracy was monitored by the comparison with Biorad Level 1 and Level 2 lyphochek control serum. All reagents used were analytical, and the glassware used was cleaned with acid. The serum magnesium level was measured with the original kits of Abbott Aeroset autoanaylzer (Abbott Laboratories, Abbott Park, IL, USA). The principle of the study is based on measuring the absorbance of the magnesium-Arsenazo stain complex at 572 nm. Absorbance is proportional to the magnesium level. The intra-assay CV%
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of the measurement is 2.6% for serum, whereas the interassay CV% is 0.6%. Statistical analysis Statistical package for social sciences (SPSS) software, version 11.0 for windows, was used for all statistical analysis. DiVerences between patients and NHC were evaluated by the Student’s t test. For correlation between results, the Pearson’s correlation coeYcient was performed. The level of signiWcance was set at P value less than 0.05.
Results The mean ages of patients in FM group and NHC were 42.9 (SD = 7.7) years and 41.3 (SD = 9.7) years, respectively. There was no signiWcant diVerence between ages of the both groups (P = 0.476). Some of the clinical characteristics of the patient and NHC are given in Table 1. The most frequently encountered symptoms accompanying patients with FM were fatigue (100%) and sleep disturbance (90.6%), as shown in Table 2. There was a considerable diVerence in serum zinc (P = 0.001) and serum magnesium (P = 0.002) levels, whereas no signiWcant diVerence was found (P > 0.05) for serum selenium level between two groups as shown in Table 3. There was signiWcant correlation between serum zinc level and number of the tender points (P = 0.008) (Table 4). Additionally, correlation between magnesium level and severity of fatigue were found signiWcant (P = 0.003) as shown in Table 4.
Discussion Although disturbances in the musculoskeletal system, in the neuro-endocrine system and in the central nervous system have been implicated in the pathophysiology of FM, Table 1 Some of the clinical characteristics of patients with Wbromyalgia Patients
NHC
P 0.476
Age [year, mean (SD)]
42.9 (7.7)
41.3 (9.7)
Sex (F/M)
32/0
32/0
BMI [kg/m2, mean (SD)]
27.4 (4.3)
25.2 (4.2)
Disease duration [month, mean (SD)]
15.8 (4.4)
–
FIQ score [mean (SD)]
53.3 (7.9)
–
Morning stiVness (min)
25.5 (6.5)
–
VAS pain [cm, mean (SD)]
6.6 (1.5)
–
0.034
F/M female/male, BMI body mass index, FIQ Wbromyalgia impact questionnaire
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Table 2 Common signs and symptoms of patients with Wbromyalgia Signs and symptoms
Frequency n (%)
Fatigue
32 (100)
Sleep disorders
29 (90.6)
Headache
27 (84.4)
Paresthesia
26 (81.3)
Irritable bowel syndrome
13 (40.6)
Sicca symptoms
10 (31.3)
Raynaud’s phenomena
6 (18.8)
Table 3 Serum trace element levels in patients with Wbromyalgia and in normal healthy controls Patients NHC [Mean (SD)] [Mean (SD)] Serum zinc level (g/dL)
102.8 (24.7)
Serum selenium level (g/dL)
P
77.2 (31)
0.001*
44.4 (12.1)
38.7 (13.9)
>0.05
1.8 (0.4)
1.5 (0.5)
0.002*
Serum magnesium level (mmol/L)
* Statically signiWcantly by Student’s t test Table 4 Correlation between serum trace element levels and clinical, functional Wndings in patients with Wbromyalgia Zinc
Selenium
Magnesium
r
¡0.173
¡0.174
¡0.085
P
0.342
0.342
0.644
r
¡0.280
¡0.180
¡0.501
P
0.121
0.323
r
¡0.141
¡0.094
¡0.298
P
0.440
0.611
0.098
Disease duration
VAS fatigue 0.003*
VAS pain
Number tender points r P
¡0.461 0.008*
¡0.19
¡0.001
0.917
0.996
FIQ r
¡0.106
0.011
¡0.040
P
0.565
0.954
0.830
r
¡0.322
0.208
¡0.097
P
0.072
0.254
0.59
Morning stiVness
r Pearson’s correlation coeYcient * Statistically signiWcant
primary mechanisms underlying the etiopathogenesis of FM is unknown [14]. In recent years, serum trace element levels have been researched to reveal etiopathogenesis of patients with FM [15–18]. However, the results of these studies have appeared to be ambiguous.
In this study, serum magnesium and zinc levels were found signiWcantly lower in patients with FM when compared to NHC, but the same diVerence was not observed between two groups when selenium level is considered. In contrast to our study in past years, Prescott et al. reported that serum magnesium level of patients with FM did not change. Eisinger et al. found decreased levels of red blood cell magnesium in patients with FM [17]. Similarly, Abraham and Flechas also found that magnesium deWciency plays a possible role in mechanism of pain in FM. They thought this was related to the role of magnesium in the production of ATP [15]. Some evidence exists supporting the possibility of deWciency of components required for ATP synthesis in etiopathogenesis of FM [8]. On the other hand, several Wbromyalgia manifestations such as fatigue, muscle weakness, irritable bowel and paresthesia are similar to symptoms of magnesium deWciency [15]. In literature, we encountered only one study that investigates serum zinc level in patients with FM [18]. Similarly, in this study, we found lower serum zinc level in patients with FM. The importance of zinc for antioxidant stress response is well documented [19]. As reported in many studies, zinc plays essential role for many antioxidant enzymes as cofactor [4, 7]. Altindag and Celik reported that total antioxidant capacity of plasma was signiWcantly lower in patients with Wbromyalgia than in healthy controls [20]. Additionally, recent studies showed that the imbalance of antioxidant enzymes plays role in etiopathogenesis of FM [18, 21]. Maes et al. found that serum zinc levels were considerably lower in comparison to the control group, in the patients with chronic fatigue syndrome. In the same study, the need for essential zinc supplement in the treatment of chronic fatigue syndrome has eventually been emphasized [22]. In the patients diagnosed as having Wbromyalgia, the frequency of appearance of chronic fatigue syndrome is in the range of 20–70% [23]. On the other hand, the symptoms of these two diseases have considerable similarities. Recently, in a report, it is stated that the mechanism of pain appearance in the both two diseases are the same [24]. Selenium is an essential component of the enzyme glutathione peroxidase. Glutathione peroxidase is the general name of an enzyme family with activity peroxidase whose main biological role is to protect the organism from oxidative damage [25]. There are several studies investigating the serum selenium level in patients with FM. However, these studies had contradictory results [17, 26]. Reinhard et al. found lower serum selenium concentrations in patients with FM compared to controls [26]. Eisinger et al. found no diVerence in serum selenium level in patients with FM and controls [17]. The study of Eisenger et al. and our study do not support that the deWciency of selenium is related to FM disease. In some studies released in past years, it is reported that muscle pain has signiWcant association with
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the selenium deWciency [27]. However, in our study, there was not any meaningful correlation between VAS pain and selenium level. Therefore, more clinical trials are needed to explore the issue. Fatigue, sleep disorders, stress-dependent headache, paresthesia, irritable bowel syndrome, sicca and Raynaud’s phenomena are frequently observed in patients with FM [28, 29]. Whites et al. found that the most frequent symptom was fatigue among patients with FM [30]. Similar results are present in our study; the most frequently observed symptom was also fatigue (100%) as shown in Table 4. In our study, a signiWcant correlation was found between fatigue and serum magnesium level. Magnesium plays an important role in enzymatic reactions, especially in energy production. As the magnesium level decreases, the energy levels also decrease simultaneously. As a result of this situation, fatigue may occur [31]. Magnesium supplementation may beneWt in the treatment of chronic fatigue [31, 32]. In the present study, although there was signiWcant correlation between serum zinc level and number of the tender points, no similar association was found between serum magnesium and serum selenium levels. Meaningful correlation between FIQ and serum trace element levels was not found. Disease duration was not too long; so, the functional capacity of our patients with FM may be less aVected. We did not Wnd meaningful correlation between serum trace element level and the pain severity in patients with FM. In a report released recently, it was reported that the pain occurred by central sensitization rather than peripheral resources in patients with FM [24]. Not surprisingly, serum trace element level was not in any correlation with pain severity in our patients with FM. We observed no association between serum selenium level and clinical parameters in patients with FM. In literature, we encountered no study investigating the correlation between trace elements and clinical Wndings in patients with FM. Subsequently, the serum magnesium and zinc levels were found to be lower in patients with FM compared to the NHC in the present study. The association between these two elements and clinical parameters makes us to think that these elements may play role in etiopathogenesis of FM. Further investigations are required about trace elements and FM etiopathogenesis. Importantly, this study provides useful information for the design of future studies.
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