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Gastroenterology. 2002 Apr;122(4):931-9.

Effect of iron depletion in carbohydrate-intolerant patients with clinical evidence of nonalcoholic fatty liver disease.

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Department of Medicine, University of California San Francisco and San Francisco General Hospital, San Francisco, California, USA.



Increased body iron, genetic hemochromatosis (GH) mutations, and nonalcoholic fatty liver disease (NAFLD) tend to cluster in carbohydrate-intolerant patients. In an attempt to further clarify the interrelationships among these conditions, we studied 42 carbohydrate-intolerant patients who were free of the common GH mutations C282Y and H63D, and had a serum iron saturation lower than 50%.


We measured body iron stores, and induced iron depletion to a level of near-iron deficiency (NID) by quantitative phlebotomy.


In the 17 patients with clinical evidence of NAFLD, we could not demonstrate supranormal levels of body iron (1.6 +/- 0.2 vs. 1.4 +/- 0.2 g; P = 0.06). However, at NID, there was a 40%-55% improvement (P = 0.05-0.0001) of both fasting and glucose-stimulated plasma insulin concentrations, and near-normalization of serum alanine aminotransferase activity (from 61 +/- 5 to 32 +/- 2 IU/L; P < 0.001).


These results reflect the insulin-sparing effect of iron depletion and indicate a key role of iron and hyperinsulinemia in the pathogenesis of NAFLD.

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