Professor Ian Sanderson
2010 BSPGHAN/Guts UK Development Award Winner
Title: Treatment of Iron Deficiency Anaemia in Adolescents with Inflammatory Bowel Disease: Tolerance and Effects on Haemoglobin, Disease Activity, Mood, Quality of Life and Autonomic Nervous System Activity.
Project Start Date: 1 October 2010
Completion Date: April 2015
Iron deficiency anaemia (IDA), largely as a consequence of intestinal blood loss, is common in inflammatory bowel disease (IBD). IBD in young people is increasing, and their disease tends to be more extensive than in adults. It is not surprising therefore that IDA seems to be commoner in young people than adults with IBD. Under-treatment with oral iron tablets may be a contributory factor, possibly due to a perceived lack of benefit of iron supplementation or gastroenterologists’ concerns about possible side effects.
IBD in adolescence impairs growth, education, employment and sexual development. Adolescents with IBD suffer more psychological distress than their peers, but whether being anaemic affects mood is unknown. Quality of life (QOL) scores in anaemic adults with IBD resemble those recorded in malignancy. Iron supplementation and correction of anaemia in adults improves QOL, implying that IBD patients when anaemic adapt their behaviour to their symptoms, including a degree of fatigue and reduced exercise tolerance, which may conceivably contribute to a depressed mood. Behavioural adaptation to anaemia causes activation of the autonomic nervous system, a state recently implicated in relapse of IBD.
The research team set out to test the following ideas:
- that adolescents with IBD can benefit as much as adults do from oral iron supplementation, in terms of improvement to their anaemia;
- that oral iron does not worsen symptoms of IBD or level of inflammation of the disease;
- that correction of anaemia improves quality of life, mood and fatigue in patients with IBD.
The researchers also investigated the role of hepcidin, a molecule that is involved in how the body regulates iron levels and absorption. The researchers hoped to be able to use levels of hepcidin to predict how patients with IBD and anaemia would respond to oral iron supplementation.
To test these ideas, the researchers carried out a study. They provided oral iron supplementation for 6 weeks to 43 adolescents and 46 adults with iron-deficient anaemia in IBD. To help them understand the effect of the iron supplementation, the researchers measured a set of factors in study participants both before and after providing iron treatment. These factors measured were:
- the levels of iron in the blood of the study participants (specifically levels of haemoglobin, a molecule that carries iron in the blood);
- whether study participants’ IBD symptoms and level of inflammation changed;
- how well the study participant tolerated the iron supplements;
- quality of life, perceived stress, mood and fatigue (measured using psychometric questionnaires);
- how the body processes the iron, including levels in the blood of the molecule hepcidin.
When the researchers compared the differences in the above factors before and after iron supplementation of the study participants, they found that:
- the improvement in anaemia status (represented by levels of haemoglobin in the blood) was similar in adolescents and adults study participants.
- intolerance of oral iron occurred as often in adolescents as in adults, about 20% of patients developing non-specific symptoms such as abdominal pain and changes in bowel habit (as reported in many previous studies of people with and without IBD taking iron orally). Importantly, however, there was no evidence in either group of patients that oral iron increased the amount of inflammation in the bowel as measured by special blood (C-reactive protein, CRP) and stool (calprotectin) tests done before and at the end of treatment with iron.
- the small improvement in anaemia status produced by oral iron did not significantly improve quality of life, mood or fatigue scores in adolescent or adult patients with IBD.
The researchers also found that patients who had low levels of the molecule hepcidin before receiving iron supplementation subsequently had a bigger rise in their haemoglobin concentration than those with high hepcidin levels at the outset.
These results should reassure paediatricians (as well as adult gastroenterologists) about the effectiveness and safety of oral iron for the treatment of anaemia in IBD. Additionally, the researcher’s finding that the level of the molecule hepcidin affects the response to oral iron supplementation could signify a change in clinical practice, provided the finding is replicated by other research teams, to confirm its validity. It shows that it may become sensible practice to check the serum hepcidin level of patients before deciding whether to give the iron by mouth (if the baseline hepcidin is low) or intravenously (if the hepcidin is high).
The lack of improvement in quality of life, mood or fatigue could be because the improvement in anaemia status induced by oral iron supplementation for only 6 weeks was too small to influence those factors. Another explanation might be that study participants did not complete the questionnaire with sufficient detail to allow the researchers to analyse that information with sufficient accurately.
The next step for the researchers is to analyse, in a separate study, the stools that were collected before and after iron supplementation. This will allow them to assess whether oral iron alters the bacterial populations of the large intestine. This is a key question to answer given the important role of gut bacteria in a range of human disorders, including not only IBD but also, for example, obesity.