Zinc Status and Autoimmunity: A Systematic Review and Meta-Analysis

Nutrients - Tập 10 Số 1 - Trang 68
Alessandro Sanna1, Davide Firinu2, Patrizia Zavattari3, Paolo Valera1
1Department of Civil, Environmental Engineering and Architecture, University of Cagliari, 09123 Cagliari, Italy.
2Department of Medical Sciences and Public Health, Monserrato Campus, University of Cagliari, 09042 Monserrato, Italy
3Unit of Biology and Genetics, Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy

Tóm tắt

Zinc is an essential trace element for living organisms and their biological processes. Zinc plays a key role in more than 300 enzymes and it is involved in cell communication, proliferation, differentiation and survival. Zinc plays also a role in regulating the immune system with implications in pathologies where zinc deficiency and inflammation are observed. In order to examine the experimental evidence reported in the literature regarding zinc levels in the body of patients with autoimmune disorders compared to control individuals, a systematic review and meta-analysis were performed. From 26,095 articles identified by literature search, only 179 of them were considered potentially relevant for our study and then examined. Of the 179 articles, only 62 satisfied the inclusion criteria. Particularly for Fixed Model, Zn concentration in both serum (mean effect = −1.19; confidence interval: −1.26 to −1.11) and plasma (mean effect = −3.97; confidence interval: −4.08 to −3.87) samples of autoimmune disease patients was significantly lower than in controls. The data presented in our work, although very heterogeneous in the manner of collecting and investigating samples, have proved to be extremely consistent in witnessing a deficiency of zinc in serum and plasma of patients compared to controls.

Từ khóa


Tài liệu tham khảo

Raulin, 1869, Etude chimique sur la vegetation, Ann. Sci. Nat. Bot. Biol. Veg., 11, 293

Wessels, I., Maywald, M., and Rink, L. (2017). Zinc as a Gatekeeper of Immune Function. Nutrients, 9.

Beyersmann, 2001, Functions of zinc in signaling, proliferation and differentiation of mammalian cells, Biometals, 14, 331, 10.1023/A:1012905406548

Harris, 2002, Cellular transporter for zinc, Nutr. Rev., 60, 121, 10.1301/00296640260085877

Foster, 2012, Zinc and Regulation of inflammatory cytokines: Implications for cardiometabolic disease, Nutrients, 4, 676, 10.3390/nu4070676

Maret, 2006, Zinc requirements and the risks and benefits of zinc supplementation, J. Trace Elem. Med. Biol., 20, 3, 10.1016/j.jtemb.2006.01.006

Wuehler, 2005, Use of national food balance data to estimate the adequacy of zinc in national food supplies: Methodology and regional estimates, Public Health Nutr., 8, 812, 10.1079/PHN2005724

(2017, July 03). World Health Organization. Available online: http://www.who.int/whr/2002.

Chandel, 2010, Detection of genomic changes in transgenic Bt rice populations through genetic fingerprinting using amplified fragment length polymorphism (AFLP), GM Crops, 1, 327, 10.4161/gmcr.1.5.14764

Giraudet, 2002, Identification of SLC39A4, a gene involved in acrodermatitis enteropathica, Nat. Genet., 31, 239, 10.1038/ng913

Wapnir, 2000, Zinc deficiency, malnutrition and the gastrointestinal tract, J. Nutr., 130, 1388, 10.1093/jn/130.5.1388S

Miller, 2007, A mathematical model of zinc absorption in humans as a function of dietary zinc and phytate, J. Nutr., 137, 135, 10.1093/jn/137.1.135

Prasad, 1985, Clinical manifestations of zinc deficiency, Annu. Rev. Nutr., 5, 341, 10.1146/annurev.nu.05.070185.002013

Prasad, 2009, Zinc: Role in immunity, oxidative stress and chronic inflammation, Curr. Opin. Clin. Nutr. Metab. Care, 12, 646, 10.1097/MCO.0b013e3283312956

Fraker, 1984, Interference in the development of a secondary immune response in mice by zinc deprivation: Persistence of effects, J. Nutr., 114, 1762, 10.1093/jn/114.10.1762

Liberati, 2009, The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration, BMJ, 6, 354

Moher, 2010, Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement, Int. J. Surg., 8, 336, 10.1016/j.ijsu.2010.02.007

(2017, July 03). American Autoimmune Related Diseases Association. Available online: https://www.aarda.org/diseaselist/.

Egger, 1997, Bias in meta-analysis detected by a simple, graphical test, BMJ, 315, 629, 10.1136/bmj.315.7109.629

Aaseth, 1978, Trace elements in serum and urine of patients with rheumatoid arthritis, Scand. J. Rheumatol., 7, 237, 10.3109/03009747809095662

Atef, 2016, Evaluation of serum zinc level in patients with newly diagnosed and resistant alopecia areata, Int. J. Dermatol., 55, 24, 10.1111/ijd.12769

Arreola, 1990, Bone mineral content, 25-hydroxycalciferol and zinc serum levels in insulin-dependent (type I) diabetic patients, Arch. Investig. Med., 21, 195

Banford, 1982, Serum copper and erythrocyte superoxide dismutase in rheumatoid arthritis, Ann. Rheum. Dis., 41, 458, 10.1136/ard.41.5.458

Bhat, 2009, Trace element levels in alopecia areata, Indian J. Dermatol. Venereol. Leprol., 75, 29, 10.4103/0378-6323.45216

Bideci, 2005, Serum zinc, insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels in children with type 1 diabetes mellitus, J. Pediatr. Endocrinol. Metab., 18, 1007, 10.1515/JPEM.2005.18.10.1007

Figueiredo, 1999, Lack of acute zinc effects in glucose metabolism in healthy and insulin-dependent diabetes mellitus patients, Biometals, 12, 161, 10.1023/A:1009254424394

Car, 1992, Zinc and copper in the serum of diabetic patients, Biol. Trace Elem. Res., 32, 325, 10.1007/BF02784618

Dijkmans, 1987, Serum aluminium concentrations in patients with rheumatoid arthritis, Scand. J. Rheumatol., 16, 361, 10.3109/03009748709102508

Peterson, 1990, Zinc profiles in rheumatoid arthritis, Clin. Exp. Rheumatol., 8, 541

Catalanotto, 1983, Zinc in multiple sclerosis, Ann. Neurol., 14, 450, 10.1002/ana.410140409

Erdal, 2008, Trace element levels in hashimoto thyroiditis patients with subclinical hypothyroidism, Biol. Trace Elem. Res., 123, 1, 10.1007/s12011-008-8117-8

Ghazavi, 2012, High copper and low zinc serum levels in Iranian patients with multiple sclerosis: A case control study, Clin. Lab., 58, 161

Hallmans, 1983, Prospective and retrospective studies of zinc concentrations in serum, blood clots, hair and urine in young patients with insulin-dependent diabetes mellitus, Acta Endocrinol., 102, 88

Hansson, 1975, The content of calcium, magnesium, copper, zinc, lead and chromium in the blood of patients with rheumatoid arthritis, Scand. J. Rheumatol., 4, 33, 10.1080/03009747509095612

Haugen, 1992, Nutrient intake and nutritional status in children with juvenile chronic arthritis, Scand. J. Rheumatol., 21, 165, 10.3109/03009749209099216

Helgeland, 2000, Dietary intake and serum concentrations of antioxidants in children with juvenile arthritis, Clin. Exp. Rheumatol., 18, 637

Helliwell, 1984, Nutritional status in patients with rheumatoid arthritis, Ann. Rheum. Dis., 43, 386, 10.1136/ard.43.3.386

Isbir, 1994, Zinc, copper and magnesium status in insulin-dependent diabetes, Diabetes Res., 26, 41

Jansen, 2012, Disturbed zinc homeostasis in diabetic patients by in vitro and in vivo analysis of insulinomimetic activity of zinc, J. Nutr. Biochem., 23, 1458, 10.1016/j.jnutbio.2011.09.008

Javanbakht, 2012, Serum selenium, zinc, and copper in early diagnosed patients with pemphigus vulgaris, Iran J. Public Health, 41, 105

Kapaki, 1989, Zinc, copper and magnesium concentration in serum and CSF of patients with neurological disorders, Acta Neurol. Scand., 79, 373, 10.1111/j.1600-0404.1989.tb03803.x

Kiilerich, 1990, 65 Zinc absorption in patients with insulin-dependent diabetes mellitus assessed by whole-body counting technique, Clin. Chim. Acta, 189, 13, 10.1016/0009-8981(90)90229-L

Kiilerich, 1986, Distribution of serum zinc between albumin and alpha 2-macroglobulin in patients with different zinc metabolic disorders, Clin. Chim. Acta, 154, 1, 10.1016/0009-8981(86)90082-3

Kobbah, 1988, Early changes of some serum proteins and metals in diabetic children, Acta Paediatr. Scand., 77, 734, 10.1111/j.1651-2227.1988.tb10739.x

Lin, 2016, Magnesium, zinc, and chromium levels in children, adolescents, and young adults with type 1 diabetes, Clin. Nutr., 35, 880, 10.1016/j.clnu.2015.05.022

Iyanda, 2011, Serum levels of minerals and vitamins in two categories of female alopecia subjects using hair relaxer, DSI, 29, 121

Maldonado, 1991, Zinc levels after intravenous administration of zinc sulphate in insulin-dependent diabetes mellitus patients, Klin. Wochenschr., 69, 640, 10.1007/BF01649424

Mierzecki, 2011, A pilot study on zinc levels in patients with rheumatoid arthritis, Biol. Trace Elem. Res., 143, 854, 10.1007/s12011-010-8952-2

Negoro, 2004, Taste function in Sjögren’s syndrome patients with special reference to clinical tests, Auris Nasus Larynx, 31, 141, 10.1016/j.anl.2004.01.005

Nicoloff, 2005, Serum fibrillin-antifibrillin immune complexes among diabetic children, Vascul. Pharmacol., 43, 171, 10.1016/j.vph.2005.06.005

Bulut, 2011, Effects of different medical treatments on serum copper, selenium and zinc levels in patients with rheumatoid arthritis, Biol. Trace Elem. Res., 142, 447, 10.1007/s12011-010-8826-7

Palm, 1982, Zinc and copper in multiple sclerosis, J. Neurol. Neurosurg. Psychiatry, 45, 691, 10.1136/jnnp.45.8.691

Raz, 1989, Trace elements in blood cells of diabetic subjects, Diabetes Res., 10, 21

Sahebari, 2014, Association between serum trace element concentrations and the disease activity of systemic lupus erythematosus, Lupus, 23, 793, 10.1177/0961203314530792

Yanaguibashi, 2003, Copper and zinc intake and serum levels in patients with juvenile rheumatoid arthritis, Eur. J. Clin. Nutr., 57, 706, 10.1038/sj.ejcn.1601601

Ullah, 2017, Determination of Serum Trace Elements (Zn, Cu, and Fe) in Pakistani Patients with Rheumatoid Arthritis, Biol. Trace Elem. Res., 175, 10, 10.1007/s12011-016-0746-8

Yazdanpanah, 2011, Serum zinc and copper status in Iranian patients with pemphigus vulgaris, Int. J. Dermatol., 50, 1343, 10.1111/j.1365-4632.2011.04968.x

Yilmaz, 2005, Trace elements and some extracellular antioxidant proteins levels in serum of patients with systemic lupus erythematosus, Clin. Rheumatol., 24, 331, 10.1007/s10067-004-1028-y

Zoli, 1998, Serum zinc and copper in active rheumatoid arthritis: Correlation with interleukin 1 beta and tumour necrosis factor alpha, Clin. Rheumatol., 17, 378, 10.1007/BF01450895

Arreola, 1986, Low plasma zinc and androgen in insulin-dependent diabetes mellitus, Arch. Androl., 16, 151, 10.3109/01485018608986935

Bacon, 1990, Nutritional status and growth in juvenile heumatoid arthritis, Semin. Arthritis Rheum., 20, 97, 10.1016/0049-0172(90)90022-8

Balogh, 1980, Plasma zinc and its relationship to clinical symptoms and drug treatment in rheumatoid arthritis, Ann. Rheum. Dis., 39, 329, 10.1136/ard.39.4.329

Crofton, 1983, Zinc absorption in celiac disease and dermatitis herpetiformis: A test of small intestinal function, Am. J. Clin. Nutr., 38, 706, 10.1093/ajcn/38.5.706

Cunningham, 1994, Hyperzincuria in individuals with insulin-dependent diabetes mellitus: Concurrent zinc status and the effect of high-dose zinc supplementation, Metabolism, 43, 1558, 10.1016/0026-0495(94)90016-7

Ho, 1986, Zinc in multiple sclerosis. II: Correlation with disease activity and elevated plasma membrane-bound zinc in erythrocytes from patients with multiple sclerosis, Ann. Neurol., 20, 712, 10.1002/ana.410200610

Kennedy, 1975, Zinc: Its relationship to osteoporosis in rheumatoid arthritis, Scand. J. Rheumatol., 4, 243, 10.3109/03009747509165264

Melchior, 1989, Plasma zinc concentrations during the first 2 years after diagnosis of insulin-dependent diabetes mellitus: A prospective study, J. Intern. Med., 226, 53, 10.1111/j.1365-2796.1989.tb01353.x

Milanino, 1993, Copper and zinc status in rheumatoid arthritis: Studies of plasma, erythrocytes, and urine, and their relationship to disease activity markers and pharmacological treatment, Clin. Exp. Rheumatol., 11, 271

Mocchegiani, 1989, Zinc-dependent low thymic hormone level in type I diabetes, Diabetes, 38, 932, 10.2337/diab.38.7.932

Naveh, 1997, Zinc metabolism in rheumatoid arthritis: Plasma and urinary zinc and relationship to disease activity, J. Rheumatol., 24, 643

Pereira, 2011, Research on zinc blood levels and nutritional status in adolescents with autoimmune hepatitis, Arq. Gastroenterol., 48, 62, 10.1590/S0004-28032011000100013

Quilliot, 2001, Evidence that diabetes mellitus favors impaired metabolism of zinc, copper, and selenium in chronic pancreatitis, Pancreas, 22, 299, 10.1097/00006676-200104000-00012

Rohn, 1993, Magnesium, zinc and copper in plasma and blood cellular components in children with IDDM, Clin. Chim. Acta, 215, 21, 10.1016/0009-8981(93)90245-Y

Lagarda, 1998, Selenium, Zinc and Copper in Plasma of patients with Type 1 Diabetes Mellitus in Different Metabolic Control States, J. Trace Elem. Med. Biol., 12, 91, 10.1016/S0946-672X(98)80031-X

Smith, 1989, Trace element status in multiple sclerosis, Am. J. Clin. Nutr., 50, 136, 10.1093/ajcn/50.1.136

Tuncer, 1999, Trace element and magnesium levels and superoxide dismutase activity in rheumatoid arthritis, Biol. Trace Elem. Res., 68, 137, 10.1007/BF02784402

Krizko, 2009, Altered metabolism of copper, zinc, and magnesium is associated with increased levels of glycated hemoglobin in patients with diabetes mellitus, Metabolism, 58, 1477, 10.1016/j.metabol.2009.04.035

Yazar, 2005, Synovial fluid and plasma selenium, copper, zinc, and iron concentrations in patients with rheumatoid arthritis and osteoarthritis, Biol. Trace Elem. Res., 106, 123, 10.1385/BTER:106:2:123

Afridi, 2012, Interaction between zinc, cadmium, and lead in scalp hair samples of Pakistani and Irish smokers rheumatoid arthritis subjects in relation to controls, Biol. Trace Elem. Res., 148, 139, 10.1007/s12011-012-9352-6

Afridi, 2015, Estimation of toxic elements in the samples of different cigarettes and their effect on the essential elemental status in the biological samples of Irish smoker rheumatoid arthritis consumers, Environ. Monit. Assess., 187, 157, 10.1007/s10661-015-4353-5

Larsen, 2003, Manganese, copper, and zinc in cerebrospinal fluid from patients with multiple sclerosis, Biol. Trace Elem. Res., 93, 1, 10.1385/BTER:93:1-3:1

Peters, 2008, Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry, J. Clin. Epidemiol., 61, 991, 10.1016/j.jclinepi.2007.11.010

Marrosu, 2001, Dissection of the HLA association with multiple sclerosis in the founder isolated population of Sardinia, Hum. Mol. Genet., 10, 2907, 10.1093/hmg/10.25.2907

Zavattari, 2000, Confirmation of the DRB1-DQB1 loci as the major component of IDDM1 in the isolated founder population of Sardinia, Hum. Mol. Genet., 9, 2967, 10.1093/hmg/9.20.2967

Pitzalis, M., Zavattari, P., Murru, R., Deidda, E., Zoledziewska, M., Murru, D., Moi, L., Motzo, C., Orrù, V., and Costa, G. (2008). Genetic loci linked to Type 1 Diabetes and Multiple Sclerosis families in Sardinia. BMC Med. Genet., 9.

Steri, 2013, Genetic variants regulating immune cell levels in health and disease, Cell, 155, 242, 10.1016/j.cell.2013.08.041

Steri, 2017, Overexpression of the cytokine BAFF and autoimmunity risk, N. Engl. J. Med., 376, 1615, 10.1056/NEJMoa1610528

Contu, 2002, Sex-related bias and exclusion mapping of the nonrecombinant portion of chromosome Y in human type 1 diabetes in the isolated founder population of Sardinia, Diabetes, 51, 3573, 10.2337/diabetes.51.12.3573

Monti, M.C., Guido, D., Montomoli, C., Sardu, C., Sanna, A., Pretti, S., Lorefice, L., Marrosu, M.G., Valera, P., and Cocco, E. (2016). Is Geo-Environmental Exposure a Risk Factor for Multiple Sclerosis? A Population-Based Cross-Sectional Studyin South-Western Sardinia. PLoS ONE, 11.

Brodin, 2015, Variation in the human immune system is largely driven by non-heritable influences, Cell, 160, 37, 10.1016/j.cell.2014.12.020

Wu, 2013, Induction of pathogenic TH 17 cells by inducible salt-sensing kinase SGK1, Nature, 496, 513, 10.1038/nature11984

Haase, 2014, Multiple impacts of zinc on immune function, Metallomics, 6, 1175, 10.1039/c3mt00353a

Prasad, 2000, Effects of zinc deficiency on Th1 and Th2 cytokine shifts, J. Infect. Dis., 182, 62, 10.1086/315916

Lee, 2015, Inhibition of interleukin-1β-mediated interleukin-1 receptor-associated kinase 4 phosphorylation by zinc leads to repression of memory T helper type 17 response in humans, Immunology, 146, 645, 10.1111/imm.12536

Hojyo, 2014, Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength, Proc. Natl. Acad. Sci. USA, 111, 11786, 10.1073/pnas.1323557111

Rosenkranz, 2016, Zinc supplementation induces regulatory T cells by inhibition of Sirt-1 deacetylase in mixed lymphocyte cultures, Mol. Nutr. Food Res., 60, 661, 10.1002/mnfr.201500524

Rosenkranz, 2016, Induction of regulatory T cells in Th1-/Th17-driven experimental autoimmune encephalomyelitis by zinc administration, J. Nutr. Biochem., 29, 116, 10.1016/j.jnutbio.2015.11.010

Kitabayashi, 2010, Zinc suppresses Th17 development via inhibition of STAT3 activation, Int. Immunol., 22, 375, 10.1093/intimm/dxq017

Bredholt, M., and Frederiksen, J.L. (2016). Zinc in multiple sclerosis: A systematic review and meta-analysis. ASN Neuro, 8.

Socha, 2017, Dietary habits; concentration of copper, zinc, and Cu-to-Zn ratio in serum and ability status of patients with relapsing-remitting multiple sclerosis, Nutrition, 39, 76, 10.1016/j.nut.2017.03.009

Popescu, 2017, Pathogenic implications of distinct patterns of iron and zinc in chronic MS lesions, Acta Neuropathol., 134, 45, 10.1007/s00401-017-1696-8

Campo, 2001, Zinc inhibits the mixed lymphocyte culture, Biol. Trace Elem. Res., 79, 15, 10.1385/BTER:79:1:15

Faber, 2004, Zinc in pharmacological doses suppresses allogeneic reaction without affecting the antigenic response, Bone Marrow Transpl., 33, 1241, 10.1038/sj.bmt.1704509

Kown, 2002, Zinc chloride-mediated reduction of apoptosis as an adjunct immunosuppressive modality in cardiac transplantation, J. Heart Lung Transplant., 21, 360, 10.1016/S1053-2498(01)00384-9

Schubert, 2014, Oral zinc aspartate treats experimental autoimmune encephalomyelitis, Biometals, 27, 1249, 10.1007/s10534-014-9786-8

Rungby, 2010, Zinc, zinc transporters and diabetes, Diabetologia, 53, 1549, 10.1007/s00125-010-1793-x

Jansen, 2009, Zinc and diabetes—Clinical links and molecular mechanisms, J. Nutr. Biochem., 20, 399, 10.1016/j.jnutbio.2009.01.009

Nicolson, 2009, Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes–associated variants, Diabetes, 58, 2070, 10.2337/db09-0551

Lemaire, 2009, Insulin crystallization depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice, Proc. Natl. Acad. Sci. USA, 106, 14872, 10.1073/pnas.0906587106

Wijesekara, 2010, Beta cell-specific ZnT8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion, Diabetologia, 53, 1656, 10.1007/s00125-010-1733-9

Liuzzi, 2005, Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response, Proc. Natl. Acad. Sci. USA, 102, 6843, 10.1073/pnas.0502257102

Brambila, 2017, Hepatic mobilization of zinc after an experimental surgery, and its relationship with inflammatory cytokines release, and expression of metallothionein and Zip14 transporter, Inflamm. Res., 66, 167, 10.1007/s00011-016-1003-5

Bonaventura, P., Lamboux, A., Albarède, F., and Miossec, P. (2016). A Feedback Loop between Inflammation and Zn Uptake. PLoS ONE, 11.

Davis, 2004, DNA methylation, cancer susceptibility, and nutrient interactions, Exp. Biol. Med., 229, 988, 10.1177/153537020422901002

Keen, 2010, Zinc and reproduction: Effects of zinc deficiency on prenatal and early postnatal development, Birth Defects Res. B Dev. Reprod. Toxicol., 89, 313, 10.1002/bdrb.20264

Beach, 1982, Gestational zinc deprivation in mice: Persistence of immunodeficiency for three generations, Science, 218, 469, 10.1126/science.7123244

Tomat, 2008, Moderate zinc restriction during fetal and postnatal growth of rats: Effects on adult arterial blood pressure and kidney, Am. J. Physiol. Regul. Integr. Comp. Physiol., 295, 543, 10.1152/ajpregu.00050.2008

Valera, 2014, A correlation study between multiple sclerosis and type 1 diabetes incidences and geochemical data in Europe, Environ. Geochem. Health, 36, 79, 10.1007/s10653-013-9520-4

Valera, P., Zavattari, P., Sanna, A., Pretti, S., Marcello, A., Mannu, C., Targhetta, C., Bruno, G., and Songini, M. (2015). Zinc and Other Metals Deficiencies and Risk of Type 1 Diabetes: An Ecological Study in the High Risk Sardinia Island. PLoS ONE, 10.

Dinelli, 2010, Hydrogeochemical analysis on Italian bottled mineral waters: Effects of geology, J. Geochem. Explor., 107, 317, 10.1016/j.gexplo.2010.06.004

Cicchella, 2010, Trace elements and ions in Italian bottled mineral waters: Identification of anomalous values and human health related effects, J. Geochem. Explor., 107, 336, 10.1016/j.gexplo.2010.04.004

Dinelli, 2012, Comparative study between bottled mineral and tap water in Italy, J. Geochem. Explor., 112, 368, 10.1016/j.gexplo.2011.11.002

Dinelli, 2012, Major and trace elements in tap water from Italy, J. Geochem. Explor., 112, 54, 10.1016/j.gexplo.2011.07.009

Valera, 2014, Impact of mine tailings on surrounding soils and ground water: Case of Kettara old mine, Morocco, J. Afr. Earth Sci., 100, 437, 10.1016/j.jafrearsci.2014.07.017

Pompili, 2015, Relationships of local lithium concentrations in drinking water to regional suicide rates in Italy, World J. Biol. Psychiatry, 16, 567, 10.3109/15622975.2015.1062551

Pompili, 2017, Arsenic: Association of regional concentrations in drinking water with suicide and natural causes of death in Italy, Psychiatry Res., 249, 311, 10.1016/j.psychres.2017.01.041

Scheib, 2012, The geochemistry of niobium and its distribution and relative mobility in agricultural soils of Europe, Geochem. Explor. Environ. A, 12, 293, 10.1144/geochem2011-096

Mann, 2015, Mobile metal ion® analysis of european agricultural soils: Bioavailability, weathering, Geogenic patterns and anthropogenic anomalies, Geochem. Explor. Environ. A, 15, 99, 10.1144/geochem2014-279

Sadeghi, 2015, Geochemical fingerprinting and source discrimination of agricultural soils at continental scale, Chem. Geol., 396, 1, 10.1016/j.chemgeo.2014.12.004

Ladenberger, 2015, GEMAS: Indium in agricultural and grazing land soil of Europe—Its source and geochemical distribution patterns, J. Geochem. Explor., 154, 61, 10.1016/j.gexplo.2014.11.020

Birke, 2016, The GEMAS Project Team. Use of GEMAS data for risk assessment of cadmium in European agricultural and grazing land soil under the REACH Regulation, Appl. Geochem., 74, 109, 10.1016/j.apgeochem.2016.08.014

Birke, 2017, GEMAS: Cadmium distribution and its sources in agricultural and grazing land soil of Europe—Original data versus clr-transformed data, J. Geochem. Explor., 173, 13, 10.1016/j.gexplo.2016.11.007

Scheib, 2014, Geochemical evidence of aeolian deposits in European soils, Boreas, 43, 175, 10.1111/bor.12029