Association of Copper Status with Lipid Profile and Functional Status in Patients with Amyotrophic Lateral Sclerosis

Barros, Acsa Nara A. B.; Dourado, Mário Emílio T.; Pedrosa, Lucia de Fatima C.; Leite-Lais, Lucia

doi:https://doi.org/10.1155/2018/5678698

Journal of Nutrition and Metabolism

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Abstract Introduction Materials and Methods Results Discussion Conclusion Data Availability Conflicts of Interest Acknowledgments References Copyright Related Articles

Research Article | Open Access

Volume 2018 | Article ID 5678698 | https://doi.org/10.1155/2018/5678698

Association of Copper Status with Lipid Profile and Functional Status in Patients with Amyotrophic Lateral Sclerosis

Acsa Nara A. B. Barros,¹Mário Emílio T. Dourado,²Lucia de Fatima C. Pedrosa,¹and Lucia Leite-Lais¹

Academic Editor: Michael B. Zemel

Received06 Mar 2018

Accepted14 Jun 2018

Published19 Jul 2018

Abstract

Oxidative stress is one of the main mechanisms associated with the pathogenesis of amyotrophic lateral sclerosis (ALS). Copper can affect cellular oxidation and lipid metabolism. The aim of this study was to evaluate the association of copper status with lipid profile and functional status in patients with ALS. A cross-sectional study was carried out including 27 patients with ALS (case group) and 26 healthy individuals (control group). Copper status was evaluated by habitual dietary copper intake, plasma copper, and serum ceruloplasmin concentrations. The lipid profile included analysis of serum total cholesterol (TC), LDL-cholesterol (LDL-c), HDL-cholesterol (HDL-c), and triglycerides (TGL). The functional status of patients with ALS was assessed by the ALS Functional Rating Scale-Revised (ALSFRS-R). In the case group, plasma copper was lower compared with the control group (133.9 versus 164.1 μg/dL, ) and was positively correlated with HDL-c (, ). In the control group, plasma copper was positively correlated with serum ceruloplasmin (, ), TC (, ), LDL-c (, ), and HDL-c (, ), and serum ceruloplasmin was positively correlated only with LDL-c (, ). In the case group, dietary copper intake (, ), plasma copper (, ), and TC (, ) were inversely associated with the functional status of patients with ALS. In contrast, serum ceruloplasmin (, ), LDL-c (, ), HDL-c (, ), and TGL (; ) were positively associated with their functional status. In conclusion, this study suggests a disturbance of copper status and its connection with the lipid profile in patients with ALS. Furthermore, copper status and lipid profile may influence the functional status of patients with ALS, standing out as potential biomarkers of disease severity.

1. Introduction

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease characterized by degeneration of motor neurons in the brain and spinal cord, leading to skeletal muscle atrophy, paralysis, and death. The incidence of ALS is about 1/100,000, with a survival time since onset ranging from 24 to 48 months and an estimated mortality of 30,000 patients a year worldwide [1]. The etiology of ALS remains unknown. However, several mechanisms have been implicated in ALS pathophysiology and progression, such as oxidative stress, glutamate excitotoxicity, mitochondrial dysfunction, neuroinflammation, and protein aggregation [2].

Abnormal metal homeostasis may have an important role in the onset and progression of neurodegenerative disorders [3]. In this sense, copper has been extensively studied and plays an important role in the central nervous system (CNS). This micronutrient is essential for angiogenesis, myelination, neurotransmission, cellular respiration, and antioxidant defense. Thus, disturbances in copper homeostasis generate functional impairments in the CNS, including neurodegeneration [4], one of the characteristics found in ALS. In addition, both copper excess and deficiency contribute to oxidative stress, a key component of ALS progression [5]. Copper excess catalyzes biochemical reactions that produce reactive oxygen species. Copper deficiency, in turn, leads to poor activity of copper-dependent antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and metallothionein [6]. Copper-mediated oxidative stress is associated with changes in genes expression, lipoprotein structure, membrane receptors, and consequently lipid profile [7].

Some studies have demonstrated that higher serum lipid concentrations are associated with slower progression, better prognosis, and prolonged survival in ALS patients [8–11]. The link between copper status and lipid metabolism has been reviewed [7, 12, 13]. Clinical studies have found different associations between serum copper and lipids, depending on the population studied and the presence of comorbidities [14–19]. Thus, both copper excess and deficiency not only contribute to oxidative stress but also alter serum lipid concentrations [7].

Copper status and lipid profile have been studied in ALS patients separately; however, these two subjects have not been investigated together in these patients. Considering the scarcity of studies on this subject, the present study aimed at evaluating the association of copper status with lipid profile and functional status in patients with ALS.

2. Materials and Methods

2.1. Participants and Study Design

This cross-sectional study was reviewed and approved by the Ethics Committee of the Onofre Lopes University Hospital in Natal, Brazil (CAAE 40467214.0.0000.5292). All subjects provided written, informed consent before enrollment.

The case group consisted of patients with ALS treated at the multidisciplinary outpatient facility at the Onofre Lopes University Hospital in Natal, Brazil, between March 2016 and December 2016. Inclusion criteria were patients of both sexes with probable or definite ALS diagnosis and under the care of a literate family member or caregiver. Exclusion criteria were patients with suspected or possible ALS diagnosis, taking micronutrient supplements, undergoing estrogen treatment, and with another neurological disease, inflammatory bowel disease, biliary diseases, thyroid dysfunction, diabetes mellitus, and renal and hepatic diseases. These exclusion criteria were adopted due to their possible influence on copper status.

For comparison purposes, healthy adults and elderly individuals were recruited as the control group. The recruitment of the control group occurred through social media invitations sent to the local community. A matching based on age and sex was adopted to improve the quality of the data. The same exclusion criteria were adopted for the control group.

2.2. Clinical Characterization

Patients with ALS were characterized by the onset site of symptoms (bulbar or spinal), time of symptoms (in months), feeding route (oral and/or enteral), and functional status using the ALS Functional Rating Scale-Revised (ALSFRS-R) [20] and validated to the Portuguese language [21]. This instrument evaluates the progression of patients’ disability and the severity of the disease through a 12-item questionnaire, covering aspects related to dysphagia, daily life activities, and respiratory function. The overall ALSFRS-R score ranged from 0 to 48, where 0 represents the worst stage of disability and 48 represents the normal functional status.

2.3. Anthropometric Assessment

The anthropometric assessment was performed utilizing the body mass index (BMI) [22]. The body weight was measured in a calibrated digital Knwaagen® scale with maximum capacity of 500 kg. The height was measured using a Medjet® stadiometer. For wheelchair patients, the height was estimated according to Chumlea et al. [23, 24].

2.4. Copper Status and Lipid Profile Evaluation

2.4.1. Dietary Copper Intake

Habitual dietary copper intake was investigated using two nonconsecutive 24-hour recalls for each participant, obtained from weekdays, 30 to 45 days apart [25]. Food intake data were calculated using Virtual Nutri Plus® 2.0 software. Food items or preparations that were not found in the software’s databank were added based on the nutrition labels of industrialized products. Habitual dietary copper intake was estimated after adjustments of interpersonal variability, according to Nusser et al. [26]. Next, copper intake was adjusted for energy, applying the residual method described by Willett et al. [27]. The estimated average requirement (EAR) for copper (0.7 mg/day) [28] was used as a parameter to assess copper intake.

2.4.2. Plasma Copper, Serum Ceruloplasmin, and Lipid Profile

After an overnight fast, blood samples were collected from participants in specific tubes to perform all hematological analysis. For plasma copper evaluation, blood samples were collected in metal-free tubes with 100 μL of 30% sodium citrate anticoagulant. For serum ceruloplasmin evaluation, blood samples were collected in tubes with gel clot activator (BD Vacutainer® SST™ II Advance, BD, UK). For lipid profile evaluation, blood samples were collected in tubes with gel clot activator (VacuTube, Biocon, BR).

Plasma copper concentrations were determined by atomic absorption spectrophotometry (SpectrAA200, Varian, Victoria, Australia). The samples were centrifuged at 3000 rpm for 15 minutes at 4°C, and the plasma was separated and stored in a freezer at −20°C until analysis. The calibration curves were prepared with Titrisol® standard solution (Merck, Germany), at the following concentrations: 0.00, 0.10, 0.20, 0.30, 0.50, and 1.00 μg/mL. Aliquots of 600 μL of plasma were diluted in deionized water at 1 : 5 ratio. After reading, the results were expressed as μg/dL. Analysis was conducted in duplicate, and the results were calculated from the average of the readings, establishing a coefficient of variation of less than 10%. A range of 70–140 μg/dL was considered as the reference value for plasma copper for both sexes [29].

Analysis of serum ceruloplasmin and lipid profile was performed in a private certified laboratory. The nephelometry method was used to measure serum ceruloplasmin and 21–53 mg/dL was considered as the reference range for both sexes. Serum total cholesterol (TC) and triglycerides (TGL) were measured by the enzymatic method and HDL-cholesterol (HDL-c) by direct calorimetric method. The LDL-cholesterol values (LDL-c) were calculated using the Friedewald formula [30].

2.5. Statistical Analysis

The descriptive analysis was performed using measures of central tendency and dispersion, according to the data type. The Shapiro–Wilk test was applied to verify the normality of the data. To verify differences between the continuous variables, Student’s t-test and Wilcoxon–Mann–Whitney test were used. The inferential analysis was performed by estimating the correlation between copper status and the lipid profile by Spearman correlation test.

The effect of independent variables on the outcome (discrete), measured by the ALSFRS-R score, was estimated after the univariate analysis. An adjusted model based on the Poisson distribution was used, as recommended for discrete outcomes in transversal studies. Dietary copper, plasma copper, serum ceruloplasmin, TC, LDL-c, HDL-c, and TGL were considered independent variables.

The cutoff point for the inclusion of the variables in the adjusted final model was . In order to accept the final model, its significance was assessed using the chi-square test phrased as likelihood ratio. The variables were assessed separately by Wald chi-square test to estimate the regression coefficients. The presence of normality was tested for residues to guarantee the validity of the model. Statistical analysis was performed using SPSS v.22, and a significance level of 5% was adopted for all analyses.

3. Results

Of the 53 subjects enrolled in the study, 27 comprised the case group and 26 the control group. The mean age of the participants in the case and control groups was 56 (12.6) and 55.4 (12.5) years, respectively. The case group presented a significantly lower BMI () compared with the control group. The case group had a disease time of 46 (22–72) months, and 60% of the patients had ≤24 points in the ALSFRS-R score (Table 1).

Dietary copper intake did not differ significantly between the groups (). Also, the values of copper biomarkers and lipid profile were similar between the groups. However, plasma copper concentrations in the case group were significantly lower than those in the control group (133.9 versus 164.1 μg/dL, ) (Table 1).

In the case group, plasma copper was positively correlated only with HDL-c (, ). In the control group, plasma copper was positively correlated not only with HDL-c (, ) but also with serum ceruloplasmin (, ), TC (, ), and LDL-c (, ). Serum ceruloplasmin was positively correlated only with the LDL-c in the control group (, ). Neither plasma copper nor serum ceruloplasmin was correlated with dietary copper (Table 2).

In the case group, dietary copper (, ), plasma copper (, ), and TC (, ) were inversely associated with the ALSFRS-R score. Among them, dietary copper had the strongest association. On the other hand, serum ceruloplasmin (, ), LDL-c (, ), HDL-c (, ), and TGL (, ) were positively associated with the ALSFRS-R score (Table 3).

4. Discussion

The case group presented a significantly lower mean BMI compared with the control group. Weight loss and reduced BMI are associated with accelerated disease progression and lower survival rate [31]. Spinal-onset ALS, as found in most patients of this study, has less impairment in the swallowing ability than bulbar-onset ALS. This explains the use of enteral nutrition by the minority of the patients studied. The majority of patients presented low ALSFRS-R score, representing high disability and disease severity.

Our results showed that there was no difference in dietary copper intake between the groups. In addition, the median of dietary copper intake in the case and control groups was in agreement with the recommendations adopted [28]. Park et al. [32] found that the dietary copper intake among patients with ALS ranged from 0.9 mg/day to 1.2 mg/day. In our study, this variation was broader (Table 1), demonstrating a greater copper supply by the diet.

Contrary to our results, Forte et al. [33] found a significantly higher concentration of blood copper in patients with ALS (103.5 μg/dL) compared with the control group (95.4 μg/dL). However, other studies found no significant difference in plasma copper concentrations between ALS patients and healthy subjects [34, 35]. Differences in blood copper concentrations between studies may be explained by differences in food eating pattern, molecular profile of the population studied, and the method used to perform the lab tests. Considering the clinical heterogeneity among ALS patients, Forte et al. [33] suggest that the reference range for blood copper concentrations in subjects with and without ALS should be reviewed.

Mineral metabolism disturbances in patients with ALS may be due to several factors, such as malnutrition, malabsorption, increased excretion, and competition between minerals at binding sites [34]. Also, oxidative stress in patients with ALS may alter copper homeostasis [6, 36] and contribute to neurodegeneration [37]. At the same time, copper-deficient SOD-1 has a loss of antioxidant function and exerts a prooxidant function [38]. In addition, the level of copper deficiency seems to be proportional to the clinical severity of ALS [39].

In agreement with our results, some authors did not observe significant differences in the lipid profile between patients with ALS and healthy individuals [8, 40]. Interestingly, some authors found significantly lower concentrations of TGL in male, but not in female, individuals with ALS compared with their control group [41]. Although there was no difference of serum lipids between males and females in both groups of our study (data not shown), Ikeda et al. [42] found significantly higher concentrations of TC, LDL-c, and TGL in female Japanese patients with ALS, compared with male ones. These controversial results may be explained by several genetic polymorphisms associated with lipid metabolism, able to develop individual biochemical phenotypes [43].

No correlation of dietary copper with plasma copper and serum ceruloplasmin was observed in both groups studied. In a recent review, Bost et al. [44] found that biomarkers of copper not necessarily respond to changes in dietary copper intake, probably due to homeostatic mechanisms controlling the absorption and excretion of this mineral. Also, there was no correlation between plasma copper and serum ceruloplasmin in the case group, but this correlation was positive in the control group. In healthy subjects, we expect to find a positive correlation between copper and ceruloplasmin, which is the main copper-binding protein [45]. Patients with ALS may have disturbances of ceruloplasmin activity [46] and lack of copper incorporation during ceruloplasmin biosynthesis [47], weakening a possible correlation between these two parameters.

In our study, the only correlation found between the copper biomarkers and the lipid profile in the case group was a positive correlation between plasma copper and HDL-c. It is possible that changes in serum lipids, oxidative stress, and alterations in copper metabolism in ALS are responsible for the absence of correlation between copper and serum lipids, differing from what was found in the control group. Several studies have found different associations between serum or plasma copper and serum lipids, demonstrating great metabolomic variation among individuals [14–19]. Circulating lipids are influenced by genetics, metabolism, habitual diet, lifestyle, and their interactions [48]. Moreover, disturbance of copper metabolism influences serum lipids through oxidative stress [49–51].

In our study, the association of ALSFRS-R with copper and lipid biomarkers was very divergent (Table 3). Dietary copper and plasma copper were inversely associated, while serum ceruloplasmin was positively associated with the functional status of ALS patients. Authors have found positive association between the concentration of copper in the nails of patients with ALS and functional status assessed by ALSFRS-R [52]. However, Peters et al. [34] found no association between the ALSFRS-R score and concentrations of plasma copper. Despite the conflicting results, it is known that copper is indirectly involved with motor neuron degeneration mechanisms in ALS by mutation of the copper-dependent enzyme SOD-1, TDP-43 protein aggregation, and mitochondrial dysfunction [39]. Among the serum lipid biomarkers, only TC was inversely associated with the functional status of ALS patients studied. This fact may occur due to possible oxidation of cholesterol mediated by the copper as the disease progresses. On the other hand, the positive association found between the functional status and LDL-c, HDL-c, and TGL corroborates with the possible protective effect of hyperlipidemia in the survival of patients with ALS demonstrated in some studies [8–11].

The main limitations of this study were (1) the small number of participants in both groups due to the disease rarity and difficulty in finding healthy matches and (2) the few numbers of copper biomarkers evaluated. These limitations may have weakened the statistical power of the analysis and restricted deeper inferences in the discussion. Therefore, further studies are needed on this topic, considering larger samples and including other biomarkers of copper status and oxidative stress, as well as the presence of genetic polymorphisms related to lipid metabolism.

5. Conclusion

This study suggests a disturbance of copper status and its connection with the lipid profile in patients with ALS. Furthermore, copper status and lipid profile may influence the functional status of patients with ALS, standing out as potential biomarkers of disease severity.

Data Availability

Data are available upon request.

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Acknowledgments

This work was supported in part by the Foundation for Research Support from the State of Rio Grande do Norte (FAPERN) and Coordination for the Improvement of Higher Education Personnel (CAPES), Grant no. 006/2014.

References

D. Petrov, C. Mansfield, A. Moussy, and O. Hermine, “ALS clinical trials review: 20 years of failure. are we any closer to registering a new treatment?” Frontiers in Aging Neuroscience, vol. 9, no. 68, 2017.
View at: Publisher Site | Google Scholar
R. H. Brown and A. Al-Chalabi, “Amyotrophic lateral sclerosis,” New England Journal of Medicine, vol. 377, no. 2, pp. 162–172, 2017.
View at: Publisher Site | Google Scholar
A. R. White, K. M. Kanninen, and P. J. Crouch, “Editorial: metals and neurodegeneration: restoring the balance,” Frontiers in Aging Neuroscience, vol. 7, p. 127, 2015.
View at: Publisher Site | Google Scholar
G. Crisponi, V. M. Nurchi, D. Fanni, C. Gerosa, S. Nemolato, and G. Faa, “Copper-related diseases: from chemistry to molecular pathology,” Coordination Chemistry Reviews, vol. 254, no. 7-8, pp. 876–889, 2010.
View at: Publisher Site | Google Scholar
F. Bozzo, A. Mirra, and M. T. Carrì, “Oxidative stress and mitochondrial damage in the pathogenesis of ALS: New perspectives,” Neuroscience Letters, vol. 636, pp. 3–8, 2017.
View at: Publisher Site | Google Scholar
J. Y. Uriu-Adams and C. L. Keen, “Copper, oxidative stress, and human health,” Molecular Aspects of Medicine, vol. 26, no. 4-5, pp. 268–298, 2005.
View at: Publisher Site | Google Scholar
J. L. Burkhead and S. Lutsenko, “The role of copper as a modifier of lipid metabolism,” in Lipid Metabolism, R. V. Baez, Ed., pp. 39–60, InTech, Rijeka, Croatia, 2013.
View at: Google Scholar
R. Huang, X. Guo, X. Chen et al., “The serum lipid profiles of amyotrophic lateral sclerosis patients: a study from south-west China and a meta-analysis,” Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, vol. 16, no. 5-6, pp. 359–365, 2015.
View at: Publisher Site | Google Scholar
N. A. Sutedja, Y. T. van der Schouw, K. Fischer et al., “Beneficial vascular risk profile is associated with amyotrophic lateral sclerosis,” Journal of Neurology, Neurosurgery, and Psychiatry, vol. 82, no. 6, pp. 638–642, 2011.
View at: Publisher Site | Google Scholar
M. K. Rafiq, E. Lee, M. Bradburn, C. J. McDermott, and P. J. Shaw, “Effect of lipid profile on prognosis in the patients with amyotrophic lateral sclerosis: insights from the olesoxime clinical trial,” Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, vol. 16, no. 7-8, pp. 478–484, 2015.
View at: Publisher Site | Google Scholar
J. Dorst, P. Kühnlein, C. Hendrich, J. Kassubek, A. D. Sperfeld, and A. C. Ludolph, “Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis,” Journal of Neurology, vol. 258, no. 4, pp. 613–617, 2011.
View at: Publisher Site | Google Scholar
S. Lutsenko, “Human copper homeostasis: a network of interconnected pathways,” Current Opinion in Chemical Biology, vol. 14, no. 2, pp. 211–217, 2010.
View at: Publisher Site | Google Scholar
D. Huster and S. Lutsenko, “Wilson disease: not just a copper disorder. Analysis of a Wilson disease model demonstrates the link between copper and lipid metabolism,” Molecular BioSystems, vol. 3, no. 2, pp. 816–824, 2007.
View at: Publisher Site | Google Scholar
A. Tsuboi, M. Terazawa Watanabe, T. Kazumi et al., “Serum copper, zinc and risk factors for cardiovascular disease in community-living Japanese elderly women,” Asia Pacific Journal of Clinical Nutrition, vol. 23, no. 2, pp. 239–245, 2014.
View at: Google Scholar
N. M. Tasić, D. Tasić, P. N. Otašević et al., “Copper and zinc concentrations in atherosclerotic plaque and serum in relation to lipid metabolism in patients with carotid atherosclerosis,” Vojnosanitetski Pregled, vol. 72, no. 9, pp. 801–806, 2015.
View at: Publisher Site | Google Scholar
K. N. Rai, N. S. Kumari, K. M. D. Gowda et al., “The evaluation of micronutrients and oxidative stress and their relationship with the lipid profile in healthy adults,” Journal of Clinical and Diagnostic Research, vol. 7, no. 7, pp. 1314–1318, 2013.
View at: Publisher Site | Google Scholar
S. Bo, M. Durazzo, R. Gambino et al., “Associations of dietary and serum copper with inflammation, oxidative stress, and metabolic variables in adults,” Journal of Nutrition, vol. 138, no. 2, pp. 305–310, 2008.
View at: Publisher Site | Google Scholar
S. C. V. C. Lima, R. F. Arrais, C. H. Sales et al., “Assessment of copper and lipid profile in obese children and adolescents,” Biological Trace Element Research, vol. 114, no. 1–3, pp. 19–29, 2006.
View at: Publisher Site | Google Scholar
E. Al-khateeb, E. Al-zayadneh, O. Al-dalahmah et al., “relation between copper, lipid profile, and cognition in elderly jordanians,” Journal of Alzheimer’s Disease, vol. 41, no. 1, pp. 203–211, 2014.
View at: Publisher Site | Google Scholar
J.M. Cedarbaum, N. Stambler, E. Malta et al., “The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function,” Journal of the Neurological Sciences, vol. 169, no. 1-2, pp. 13–21, 1999.
View at: Publisher Site | Google Scholar
K. Guedes, C. Pereira, K. Pavan, B. Cataldo, and O. Valério, “Cross-cultural adaptation and validation of ALS functional rating scale-revised in Portuguese language,” Arquivos de Neuro-Psiquiatria, vol. 68, no. 1, pp. 44–47, 2010.
View at: Publisher Site | Google Scholar
World Health Organization, “Physical status: the use and interpretation of anthropometry,” World Health Organization, Geneva, Switzerland, 1995, Technical Report Series.
View at: Google Scholar
W. C. Chumlea, A. F. Roche, and M. L. Steinbaugh, “Estimating stature from knee height for persons 60 to 90 years of age,” Journal of the American Geriatrics Society, vol. 33, no. 2, pp. 116–120, 1985.
View at: Publisher Site | Google Scholar
W. C. Chumlea, S. S. Guo, and M. L. Steinbaugh, “Prediction of stature from knee height for black and white adults and children with application to mobility-impaired or handicapped persons,” Journal of the American Dietetic Association, vol. 94, no. 12, pp. 1385–1388, 1994.
View at: Publisher Site | Google Scholar
F. E. Thompson and T. Byers, “Dietary assessment resource manual,” Journal of Nutrition, vol. 124, no. 11, pp. 2245S–2317S, 1994.
View at: Google Scholar
S. M. Nusser, A. L. Carriquiry, K. W. Dodd, and W. A. Fuller, “A semiparametric transformation approach to estimating usual daily intake distributions,” Journal of the American Statistical Association, vol. 91, no. 436, pp. 1440–1449, 1996.
View at: Publisher Site | Google Scholar
W. C. Willett, G. R. Howe, and L. H. Kushi, “Adjustment for total energy intake in epidemiologic studies,” American Journal of Clinical Nutrition, vol. 65, no. 4, pp. 1220S–1228S, 1997.
View at: Publisher Site | Google Scholar
Institute of Medicine, Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc, The National Academies Press, Washington, DC, USA, 2001.
D. S. Young, “Implementation of SI units for clinical laboratory data,” Annals of Internal Medicine, vol. 106, no. 1, pp. 114–129, 1987.
View at: Publisher Site | Google Scholar
W. T. Friedewald, R. I. Levy, and D. S. Fredrickson, “Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge,” Clinical Chemistry, vol. 18, no. 6, pp. 499–502, 1972.
View at: Google Scholar
S.T. Ngo, F. J. Steyn, and P. A. McCombe, “Body mass index and dietary intervention: implications for prognosis of amyotrophic lateral sclerosis,” Journal of the Neurological Sciences, vol. 340, no. 1-2, pp. 5–12, 2014.
View at: Publisher Site | Google Scholar
Y. Park, J. Park, Y. Kim, H. Baek, and S. Hyun Kim, “Association between nutritional status and disease severity using the amyotrophic lateral sclerosis (ALS) functional rating scale in ALS patients,” Nutrition, vol. 31, no. 11-12, pp. 1362–1367, 2015.
View at: Publisher Site | Google Scholar
G. Forte, B. Bocca, R. Oggiano et al., “Essential trace elements in amyotrophic lateral sclerosis (ALS): results in a population of a risk area of Italy,” Neurological Sciences, vol. 38, no. 9, pp. 1609–1615, 2017.
View at: Publisher Site | Google Scholar
T. L. Peters, J. D. Beard, D. M. Umbach et al., “Blood levels of trace metals and amyotrophic lateral sclerosis,” NeuroToxicology, vol. 54, pp. 119–126, 2016.
View at: Publisher Site | Google Scholar
P. M. Roos, O. Vesterberg, T. Syversen, T. P. Flaten, and M. Nordberg, “Metal concentrations in cerebrospinal fluid and blood plasma from patients with amyotrophic lateral sclerosis,” Biological Trace Element Research, vol. 151, no. 2, pp. 159–170, 2013.
View at: Publisher Site | Google Scholar
M. Ikawa, H. Okazawa, T. Tsujikawa et al., “Increased oxidative stress is related to disease severity in the ALS motor cortex: a PET study,” Neurology, vol. 84, no. 20, pp. 2033–2039, 2015.
View at: Publisher Site | Google Scholar
E. Tokuda, S. Watanabe, E. Okawa, and S. I. Ono, “Regulation of intracellular copper by induction of endogenous metallothioneins improves the disease course in a mouse model of amyotrophic lateral sclerosis,” Neurotherapeutics, vol. 12, no. 2, pp. 461–476, 2015.
View at: Publisher Site | Google Scholar
A. Ahuja, K. Dev, R. S. Tanwar, K. K. Selwal, and P. K. Tyagi, “Copper mediated neurological disorder: visions into amyotrophic lateral sclerosis, Alzheimer and Menkes disease,” Journal of Trace Elements in Medicine and Biology, vol. 29, pp. 11–23, 2015.
View at: Publisher Site | Google Scholar
F. J. Gil-Bea, G. Aldanondo, H. Lasa-Fernández, A. L. de Munain, and A. Vallejo-Illarramendi, “Insights into the mechanisms of copper dyshomeostasis in amyotrophic lateral sclerosis,” Expert Reviews in Molecular Medicine, vol. 19, p. e7, 2017.
View at: Publisher Site | Google Scholar
A. Chiò, A. Calvo, A. Ilardi et al., “Lower serum lipid levels are related to respiratory impairment in patients with ALS,” Neurology, vol. 73, no. 20, pp. 1681–1685, 2009.
View at: Publisher Site | Google Scholar
A. Wuolikainen, J. Acimovic, A. Lövgren-Sandblom, P. Parini, P. M. Andersen, and I. Björkhem, “Cholesterol, oxysterol, triglyceride, and coenzyme Q homeostasis in ALS. Evidence against the hypothesis that elevated 27-hydroxycholesterol is a pathogenic factor,” PLoS One, vol. 9, no. 11, Article ID e113619, 2014.
View at: Publisher Site | Google Scholar
K. Ikeda, T. Hirayama, T. Takazawa, K. Kawabe, and Y. Iwasaki, “Relationships between disease progression and serum levels of lipid, urate, creatinine and ferritin in Japanese patients with amyotrophic lateral sclerosis: a cross-sectional study,” Internal Medicine, vol. 51, no. 12, pp. 1501–1508, 2012.
View at: Publisher Site | Google Scholar
M. L. Curti, P. Jacob, M. C. Borges, M. M. Rogero, and S. R. G. Ferreira, “Studies of gene variants related to inflammation, oxidative stress, dyslipidemia, and obesity: implications for a nutrigenetic approach,” Journal of Obesity, vol. 2011, Article ID 497401, 31 pages, 2011.
View at: Publisher Site | Google Scholar
M. Bost, S. Houdart, M. Oberli, E. Kalonji, J. F. Huneau, and I. Margaritis, “Dietary copper and human health: current evidence and unresolved issues,” Journal of Trace Elements in Medicine and Biology, vol. 35, pp. 107–115, 2016.
View at: Publisher Site | Google Scholar
J. Osredkar and S. Natasa, “Copper and zinc, biological role and significance of copper/zinc imbalance,” Journal of Clinical Toxicology, vol. S3, pp. 1–18, 2011.
View at: Google Scholar
G. Tórsdóttir, J. Kristinsson, G. Gudmundsson, J. Snaedal, and T. Johannesson, “Copper, ceruloplasmin and superoxide dismutase (SOD) in amyotrophic lateral sclerosis,” Pharmacology and Toxicology, vol. 87, no. 3, pp. 126–130, 2000.
View at: Publisher Site | Google Scholar
E. Sedlak and P. Wittung-Stafshede, “Discrete roles of copper ions in chemical unfolding of human ceruloplasmin,” Biochemistry, vol. 46, no. 33, pp. 9638–9644, 2007.
View at: Publisher Site | Google Scholar
Y. Zheng and L. Qi, “Diet and lifestyle interventions on lipids: combination with genomics and metabolomics,” Clinical Lipidology, vol. 9, no. 4, pp. 417–427, 2014.
View at: Publisher Site | Google Scholar
R. Gutiérrez-García, T. Pozo, M. Suazo, V. Cambiazo, and M. González, “Physiological copper exposure in Jurkat cells induces changes in the expression of genes encoding cholesterol biosynthesis proteins,” BioMetals, vol. 26, no. 6, pp. 1033–1040, 2013.
View at: Publisher Site | Google Scholar
Y. Liu, H. Yang, Z. Song, and S. Gu, “Copper excess in liver HepG2 cells interferes with apoptosis and lipid metabolic signaling at the protein level,” Turkish Journal of Gastroenterology, vol. 25, no. S1, pp. 116–121, 2014.
View at: Google Scholar
A. Morrell, S. Tallino, L. Yu, and J. L. Burkhead, “The role of insufficient copper in lipid synthesis and fatty-liver disease,” IUBMB Life, vol. 69, no. 4, pp. 263–270, 2017.
View at: Publisher Site | Google Scholar
M. Bergomi, M. Vinceti, G. Nacci et al., “Environmental exposure to trace elements and risk of amyotrophic lateral sclerosis: a population-based case–control study,” Environmental Research, vol. 89, no. 2, pp. 116–123, 2002.
View at: Publisher Site | Google Scholar

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Copyright © 2018 Acsa Nara A. B. Barros et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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