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
- Iron Metabolism Part 1 - Introduction to Iron Metabolism
- Iron Metabolism Part 2 - The physiology of iron
- Iron Metabolism Part 3 - Disorders associated with altered iron status: Iron Deficiency Anemia
- Iron Metabolism Part 4 - Disorders associated with altered iron status: Iron Overload
- Iron Metabolism Part 5 - Biomarkers of iron status
- Iron Metabolism Part 6 - Addressing disorders associated with altered Iron status
- 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/ inflammation |
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
PLEASE NOTE:
Clinicians must recognize and address alterations in iron status, as both deficiency and overload can be life-threatening.
References
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. http://irondisorders.org/tests-to-determine-iron-levels/
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
Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 16th ed., Mosby, 2022.
McDowell, Lisa A., et al. “Iron Overload.” StatPearls, StatPearls Publishing, 28 April 2022.
Merck Manual Professional Version. Iron Deficiency Anemia. Reviewed/Revised Jun 2023 https://www.merckmanuals.com/professional/hematology-and-oncology/anemias-caused-by-deficient-erythropoiesis/iron-deficiency-anemia
Merck Manual. Overview of Iron Overload. https://www.merckmanuals.com/professional/hematology-and-oncology/iron-overload/overview-of-iron-overload
Merck Manual. Diagnosis of Hereditary Hemochromatosis https://www.merckmanuals.com/professional/hematology-and-oncology/iron-overload/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
