Does weight affect iron deficiency?

Does Weight Affect Iron Deficiency?

Yes, weight significantly affects iron deficiency—obesity increases the risk of iron deficiency through inflammation-mediated elevation of hepcidin, which reduces iron absorption and availability, independent of dietary iron intake.

Mechanism: The Hepcidin-Obesity Connection

Obesity creates a state of chronic low-grade inflammation that directly impairs iron homeostasis through hepcidin dysregulation. 1, 2

• Hepcidin is the master regulator of systemic iron balance, controlling iron export from cells by regulating ferroportin-1 activity 1
• In obesity, elevated inflammatory markers (CRP, IL-6, leptin) drive increased hepcidin production 3
• Elevated hepcidin blocks iron absorption in the duodenum and sequesters iron in macrophages and hepatocytes, reducing bioavailable iron 1, 2

Evidence in Overweight Children and Adults

Overweight children demonstrate higher hepcidin levels and reduced functional iron status despite consuming adequate dietary iron. 3

• Overweight children (ages 6-14) had significantly higher rates of iron-deficient erythropoiesis (20% vs 6% in normal weight children, P=0.022) 3
• Serum hepcidin levels were significantly elevated in overweight children (P=0.001) 3
• Critically, dietary iron intake and bioavailability were comparable between normal and overweight children, indicating the problem is absorption/utilization, not intake 3
• BMI correlated significantly with elevated soluble transferrin receptor (sTfR), hepcidin, and inflammatory markers (CRP, IL-6, leptin) 3

Body Weight and Iron Stores: The Physiological Relationship

Total body iron is calculated per kilogram of body weight, with men averaging 50 mg/kg and women 42 mg/kg. 4

• Men store approximately 1.0-1.4 g total body iron, women 0.2-0.4 g 4
• Low birthweight infants have the same ratio of iron to body weight as normal weight infants, but their absolute stored iron is proportionally lower 4
• This demonstrates that lower body weight directly translates to lower absolute iron stores, making these individuals more vulnerable to depletion 4

Weight Loss Reverses Iron Deficiency

Bariatric surgery and weight loss improve iron status by reducing inflammation and hepcidin levels. 5

• Six months post-restrictive bariatric surgery in obese premenopausal women: 5
  • Serum hepcidin decreased dramatically (111.25 vs 31.35 ng/ml, P<0.0001)
  • sTfR improved (29.97 vs 23.08 nmol/l, P=0.001)
  • Hemoglobin increased (12.10 vs 13.30 g/dl, P<0.0001)
  • CRP decreased (10.83 vs 5.71 mg/l, P<0.0001)
• At baseline, 45% of obese women had iron-deficient erythropoiesis 5
• Change in IL-6 was associated with decreased hepcidin (β=-0.22), while dietary iron intake remained unchanged 5

Clinical Implications for Iron Assessment

Standard ferritin cutoffs must be adjusted upward in the presence of obesity-related inflammation. 4

• Without inflammation: ferritin <30 μg/L indicates iron deficiency 4
• With inflammation (including obesity): ferritin up to 100 μg/L may still represent iron deficiency 4
• Ferritin 30-100 μg/L with inflammation suggests combined true iron deficiency and anemia of chronic disease 4
• Transferrin saturation <20% with ferritin >100 μg/L indicates anemia of chronic disease 4

Bariatric Surgery Considerations

While weight loss improves iron absorption through reduced hepcidin, certain bariatric procedures create new malabsorption risks. 2

• Gastric bypass (RYGB) and sleeve gastrectomy can induce malabsorption that may accentuate iron deficiency 2
• Post-bariatric patients require ongoing iron status monitoring and supplementation 2
• The competing effects of improved absorption (from reduced inflammation/hepcidin) versus anatomical malabsorption must be balanced 2

Key Clinical Pitfalls

• Do not assume adequate dietary iron intake excludes iron deficiency in obese patients—the problem is absorption and sequestration, not intake 3
• Do not use standard ferritin cutoffs (<30 μg/L) in obese patients with inflammation—use <100 μg/L as the threshold 4
• Do not overlook iron deficiency screening in overweight children—they have 3-fold higher rates of iron-deficient erythropoiesis 3
• Weight loss interventions improve iron status but require monitoring, as bariatric procedures may create new absorption challenges 2, 5