Skip to main content
SpringerLink
Log in

Effects of Iron Supplementation With and Without Docosahexaenoic Acid on the Cardiovascular Disease Risk Based on Paraoxonase-1, hs-CRP, and ApoB/ApoA-I Ratio in Women with Iron Deficiency Anemia

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Numerous studies have demonstrated that tissue deposition of iron following prolonged high dose of oral supplementation for treatment of iron deficiency anemia (IDA) leads to body iron overload and oxidative stress, which starts the process of atherosclerosis. This study aimed to determine the effect of iron supplementation in combination with docosahexaenoic acid (DHA) on the cardiovascular disease risk based on paraoxonase-1 (PON-1), high-sensitivity C-reactive protein (hs-CRP), and ApoB/ApoA-I ratio in women with IDA. In this randomized controlled trial, 76 women with IDA, aged 15–45 years, were included. The patients were randomly assigned to receive 500 mg of DHA supplement or placebo with an iron tablet, once daily for 12 weeks. The participants were assessed by measurement of the serum iron, ferritin, PON-1, hs-CRP levels, and the ApoB/ApoA-I ratio at the beginning and end of study. Serum hs-CRP decreased in the DHA-supplemented group (p = 0.036), and ApoA-I decreased in the placebo group (p = 0.013). No significant difference was detected for the serum PON-1 concentration and the ApoB/ApoA-I ratio in two groups. Iron supplementation combined with DHA may have favorable effects on serum hs-CRP in women with IDA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mendes JF, Arruda SF, Siqueira EM, Ito MK, Silva EF (2009) Iron status and oxidative stress biomarkers in adults: a preliminary study. Nutrition 25:379–384

    Article  PubMed  CAS  Google Scholar 

  2. Schümann K, Ettle T, Szegner B, Elsenhans B, Solomons NW (2007) On risks and benefits of iron supplementation recommendations for iron intake revisited. J Trace Elem Med Biol 21(3):147–168

    Article  PubMed  CAS  Google Scholar 

  3. Schümann K (2001) Safety aspects of iron in food. Ann Nutr Metab 45(3):91–101

    Article  PubMed  Google Scholar 

  4. Yip R (2002) Iron supplementation: country level experiences and lessons learned. J Nutr 132:859–861

    Google Scholar 

  5. UNICEF (1999) Preventing iron deficiency in women and children. Technical Workshop, New York, pp 13–17 [Chapter 2]

    Google Scholar 

  6. Krishnamoorthy PM, Prabu RN, Mohan DM, Sabitha N, Janakarajan VN, Natesan B (2010) Role of oxidative stress and antioxidants in children with IDA. Rev Glob Med Healthc Res 395

  7. Buijsse B, Feskens EJ, Moschandreas J, Jansen EH, Jacobs DR Jr, Kafatos A et al (2007) Oxidative stress and iron and antioxidant status in elderly men: differences between the Mediterranean south (Crete) and northern Europe (Zutphen). Eur J Cardiovasc Prev Rehabil 14:495–500

    Article  PubMed  Google Scholar 

  8. Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40

    Article  PubMed  CAS  Google Scholar 

  9. Liu K, Kaffes AJ (2012) Iron deficiency anaemia: a review of diagnosis, investigation and management. Eur J Gastroenterol Hepatol 24:109–116

    Article  PubMed  CAS  Google Scholar 

  10. Pena-Rosas JP, De-Regil LM, Dowswell T, Viteri FE (2012) Intermittent oral iron supplementation during pregnancy. Cochrane Database Syst Rev 7, CD009997

    PubMed  PubMed Central  Google Scholar 

  11. Erichsen K, Hausken T, Berge R, Ulvik R, Berstad A (1998) Effect of oral iron therapy on antioxidant defence in active Crohn’s disease. Digestion 59(31), FOLM1287

    Google Scholar 

  12. Galaris D, Pantopoulos K (2008) Oxidative stress and iron homeostasis: mechanistic and health aspects. Crit Rev Clin Lab Sci 45:1–23

    Article  PubMed  CAS  Google Scholar 

  13. Lopez-Huertas E (2010) Health effects of oleic acid and long chain omega-3 fatty acids (EPA and DHA) enriched milks. A review of intervention studies. Pharmacol Res 61(3):200–207

    Article  PubMed  CAS  Google Scholar 

  14. Shidfar F, Keshavarz A, Hosseyni S, Ameri A, Yarahmadi S (2008) Effects of omega-3 fatty acid supplements on serum lipids, apolipoproteins, and malondialdehyde in type 2 diabetes patients. East Mediterr Health J 14(2):305–313

    PubMed  CAS  Google Scholar 

  15. Das UN (2006) Essential fatty acids—a review. Curr Pharm Biotechnol 7(6):467–482

    Article  PubMed  CAS  Google Scholar 

  16. Dupertuis YM, Meguid MM, Pichard C (2007) Colon cancer therapy: new perspectives of nutritional manipulations using polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care 4:427–432

    Article  Google Scholar 

  17. Shoji H, Franke C, Campoy C, Rivero M, Demmelmair H, Koletzko B (2006) Effect of docosahexaenoic acid and eicosapentaenoic acid supplementation on oxidative stress levels during pregnancy. Free Radic Res 40(4):379–384

    Article  PubMed  CAS  Google Scholar 

  18. Shidfar F, Heydari I, Hajimiresmaiel SJ, Hosseini S, Shidfar S, Amiri F (2012) The effects of cranberry juice on serum glucose, apoB, apoA-I, Lp(a), and Paraoxonase-1 activity in type 2 diabetic male patients. J Res Med Sci 17(4):355–360

    PubMed  PubMed Central  Google Scholar 

  19. Calabresi L, Villa B, Canavesi M, Sirtori CR, James RW, Bernini F et al (2004) An omega-3 polyunsaturated fatty acid concentrate increases plasma high-density lipoprotein 2 cholesterol and paraoxonase levels in patients with familial combined hyperlipidemia. Metabolism 53(2):153–158

    Article  PubMed  CAS  Google Scholar 

  20. Lien EL (2009) Toxicology and safety of DHA. Prostaglandins Leukot Essent Fat Acids 81(2):125–132

    Article  CAS  Google Scholar 

  21. Vaquero MP, Veldhuizen M, Sarria B (2001) Consumption of an infant formula supplemented with long chain polyunsaturated fatty acids and iron metabolism in rats. Innovative Food Sci Emerg Technol 2(3):211–217

    Article  CAS  Google Scholar 

  22. Woodman RJ, Mori TA, Burke V, Puddey IB, Watts GF, Best JD, Beilin LJ (2003) Docosahexaenoic acid but not eicosapentaenoic acid increases LDL particle size in treated hypertensive type 2 diabetic patients. Diabetes Care 26(1):253

    Article  PubMed  Google Scholar 

  23. McAnulty SR, Nieman DC, Fox-Rabinovich M, Duran V, McAnulty LS, Henson DA et al (2010) Effect of n-3 fatty acids and antioxidants on oxidative stress after exercise. Med Sci Sports Exerc 42(9):1704

    Article  PubMed  CAS  Google Scholar 

  24. Petersson H, Risérus U, McMonagle J, Gulseth HL, Tierney AC, Morange S et al (2010) Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study. Br J Nutr 104(09):1357–1362

    Article  PubMed  CAS  Google Scholar 

  25. Wilkinson P, Leach C, Ah-Sing EE, Hussain N, Miller GJ, Millward DJ et al (2005) Influence of alpha-linolenic acid and fish-oil on markers of cardiovascular risk in subjects with an atherogenic lipoprotein phenotype. Atherosclerosis 181(1):115

    Article  PubMed  CAS  Google Scholar 

  26. Ferretti G, Bacchetti T (2011) Effect of dietary lipids on paraoxonase-1 activity and gene expression. Nutr Metab Cardiovasc Dis

  27. Lee DH, Jacobs DR (2005) Association between serum gamma-glutamyltransferase and C-reactive protein. Atherosclerosis 178(2):327–330

    Article  PubMed  CAS  Google Scholar 

  28. Kooshki A, Taleban FA, Tabibi H, Hedayati M (2011) Effects of omega-3 fatty acids on serum lipids, lipoprotein (a), and hematologic factors in hemodialysis patients. Ren Fail 33(9):892–898

    Article  PubMed  CAS  Google Scholar 

  29. Potsch AA, Siqueira Filho AG, Rangel Tura B, Gamarski R, Bassan R, Nogueira MV et al (2006) C-Reactive protein diagnostic and prognostic value in patients presenting at the emergency room with chest pain. Arq Bras Cardiol 87(3):275–280

    Article  PubMed  Google Scholar 

  30. Ceron JJ, Tecles F, Tvarijonaviciute A (2014) Serum paraoxonase 1 (PON1) measurement: an update. BMC Vet Res 10:74

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Calzada C, Colas R, Guillot N, Guichardant M, Laville M, Véricel E et al (2010) Subgram daily supplementation with docosahexaenoic acid protects low-density lipoproteins from oxidation in healthy men. Atherosclerosis 208(2):467–472

    Article  PubMed  CAS  Google Scholar 

  32. Donnelly SM, Ali MA, Churchill DN (1992) Effect of n-3 fatty acids from fish oil on hemostasis, blood pressure, and lipid profile of dialysis patients. J Am Soc Nephrol 2(11):1634–1639

    PubMed  CAS  Google Scholar 

  33. Micallef MA, Munro IA, Garg ML (2009) An inverse relationship between plasma n-3 fatty acids and C-reactive protein in healthy individuals. Eur J Clin Nutr 63(9):1154–1156

    Article  PubMed  CAS  Google Scholar 

  34. Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J (2006) Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis 189(1):19–30

    Article  PubMed  CAS  Google Scholar 

  35. Pischon T, Hankinson SE, Hotamisligil GS, Rifai N, Willett WC, Rimm EB (2003) Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation 108(2):155–160

    Article  PubMed  CAS  Google Scholar 

  36. Tayyebi-Khosroshahi H, Houshyar J, Dehgan-Hesari R, Alikhah H, Vatankhah AM, Safaeian AR et al (2012) Effect of treatment with omega-3 fatty acids on C-reactive protein and tumor necrosis factor-alphaa in hemodialysis patients. Saudi J Kidney Dis Transpl 23(3):500

    PubMed  Google Scholar 

  37. Geelen A, Brouwer IA, Schouten EG, Kluft C, Katan MB, Zock PL (2004) Intake of n-3 fatty acids from fish does not lower serum concentrations of C-reactive protein in healthy subjects. Eur J Clin Nutr 58(10):1440–1442

    Article  PubMed  CAS  Google Scholar 

  38. Madsen T, Christensen JH, Blom M, Schmidt EB (2003) The effect of dietary n-3 fatty acids on serum concentrations of C-reactive protein: a dose–response study. Br J Nutr 89(04):517–522

    Article  PubMed  CAS  Google Scholar 

  39. Chan DC, Watts GF, Barrett PH, Beilin LJ, Mori TA (2002) Effect of Atorvastatin and fish oil on plasma high-sensitivity C-reactive protein concentrations in individuals with visceral obesity. Clin Chem 48(6):877–883

    PubMed  CAS  Google Scholar 

  40. Hartweg J, Farmer AJ, Perera R, Holman RR, Neil HA (2007) Meta-analysis of the effects of n-3 polyunsaturated fatty acids on lipoproteins and other emerging lipid cardiovascular risk markers in patients with type 2 diabetes. Diabetologia 50(8):1593–1602

    Article  PubMed  CAS  Google Scholar 

  41. Rodriguez MC, Sáiz MP, Muntané J, Mitjavila MT (1996) Fatty acid composition of erythrocyte membranes affects iron absorption in rats. J Nutr 126(12):3109–3117

    PubMed  CAS  Google Scholar 

  42. Chan DC, Watts GF, Mori TA, Barrett PH, Redgrave TG, Beilin LJ (2003) Randomized controlled trial of the effect of n–3 fatty acid supplementation on the metabolism of apolipoprotein B-100 and chylomicron remnants in men with visceral obesity. Am J Clin Nutr 77(2):300–307

    PubMed  CAS  Google Scholar 

  43. Eftekhari MH, Mozaffari-Khosravi H, Shidfar F, Zamani A (2013) Relation between body iron status and cardiovascular risk factors in patients with cardiovascular disease. Int J Prev Med 4(8):911–916

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

Authors are very thankful to the patients who participated in the study, Tooba clinic and Razi hospital nurses and physicians for their valuable help.

Conflict of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Nutrition, School of Health, Iran University of Medical Sciences, Tehran, Iran

    Farzad Shidfar, Samira Amani, Mohammadreza Vafa & Seyedeh Neda Mousavi

  2. Department of Internal Medicine, School of Medicine, Mazandaran University of Medical Sciences, Mazandaran, Iran

    Ramin Shekarriz

  3. Department of Chemistry, Robat Karim Branch, Islamic Azad University, Robat Karim, Iran

    Sharieh Hosseini

  4. Worcester Memorial Hospital, University of Massachusetts, Worcester, USA

    Shahrzad Shidfar

  5. Department of Statistics, School of Health, Tehran University of Medical Sciences, Tehran, Iran

    Mohammadreza Eshraghian

Authors
  1. Farzad Shidfar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samira Amani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammadreza Vafa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ramin Shekarriz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sharieh Hosseini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shahrzad Shidfar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mohammadreza Eshraghian
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Seyedeh Neda Mousavi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seyedeh Neda Mousavi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shidfar, F., Amani, S., Vafa, M. et al. Effects of Iron Supplementation With and Without Docosahexaenoic Acid on the Cardiovascular Disease Risk Based on Paraoxonase-1, hs-CRP, and ApoB/ApoA-I Ratio in Women with Iron Deficiency Anemia. Biol Trace Elem Res 169, 34–40 (2016). https://doi.org/10.1007/s12011-015-0383-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-015-0383-7

Keywords

Search

Navigation