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A Case of Pica-like, Nutrient-induced, Severe Iron-deficiency Anemia

      To the Editor:
      Data from the Third National Health and Nutrition Examination Survey (1988-1994) indicate that iron deficiency is present in 1% to 2% of adults in industrialized countries.
      • Looker A.C.
      • Dallman P.R.
      • Carroll M.D.
      • Gunter E.W.
      • Johnson C.L.
      Prevalence of iron deficiency in the United States.
      Foods and medications can impair iron absorption. We recently observed a patient with severe iron-deficient anemia mimicking impaired iron absorption in the absence of gastrointestinal pathology.

      Case Summary

      A 44-year-old woman was referred to our outpatient clinic because of recurrent symptoms of iron deficiency. One year ago, she was treated with oral iron (100 mg/d) because of severe iron-deficiency anemia with a hemoglobin level of 7.0 g/dL. Guaiac-based fecal occult blood test results were negative. Endoscopies of the whole gastrointestinal tract, including a small bowel biopsy for exclusion of celiac disease, revealed no abnormalities. A gynecologic examination excluded uterine bleeding. Oral iron therapy was terminated after remission of symptoms 3 months later when hemoglobin had increased to 14.6 g/dL. Nonetheless, reviewing the patient's file suggested that repletion of her iron stores was not yet accomplished at that time.
      On referral, she reported fatigue, headache, a burning tongue, and exercise intolerance. She appeared to be in a normal nutritional condition. Her skin was pale, and inspection of her oral cavity revealed atrophic glossitis. Pulse rate and blood pressure were normal. Blood tests indicated a hemoglobin level of 10.0 g/dL with a low mean cell volume (70 fl) and a low mean corpuscular hemoglobin (21 pg). Erythrocyte count was not decreased (4.8 × 1012/L), suggesting long-lasting iron-deficient hemostasis rather than bleeding. The most recent laboratory values of serum iron, transferrin saturation, ferritin, and blood counts are shown in Table 1.
      Table 1Blood Count and Biochemical Laboratory Findings
      May 23, 2013

      3 Weeks After Definite Cessation of Raisin Consumption
      May 3, 2013

      1 Week After Reexposure to Raisins
      April 26, 2013

      1 Week After Cessation of Raisin Consumption
      CRP, mg/dL<0.5<0.5
      Hemoglobin, g/dL12.210.110.0
      Erythrocytes, ×1012/L5.24.74.8
      Mean cell volume, fl767170
      Mean corpuscular hemoglobin, pg232121
      Hematocrit, %403333
      Reticulocytes, %0.91.02.9
      Leukocytes, ×109/L4.64.34.0
      Platelets, ×109/L262366297
      Serum iron, μg/dL171115
      Transferrin, mg/dL315322335
      Transferrin saturation, %744
      Ferritin, ng/mL171115
      Oral iron absorption test
       Serum iron at 1 h, μg/dL178165
       Serum iron at 2 h, μg/dL168313
      CRP = C-reactive protein.
      When asked about her food pattern, our patient recounted a daily intake of 100 to 150 g of blue raisins for more than 2 years. She craved sweet raisins because she was doing regular endurance training. After cessation of raisin intake for 1 week, an oral iron absorption test using 225 mg of iron(II)-glycine-sulfate (equivalent to 40 mg of Fe2+) revealed no abnormalities. Thereafter, she was requested to continue with her previous food pattern, and enteric iron absorption was reexamined 1 week later after daily ingestion of 100 to 150 g of blue raisins. The oral absorption test at that time indicated a markedly lower serum iron at 2 hours. In addition, reticulocyte count decreased during reexposure to raisins, whereas the degree of iron-deficiency anemia was similar. Three weeks after definite cessation of raisin consumption, anemia had resolved to subnormal hemoglobin levels without any oral iron supplementation (Table 1).

      Discussion

      Grape products, including raisins, contain high concentrations of specific natural phenolic compounds.
      • Williamson G.
      • Carughi A.
      Polyphenol content and health benefits of raisins.
      Polyphenols released through the indigestible carbohydrate matrix of the fruit skin bind to iron and form a nontransportable complex that cannot enter the bloodstream. It was shown that bioactive dietary polyphenols inhibit heme iron absorption in a dose-dependent manner.
      • Ma Q.
      • Kim E.Y.
      • Lindsay E.A.
      • Han O.
      Bioactive dietary polyphenols inhibit heme iron absorption in a dose-dependent manner in human intestinal Caco-2 cells.
      Thus, we suspected that consumption of raisins in larger quantities would interfere with the bioavailability of dietary iron,
      • Bryant B.J.
      • Yau Y.Y.
      • Arceo S.M.
      • Hopkins J.A.
      • Leitman S.F.
      Ascertainment of iron deficiency and depletion in blood donors through screening questions for pica and restless legs syndrome.
      similar to pica syndrome. For testing of our hypothesis, we administered a lower than standard dose of iron in the absorption tests, because we were aware from our patient's history that oral iron supplementation was capable of offseting the dietary deficiencies.

      Conclusions

      To our knowledge, this is the first clinical case indicating that blue raisins decrease the absorption of iron from foods. Although our observation comprises a rare cause of iron-deficiency anemia, natural bioactive polyphenols may offer an adjunct dietetic treatment in patients with hereditary hemochromatosis, who experience iron overload because of an accelerated rate of intestinal iron absorption.
      • Fleming R.E.
      • Ponka P.
      Iron overload in human disease.

      References

        • Looker A.C.
        • Dallman P.R.
        • Carroll M.D.
        • Gunter E.W.
        • Johnson C.L.
        Prevalence of iron deficiency in the United States.
        JAMA. 1997; 277: 973-976
        • Williamson G.
        • Carughi A.
        Polyphenol content and health benefits of raisins.
        Nutr Res. 2010; 30: 511-519
        • Ma Q.
        • Kim E.Y.
        • Lindsay E.A.
        • Han O.
        Bioactive dietary polyphenols inhibit heme iron absorption in a dose-dependent manner in human intestinal Caco-2 cells.
        J Food Sci. 2011; 76: H143-H150
        • Bryant B.J.
        • Yau Y.Y.
        • Arceo S.M.
        • Hopkins J.A.
        • Leitman S.F.
        Ascertainment of iron deficiency and depletion in blood donors through screening questions for pica and restless legs syndrome.
        Transfusion. 2013; 53: 1637-1644
        • Fleming R.E.
        • Ponka P.
        Iron overload in human disease.
        N Engl J Med. 2012; 366: 348-359