Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: a meta-analysis

D. I. Thurnham, L McCabe, S Haldar, F Wieringa, CA Clewes, G McCabe

    Research output: Contribution to journalArticle

    292 Citations (Scopus)

    Abstract

    Background: The World Health Organization recommends serumferritin concentrations as the best indicator of iron deficiency (ID).Unfortunately, ferritin increases with infections; hence, the prevalence of ID is underestimated.Objective: The objective was to estimate the increase in ferritin in32 studies of apparently healthy persons by using 2 acute-phase proteins (APPs), C-reactive protein (CRP) and a1-acid glycoprotein (AGP), individually and in combination, and to calculate factors toremove the influence of inflammation from ferritin concentrations.Design: We estimated the increase in ferritin associated with inflammation(ie, CRP .5 mg/L and/or AGP .1 g/L). The 32 studies comprised infants (5 studies), children (7 studies), men (4 studies),and women (16 studies) (n = 8796 subjects). In 2-group analyses(either CRP or AGP), we compared the ratios of log ferritin with or without inflammation in 30 studies. In addition, in 22 studies, the data allowed a comparison of ratios of log ferritin between 4 subgroups:reference (no elevated APP), incubation (elevated CRP only), early convalescence (both APP and CRP elevated), and late convalescence (elevated AGP only).Results: In the 2-group analysis, inflammation increased ferritin by 49.6% (CRP) or 38.2% (AGP; both P , 0.001). Elevated AGP was more common than CRP in young persons than in adults. In the 4-group analysis, ferritin was 30%, 90%, and 36% (all P , 0.001)higher in the incubation, early convalescence, and late convalescence subgroups, respectively, with corresponding correction factors of 0.77, 0.53, and 0.75. Overall, inflammation increased ferritin by ’30% and was associated with a 14% (CI: 7%, 21%) underestimation of ID.Conclusions: Measures of both APP and CRP are needed to estimate the full effect of inflammation and can be used to correct ferritin concentrations. Few differences were observed between age and sex subgroups
    LanguageEnglish
    Pages546-555
    JournalAmerican Journal of Clinical Nutrition
    Volume92
    Issue number2
    Publication statusPublished - 2010

    Fingerprint

    Ferritins
    Meta-Analysis
    Iron
    C-Reactive Protein
    Inflammation
    Acute-Phase Proteins
    Glycoproteins
    Acids
    Protein C
    P-Glycoprotein

    Keywords

    • ferritin
    • inflammation
    • CRP
    • AGP
    • iron deficiency

    Cite this

    Thurnham, D. I. ; McCabe, L ; Haldar, S ; Wieringa, F ; Clewes, CA ; McCabe, G. / Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: a meta-analysis. In: American Journal of Clinical Nutrition. 2010 ; Vol. 92, No. 2. pp. 546-555.
    @article{2142ed3d4b65445393d229adf76e09a5,
    title = "Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: a meta-analysis",
    abstract = "Background: The World Health Organization recommends serumferritin concentrations as the best indicator of iron deficiency (ID).Unfortunately, ferritin increases with infections; hence, the prevalence of ID is underestimated.Objective: The objective was to estimate the increase in ferritin in32 studies of apparently healthy persons by using 2 acute-phase proteins (APPs), C-reactive protein (CRP) and a1-acid glycoprotein (AGP), individually and in combination, and to calculate factors toremove the influence of inflammation from ferritin concentrations.Design: We estimated the increase in ferritin associated with inflammation(ie, CRP .5 mg/L and/or AGP .1 g/L). The 32 studies comprised infants (5 studies), children (7 studies), men (4 studies),and women (16 studies) (n = 8796 subjects). In 2-group analyses(either CRP or AGP), we compared the ratios of log ferritin with or without inflammation in 30 studies. In addition, in 22 studies, the data allowed a comparison of ratios of log ferritin between 4 subgroups:reference (no elevated APP), incubation (elevated CRP only), early convalescence (both APP and CRP elevated), and late convalescence (elevated AGP only).Results: In the 2-group analysis, inflammation increased ferritin by 49.6{\%} (CRP) or 38.2{\%} (AGP; both P , 0.001). Elevated AGP was more common than CRP in young persons than in adults. In the 4-group analysis, ferritin was 30{\%}, 90{\%}, and 36{\%} (all P , 0.001)higher in the incubation, early convalescence, and late convalescence subgroups, respectively, with corresponding correction factors of 0.77, 0.53, and 0.75. Overall, inflammation increased ferritin by ’30{\%} and was associated with a 14{\%} (CI: 7{\%}, 21{\%}) underestimation of ID.Conclusions: Measures of both APP and CRP are needed to estimate the full effect of inflammation and can be used to correct ferritin concentrations. Few differences were observed between age and sex subgroups",
    keywords = "ferritin, inflammation, CRP, AGP, iron deficiency",
    author = "Thurnham, {D. I.} and L McCabe and S Haldar and F Wieringa and CA Clewes and G McCabe",
    note = "Reference text: 1. Lipschitz DA, Cook JD, Finch CA. A clinical examination of serum ferritin as an index of iron stores. N Engl J Med 1974;290:1213–6. 2. Witte DL. Can ferritin be effectively interpreted in the presence of the acute-phase response? Clin Chem 1991;37:484–5. 3. UNICEF, UNU, WHO. Iron deficiency anaemia. Assessment, prevention and control. A guide for programme managers. IDA Consultation, Geneva 1993. Geneva, Switzerland: World Health Organization, 2001. (Publication no. WHO/NHD/01.3, 1-114.) 4. Mei Z, Cogswell ME, Parvanta I, et al. Hemoglobin and ferritin are currently the most efficient indicators of population response to iron interventions: an analysis of nine randomized controlled trials. J Nutr 2005;135:1974–80. 5. World Health Organization, Centers for Disease Control and Prevention. Assessing the iron status of populations. Geneva, Switzerland: WHO Press, 2004. 6. Finch CA, Belotti V, Stray S, et al. Plasma ferritin as a diagnostic tool. West J Med 1986;145:657–63. 7. Baynes R, Bezwoda W, Bothwell TH, Khan Q, Mansoor N. The nonimmune inflammatory response: serial changes in plasma iron, ironbinding capacity, lactoferrin, ferritin and C-reactive protein. Scand J Clin Lab Invest 1986;46:695–704. 8. World Health Organization, Centers for Disease Control and Prevention. Assessing the iron status of populations. Geneva, Switzerland: WHO Press, 2007. 9. Beard JL, Murray-Kolb LE, Rosales FJ, Solomons NW, Angelilli ML. Interpretation of serum ferritin concentrations as indicators of total-body iron stores in survey populations: the role of biomarkers for the acute phase response. Am J Clin Nutr 2006;84:1498–505. 10. Gibson RS, Abebe Y, Stabler S, et al. Zinc, gravida, infection, and iron, but not vitamin B-12 or folate status, predict hemoglobin during pregnancy in Southern Ethiopia. J Nutr 2008;138:581–6. 11. Darboe MK, Thurnham DI, Morgan G, et al. Effectiveness of the new IVACG early high-dose vitamin A supplementation scheme compared to the standard WHO protocol: a randomised controlled trial in Gambian mothers and infants. Lancet 2007;369:2088–96. 12. Northrop-Clewes CA. Interpreting indicators of iron status during an acute phase response—lessons from malaria and HIV. Ann Clin Biochem 2008;45:18–32. 13. Fleck A, Myers MA. Diagnostic and prognostic significance of acute phase proteins. In: Gordon AH, Koj A, eds. The acute phase response to injury and infection. Amsterdam, Netherlands: Elsevier Scientific Publishers, 1985:249–71. 14. Feelders RA, Vreugdenhil G, Eggermont AMM, Kuiper-Kramer PA, van Eijk HG, Swaak AJG. Regulation of iron metabolism in the acute-phase response: interferon- and tumor necrosis factor- induce hypoferraemia, ferritin production and a decrease in circulating transferrin receptors in cancer patients. Eur J Clin Invest 1998;28:520–7. 15. Thurnham DI, McCabe GP, Northrop-Clewes CA, Nestel P. Effect of subclinical infection on plasma retinol concentrations and assessment of prevalence of vitamin A deficiency: meta-analysis. Lancet 2003;362:2052–8. 16. Calvin J, Neale G, Fotherby KJ, Price CP. The relative merits of acute phase proteins in the recognition of inflammatory conditions. Ann Clin Biochem 1988;25:60–6. 17. Kuvibidila S, Gauthier T, Warrier RP, Rayford W. Increased levels of serum transferrin receptor and serum transferrin receptor/log ferritin 554 THURNHAM ET AL Downloaded from ajcn.nutrition.org by guest on January 15, 2013 ratios in men with prostate cancer and the implications for body-iron stores. J Lab Clin Med 2004;144:176–82. 18. Mancini G, Carbonara O, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 1965;2: 235–54. 19. Paracha PI, Jamil A, Northrop-Clewes CA, Thurnham DI. Interpretation of vitamin A status in apparently-healthy Pakistani children using markers of sub-clinical infection. Am J Clin Nutr 2000;72:1164–9. 20. Thurnham DI, Mburu ASW, Mwaniki DL, Muniu EM, Alumasa F, de Wagt A. Using plasma acute-phase protein concentrations to interpret nutritional biomarkers in apparently healthy HIV-1-seropositive Kenyan adults. Br J Nutr 2008;100:174–82. 21. Erhardt JG, Estes JE, Pfeiffer CM, Biesalski HK, Craft NE. Combined measurement of ferritin, soluble transferrin receptor, retinol binding protein, and C-reactive protein by an inexpensive, sensitive, and simple sandwich enzyme-linked immunosorbent assay technique. J Nutr 2004; 134:3127–32. 22. Beesley R, Filteau SM, Tomkins A, et al. Impact of acute malaria on plasma concentrations of transferrin receptors. Trans R Soc Trop Med Hyg 2000;94:295–8. 23. Gil CI, Haldar S, Boyd LA, et al. Watercress supplementation in diet reduces lymphocyte DNA damage and alters blood antioxidant status in healthy adults. Am J Clin Nutr 2007;85:504–10. 24. Kuvibidila S, Yu LC, Ode DL, Warrier RP, Mbele V. Assessment of iron status of Zairean women of childbearing age by serum transferrin receptor. Am J Clin Nutr 1994;60:603–9. 25. Winichagoon P, McKenzie JE, Chavasit V, et al. A multimicronutrient- fortified seasoning powder enhances the hemoglobin, zinc, and iodine status of primary school children in North East Thailand: a randomized controlled trial of efficacy. J Nutr 2006;136:1617–23. 26. Hindle LJ, Gitau R, Filteau SM, et al. Effect of multiple micronutrient supplementation during pregnancy on inflammatory markers in Nepalese women. Am J Clin Nutr 2006;86:1086–92. 27. Wieringa FT, Dijkhuizen MA, West CE, Northrop-Clewes CA, Muhilal. Estimation of the effect of the acute phase response on indicators of micronutrient status in Indonesian infants. J Nutr 2002;132:3061–6. 28. Wieringa FT, Dijkhuizen MA, West CE, Thurnham DI. Muhilal, Van Der Meer JWM. Redistribution of vitamin A after iron supplementation in Indonesian infants. Am J Clin Nutr 2003;77:651–7. 29. Hubbs-Tait L, Mulugeta A, Bogele A, Kennedy TS, Stoecker BJ. Main and interaction effects of iron, zinc, lead and parenting on children’s cognitive outcomes. Dev Neuropsychol 2009;34:175–95. 30. Papathakis PC, Rollins NC, Chantry CJ, Bennish ML, Brown KH. Micronutrient status during lactation in HIV-infected and HIVuninfected South African women during the first 6 mo after delivery. Am J Clin Nutr 2007;85:182–92. 31. Dijkhuizen MA, Wieringa FT, West CE, Muhilal. Zinc plus betacarotene supplementation of pregnant women is superior to betacarotene supplementation alone in improving vitamin A status in both mothers and infants. Am J Clin Nutr 2004;80:1299–307. 32. Kuvibidila S, Mbela K, Masabi M, Mbendi N. Iron status of Zairean pregnant women with and without serological markers of hepatitis B virus infection. J Trop Med Hyg 1991;94:104–9. 33. Vinodkumar M, Erhardt JG, Rajagopalan S. Impact of a multiplemiconutrient fortified salt on the nutritional status and memory of schoolchildren. Int J Vitam Nutr Res 2009;79:348–61. 34. Maqsood M, Dancheck B, Gamble MV, et al. Vitamin A deficiency and inflammatory markers among preschool children in the Republic of the Marshall Islands. Nutr J 2004;3:21–7. 35. Gamble MV, Palafox NA, Dancheck B, Ricks MO, Briand K, Semba RD. Relationship of vitamin A deficiency, iron deficiency, and inflammation to anemia among preschool children in the Republic of the Marshall Islands. Eur J Clin Nutr 2004;58:1396–401. 36. Christian P, Jiang T, Khatry SK, LeClerq SC, Shresta SR, West KP Jr. Antenatal supplementation with micronutrients and biochemical indicators of status and subclinical infection in rural Nepal. Am J Clin Nutr 2006;83:788–94. 37. Christian P, Schultz K, Stoltzfus MC. Hyporetinolemia, illness symptoms and APP response in pregnant women with and without nightblindness. Am J Clin Nutr 1998;67:1237–43. 38. Rawat R, Stoltzfus RJ, Ntozini R, Mutasa K, Iliff PJ, Humphrey JH. Influence of inflammation as measured by alpha-1-acid glycoprotein on iron status indicators among HIV-positive postpartum Zimbabwean women. Eur J Clin Nutr 2009;63:787–93. 39. Kung’u JK, Wright VJ, Haji HJ, et al. Adjusting for the acute phase response is essential to interpret iron status indicators among young Zanzibari children prone to chronic malaria and helminth infections. J Nutr 2009;139:2124–31.",
    year = "2010",
    language = "English",
    volume = "92",
    pages = "546--555",
    journal = "American Journal of Clinical Nutrition",
    issn = "0002-9165",
    number = "2",

    }

    Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: a meta-analysis. / Thurnham, D. I.; McCabe, L; Haldar, S; Wieringa, F; Clewes, CA; McCabe, G.

    In: American Journal of Clinical Nutrition, Vol. 92, No. 2, 2010, p. 546-555.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: a meta-analysis

    AU - Thurnham, D. I.

    AU - McCabe, L

    AU - Haldar, S

    AU - Wieringa, F

    AU - Clewes, CA

    AU - McCabe, G

    N1 - Reference text: 1. Lipschitz DA, Cook JD, Finch CA. A clinical examination of serum ferritin as an index of iron stores. N Engl J Med 1974;290:1213–6. 2. Witte DL. Can ferritin be effectively interpreted in the presence of the acute-phase response? Clin Chem 1991;37:484–5. 3. UNICEF, UNU, WHO. Iron deficiency anaemia. Assessment, prevention and control. A guide for programme managers. IDA Consultation, Geneva 1993. Geneva, Switzerland: World Health Organization, 2001. (Publication no. WHO/NHD/01.3, 1-114.) 4. Mei Z, Cogswell ME, Parvanta I, et al. Hemoglobin and ferritin are currently the most efficient indicators of population response to iron interventions: an analysis of nine randomized controlled trials. J Nutr 2005;135:1974–80. 5. World Health Organization, Centers for Disease Control and Prevention. Assessing the iron status of populations. Geneva, Switzerland: WHO Press, 2004. 6. Finch CA, Belotti V, Stray S, et al. Plasma ferritin as a diagnostic tool. West J Med 1986;145:657–63. 7. Baynes R, Bezwoda W, Bothwell TH, Khan Q, Mansoor N. The nonimmune inflammatory response: serial changes in plasma iron, ironbinding capacity, lactoferrin, ferritin and C-reactive protein. Scand J Clin Lab Invest 1986;46:695–704. 8. World Health Organization, Centers for Disease Control and Prevention. Assessing the iron status of populations. Geneva, Switzerland: WHO Press, 2007. 9. Beard JL, Murray-Kolb LE, Rosales FJ, Solomons NW, Angelilli ML. Interpretation of serum ferritin concentrations as indicators of total-body iron stores in survey populations: the role of biomarkers for the acute phase response. Am J Clin Nutr 2006;84:1498–505. 10. Gibson RS, Abebe Y, Stabler S, et al. Zinc, gravida, infection, and iron, but not vitamin B-12 or folate status, predict hemoglobin during pregnancy in Southern Ethiopia. J Nutr 2008;138:581–6. 11. Darboe MK, Thurnham DI, Morgan G, et al. Effectiveness of the new IVACG early high-dose vitamin A supplementation scheme compared to the standard WHO protocol: a randomised controlled trial in Gambian mothers and infants. Lancet 2007;369:2088–96. 12. Northrop-Clewes CA. Interpreting indicators of iron status during an acute phase response—lessons from malaria and HIV. Ann Clin Biochem 2008;45:18–32. 13. Fleck A, Myers MA. Diagnostic and prognostic significance of acute phase proteins. In: Gordon AH, Koj A, eds. The acute phase response to injury and infection. Amsterdam, Netherlands: Elsevier Scientific Publishers, 1985:249–71. 14. Feelders RA, Vreugdenhil G, Eggermont AMM, Kuiper-Kramer PA, van Eijk HG, Swaak AJG. Regulation of iron metabolism in the acute-phase response: interferon- and tumor necrosis factor- induce hypoferraemia, ferritin production and a decrease in circulating transferrin receptors in cancer patients. Eur J Clin Invest 1998;28:520–7. 15. Thurnham DI, McCabe GP, Northrop-Clewes CA, Nestel P. Effect of subclinical infection on plasma retinol concentrations and assessment of prevalence of vitamin A deficiency: meta-analysis. Lancet 2003;362:2052–8. 16. Calvin J, Neale G, Fotherby KJ, Price CP. The relative merits of acute phase proteins in the recognition of inflammatory conditions. Ann Clin Biochem 1988;25:60–6. 17. Kuvibidila S, Gauthier T, Warrier RP, Rayford W. Increased levels of serum transferrin receptor and serum transferrin receptor/log ferritin 554 THURNHAM ET AL Downloaded from ajcn.nutrition.org by guest on January 15, 2013 ratios in men with prostate cancer and the implications for body-iron stores. J Lab Clin Med 2004;144:176–82. 18. Mancini G, Carbonara O, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 1965;2: 235–54. 19. Paracha PI, Jamil A, Northrop-Clewes CA, Thurnham DI. Interpretation of vitamin A status in apparently-healthy Pakistani children using markers of sub-clinical infection. Am J Clin Nutr 2000;72:1164–9. 20. Thurnham DI, Mburu ASW, Mwaniki DL, Muniu EM, Alumasa F, de Wagt A. Using plasma acute-phase protein concentrations to interpret nutritional biomarkers in apparently healthy HIV-1-seropositive Kenyan adults. Br J Nutr 2008;100:174–82. 21. Erhardt JG, Estes JE, Pfeiffer CM, Biesalski HK, Craft NE. Combined measurement of ferritin, soluble transferrin receptor, retinol binding protein, and C-reactive protein by an inexpensive, sensitive, and simple sandwich enzyme-linked immunosorbent assay technique. J Nutr 2004; 134:3127–32. 22. Beesley R, Filteau SM, Tomkins A, et al. Impact of acute malaria on plasma concentrations of transferrin receptors. Trans R Soc Trop Med Hyg 2000;94:295–8. 23. Gil CI, Haldar S, Boyd LA, et al. Watercress supplementation in diet reduces lymphocyte DNA damage and alters blood antioxidant status in healthy adults. Am J Clin Nutr 2007;85:504–10. 24. Kuvibidila S, Yu LC, Ode DL, Warrier RP, Mbele V. Assessment of iron status of Zairean women of childbearing age by serum transferrin receptor. Am J Clin Nutr 1994;60:603–9. 25. Winichagoon P, McKenzie JE, Chavasit V, et al. A multimicronutrient- fortified seasoning powder enhances the hemoglobin, zinc, and iodine status of primary school children in North East Thailand: a randomized controlled trial of efficacy. J Nutr 2006;136:1617–23. 26. Hindle LJ, Gitau R, Filteau SM, et al. Effect of multiple micronutrient supplementation during pregnancy on inflammatory markers in Nepalese women. Am J Clin Nutr 2006;86:1086–92. 27. Wieringa FT, Dijkhuizen MA, West CE, Northrop-Clewes CA, Muhilal. Estimation of the effect of the acute phase response on indicators of micronutrient status in Indonesian infants. J Nutr 2002;132:3061–6. 28. Wieringa FT, Dijkhuizen MA, West CE, Thurnham DI. Muhilal, Van Der Meer JWM. Redistribution of vitamin A after iron supplementation in Indonesian infants. Am J Clin Nutr 2003;77:651–7. 29. Hubbs-Tait L, Mulugeta A, Bogele A, Kennedy TS, Stoecker BJ. Main and interaction effects of iron, zinc, lead and parenting on children’s cognitive outcomes. Dev Neuropsychol 2009;34:175–95. 30. Papathakis PC, Rollins NC, Chantry CJ, Bennish ML, Brown KH. Micronutrient status during lactation in HIV-infected and HIVuninfected South African women during the first 6 mo after delivery. Am J Clin Nutr 2007;85:182–92. 31. Dijkhuizen MA, Wieringa FT, West CE, Muhilal. Zinc plus betacarotene supplementation of pregnant women is superior to betacarotene supplementation alone in improving vitamin A status in both mothers and infants. Am J Clin Nutr 2004;80:1299–307. 32. Kuvibidila S, Mbela K, Masabi M, Mbendi N. Iron status of Zairean pregnant women with and without serological markers of hepatitis B virus infection. J Trop Med Hyg 1991;94:104–9. 33. Vinodkumar M, Erhardt JG, Rajagopalan S. Impact of a multiplemiconutrient fortified salt on the nutritional status and memory of schoolchildren. Int J Vitam Nutr Res 2009;79:348–61. 34. Maqsood M, Dancheck B, Gamble MV, et al. Vitamin A deficiency and inflammatory markers among preschool children in the Republic of the Marshall Islands. Nutr J 2004;3:21–7. 35. Gamble MV, Palafox NA, Dancheck B, Ricks MO, Briand K, Semba RD. Relationship of vitamin A deficiency, iron deficiency, and inflammation to anemia among preschool children in the Republic of the Marshall Islands. Eur J Clin Nutr 2004;58:1396–401. 36. Christian P, Jiang T, Khatry SK, LeClerq SC, Shresta SR, West KP Jr. Antenatal supplementation with micronutrients and biochemical indicators of status and subclinical infection in rural Nepal. Am J Clin Nutr 2006;83:788–94. 37. Christian P, Schultz K, Stoltzfus MC. Hyporetinolemia, illness symptoms and APP response in pregnant women with and without nightblindness. Am J Clin Nutr 1998;67:1237–43. 38. Rawat R, Stoltzfus RJ, Ntozini R, Mutasa K, Iliff PJ, Humphrey JH. Influence of inflammation as measured by alpha-1-acid glycoprotein on iron status indicators among HIV-positive postpartum Zimbabwean women. Eur J Clin Nutr 2009;63:787–93. 39. Kung’u JK, Wright VJ, Haji HJ, et al. Adjusting for the acute phase response is essential to interpret iron status indicators among young Zanzibari children prone to chronic malaria and helminth infections. J Nutr 2009;139:2124–31.

    PY - 2010

    Y1 - 2010

    N2 - Background: The World Health Organization recommends serumferritin concentrations as the best indicator of iron deficiency (ID).Unfortunately, ferritin increases with infections; hence, the prevalence of ID is underestimated.Objective: The objective was to estimate the increase in ferritin in32 studies of apparently healthy persons by using 2 acute-phase proteins (APPs), C-reactive protein (CRP) and a1-acid glycoprotein (AGP), individually and in combination, and to calculate factors toremove the influence of inflammation from ferritin concentrations.Design: We estimated the increase in ferritin associated with inflammation(ie, CRP .5 mg/L and/or AGP .1 g/L). The 32 studies comprised infants (5 studies), children (7 studies), men (4 studies),and women (16 studies) (n = 8796 subjects). In 2-group analyses(either CRP or AGP), we compared the ratios of log ferritin with or without inflammation in 30 studies. In addition, in 22 studies, the data allowed a comparison of ratios of log ferritin between 4 subgroups:reference (no elevated APP), incubation (elevated CRP only), early convalescence (both APP and CRP elevated), and late convalescence (elevated AGP only).Results: In the 2-group analysis, inflammation increased ferritin by 49.6% (CRP) or 38.2% (AGP; both P , 0.001). Elevated AGP was more common than CRP in young persons than in adults. In the 4-group analysis, ferritin was 30%, 90%, and 36% (all P , 0.001)higher in the incubation, early convalescence, and late convalescence subgroups, respectively, with corresponding correction factors of 0.77, 0.53, and 0.75. Overall, inflammation increased ferritin by ’30% and was associated with a 14% (CI: 7%, 21%) underestimation of ID.Conclusions: Measures of both APP and CRP are needed to estimate the full effect of inflammation and can be used to correct ferritin concentrations. Few differences were observed between age and sex subgroups

    AB - Background: The World Health Organization recommends serumferritin concentrations as the best indicator of iron deficiency (ID).Unfortunately, ferritin increases with infections; hence, the prevalence of ID is underestimated.Objective: The objective was to estimate the increase in ferritin in32 studies of apparently healthy persons by using 2 acute-phase proteins (APPs), C-reactive protein (CRP) and a1-acid glycoprotein (AGP), individually and in combination, and to calculate factors toremove the influence of inflammation from ferritin concentrations.Design: We estimated the increase in ferritin associated with inflammation(ie, CRP .5 mg/L and/or AGP .1 g/L). The 32 studies comprised infants (5 studies), children (7 studies), men (4 studies),and women (16 studies) (n = 8796 subjects). In 2-group analyses(either CRP or AGP), we compared the ratios of log ferritin with or without inflammation in 30 studies. In addition, in 22 studies, the data allowed a comparison of ratios of log ferritin between 4 subgroups:reference (no elevated APP), incubation (elevated CRP only), early convalescence (both APP and CRP elevated), and late convalescence (elevated AGP only).Results: In the 2-group analysis, inflammation increased ferritin by 49.6% (CRP) or 38.2% (AGP; both P , 0.001). Elevated AGP was more common than CRP in young persons than in adults. In the 4-group analysis, ferritin was 30%, 90%, and 36% (all P , 0.001)higher in the incubation, early convalescence, and late convalescence subgroups, respectively, with corresponding correction factors of 0.77, 0.53, and 0.75. Overall, inflammation increased ferritin by ’30% and was associated with a 14% (CI: 7%, 21%) underestimation of ID.Conclusions: Measures of both APP and CRP are needed to estimate the full effect of inflammation and can be used to correct ferritin concentrations. Few differences were observed between age and sex subgroups

    KW - ferritin

    KW - inflammation

    KW - CRP

    KW - AGP

    KW - iron deficiency

    M3 - Article

    VL - 92

    SP - 546

    EP - 555

    JO - American Journal of Clinical Nutrition

    T2 - American Journal of Clinical Nutrition

    JF - American Journal of Clinical Nutrition

    SN - 0002-9165

    IS - 2

    ER -