In a woman with iron‑deficiency anemia taking 325 mg elemental iron daily, whose iron studies show fluctuating low to high transferrin saturation and serum iron, ferritin ranging from low to normal, mild elevated liver enzymes, and persistent anemia, should I reduce iron supplementation to every other day or less frequently?

Reduce Iron Supplementation to Alternate-Day Dosing

Given your patient's fluctuating iron parameters and persistent anemia despite daily 325 mg ferrous sulfate, you should switch to alternate-day dosing with 100–200 mg elemental iron (approximately 300–600 mg ferrous sulfate) taken as a single morning dose on an empty stomach. This regimen will increase fractional iron absorption by 40–50% compared to daily dosing while reducing gastrointestinal side effects and hepcidin-mediated absorption blockade 1, 2, 3.

Why Alternate-Day Dosing Is Superior

The physiological rationale is compelling:

• Oral iron doses ≥60 mg elemental iron trigger an acute hepcidin surge that persists for 24 hours, blocking iron absorption from subsequent doses given on the same or next day 1, 2, 3
• In women with iron deficiency anemia, fractional iron absorption on alternate days is 40–50% higher than on consecutive days (P<0.001), even though serum hepcidin remains suppressed by anemia and erythropoietic drive 2
• Alternate-day dosing with 200 mg elemental iron provides approximately twice the total absorbed iron compared to 100 mg given daily, making it both more effective and better tolerated 2, 3

Interpreting Your Patient's Laboratory Pattern

Your patient's labs reveal functional iron deficiency with erratic absorption:

• The dramatic swing in transferrin saturation (4% → 52.7%) and serum iron (17 → 251 µg/dL) suggests intermittent iron overload in the gut lumen with poor systemic absorption 2
• Ferritin rising from 38.4 to 114 ng/mL indicates some iron repletion, but hemoglobin improvement from 7.6 to 11.8 g/dL remains suboptimal after what appears to be months of daily therapy 4
• The mildly elevated transaminases (ALT 69–117, AST 54–83) may reflect iron-induced oxidative stress in the liver from unabsorbed luminal iron 5

Specific Dosing Algorithm

Implement this evidence-based regimen:

• Dose: 200 mg elemental iron (approximately 600 mg ferrous sulfate, or three 200 mg ferrous sulfate tablets) 2, 3
• Frequency: Every other day (Monday-Wednesday-Friday or Tuesday-Thursday-Saturday pattern) 1, 2, 3
• Timing: Single morning dose at 8 AM on an empty stomach, at least 1 hour before food 1, 3
• Adjunct: Consider adding 250–500 mg vitamin C with each dose to enhance absorption 4

Expected Response and Monitoring

Establish clear benchmarks:

• Recheck hemoglobin at 2 weeks; an increase of ≥10 g/L predicts treatment success with 90% sensitivity 4
• If hemoglobin fails to rise ≥10 g/L at 2 weeks, this strongly predicts treatment failure and warrants investigation for ongoing blood loss, malabsorption, or consideration of intravenous iron 4
• Monitor complete iron panel (ferritin, transferrin saturation, serum iron) at 4 weeks 6, 4
• Continue therapy for 3 months after hemoglobin normalizes to replete iron stores 4, 7

When to Escalate to Intravenous Iron

Consider IV iron if:

• Hemoglobin does not increase by ≥10 g/L at 2 weeks on alternate-day dosing 4
• Ferritin fails to rise or transferrin saturation remains <20% despite 4–8 weeks of optimized oral therapy 6
• The declining GFR (85 → 45 mL/min) suggests evolving chronic kidney disease, where IV iron is preferred once GFR falls below 45 mL/min 6
• Gastrointestinal side effects remain intolerable even with alternate-day dosing 4

Modern IV iron formulations (ferric carboxymaltose, ferric derisomaltose) can replete total body iron stores in 1–2 infusions and produce clinically meaningful hemoglobin response within one week 4.

Critical Pitfalls to Avoid

Do not continue the current daily regimen:

• Daily dosing at 325 mg (65 mg elemental iron) is suboptimal because the hepcidin surge from each dose blocks absorption of the next day's dose by 35–45% 1, 3
• Multiple daily doses further increase hepcidin and gastrointestinal side effects without improving absorption 3
• Modified-release iron preparations should never be used, as they release iron beyond the duodenum (the primary absorption site) and are classified as "less suitable for prescribing" 4

Address the rising TSH (2.858 → 5.441 mIU/mL):

• Iron and levothyroxine (if she is taking thyroid replacement) must be separated by at least 4 hours, as iron chelates thyroid hormone and reduces its absorption 4
• The TSH elevation may reflect inadequate thyroid hormone absorption due to concurrent iron dosing

Investigate the declining renal function:

• GFR falling from 85 to 45 mL/min warrants evaluation for chronic kidney disease, which itself can cause anemia of chronic disease and impair oral iron absorption 6
• If CKD is confirmed, IV iron becomes the preferred route once GFR <45 mL/min 6