title: Circulating non-transferrin-bound iron after oral administration of supplemental and fortification doses of iron to healthy women: a randomized study.
abstract: BACKGROUND
  After the oral administration of iron, the production of circulating non-transferrin-bound iron may contribute to an increased risk of illness in malaria-endemic areas that lack effective medical services.
  
  
  OBJECTIVE
  In healthy women with a range of body iron stores, we aimed to determine effects on the production of circulating non-transferrin-bound iron resulting from the oral administration of 1) a supplemental dose of iron (60 mg) with water, 2) a supplemental dose of iron (60 mg) with a standard test meal, and 3) a fortification dose of iron (6 mg) with a standard test meal.
  
  
  METHODS
  With the use of serum ferritin as the indicator, healthy women with replete iron stores (ferritin concentration >25 μg/L; n = 16) and reduced iron stores (ferritin concentration ≤25 μg/L; n = 16) were enrolled in a prospective, randomized, crossover study. After the oral administration of aqueous solutions of ferrous sulfate isotopically labeled with ⁵⁴Fe, ⁵⁷Fe, or ⁵⁸Fe, blood samples were collected for 8 h, and iron absorption was estimated by erythrocyte incorporation at 14 d.
  
  
  RESULTS
  At 4 h, serum non-transferrin-bound iron reached peaks with geometric mean (95% CI) concentrations of 0.81 μmol/L (0.56, 1.1 μmol/L) for 60 mg Fe with water and 0.26 μmol/L (0.15, 0.38 μmol/L) for 60 mg Fe with food but was at assay limits of detection (0.1 μmol Fe/L) for 6 mg Fe with food. For the 60 mg Fe without food, the area under the curve over 8 h for serum non-transferrin-bound iron was positively correlated with the amount of iron absorbed (R = 0.49, P < 0.01) and negatively correlated with serum ferritin (R = -0.39, P < 0.05).
  
  
  CONCLUSIONS
  In healthy women, the production of circulating non-transferrin-bound iron is determined by the rate and amount of iron absorbed. The highest concentrations of non-transferrin-bound iron resulted from the administration of supplemental doses of iron without food. Little or no circulating non-transferrin-bound iron resulted from the consumption of a meal with a fortification dose of iron.
authors: From the Human Nutrition Laboratory, Institute of Food, Nutrition and Health, ETH Zürich, Zürich, Switzerland (IE, JTF, CZ, MA, and RFH); the Intrinsic LifeSciences LLC, La Jolla, CA (MEW); and the Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY (GMB).
authors: Gary M
authors: GM
authors: Brittenham
authors: From the Human Nutrition Laboratory, Institute of Food, Nutrition and Health, ETH Zürich, Zürich, Switzerland (IE, JTF, CZ, MA, and RFH); the Intrinsic LifeSciences LLC, La Jolla, CA (MEW); and the Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY (GMB).
authors: Maria
authors: M
authors: Andersson
authors: From the Human Nutrition Laboratory, Institute of Food, Nutrition and Health, ETH Zürich, Zürich, Switzerland (IE, JTF, CZ, MA, and RFH); the Intrinsic LifeSciences LLC, La Jolla, CA (MEW); and the Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY (GMB).
authors: Ines
authors: I
authors: Egli
authors: From the Human Nutrition Laboratory, Institute of Food, Nutrition and Health, ETH Zürich, Zürich, Switzerland (IE, JTF, CZ, MA, and RFH); the Intrinsic LifeSciences LLC, La Jolla, CA (MEW); and the Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY (GMB).
authors: Jasmin Tajeri
authors: JT
authors: Foman
authors: From the Human Nutrition Laboratory, Institute of Food, Nutrition and Health, ETH Zürich, Zürich, Switzerland (IE, JTF, CZ, MA, and RFH); the Intrinsic LifeSciences LLC, La Jolla, CA (MEW); and the Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY (GMB).
authors: Christophe
authors: C
authors: Zeder
authors: From the Human Nutrition Laboratory, Institute of Food, Nutrition and Health, ETH Zürich, Zürich, Switzerland (IE, JTF, CZ, MA, and RFH); the Intrinsic LifeSciences LLC, La Jolla, CA (MEW); and the Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY (GMB).
authors: Mark E
authors: ME
authors: Westerman
authors: From the Human Nutrition Laboratory, Institute of Food, Nutrition and Health, ETH Zürich, Zürich, Switzerland (IE, JTF, CZ, MA, and RFH); the Intrinsic LifeSciences LLC, La Jolla, CA (MEW); and the Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY (GMB).
authors: Richard F
authors: RF
authors: Hurrell
mesh_terms: D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D019587:Dietary Supplements / Q000009:adverse effects; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000097:blood; D005296:Ferrous Compounds / Q000008:administration & dosage; D005527:Food, Fortified / Q000009:adverse effects; D006801:Humans; D007408:Intestinal Absorption; D007501:Iron / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D007504:Iron Radioisotopes; D019266:Iron, Dietary / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D007700:Kinetics; D062407:Meals; D009752:Nutritional Status; D012995:Solubility; D013557:Switzerland; D055815:Young Adult
chemical_list: D005296:Ferrous Compounds; D007504:Iron Radioisotopes; D019266:Iron, Dietary; C020748:ferrous sulfate; D005293:Ferritins; D007501:Iron