Iron Supplementation Guidelines

Introduction to Iron Supplementation

Iron supplementation is strongly recommended for patients with iron deficiency anemia as it significantly increases hemoglobin levels and improves iron stores, according to the Journal of Crohn's and Colitis guidelines 1

In randomized controlled trials, iron supplementation resulted in significantly higher mean hemoglobin levels in supplemented groups (122-139 g/L) compared to control groups (115-128 g/L), as reported by the Annals of Internal Medicine 2
Serum ferritin levels were significantly higher in supplemented groups (12.0-30.0 μg/L) versus control groups (6.2-24.9 μg/L), as reported by the Annals of Internal Medicine 2

Iron supplementation is indicated for patients with intolerance to oral preparations, poor compliance with oral therapy, need for rapid iron repletion, ongoing blood loss exceeding intestinal absorption capacity, chronic inflammatory conditions, or poor response to oral iron after 4 weeks, according to the Journal of Crohn's and Colitis guidelines 1
Iron supplementation during pregnancy increases maternal hemoglobin and ferritin levels, as reported by the Annals of Internal Medicine 2

Diagnostic criteria for iron deficiency anemia include hemoglobin below the lower limit of normal for the relevant population (<12 g/dL for women, <13 g/dL for men), and serum ferritin <45 ng/mL, as well as transferrin saturation below 20%, ferritin levels below 30 μg/L, high TIBC, and low serum iron, as recommended by the American Gastroenterological Association 3, 4, 5

Normal values for serum ferritin, transferrin saturation, and hemoglobin are:

Parameter	Normal Value	Iron Deficiency	Iron Overload
Serum Ferritin	30-300 μg/L	<30 μg/L	>500 μg/L
Transferrin Saturation	16-45%	<16%	>45%
Hemoglobin	>12 g/dL (women), >13 g/dL (men)	<12 g/dL (women), <13 g/dL (men)	Normal or elevated

Oral iron supplementation is the first-line treatment for most patients, with ferrous sulfate 200 mg (containing approximately 65 mg elemental iron) once daily or three times daily recommended by the Clinical Gastroenterology and Hepatology society and the American Gastroenterological Association 6, 7
Alternative regimen: Ferrous sulfate 324 mg (containing 65 mg elemental iron) 2-3 times daily, as recommended by the European Society of Gastroenterology 7, 8
Adding ascorbic acid (vitamin C) 250-500 mg with iron doses enhances absorption, as recommended by the European Society of Gastroenterology 7, 8
Parenteral iron is indicated for patients who are intolerant to at least two oral preparations, have poor compliance with oral therapy, or require rapid iron repletion, as recommended by the European Society of Gastroenterology 7, 8
Single doses of 500-1000 mg (up to 20 mg/kg body weight) of ferric carboxymaltose are appropriate for treating iron deficiency, as recommended by the European Crohn's and Colitis Organisation 1

In patients with inflammatory bowel disease (IBD) and anemia, iron supplementation is recommended when iron deficiency anemia is present, as stated by the Journal of Crohn's and Colitis guidelines 1
IV iron may be preferable in patients with active IBD due to better absorption and fewer GI side effects, according to the Journal of Crohn's and Colitis guidelines 1
Iron should be administered to maintain ferritin ≥100 ng/ml and transferrin saturation ≥20% in chronic kidney disease (CKD) patients with hemoglobin <110 g/L, as recommended by the Kidney International Supplements guidelines 9
Consider IV iron in CKD patients with poor response to oral therapy, as suggested by the Kidney International Supplements guidelines 9
Pregnant women should receive 30 mg/day oral iron supplements at their first prenatal visit, increasing to 60-120 mg/day if anemia is diagnosed, according to the CDC guidelines 10
Elderly patients with severe iron deficiency may benefit from IV iron due to better absorption, more rapid repletion of iron stores, and fewer GI side effects common with oral preparations, as stated by the Clinical Nutrition guidelines 11
Athletes and individuals with high physical activity may be at higher risk of iron deficiency due to increased losses and demands, and should consider regular screening and prophylactic supplementation, according to the International Society of Sports Nutrition 12

Iron therapy should be continued for 3 months after hemoglobin normalizes to replenish iron stores, and consider IV iron if no improvement in hemoglobin after 4 weeks of oral therapy, as recommended by the American Gastroenterological Association 3
Expect hemoglobin to rise by approximately 2 g/dL after 3-4 weeks of iron therapy, and consider IV iron therapy or further investigation if no response after 4 weeks, as recommended by the European Society of Gastroenterology 7, 3
The American Gastroenterological Association suggests continuing iron supplementation for 3 months after normalization of ferritin levels to adequately replenish iron stores, and monitoring ferritin levels every 3 months for one year, then every 6-12 months 7
Re-treatment with iron should be initiated as soon as serum ferritin drops below 100 μg/L, according to the European Crohn's and Colitis Organisation 1

The Gut society recommends always investigating and treating the underlying cause of iron deficiency, as stated by the Gut society 7
The American Gastroenterological Association recommends investigating the cause of iron deficiency anemia in elderly patients once they are stable, as it is often multifactorial and requires thorough investigation 3
Gastroscopy and colonoscopy should be performed to investigate the cause of iron deficiency anemia, and consider small bowel evaluation if anemia persists despite negative bidirectional endoscopy, as recommended by the American Gastroenterological Association 3
Bidirectional endoscopy (gastroscopy and colonoscopy) is recommended for men and postmenopausal women with iron deficiency anemia, as well as premenopausal women with iron deficiency anemia not explained by menstrual blood loss, as recommended by the American Gastroenterological Association 4, 3
CT colonography is a reasonable alternative for those not suitable for colonoscopy, as recommended by the American Gastroenterological Association 3
Urinalysis/urine microscopy should be performed to rule out hematuria in patients with iron deficiency anemia, as recommended by the American Gastroenterological Association 3
Screening for celiac disease is recommended in patients with iron deficiency anemia, with serological testing found in 3-5% of cases, as recommended by the American Gastroenterological Association 3

Regular screening for high-risk individuals, a balanced diet including iron-rich foods, and consideration of fortified foods in populations with high prevalence of deficiency can help prevent iron deficiency, as stated by the World Health Organization and various guideline societies 13, 12
Limit red meat consumption, as recommended by the European Association for the Study of the Liver 14
Avoid iron-fortified foods and iron supplements beyond prescribed treatment, according to the European Association for the Study of the Liver 14
Avoid excessive vitamin C supplementation until iron stores are replenished, as suggested by the European Association for the Study of the Liver 14