Hostname: page-component-76fb5796d-vvkck Total loading time: 0 Render date: 2024-04-27T02:25:47.144Z Has data issue: false hasContentIssue false
  • English
  • Français

Iron overload in Sub-Saharan Africa: to what extent is it a public health problem?

Published online by Cambridge University Press:  09 March 2007

Alexander R. P. Walker  and
Isidor Segal
Alexander R. P. Walker*
Affiliation:
Human Biochemistry Research Unit, Department of Tropical Diseases, School of Pathology of the University of the Witwatersrand, and the South African Institute for Medical Research, Johannesburg, South Africa
Isidor Segal
Affiliation:
Gastroenterology Unit Department of Medicine, Baragwanath Hospital and the University of the Witwatersrand, Johannesburg 2000, South Africa
*
*Corresponding author: Dr A. R. P. Walker, fax +27 11 489 9001, email alexw@mail.saimr.wits.ac.za
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Excessive deposition of Fe in the organs and tissues of Sub-Saharan Africans was first described in South Africa in 1929. Fe overload, or siderosis, was initially attributed to infections and to metallic poisoning (Cu, Sn, Zn), and then to malnutrition. In 1953 it was hypothesized that it was due primarily to excessive Fe intake derived from foods and drinks prepared in Fe vessels. Recently, in 1992 it was advanced that a gene distinct from any HLA-linked locus may also play a role. As to sequelae, in early research on series of hospital patients, the condition was linked to scurvy, osteoporosis, diabetes, cirrhosis, and latterly, to hepatocellular cancer and tuberculosis. Accordingly, many have concluded that Fe overload is responsible for considerable morbidity and mortality, that adventitious Fe intake should be reduced, and that phlebotomy be recommended for those severely affected. However, there are numerous limitations in the evidence. There are also problems in interpretation, since levels of Fe in the serum are affected additionally by a variety of factors: infection, inflammation, certain cancers and alcohol intake. These considerations complicate attempts to assess to what extent the associations described denote causation, and whether Fe overload has significant ramifications for ill in the general African population. While the adverse sequelae of overload may be less of significance than many believe, the precise pathogenicity of the phenomenon will remain uncertain until further investigations, including prospective studies, are undertaken.

Keywords

Iron overloadAfricaCirrhosisHepatocellular carcinoma
Type
Review article
Information
British Journal of Nutrition , Volume 81 , Issue 6 , June 1999 , pp. 427 - 434
Copyright
Copyright © The Nutrition Society 1999

References

Alderman, MH, Anderson, S, Bennett, WM, Drueke, TB, Haynes, RB, Kincaid-Smith, PS, Kurtz, TW, Laragh, JH, Linas, SL, Logan, AG, Luft, FC, Mancia, G, McCarron, DA, Oparil, S, Staessen, JAH & Stern, JS (1997) Scientists' statement regarding data on the sodium–hypertension relationship and sodium health claims on food labeling. Nutrition Reviews 55, 172–175.Google Scholar
Alexander, D, Ball, MJ & Mann, J (1994) Nutrient intake and haematological status of vegetarians and age-sex matched omnivores. European Journal of Clinical Nutrition 48, 538–546.Google ScholarPubMed
Annual Report of the City Health Department (1996) Pp. 5, 14. City of Harare, Zimbabwe.Google Scholar
Annual Report of the Medical Officer of Health (1995/1996) Vol. 2, pp. 1, 6, 8. City of Cape Town, South Africa.Google Scholar
Baer, D (1996) Hereditary iron overload and African Americans. American Journal of Medicine 100, 5–8.CrossRefGoogle Scholar
Bassett, MT, Chokunonga, E, Mauchaza, B, Levy, L, Ferlay, J & Parkin, DM (1995 a) Cancer in the African population of Harare, Zimbabwe, 1990–1992. International Journal of Cancer 63, 29–36.CrossRefGoogle ScholarPubMed
Bassett, MT, Levy, L, Chokunonga, E, Mauchaza, B, Ferlay, J & Parkin, DM (1995 b) Cancer in the European population of Harare, Zimbabwe, 1990–1992. International Journal of Cancer 63, 24–28.CrossRefGoogle ScholarPubMed
Bothwell, TH, Seftel, HC, Jacobs, P, Torrance, JD & Baumslag, N (1964) Iron overload in Bantu subjects. Studies on the availability of iron in Bantu beer. American Journal of Clinical Nutrition 14, 47–51.CrossRefGoogle ScholarPubMed
Cooper, ES, Ramdath, DD, Whyte-Alleng, C, Howell, S & Serjeant, BE (1997) Plasma proteins in children with trichuris dysentery syndrome. Journal of Clinical Pathology 50, 236–240.CrossRefGoogle ScholarPubMed
Evans, AE, Ruidavets, J-B, McCrum, EE, Cambou, J-P, McClean, R, Douste-Blazy, P, McMaster, D, Bingham, A, Patterson, C, Richard, JL, Mathewson, ZM & Cambien, F (1995) Autres pays, autres coeurs? Dietary patterns, risk factors and ischaemic heart disease in Belfast and Toulouse. Quarterly Journal of Medicine 88, 469–477.Google ScholarPubMed
Expert Scientific Working Group (1985) Summary of a report on an assessment of the iron nutritional status of the United States population. American Journal of Clinical Nutrition 42, 1318–1330.CrossRefGoogle Scholar
Feder, JN, Gnirke, A, Thomas, W, Tsuchhashi, Z, Ruddy, DA, Basava, A, Dormishian, F, Domingo, R, Ellis, MC, Fullan, A, Hinton, LM, Jones, NL, Kimmel, BE, Kronmal, GS, Lauer, P, Lee, VK, Loeb, DB, Mapa, FA, McClelland, E, Meyer, NC, Mintier, GA, Moeller, N, Moore, T, Morikang, E, Prass, CE, Quintana, L, Starnes, SM, Schatzman, RC, Brunke, KJ, Drayna, DT, Risch, NJ, Bacon, BR & Wolff, RK (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature Genetics 13, 399–408.CrossRefGoogle ScholarPubMed
Finch, CA, Hegsted, M, Kinney, TD, Thomas, ED, Rath, CE, Haskins, D, Finch, S & Fluharty, RG (1950) Iron metabolism. The pathophysiology of iron storage. Blood 5, 893–1008.Google Scholar
Fowler, WM & Barer, AP (1937) Retention and utilization of orally administered iron. Archives of Internal Medicine 59, 561–571.CrossRefGoogle Scholar
Friedman, BM, Baynes, RD, Bothwell, TH, Gordeuk, VR, Macfarlane, BJ, Lamparelli, RD, Robinson, EJ, Sher, R & Hamberg, S (1990) Dietary iron overload in southern African rural blacks. South African Medical Journal 78, 301–305.Google ScholarPubMed
Gangaidzo, IT & Gordeuk, VR (1996) Hepatocellular carcinoma and African iron overload. Gut 38, 937–938.CrossRefGoogle Scholar
Gerritsen, T & Walker, ARP (1953) Serum iron and iron-binding capacity in the South African Bantu. South African Medical Journal 2, 577–581.Google Scholar
Gillman, J & Gillman, T (1947) The pathogenesis of cytosiderosis (hemochromatosis) as evidenced in malnourished Africans. Gastroenterology 8, 19–23.Google ScholarPubMed
Gillman, J & Gillman, T (1951) Perspectives in Human Malnutrition. New York, NY: Grune and Stratton.Google Scholar
Gordeuk, VR, Boyd, RD & Brittenham, GM (1986) Dietary iron overload persists in rural Sub-Saharan Africa. Lancet i, 1310–1313.CrossRefGoogle Scholar
Gordeuk, VR, McLaren, CE, MacPhail, AP, Deichsel, G & Bothwell, TH (1996) Associations of iron overload in Africa with hepatocellular carcinoma and tuberculosis: Strachan's 1929 thesis revisited. Blood 87, 3470–3476.CrossRefGoogle Scholar
Gordeuk, VR, Mukhibi, J, Hasstedt, SJ, Samowitz, W, Edwards, CQ, West, G, Ndambire, S, Emmanuel, J, Nkanza, N, Chapanduka, Z, Randall, M, Boone, P, Romano, P, Martell, RW, Yamashita, T, Effler, P & Brittenham, G (1992) Iron overload in Africa - interactions between a gene and dietary iron content. New England Journal of Medicine 326, 95–100.CrossRefGoogle ScholarPubMed
Grusin, H & Samuel, E (1957) A syndrome of osteoporosis in Africans and its relationship to scurvy. American Journal of Clinical Nutrition 5, 644–650.CrossRefGoogle ScholarPubMed
Hallberg, L, Hultén, L & Gramatkovski, E (1997) Iron absorption from the whole diet in men: how effective is the regulation of iron absorption?. American Journal of Clinical Nutrition 66, 347–356.CrossRefGoogle ScholarPubMed
Hann, H-WL, Kim, CY, London, T & Blumberg, BS (1989) Increased serum ferritin in chronic liver disease: a risk factor for primary hepatocellular carcinoma. International Journal of Cancer 43, 376–379.CrossRefGoogle ScholarPubMed
Hercberg, S, Chauliac, M, Galan, P, Devanlay, M, Zohoun, I, Agboton, Y, Soustre, Y, Bovies, C, Christides, J-P, Potier de Courcy, G, Masse-Raimbault, AM & Dupin, H (1986) Relationship between anaemia, iron deficiency and folacin deficiency, haemoglobinopathies and parasitic infections. Human Nutrition: Clinical Nutrition 40C, 371–379.Google Scholar
Higginson, J, Gerritsen, T & Walker, ARP (1953) Siderosis in the Bantu of Southern Africa. American Journal of Pathology 29, 779–815.Google ScholarPubMed
Hulthen, L, Lindstedt, G, Lundberg, PA & Hallberg, L (1998) Effect of a mild infection on serum ferritin concentration - clinical and epidemiological implications. European Journal of Clinical Nutrition 52, 376–379.CrossRefGoogle ScholarPubMed
Jaskiewicz, K, Stephen, A & Banach, L (1991) Hepatocellular carcinoma in a rural population at risk. Anticancer Research 11, 2187–2190.Google Scholar
Kew, MC (1994) Hepatitis viruses and hepatocellular carcinoma. South African Medical Journal 84, 550–556.Google ScholarPubMed
Kew, MC (1995) Hepatocellular carcinoma: epidemiology. In Gastroenterology in the Tropics and Subtropics, pp. 184–186 [Watters, D and Kiire, CF, editors]. London: Macmillan.Google Scholar
Konijn, AM (1994) Iron metabolism in inflammation. Baillières Clinical Haematology 7, 829–849.CrossRefGoogle ScholarPubMed
Leeder, S & Gliksman, M (1990) Prospects for preventing heart disease. British Medical Journal 301, 1004–1005.CrossRefGoogle ScholarPubMed
Lynch, SR (1995) Iron overload: prevalence and impact on health. Nutrition Reviews 53, 255–260.CrossRefGoogle ScholarPubMed
McCance, RA & Widdowson, EM (1937) Absorption and excretion of iron. Lancet ii, 680–684.CrossRefGoogle Scholar
MacPhail, AP, Simon, MO, Torrance, JD, Charlton, RW, Bothwell, TH & Isaacson, C (1979) Changing patterns of dietary iron overload in black South Africans. American Journal of Clinical Nutrition 32, 1272–1278.CrossRefGoogle ScholarPubMed
Mandishona, E, MacPhail, AP, Gordeuk, VR, Kedda, MA, Paterson, AC, Rouault, TA & Kew, MC (1998) Dietary iron overload as a risk factor for hepatocellular carcinoma in Black Africans. Hepatology 27, 1563–1566.CrossRefGoogle ScholarPubMed
Milman, N, Rosenstock, S, Andersen, L, Jorgensen, T & Bonnevie, O (1998) Serum ferritin, hemoglobin, and Helicobacter pylori infection: a seroepidemiologic survey comprising 2794 Danish adults. Gastroenterology 115, 268–274.CrossRefGoogle ScholarPubMed
Moyo, VM, Gangaidzo, IT, Khumalo, H, Saungweme, T, Kiire, CF, Rouault, T & Gordeuk, VR (1997) Traditional beer consumption and the iron status of spouse pairs from a rural community in Zimbabwe. Blood 89, 2159–2166.CrossRefGoogle ScholarPubMed
Moyo, VM, Mandishona, E, Hasstedt, SJ, Gangaidzo, IT, Gomo, ZAR, Khumalo, H, Saungweme, T, Kiire, CF, Paterson, AC, Bloom, P, MacPhail, AP, Rouault, T & Gordeuk, VR (1998) Evidence of genetic transmission in African iron overload. Blood 91, 1076–1082.Google ScholarPubMed
Nesamvuni, AE, Badenhorst, CJ, Bourne, L, Kruger, M, Steyn, NP, Lombard, CJ, Loubsher, R, Marais, M, Steyn, K & Jooste, PL (1996) Iron overload in adult black men aged 15–64 years residing in the Cape Peninsula: is it a problem?. (The BRISK Study) South African Journal of Food Science and Nutrition 8, 13 Abstr.Google Scholar
Ola, SO, Akanji, AO & Ayoola, EA (1995) The diagnostic utility of serum ferritin estimation in Nigerian patients with primary hepatocellular carcinoma. Nutrition 11, 532–534.Google ScholarPubMed
Parkin, BM, Muir, CS, Whelan, SL, Gao, YT, Ferlay, J & Powell, J (1992) Cancer Incidence in Five Continents, vol. 6, Scientific Publications no. 120, p. 930. Lyon, France: IARC.Google Scholar
Paterson, AC, Kew, MC, Herman, AAB, Becker, PJ, Hodkinson, J & Isaacson, C (1985) Liver morphology in Southern African Blacks with hepatocellular carcinoma: a study within an urban environment. Hepatology 5, 72–78.CrossRefGoogle ScholarPubMed
Pettersson, T, Kivivuori, SM & Siimes, MA (1994) Is serum transferrin receptor useful for detecting iron-deficiency in anaemic patients with chronic inflammatory diseases?. British Journal of Rheumatology 33, 740–744.CrossRefGoogle ScholarPubMed
Report of a Meeting of Physicians and Scientists at the Royal Free Hospital School of Medicine (1997) Genetic haemochromatosis. Lancet 349, 1688–1693.CrossRefGoogle Scholar
Seftel, HC, Keeley, KJ, Isaacson, C & Bothwell, TH (1961) Siderosis in the Bantu: The clinical incidence of hemochromatosis in diabetic subjects. Journal of Laboratory and Clinical Medicine 58, 837–844.Google Scholar
Seftel, HC, Malkin, C, Schmaman, A, Abrahams, C, Lynch, SR, Charlton, RW & Bothwell, TH (1966) Osteoporosis, scurvy and siderosis in Johannesburg Bantu. British Medical Journal 1, 642–646.CrossRefGoogle ScholarPubMed
Sheldon, JH (1935) Haemochromatosis. London: Oxford University Press.Google Scholar
Sitas, F, Blaauw, D, Terblanche, M, Madhoo, J & Carrara, H (1997) Cancer in South Africa, 1992. Johannesburg, South Africa: South African Institute for Medical Research.Google Scholar
Stamler, J (1997) The INTERSALT study, background, methods, findings, and implications. American Journal of Clinical Nutrition 65, Suppl., 626S–642S.CrossRefGoogle Scholar
Stoltzfus, RJ, Albonico, M, Chwaya, HM, Tielsch, JM, Schulze, KJ & Savioli, L (1998) Effects of the Zanzibar school-based deworming program on iron status of children. American Journal of Clinical Nutrition 68, 179–186.CrossRefGoogle ScholarPubMed
Stoltzfus, RJ, Chwaya, HM, Albonico, M, Schulze, KJ, Savioli, L & Tielsch, JM (1997) Serum ferritin, erythrocyte protophyrin and hemoglobin are valid indicators of iron status of school children in a malaria-holoendemic population. Journal of Nutrition 127, 293–298.Google Scholar
Strachan, AS (1929) Haemosiderosis and Haemochromatosis in South African Natives with a Comment on the Aetiology of Haemochromatosis. MD Thesis, University of Glasgow.Google Scholar
Sullivan, JL & Sullivan, LG (1996) Elevated serum ferritin levels: associated diseases and clinical significance. American Journal of Medicine 101, 120–121.Google ScholarPubMed
Theron, JJ, Hautrey, AO, Liebenberg, N & Schirren, V (1963) The pathogenesis of experimental dietary siderosis in the liver. American Journal of Pathology 43, 73–91.Google ScholarPubMed
Walker, ARP (1955) The composition and density of thoracic vertebral bodies from South African Bantu adults habituated to a very high iron intake. South African Journal of Laboratory and Clinical Medicine 1, 254–262.Google ScholarPubMed
Walker, ARP & Arvidsson, UB (1953) Iron "overload" in the South African Bantu. Transactions of the Royal Society of Tropical Medicine and Hygiene 47, 536–548.CrossRefGoogle ScholarPubMed
Walker, ARP, Fox, FW & Irving, JT (1948) Studies in human mineral metabolism. The effect of bread rich in phytate phosphorus on the metabolism of certain mineral salts with special to calcium. Biochemical Journal 42, 452–462.CrossRefGoogle Scholar
Walker, ARP & Segal, I (1996) Hepatocellular carcinoma and African iron overload. Gut 38, 937.CrossRefGoogle ScholarPubMed
Wapnick, AA, Lynch, SR, Seftel, HC, Charlton, RW & Bothwell, TH (1971) The effect of siderosis and ascorbic acid depletion on bone metabolism with special to osteoporosis in the Bantu. British Journal of Nutrition 25, 367–376.CrossRefGoogle Scholar
Widdowson, EM & McCance, RA (1937) Iron excretion and metabolism in man. Nature 152, 326–327.Google Scholar
Wiley, TE, McCarthy, M, Breidi, L, McCarthy, M & Layden, TJ (1998) Impact of alcohol on the histological and clinical progression of hepatitis C infection. Hepatology 28, 805–809.CrossRefGoogle ScholarPubMed
Zhou, X-D, DeTolla, L, Custer, P & London, T (1987) Iron, ferritin, hepatitis B surface and core antigens in the livers of Chinese patients with hepatocellular carcinoma. Cancer 59, 1430–1437.3.0.CO;2-A>CrossRefGoogle ScholarPubMed