What are the dietary sources of ferritin and how can iron levels be managed in individuals with low ferritin levels?

Dietary Sources of Ferritin and Management of Low Ferritin Levels

Ferritin-containing foods are primarily found in legumes like soybeans, and iron deficiency should be managed with oral iron supplementation (ferrous sulfate 65 mg elemental iron daily or alternate-day) while investigating the underlying cause, particularly in those with ferritin <15 μg/L. 1, 2, 3

Dietary Sources of Ferritin

• Legumes, particularly soybeans, are the major dietary source of ferritin, representing a natural form of nonheme iron where thousands of iron atoms are protected within a protein cage structure 3
• Soybean ferritin demonstrates high bioavailability and efficient utilization in iron-deficient animals and humans with borderline deficiency, making it a viable alternative to traditional iron supplementation 4
• Unlike other nonheme iron sources, ferritin iron is protected from complexation, which may enhance its absorption and effectiveness 3

Diagnostic Thresholds for Low Ferritin

In Apparently Healthy Populations

• Ferritin <15 μg/L has 99% specificity for absolute iron deficiency and definitively confirms diagnosis 1
• Ferritin 15-30 μg/L indicates low body iron stores and generally warrants treatment 1
• Ferritin <45 μg/L provides optimal sensitivity-specificity balance (specificity 0.92) for clinical decision-making 1

In Inflammatory Conditions

• In patients with inflammatory bowel disease, chronic heart failure, or chronic kidney disease, use a higher threshold of ferritin <100 μg/L to diagnose iron deficiency 1, 5
• Ferritin is an acute-phase reactant that becomes elevated during inflammation, infection, or tissue damage, potentially masking true iron deficiency 1, 5
• When ferritin is 100-300 μg/L in inflammatory conditions, transferrin saturation (TSAT) <20% is required to confirm iron deficiency 5

Management Algorithm for Low Ferritin

Immediate Treatment

• Start oral iron supplementation immediately with ferrous sulfate 65 mg elemental iron daily (324 mg ferrous sulfate tablet provides 65 mg elemental iron, which is 362% of the U.S. RDI) 1, 2
• Alternate-day dosing (60 mg every other day) may improve absorption and reduce gastrointestinal side effects compared to daily dosing 1
• Take on empty stomach for optimal absorption, or with meals if gastrointestinal symptoms occur 1
• Expected side effects include constipation, nausea, or diarrhea, which can be minimized by taking with food or switching to alternate-day dosing 1

Investigation Based on Ferritin Level

If ferritin <15 μg/L:

• Absolute iron deficiency is confirmed—no additional testing needed for diagnosis 1
• Check complete blood count to assess for anemia 1
• Calculate transferrin saturation: expect <16%, confirming impaired iron delivery to bone marrow 1
• Initiate investigation for the source of iron loss immediately 1

If ferritin 15-30 μg/L:

• Iron deficiency with low stores is likely 1
• Consider diet rich in iron and oral iron supplementation 1

If ferritin 30-100 μg/L with elevated CRP/ESR:

• Mixed picture of true iron deficiency and anemia of chronic disease is present 1
• Address the underlying inflammatory condition 1

Screening for Underlying Causes

• Screen for celiac disease with tissue transglutaminase antibodies (tTG), as it is present in 3-5% of iron deficiency cases 1
• Test for H. pylori non-invasively (stool antigen or urea breath test) 1
• Assess menstrual blood loss history in premenopausal women, as it is the most common cause of iron deficiency 1

When to Pursue GI Evaluation

Reserve bidirectional endoscopy for:

• Age ≥50 years (higher risk of GI malignancy) 1
• GI symptoms (abdominal pain, change in bowel habits, blood in stool) 1
• Positive celiac or H. pylori testing requiring confirmation 1
• Failure to respond to adequate oral iron therapy after 8-10 weeks 1
• Strong family history of colorectal cancer 1

GI evaluation is conditional rather than mandatory for premenopausal women with iron deficiency unless specific red flags are present 1

Follow-Up and Monitoring

• Repeat CBC and ferritin in 8-10 weeks to assess response to treatment 1
• Expected response is hemoglobin rise ≥10 g/L within 2 weeks 1
• Target ferritin >100 ng/mL to restore iron stores and prevent recurrence 1
• If no improvement, consider malabsorption, non-compliance, ongoing blood loss, or need for IV iron 1

Long-Term Surveillance

• For patients with recurrent low ferritin (menstruating females, vegetarians, athletes, blood donors), screen ferritin every 6-12 months 1
• Menstruating females require twice yearly screening; males require annual screening 1
• Do not continue daily iron supplementation once ferritin normalizes, as this is potentially harmful 1

Critical Pitfalls to Avoid

• Do not assume normal ferritin excludes iron deficiency—transferrin saturation is the key parameter for assessing iron availability for erythropoiesis 1
• Do not overlook celiac disease, which is present in 3-5% of iron deficiency cases and can be easily missed without serologic screening 1
• Do not perform extensive GI investigation in young, asymptomatic premenopausal women with heavy menses, as the yield is extremely low (0-6.5%) 1
• In inflammatory conditions, standard ferritin thresholds do not apply—use higher cutoffs and assess TSAT 1, 5