Studies have shown that increasing haemoglobin levels, for those with moderate or severe anaemia, improves quality of life in IBD patients [4, 25, 26] and therefore one might expect iron status to reflect quality of life. However, results from this small study show that, in the absence of moderate or severe anaemia, there is no significant difference in quality of life between IBD patients classified as iron deplete and iron replete. As noted previously, categorisation as iron replete/deplete is superior when based upon oral iron challenge (as here) rather than standard haematological parameters that can be disturbed in this patient group [17, 18, 27]. The lack of observed difference could be explained by the fact that, in this work, only 4/21 of the iron deplete patients had anaemia (which was anyway mild) and, overall, the iron deplete group had a mean haemoglobin level of 13.3 g/dL  (i.e. within the normal reference range even if iron stores where low). Similar work in patients with cancer showed the biggest improvement in quality of life when haemoglobin levels increased from 11 to 13 g/dL . Therefore, the iron deplete patients in our study appear, in the main, have haemoglobin levels above the threshold for the detection of deterioration in quality of life. From this we can conclude that iron deficiency in the absence of anaemia does not have a measurable effect on quality of life in IBD. This is important information because there is evidence that oral iron supplementation can have detrimental effects on the symptoms of IBD [5, 6, 9, 10, 29, 30], so only supplementing when necessary seems prudent.
Moreover, for the IBD patients reported herein, we found that their iron intakes, and in particular their intakes of fortificant iron, were significantly negatively associated with quality of life, as measured by both the McMaster IBDQ and EuroQol VAS percentage. However, this association appears to ‘show up’ only in patients with some degree of disease activity (Figures 1E and 2E), although we accept that patient numbers were low in these subgroups and a larger study would be required to see if there really is no such association in patients with quiescent disease.
Animal models have indicated that relatively small changes to luminal iron in the colon can lead to exacerbation of local inflammatory effects (and their biomarkers) [12, 13, 15] and, similarly, that removal of luminal iron can alleviate local inflammation . However, the gastrointestinal effects of dietary/fortificant iron in humans with IBD is not understood  and, so, these are the first data to suggest that what is observed in animal models of IBD may also be observed in the population with non-quiescent IBD. Nevertheless, we recognise that the numbers studied here were small (n=29 overall and n=15 with mildly active disease) and that the less sensitive measure for quality of life in these subjects (i.e. the generic EuroQol score) did not detect any association. Hence, the study really needs repeating with a larger cohort, preferably longitudinally, but, if other findings are consistent, then this would add further credibility to work suggesting that unabsorbed dietary iron can have adverse effects in the colon and especially in those with pre-existing inflammation.
If the above findings were verified, how might dietary fortificant iron be mediating its effect in sensitive individuals? After all, compared to oral iron supplementation (typically 60–120 mg Fe/day) the amount of iron in the diet, even allowing for fortification, is low (5–25 mgFe/day in this study) and whilst iron supplementation may be problematic in some subjects with IBD [5, 6, 9, 10, 29, 30] it is clearly not to the extent that would be expected if dietary iron alone were a problem. This is a puzzle that deserves consideration although it is possible that there is a low dose threshold for the iron effect or that long term iron-effects are required (e.g. changes in colonic flora ) that are not irreversibly experienced with the shorter duration of supplementation. Finally, the chemical form of the iron should be considered: for example, it is worth noting that an inflammatory murine model of ulcerative colitis showed that a mere doubling of dietary iron, using iron EDTA, led to a 4–5 fold increase in tumour incidence . Even in the small study presented here, the range of iron intakes was about four-fold.
To our knowledge the study presented herein is the first study carried out in humans to investigate the impact of dietary iron, particularly from iron-fortified products, on quality of life. We focused, especially, on IBD patients as a potentially vulnerable and sensitive (to effects) population. This study can be viewed as hypothesis-generating and we propose that further studies are undertaken to determine whether high dietary iron intakes are, reproducibly, negatively associated with quality of life in IBD patients (with or without active disease) and, if so, firstly if this is related to endogenous food-iron or fortificant iron (for the non-haem fraction) and, secondly, if the issue extends to the wider population in terms of dietary iron and long-term distal gut health. In which case, for a healthy population without pre-existing gut mucosal sensitivity, it is unlikely that symptoms (quality of life) would be a sufficient indicator and biochemical, microbial or histological parameters would be required.