Volume 97, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Anemia has been widely studied in global health contexts because of severe nutritional deficiency, and more recently, inflammatory status, but chemical exposures are rarely considered. Until recently, “anemia” was used synonymously with “iron deficiency anemia (IDA)” in global health settings. However, only 50% of anemia cases worldwide are IDA. Environmental toxicology studies of anemia risk have generally focused on populations in developed countries, albeit with high exposure to environmental toxicants, such as lead or cadmium. In the developing world, toxicant exposures commonly coexist with other risk factors for anemia. In particular, artisanal and small-scale gold mining (ASGM) communities are at risk for dietary methylmercury exposure through contaminated fish consumption, and for anemia due to food insecurity and infectious and chronic diseases. Here, we report analysis of total hair mercury content, hemoglobin, and serum micronutrient levels in children < 12 years of age ( = 83) near ASGM in the Peruvian Amazon. Forty-nine percent ( = 29/59) of those aged < 5 years were anemic (< 11 g/dL) and 52% ( = 12/23) of those aged 5–11 years (< 11.5 g/dL). Few children were stunted, wasted, or micronutrient deficient. Median total hair mercury was 1.18 μg/g (range: 0.06–9.70 μg/g). We found an inverse association between total mercury and hemoglobin (β = −0.12 g/dL, = 0.06) that persisted (β = −0.14 g/dL, = 0.04) after adjusting for age, sex, anthropometrics, and vitamin B in multivariate regression. This study provides preliminary evidence that methylmercury exposure is associated with anemia, which is especially relevant to children living near ASGM.


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  1. BM P, 2004. The nutrition transition: an overview of world patterns of change. Nutr Rev 62: S140S143. [Google Scholar]
  2. Popkin B, , 2002. An overview on the nutrition transition and its health implications: the Bellagio meeting. Public Health Nutr 5: 93103. [Google Scholar]
  3. Laborde A, 2015. Children’s health in Latin America: the influence of environmental exposures. Environ Health Perspect 123: 201209. [Google Scholar]
  4. Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L, , 2015. Iron deficiency anemia. Lancet 387: 907916. [Google Scholar]
  5. Oppenheimer SJ, , 2001. Iron and its relation to immunity and infectious disease. J Nutr 131: 616S633S; discussion 633S–635S. [Google Scholar]
  6. Atkinson SH, Armitage AE, Khandwala S, Mwangi TW, Uyoga S, Bejon PA, Williams TN, Prentice AM, Drakesmith H, , 2014. Combinatorial effects of malaria season, iron deficiency, and inflammation determine plasma hepcidin concentration in African children. Blood 123: 32213229. [Google Scholar]
  7. WHO, 2008. Worldwide Prevalence of Anemia 1993–2005: WHO Global Database on Anemia. Geneva, Switzerland: World Health Organization.
  8. Brito A, Mujica-Coopman MF, López de Romaña D, Cori H, Allen LH, , 2015. Folate and vitamin B12 status in Latin America and the Caribbean: an update. Food Nutr Bull 36: S109S118. [Google Scholar]
  9. Duong MC, Mora-Plazas M, Marin C, Villamor E, , 2015. Vitamin B-12 deficiency in children is associated with grade repetition and school absenteeism, independent of folate, iron, zinc, or vitamin A status biomarkers. J Nutr 145: 15411548. [Google Scholar]
  10. Raiten DJ, Sakr Ashour FA, Ross AC, Meydani SN, Dawson HD, Stephensen CB, Brabin BJ, Suchdev PS, van Ommen B, Group IC, , 2015. Inflammation and nutritional science for programs/policies and interpretation of research evidence (INSPIRE). J Nutr 145: 1039S1108S. [Google Scholar]
  11. Zlotkin S, Newton S, Aimone AM, Azindow I, Amenga-Etego S, Tchum K, Mahama E, Thorpe KE, Owusu-Agyei S, , 2013. Effect of iron fortification on malaria incidence in infants and young children in Ghana: a randomized trial. JAMA 310: 938947. [Google Scholar]
  12. Hurrell R, , 2010. Iron and malaria: absorption, efficacy and safety. Int J Vitam Nutr Res 80: 279292. [Google Scholar]
  13. Raiten DJ, Ashour FA, , 2015. Iron: current landscape and efforts to address a complex issue in a complex world. J Pediatr 167: S3S7. [Google Scholar]
  14. Burke RM, Leon JS, Suchdev PS, , 2014. Identification, prevention and treatment of iron deficiency during the first 1000 days. Nutrients 6: 40934114. [Google Scholar]
  15. WHO, 2006. Iron supplementation of young children in regions where malaria transmission is intense and infectious disease highly prevalent. World Health Organization Statement. Available at: http://www.who.int/maternal_child_adolescent/documents/pdfs/who_statement_iron.pdf. Accessed.
  16. Clark MA, Goheen MM, Fulford A, Prentice AM, Elnagheeb MA, Patel J, Fisher N, Taylor SM, Kasthuri RS, Cerami C, , 2014. Host iron status and iron supplementation mediate susceptibility to erythrocytic stage Plasmodium falciparum. Nat Commun 5: 4446. [Google Scholar]
  17. United Nations, 2015. Transforming our world: the 2030 agenda for sustainable development. Available at: https://sustainabledevelopment.un.org/content/documents/21252030%20Agenda%20for%20Sustainable%20Development%20web.pdf. Accessed.
  18. Diringer SE, Feingold BJ, Ortiz EJ, Gallis JA, Araujo-Flores JM, Berky A, Pan WK, Hsu-Kim H, , 2015. River transport of mercury from artisanal and small-scale gold mining and risks for dietary mercury exposure in Madre de Dios, Peru. Environ Sci Process Impacts 17: 478487. [Google Scholar]
  19. Seriani R, Franca JG, Lombardi JV, Brito JM, Ranzani-Paiva MJ, , 2015. Hematological changes and cytogenotoxicity in the tilapia Oreochromis niloticus caused by sub-chronic exposures to mercury and selenium. Fish Physiol Biochem 41: 311322. [Google Scholar]
  20. AfTSaDR (ATSDR), 1999. Toxicological Profile for Mercury. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.
  21. Ryrie DR, Toghill PJ, Tanna MK, Galan GN, , 1970. Marrow suppression from mercury poisoning? BMJ 1: 499. [Google Scholar]
  22. Priya N, Nagaprabhu VN, Kurian G, Seethalakshmi N, Rao GG, Unni VN, , 2012. Aplastic anemia and membranous nephropathy induced by intravenous mercury. Indian J Nephrol 22: 451454. [Google Scholar]
  23. Maramba NP, 2006. Environmental and human exposure assessment monitoring of communities near an abandoned mercury mine in the Philippines: a toxic legacy. J Environ Manage 81: 135145. [Google Scholar]
  24. Slee PH, den Ottolander GJ, de Wolff FA, , 1979. A case of merbromin (Mercurochrome) intoxication possibly resulting in aplastic anemia. Acta Med Scand 205: 463466. [Google Scholar]
  25. Lang F, Lang KS, Lang PA, Huber SM, Wieder T, , 2006. Mechanisms and significance of eryptosis. Antioxid Redox Signal 8: 11831192. [Google Scholar]
  26. Foller M, Huber SM, Lang F, , 2008. Erythrocyte programmed cell death. IUBMB Life 60: 661668. [Google Scholar]
  27. Monlezun DJ, Camargo CA, Jr Mullen JT, Quraishi SA, , 2015. Vitamin D status and the risk of anemia in community-dwelling adults: results from the national health and nutrition examination survey 2001–2006. Medicine (Baltimore) 94: e1799. [Google Scholar]
  28. Qian Y, Zhang S, Guo W, Ma J, Chen Y, Wang L, Zhao M, Liu S, , 2015. Polychlorinated biphenyls (PCBs) inhibit hepcidin expression through an estrogen-like effect associated with disordered systemic iron homeostasis. Chem Res Toxicol 28: 629640. [Google Scholar]
  29. Gibb H, O’Leary KG, , 2014. Mercury exposure and health impacts among individuals in the artisanal and small-scale gold mining community: a comprehensive review. Environ Health Perspect 122: 667672. [Google Scholar]
  30. UNEP, 2013. UNEP Global Mercury Assessment 2013: Sources, Emissions, Releases and Environmental Transport. Geneva, Switzerland: UNEP Chemical Branch.
  31. Hsu-Kim H, Kucharzyk K, Deshusses MA, , 2013. Mechanisms regulating mercury bioavailability for methylating microorganisms in the aquatic environment: a critical review. Environ Sci Technol 47: 24412456. [Google Scholar]
  32. Weihe P, Grandjean P, Jorgensen PJ, , 2005. Application of hair-mercury analysis to determine the imapct of a seafood advisory. Environ Res 97: 200207. [Google Scholar]
  33. van Wijngaarden E, Beck C, Shamlaye CF, Cernichiari E, Davidson PW, Myers GJ, Clarkson TW, , 2006. Benchmark concentrations for methyl mercury obtained from the 9-year follow-up of the Seychelles Child Development Study. Neurotoxicology 27: 702709. [Google Scholar]
  34. National Research Council, Committee on the Toxicological Effects of Methylmercury, 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press.
  35. WHO, 2011. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral Nutrition Information System. Geneva, Switzerland: World Health Organization.
  36. WHO, 2010. Nutrition Landscape Information System (NLIS) Country Profile Indicators Interpretation Guide. Geneva, Switzerland: World Health Organization.
  37. Integrated Risk Information System (IRIS) and United States Environmental Protection Agency, 2001. Chemical Assessment Summary for Methylmercury (MeHg); CASRN 22967-92-6. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/subst/0073_summary.pdf. Accessed.
  38. Joint FAO/WHO Expert Committee on Food Additives, 2006. Evaluation of Certain Food Additives and Contaminants: Sixty-fourth report of the joint FAO/WHO Expert Committee on Food Additives. Available at: http://apps.who.int/iris/bitstream/10665/43258/1/WHO_TRS_930_eng.pdf. Accessed.
  39. Kana-sop MM, Gouado I, Achu MB, Van Camp J, Amvam Zollo PH, Schweigert FJ, Oberleas D, Ekoe T, , 2015. The influence of iron and zinc supplementation on the bioavailability of provitamin A carotenoids from papaya following consumption of a vitamin A-deficient diet. J Nutr Sci Vitaminol (Tokyo) 61: 205214. [Google Scholar]
  40. Clarkson TW, Vyas JB, Ballatori N, , 2007. Mechanisms of mercury disposition in the body. Am J Ind Med 50: 757764. [Google Scholar]
  41. Mujica-Coopman MF, Brito A, López de Romana D, Rios-Castillo I, Cori H, Olivares M, , 2015. Prevalence of anemia in Latin America and the Caribbean. Food Nutr Bull 36: S119S128. [Google Scholar]
  42. Brennt CE, Smith JR, , 1989. The inhibitory effects of nitrous oxide and methylmercury in vivo on methionine synthase (EC activity in the brain, liver, ovary, and spinal cord of the rat. Gen Pharmacol 20: 427431. [Google Scholar]
  43. Smith SJ, Jr, 1990. Effects of methylmercury in vitro on methionine synthase activity in various rat tissues. Bull Environ Contam Toxicol 45: 649654. [Google Scholar]
  44. Rader JI, Niethammer D, Huennekens FM, , 1974. Effects of sulfhydryl inhibitors upon transport of folate compounds into L1210 cells. Biochem Pharmacol 23: 20572059. [Google Scholar]
  45. Saraiva BC, Soares MC, Santos LC, Pereira SC, Horta PM, , 2014. Iron deficiency and anemia are associated with low retinol levels in children aged 1 to 5 years. J Pediatr (Rio J) 90: 593599. [Google Scholar]
  46. Ricks DJ, Rees C, Osborn KA, Crookston BT, Leaver K, Merrill SB, Velasquez C, Ricks JH, , 2012. Peru’s national folic acid fortification program and its effect on neural tube defects in Lima. Rev Panam Salud Publica 32: 391398. [Google Scholar]
  47. Selhub J, Morris MS, Jacques PF, , 2007. In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations. Proc Natl Acad Sci USA 104: 19995. [Google Scholar]
  48. Morris MS, Jacques PF, Rosenberg IH, Selhub J, , 2007. Folate and vitamin B12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. American Society for Clinical Nutrition 85: 193200. [Google Scholar]
  49. Johnson MA, , 2007. If high folic acid aggravates vitamin B12 deficiency, what should be done about it? Nutr Rev 65: 451458. [Google Scholar]
  50. Vahter ME, Mottet NK, Friberg LT, Lind SB, Charleston JS, Burbachter TM, , 1995. Demethylation of methylmercury in different brain sites of Macaca fascicularis monkeys during long-term subclinical methylmercury exposure. Toxicol Appl Pharmacol 134: 273284. [Google Scholar]
  51. Suh YJ, Lee JE, Lee DH, Yi HG, Lee MH, Kim CS, Nah JW, Kim SK, , 2016. Prevalence and relationships of iron deficiency anemia with blood cadmium and vitamin D levels in Korean women. J Korean Med Sci 31: 2532. [Google Scholar]
  52. Lang E, Jilani K, Bissinger R, Rexhepaj R, Zelenak C, Lupescu A, Lang F, Qadri SM, , 2015. Vitamin D-rich diet in mice modulates erythrocyte survival. Kidney Blood Press Res 40: 403412. [Google Scholar]
  53. Eze JI, Ayogu LC, Abonyi FO, Eze UU, , 2015. The beneficial effect of dietary zinc supplementation on anaemia and immunosuppression in Trypanosoma brucei infected rats. Exp Parasitol 154: 8792. [Google Scholar]
  54. Fonseca Mde F, De Souza Hacon S, Grandjean P, Choi AL, Bastos WR, , 2014. Iron status as a covariate in methylmercury-associated neurotoxicity risk. Chemosphere 100: 8996. [Google Scholar]
  55. Carmel R, , 2009. Does high folic acid intake affect unrecognized cobalamin deficiency adn how will we know it if we see it? Am J Clin Nutr 90: 14491450. [Google Scholar]
  56. Sazawal S, 2006. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. Lancet 367: 133143. [Google Scholar]
  57. Cernichiari E, Myers GJ, Ballatori N, Zareba G, Vyas J, Clarkson T, , 2007. The biological monitoring of prenatal exposure to methylmercury. Neurotoxicology 28: 10151022. [Google Scholar]
  58. Guo W, Zhang J, Li W, Xu M, Liu S, , 2015. Disruption of iron homeostasis and resultant health effects upon exposure to various environmental pollutants: a critical review. J Environ Sci (China) 34: 155164. [Google Scholar]
  59. Jacob HS, Brain MC, Dacie JV, Carrell RW, Lehmann H, , 1968. Abnormal haem binding and globin SH group blockade in unstable haemoglobins. Nature 218: 12141217. [Google Scholar]
  60. Chatterjee S, Saxena RK, , 2015. Preferential elimination of older erythrocytes in circulation and depressed bone marrow erythropoietic activity contribute to cadmium induced anemia in mice. PLoS One 10: e0132697. [Google Scholar]
  61. Lupescu A, Bissinger R, Goebel T, Salker MS, Alzoubi K, Liu G, Chirigiu L, Mack AF, Qadri SM, Lang F, , 2015. Enhanced suicidal erythrocyte death contributing to anemia in the elderly. Cell Physiol Biochem 36: 773783. [Google Scholar]
  62. Gartner A, Berger J, Bour A, El Ati J, Traissac P, Landais E, El Kabbaj S, Delpeuch F, , 2013. Assessment of iron deficiency in the context of the obesity epidemic: importance of correcting serum ferritin concentrations for inflammation. Am J Clin Nutr 98: 821826. [Google Scholar]
  63. Eisele K, Lang PA, Kempe DS, Klarl BA, Niemoller O, Wieder T, Huber SM, Duranton C, Lang F, , 2006. Stimulation of erythrocyte phosphatidylserine exposure by mercury ions. Toxicol Appl Pharmacol 210: 116122. [Google Scholar]
  64. Ellison-Zelski SJ, Solodin N, Alarid ET, , 2009. Repression of ESR1 through actions of estrogen receptor alpha and Sin3A at the proximal promoter. Mol Cell Biol 29: 49494958. [Google Scholar]
  65. Yang Q, Jian J, Katz S, Abramson SB, Huang X, , 2012. 17beta-estradiol inhibits iron hormone hepcidin through an estrogen responsive element half-site. Endocrinology 153: 31703178. [Google Scholar]
  66. Hou Y, Zhang S, Wang L, Li J, Qu G, He J, Rong H, Ji H, Liu S, , 2012. Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element. Gene 511: 398403. [Google Scholar]
  67. Yamazaki T, Yamamoto M, Ishihara Y, Komatsu S, Munetsuna E, Onizaki M, Ishida A, Kawato S, Mukuda T, , 2013. De novo synthesized estradiol protects agains methylmercury-induced neurotoxicity in cultured rat hippocampal slices. PLoS One 8: e555559. [Google Scholar]
  68. Wang X, Xia T, , 2015. New insights into disruption of iron homeostasis by environmental pollutants. J Environ Sci (China) 1: 256258. [Google Scholar]
  69. Ahlqvist KJ, 2015. MtDNA mutagenesis impairs elimination of mitochondria during erythroid maturation leading to enhanced erythrocyte destruction. Nat Commun 6: 6494. [Google Scholar]
  70. Hadley C, DeCaro JA, , 2015. Does moderate iron deficiency protect against childhood illness? A test of the optimal iron hypothesis in Tanzania. Am J Phys Anthropol 157: 675679. [Google Scholar]

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  • Received : 03 Apr 2017
  • Accepted : 27 Jul 2017
  • Published online : 25 Sep 2017

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