Research Blog

September 9, 2023

A Deep Dive Into Iron Metabolism: Part 7 Optimal Takeaways

Welcome to part 7 of the ODX "Deep Dive Into Iron Metabolism" Series. In this final post in our series, we cover the Optimal Takeaways for the assessment and treatment of Iron Metabolism issues.

The ODX Iron Metabolism Series

Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

  1. Iron Metabolism Part 1 - Introduction to Iron Metabolism
  2. Iron Metabolism Part 2 - The physiology of iron
  3. Iron Metabolism Part 3 - Disorders associated with altered iron status: Iron Deficiency Anemia
  4. Iron Metabolism Part 4 - Disorders associated with altered iron status: Iron Overload
  5. Iron Metabolism Part 5 - Biomarkers of iron status
  6. Iron Metabolism Part 6 - Addressing disorders associated with altered Iron status
  7. Iron Metabolism Part 7 - ODX Optimal Takeaways and References


ODX Optimal Takeaways

Iron is an essential mineral for:

  • Protein synthesis
  • DNA and RNA synthesis
  • Hemoglobin production
  • Myelin formation
  • Neurotransmitter synthesis, including serotonin, dopamine, and norepinephrine
  • Energy generation
  • Oxygen transport

Signs of iron insufficiency include:

  • Behavioral disorders
  • Cardiovascular complications
  • Cognitive impairment
  • Decreased work performance
  • Depression
  • Dizziness
  • Fatigue
  • Gastritis
  • Hair, skin, and nail abnormalities
  • Headaches
  • Pallor
  • Pica
  • Pregnancy complications
  • Shortness of breath

Complications of severe iron overload can include:

  • Ascites
  • Cardiac dysfunction
  • Cirrhosis
  • Glucose intolerance
  • Liver dysfunction
  • Skin discoloration

Iron biomarkers should be evaluated in the absence of inflammation

ODX Guide to Iron Biomarkers   

   Iron Deficiency Anemia Anemia of chronic disease/
Hemolytic Anemia Iron overload, hemochromatosis
Serum iron Decreased depending on the stage of IDA Normal or decreased Increased Increased
Ferritin Decreased Increased Increased Increased
Transferrin Increased Normal or decreased Decreased Decreased
% Transferrin saturation Decreased Normal or decreased Increased Increased
Iron-binding capacity Increased depending on the stage of IDA Normal or decreased Decreased Decreased
RDW Increased Normal or slightly increased Increased Normal
Hemoglobin Decreased in the latter stages of IDA Decreased Decreased Normal
MCV Decreased Normal or decreased Normal Increased
MCH Decreased Normal or decreased Decreased Increased

Interventions for iron disorders:

Iron overload

  • Blood donation
  • Therapeutic phlebotomy
  • Chelation therapy

Iron deficiency

  • Increase iron-containing foods, especially heme iron
  • Decrease intake of iron inhibitors
  • Supplement as tolerated; chelated iron may be best tolerated
  • Intravenous iron may be indicated


Clinicians must recognize and address alterations in iron status, as both deficiency and overload can be life-threatening.


Abbaspour, Nazanin et al. “Review on iron and its importance for human health.” Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences vol. 19,2 (2014): 164-74.

Baldwin, Caitlin, et al. “Hemolytic Anemia.” StatPearls, StatPearls Publishing, 24 July 2023.

Barcellini, W, and B Fattizzo. “Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia.” Disease markers vol. 2015 (2015): 635670. doi:10.1155/2015/635670

Barton, J C et al. “Screening for hemochromatosis in routine medical care: an evaluation of mean corpuscular volume and mean corpuscular hemoglobin.” Genetic testing vol. 4,2 (2000): 103-10. doi:10.1089/10906570050114786

Bermejo, Fernando, and Santiago García-López. “A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases.” World journal of gastroenterology vol. 15,37 (2009): 4638-43. doi:10.3748/wjg.15.4638

Berthou C, Iliou JP, Barba D. Iron, neuro-bioavailability and depression. EJHaem. 2021 Dec 5;3(1):263-275. doi: 10.1002/jha2.321. PMID: 35846210; PMCID: PMC9175715.

Fava, Cristiano et al. “The role of red blood cell distribution width (RDW) in cardiovascular risk assessment: useful or hype?.” Annals of translational medicine vol. 7,20 (2019): 581. doi:10.21037/atm.2019.09.58

Gattermann, Norbert et al. “The Evaluation of Iron Deficiency and Iron Overload.” Deutsches Arzteblatt international vol. 118,49 (2021): 847-856. doi:10.3238/arztebl.m2021.0290

Gropper, Sareen S.; Smith, Jack L.; Carr, Timothy P. Advanced Nutrition and Human Metabolism. 8th edition. Wadsworth Publishing Co Inc. 2021.

Hanif, Nazma. and Faiz Anwer. “Chronic Iron Deficiency.” StatPearls, StatPearls Publishing, 10 September 2022.

Iron Disorders Institute.

Kotze, M J et al. “Pathogenic Mechanisms Underlying Iron Deficiency and Iron Overload: New Insights for Clinical Application.” EJIFCC vol. 20,2 108-23. 25 Aug. 2009

Kritharis, Athena et al. “Hereditary hemorrhagic telangiectasia: diagnosis and management from the hematologist's perspective.” Haematologica vol. 103,9 (2018): 1433-1443. doi:10.3324/haematol.2018.193003

Lee, Herng-Sheng et al. “Psychiatric disorders risk in patients with iron deficiency anemia and association with iron supplementation medications: a nationwide database analysis.” BMC psychiatry vol. 20,1 216. 11 May. 2020, doi:10.1186/s12888-020-02621-0

McDowell, Lisa A., et al. “Iron Overload.” StatPearls, StatPearls Publishing, 28 April 2022.

Merck Manual Professional Version. Iron Deficiency Anemia. Reviewed/Revised Jun 2023

Merck Manual. Overview of Iron Overload.

Merck Manual. Diagnosis of Hereditary Hemochromatosis

Northrop-Clewes, Christine A, and David I Thurnham. “Biomarkers for the differentiation of anemia and their clinical usefulness.” Journal of blood medicine vol. 4 11-22. 20 Mar. 2013, doi:10.2147/JBM.S29212

Pfeiffer, Christine M, and Anne C Looker. “Laboratory methodologies for indicators of iron status: strengths, limitations, and analytical challenges.” The American journal of clinical nutrition vol. 106,Suppl 6 (2017): 1606S-1614S. doi:10.3945/ajcn.117.155887

Raymond, Janice L., et al. Krause and Mahan's Food & the Nutrition Care Process. Elsevier, 2021.

Warner, Matthew J. and Muhammad T. Kamran. “Iron Deficiency Anemia.” StatPearls, StatPearls Publishing, 7 August 2023

Yu, Yi-Chuan et al. “Serum Biomarkers of Iron Status and Risk of Hepatocellular Carcinoma Development in Patients with Nonalcoholic Fatty Liver Disease.” Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology vol. 31,1 (2022): 230-235. doi:10.1158/1055-9965.EPI-21-0754  

Tag(s): Biomarkers

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