Impaired intestinal iron absorption in inflammatory bowel disease correlates with disease activity and markers of inflammation but is independent of disease location

Aims: Anemia in patients with inflammatory bowel disease (IBD) is multifactorial, however the two most common causes of anemia in IBD are iron deficiency and anemia of inflammation (ACI). Although the exact pathogenesis of ACI is unknown, one hypothesis suggests that-caused by the effects of inflammatory cytokines-ACI arises in part as a result of an impaired intestinal Iron absorption. Recently it has been shown, that the acute phase protein hepcidin impairs intestinal iron uptake. We therefore hypothesized that iron absorption is impaired in patients with active IBD at least in part as an increased hepcidin release by the liver.

Methods: 40 adult subjects with IBD (17 UC, 23 CD) were recruited until February 2010. After an overnight fast, serum iron and hemoglobin levels, serum markers of inflammation [IL-6, and C-reactive protein (CRP) were measured. Serum and urine samples for hepcidin assay were obtained at 8 am and measured by LC-MS. Ferrous sulfate (1mg) was administered orally, followed by determination of serum iron concentrations hourly for 4 hours. An area under the curve for iron absorption was calculated for each patient data set.

Results: Table 1 demonstrates the change in serum iron concentration in patients with active compared with those with inactive disease. There was a strong inverse correlation between the area under the curve and IL-6 (P<0.005) and area under the curve and CRP levels (P<0.05). Similarly, the difference between baseline and 3-hour serum iron level (delta[Fe]3hr) correlated with IL-6 (P<0.01) and CRP (P<0.05). Urine hepcidin levels positively correlated with IL-6 and CRP levels (P<0.005 and <0.01, respectively).

Table 1

	(delta [Fe] vs. baseline)
	1h	1.5h	2h	3h	4h
Controls (n=17)	39.24±9.51	73.06±13.90	98.00±14.43	111.18±13.24	128.71±12.17
Inactive CD (n=11)	14.25±9.76	52.38±10.30	66.33±19.47	80.83±19.15	83.29±35.83
Active CD (n=12)	15.36±8.93	48.83±16.04	56.75±24.81	64.63±11.27	71.75±20.82
Inactive CU (n=8)	10.75±8.66	31.50±11.79	84.75±38.37	120.50±48.23	126.50±42.51
Active CU (n=9)	19.67±16.66	56.29±32.24	55.29±32.67	75.86±37.78	39.33±9.46

Conclusions: Compared to healthy controls and subjects with inactive disease patients with active IBD have impaired oral iron absorption, which correlates with disease activity and markers of Inflammation but is independent of disease location.