ORIGINAL ARTICLE Oral ferrous fumarate or intravenous iron sucrose for patients with inflammatory bowel disease KARI ERICHSEN 1,2 , RUNE J. ULVIK 2 , GUNNAR NYSAETER 1 , JACK JOHANSEN 3 , JENS OSTBORG 4 , ARNOLD BERSTAD 1,2 , ROLF K. BERGE 2 & TRYGVE HAUSKEN 1,2 1 Department of Medicine, Haukeland University Hospital, 2 Institute of Medicine, University of Bergen, Bergen, 3 Department of Medicine, Forde County Hospital, Forde, and 4 Department of Medicine, Haugesund Hospital, Haugesund, Norway Abstract Objective. Iron therapy may reinforce intestinal inflammation by catalysing production of reactive oxygen species. The effects of oral ferrous fumarate and intravenous iron sucrose on clinical disease activity and plasma redox status were investigated in patients with inflammatory bowel disease (IBD). Material and methods. Nineteen patients with iron deficiency anaemia and Crohn’s disease (11) or ulcerative colitis (8) were included in a crossover study. The patients were randomly assigned to start treatment with ferrous fumarate (Neo-fer † ) 120 mg orally once daily or iron sucrose (Venofer † ) 200 mg intravenously 3 times during a period of 14 days. Clinical disease activity assessment and blood and faecal analysis were performed on days 1 and 15. Results. Following oral ferrous fumarate clinical disease activity (p  /0.037), general well-being score (i.e. patients felt worse) (p  /0.027) and abdominal pain score (p  /0.027) increased, while no changes were seen following iron sucrose treatment. C-reactive protein (CRP) and faecal calprotectin were unchanged after both treatments. As compared with iron sucrose, ferrous fumarate increased Crohn’s disease activity index (CDAI) scores of general well-being (p  /0.049), whereas alterations in clinical disease activity (p  /0.14) and abdominal pain score (p  /0.20) did not differ. Ferrous fumarate did not significantly alter plasma malondialdehyde (MDA) or plasma antioxidants. Iron sucrose increased plasma MDA (p  /0.004) and decreased plasma vitamin C (p  /0.017) and betacarotene (p  / 0.008). Conclusions. Oral ferrous fumarate, but not intravenous iron sucrose, increased clinical disease activity in IBD patients. Intravenous iron sucrose increased intravascular oxidative stress. Key Words: Anaemia, antioxidants, ferric compounds, ferrous compounds, inflammatory bowel diseases, iron, iron deficiency, malondialdehyde Introduction Iron is an essential element that is involved in many biological functions, such as energy metabolism, DNA synthesis, oxygen transport and storage, growth and immune defence. However, free iron may be harmful because it is a powerful catalytic agent in the generation of highly reactive oxygen species (ROS). One-third of patients with inflammatory bowel disease (IBD) suffer from recurrent anaemia [1,2]. Iron deficiency and anaemia of chronic diseases are the most common causes of anaemia in IBD [3]. Available compounds for oral iron supplementation, generally ferrous salts, are associated with frequent gastrointestinal side effects, leading to poor compli- ance. Most of the ingested ferrous iron is not absorbed but passed on to the ileum and colon, sites of inflammation in Crohn’s disease and ulcerative colitis. There it can react with superoxide (O 2 +  ) and hydrogen peroxide (H 2 O 2 ) from activated neu- trophils in the inflamed mucosa, leading to produc- tion of the hydroxyl radical (OH + ). Hydroxyl radicals are extremely reactive and can attack any cell component and cause oxidative damage and lead to the production of other ROS [4]. The pro- oxidative imbalance created by this overproduction of ROS may enhance intestinal injury, as demon- strated in animal models of IBD [5  /8]. Correspondence: Kari Erichsen, MD, Department of Medicine, Haukeland University Hospital, NO-5021 Bergen, Norway. Tel:  /47 5597 5000. Fax:  /47 5597 4973. E-mail: kari.erichsen@helse-bergen.no Scandinavian Journal of Gastroenterology, 2005; 40: 1058  /1065 (Received 5 November 2004; accepted 24 January 2005) ISSN 0036-5521 print/ISSN 1502-7708 online # 2005 Taylor & Francis DOI: 10.1080/00365520510023198