As many as one-third of all patients with inflammatory bowel disease (IBD) have iron-deficiency anemia (IDA), and primary care clinicians can play a key role in identifying and remedying this common but often overlooked comorbidity.
IDA is the most common complication of IBD (Gasche C. Gut, 2004, 1190-1197). Patients with IBD not only have difficulty absorbing minerals like iron, but also have blood loss due to the damaged mucosa that characterizes the disorder.
According to Jeffrey Hertzberg, MD, MS, "the most severe cases are seen in those with poorly treated or newly diagnosed IBD." Citing the work of Christoph Gasche, MD, of the Medical University of Vienna, Dr. Hertzberg added that, "anemia is a common cause of hospitalization [and] prevents physicians from discharging hospitalized patients." (Gasche C, Inflammatory Bowel Diseases, December 2007, 1545–1553).
By keeping an eye out for it, primary care practitioners can identify iron deficiency early on, potentially preventing these hospitalizations.
Assessing Iron Levels
Comprehensive lab work, including measurement of hemogloblin, ferritin, and transferrin saturation makes sense for all patients with IBD to determine if they are anemic. It's also a good idea to test for deficiencies of vitamin B12 and folate, as common IBD drugs like sulfasalazine can interfere with absorption of these vitamins.
Dr. Gasche, one of the world's foremost experts on iron deficiency in the context of IBD, and author of a textbook on the subject, has suggested adding C-reactive protein (CRP) to the screening parameters (Gasche C, Inflammatory Bowel Diseases, 2007, 1545–1553).
While many people with IBD rely on gastroenterologists for the pharmaceutical and, in some cases, surgical aspects of their care, they often turn to holistically minded clinicians for help in living with the condition, minimizing flare-ups, and optimizing health.
Dr. Andrew Chevalier, is a naturopathic physician in Portsmouth, NH with extensive experience treating IBD patients. In an interview with Holistic Primary Care, Dr. Chevalier emphasized the importance of monitoring mean corpuscular volume (MCV) and ferritin every three months.
He chooses this timeline based on the fact that it takes red blood cells 120 days to turnover, so MCV will not change significantly when tested at shorter intervals.
Dr. Chevalier adds that the B12 and folate deficiencies common in IBD can increase MCV, while an iron deficiency will decrease MCV. In patients with all three deficiencies, the result is a "false-normal" MCV reading that can be very misleading.
Therefore, it is imperative to monitor ferritin simultaneously. Look for levels of at least 40-60 ng/mL, and keep in mind that a high ferritin can indicate inflammation, as ferritin is an acute phase reactant and appears elevated in anemia of chronic disease (ACD).
This has clinical significance: iron supplementation should not be given to patients with ACD.
IV vs Oral Iron
If it seems clear that a patient has IDA, one should begin supplementation immediately.
You may be thinking, if IBD patients can't absorb iron from food how will supplementation make any difference? It is a fair question.
Not only is oral iron not well absorbed in IBD, it actually can increase the inflammatory process and exacerbate constipation, a common problem in patients with IBD. Many practitioners focused on this issue recommend intravenous rather than oral iron.
Dr. Hertzberg, a professor at the University of Minnesota, who published a review of this subject on the Rheumatology Network website, states that "multiple studies have shown that intravenous iron is more effective and better tolerated" compared to oral iron. Duration of intravenous iron will depend on the severity of each patient and close monitoring is key.
An article published in The American Journal of Gastroenterology tested the safety and efficacy of intravenous ferric carboxymaltose (FeCarb) compared to oral ferrous sulfate (FeSulf) in the treatment of IDA in IBD.
Kulnigg and colleagues studied 200 patients, with 137 receiving FeCarb and 63 receiving FeSulf for 12 weeks. Intravenous FeCarb was administered at one-week intervals at a maximum of 1,000 mg iron per infusion. The oral FeSulf was dosed at 100 mg, twice daily. Investigators measured hemoglobin concentrations to assess the benefit of treatment.
They found that both forms of iron improved hemoglobin concentrations similarly (P = 0.6967), however the intravenous FeCarb group showed faster hemoglobin increases, with the rise apparent by week 2 (P = 0.0051). The authors concluded that while both are effective and safe treatments for IDA in IBD over a 12-week period, FeCarb provides a faster way of restoring iron.
It is important to note that both groups experienced treatment-related adverse events (28.5% in the IV FeCarb and 22.2% in the oral FeSulf groups). These adverse events led to treatment discontinuation rates of 1.5% in the FeCarb and 7.9% of the FeSulf groups (Kulnigg S, et al. Am J Gastroenterol 2008; 103(5): 1182–1192).
In addition to FeCarb, there are several other intravenous iron preparations now available, including iron dextran, iron gluconate, and iron sucrose.
Iron dextran should be used cautiously due to the increased risk of associated anaphylactic reactions. Dextran is used in single high-dose preparations. However, comparative studies suggest that iron gluconate is safer and more effective than dextran, specifically in dialysis patients with IDA (Fishbane S., Am J Kidney Dis, 2001, 879–83). Bear in mind, though, there is potential of oversaturation of transferrin, leading to toxicity.
Iron sucrose has not been associated with anaphylactic reactions. Dr. Gasche and colleagues recommend it in combination with erythropoietin (Epo), which showed a 65-75% response rate in 4-8 weeks. The addition of Epo led to "faster and large hemogloblin increase" (Gasche, 2004). Iron sucrose has been administered safely in controlled trials at a dose of 3,600 mg with no signs of liver damage or iron overload (Gasche, 2007).
When Convenience Trumps Efficacy
From a patient's perspective, IV iron in whatever form is certainly less than ideal. For many, oral supplementation may be the best choice, but it is only favored for convenience not for efficacy.
Most authors recommend against using more than 100 mg of elemental iron orally. Be aware that oral iron can worsen IBD symptoms, especially the slow-release formulas, as the iron is "released beyond the area of iron absorption and may impact or cause ulceration at Crohn's strictures" (Gasche, 2007).
A Fenton reaction can also occur when ferrous iron is not absorbed, leading to increased inflammation of the intestines and production of reactive oxygen species.
Iron + Vitamin C
The combining of iron with vitamin C can reduce the oxidative stress due to vitamin C's antioxidant capabilities. Dr. Chevalier mentions that vitamin C is also a mild laxative so it makes sense to combine it with iron since the latter may cause constipation. Vitamin C also has the ability to increase iron absorption.
For oral iron supplementation, Dr. Chevalier recommends taking lower doses at the end of each meal because in the presence of foods, specifically herbs and foods high in antioxidants, iron will be less likely to induce oxidative stress. An optimal dose of oral iron has not been identified. However it is known the body can only absorb 10-20 mg of iron orally per day (Gasche, 2007).
Identification and treatment of iron-deficiency anemia in patients with inflammatory bowel disease requires careful attention and appropriate intervention. Primary care clinicians are ideally suited for this role, and can make a tremendous difference in terms of reducing morbidity and complications of IBD, and also in improving quality of life.
Elizabeth Credi holds a Master's degree in Applied Clinical Nutrition from New York Chiropractic College. She completed a post-graduate internship with Maryland University of Integrative Health and is a Certified Nutritionist Specialist candidate. Elizabeth is a certified Pilates instructor and wellness program manager in Washington, DC.