Applied nutritional investigation Heme iron-based dietary intervention for improvement of iron status in young women Michael Hoppe Ph.D. * , Beatrice Brün M.Sc., Maria Pia Larsson M.Sc., Lotta Moraeus M.Sc., Lena Hulth  en Ph.D. Department of Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden article info Article history: Received 31 October 2011 Accepted 3 April 2012 Keywords: Heme iron Iron status Iron supplementation Dietary intervention Healthy women Iron deficiency Randomized abstract Objective: Conventional iron deficiency treatment with pharmacologic iron doses often causes side effects. Heme iron has high bioavailability and a low capacity to cause gastrointestinal side effects. This study investigated the possibility of using heme iron in the form of blood-based crisp bread as a diet-based treatment program to improve the iron status of women of reproductive age. Methods: In a 12-wk intervention study, 77 women (mean age 24 y) were assigned to one of four groups: blood-based crisp bread (35 mg of iron [Fe], 27 mg of which was heme Fe), iron supple- mentation consisting of 35 mg of non-heme iron/day (Fe35), iron supplementation consisting of 60 mg of non-heme iron/day (Fe60), and controls (iron-free tablets). Results: Body iron increased significantly in the crisp bread group by a median of 2.7 mg/kg (interquartile range 3.1, n ¼ 18), in the Fe35 group by 2.7 mg/kg (interquartile range 2.8, n ¼ 11), and in the Fe60 group by 4.1 mg/kg (interquartile range 3.6, n ¼ 13), whereas no change was observed in the control group. No statistically significant difference in iron status increase was observed between the crisp bread group compared with the two iron-supplemented groups. Conclusion: Dietary-based treatment containing heme iron has few side effects and can be used efficiently to improve the iron status of women of reproductive age. Ó 2013 Elsevier Inc. All rights reserved. Introduction Iron deficiency is the most common nutrient deficiency glob- ally, affecting an estimated 2 billion people in developed and developing countries [1,2]. The prevalence of iron deficiency in European women of reproductive age has been estimated at 8% to 30% [3]. However, conventional treatment consisting of pharma- cologic doses of iron in tablet form often causes side effects such as stomach pain, constipation, diarrhea, and feelings of nausea [4,5]. An important consequence is the risk of low patient compliance in taking the conventional medication [6]. Therefore, identifying treatment options with negligible gastrointestinal side effects would be highly valuable in the battle against iron deficiency in healthy individuals and those who are especially sensitive to such side effects, e.g., patients with short bowel syndrome [7]. Dietary iron can be described as heme or non-heme. Heme iron represents a relatively small part of the total dietary iron intake but has a higher bioavailability than non-heme iron [8] and has been demonstrated to have a low ability to cause gastrointestinal side effects [9]. In many cultures around the world, heme iron–rich blood products have been used in the diet. There are also innovative approaches to developing a heme iron concentrate and a heme iron–based supplement/fortifier, e.g., hemoglobin-based meat pigment [10–12]. The potential of microbe-produced heme iron has also been studied [13]. To investigate the benefits of heme iron as a nutrition-based treatment for low iron reserves, this study explored the effec- tiveness of blood-based crisp bread to improve iron status in young women. The main research question in this study was whether a substitution of part of the diet with blood-based crisp bread each day for a 12-wk period could improve the iron status of healthy non-anemic women of fertile age. Materials and methods Study design A controlled longitudinal intervention study of 12-wk duration was con- ducted in two stages. In stage 1 (January 2007 through June 2007), 46 female subjects were recruited. Owing to a large number of withdrawals (see RESULTS) This project was funded by the Local Research and Development Council of Gothenburg and Southern Bohuslän, Sweden (reg. no. VGFOUGSB-8049). * Corresponding author. Tel.: þ46-31-786-3705; fax: þ46-31-786-3101. E-mail address: michael.hoppe@nutrition.gu.se (M. Hoppe). 0899-9007/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. doi:10.1016/j.nut.2012.04.013 Contents lists available at ScienceDirect Nutrition journal homepage: www.nutritionjrnl.com Nutrition 29 (2013) 89–95