Iron-Deficiency Anemia Is Rarely Tested for in IBD but Should Be

Inflammatory bowel disease (IBD) predisposes patients to developing anemia, a condition that negatively affects quality of life. Unfortunately, doctors do not always test for anemia, and when they do, both the screening and treatment are often incomplete. Read on to learn about the causes of anemia in IBD patients, strategies for managing iron-deficiency anemia, and what Functional Medicine has to offer for IBD patients.

---

Inflammatory bowel disease (IBD) affects 1.3 percent of U.S. adults, or more than 3 million people (1). On a basic level, in IBD the immune system targets food, bacteria, or other substances in the GI tract as foreign invaders, resulting in chronic inflammation of the digestive tract. The most common symptoms associated with IBD—abdominal pain, diarrhea, and other GI discomforts—negatively impact daily life and can be frustratingly unpredictable.

Crohn’s disease (CD) and ulcerative colitis (UC) are the two main diseases that fall under the umbrella of IBD. While the effects of UC are limited to the innermost lining of the colon, CD can manifest in any layer of the bowel walls and in any part of the digestive tract.

IBD-Associated Anemia Is Common and Complicated

The World Health Organization defines anemia as “a condition in which the number of red blood cells or their oxygen-carrying capacity is insufficient to meet physiologic needs” (2). Traditionally, low levels of hemoglobin (below 13 g/dL in men and below 12 g/dL in women) indicate anemia, but these criteria have been questioned due to variances among different ages, races, and sea levels.

The incidence of anemia in IBD patients is difficult to determine because it depends on the characteristics of the groups studied. Patients who are hospitalized, are experiencing active flare-ups, or have signs of high inflammation are more likely to also be anemic and can skew estimates. Therefore, in the literature, the prevalence of anemia in IBD has been reported to be anywhere from 6 to 74 percent (3, 4). In children with IBD, it is estimated to affect up to 75 percent (5, 6). Common symptoms include the following:

• Headache
• Fatigue
• Dizziness
• Tachycardia
• Dyspnea
• Loss of libido
• Nausea
• Vertigo
• Tinnitus
• Weight loss
• Lethargy

If left untreated, anemia can be debilitating and even life threatening (7). Anemic patients report major adverse effects on physical activity, productivity, and home life (8).

Causes of Anemia in IBD

Although dietary iron deficiency can lead to anemia, it is not the only cause. Anemia can develop in IBD patients for a variety of additional reasons, including insufficient iron absorption due to a damaged GI tract and iron loss from intestinal bleeding.

Chronic inflammation, a hallmark of IBD, affects iron transport and red blood cells. Inflammation increases hepcidin production in the liver. Hepcidin regulates iron absorption by inhibiting ferroportin, the protein responsible for transporting iron into circulation (9). Inflammatory cytokines can also decrease the production and half-life of red blood cells, further decreasing circulating iron levels (10, 11).

Studies from the U.S. and abroad show that up to 50 percent of IBD patients with iron-deficiency anemia did not receive iron supplements

Other less common causes of anemia in IBD patients include the following:

• B12 and folate deficiencies, from inadequate diet and/or insufficient absorption due to damaged intestines
• Copper deficiency, as copper facilitates iron deposition into cells
• Myelosuppression, or decreased bone marrow activity
• Side effect from drugs, like sulfasalazine and azathioprine

Diagnostic Criteria

The two main types of anemia in IBD are iron-deficiency anemia (IDA) and anemia of chronic disease (ACD). ACD is characterized by chronic inflammation present in IBD, autoimmune diseases, and cancer. However, because inflammation in IBD can influence iron availability, transport, and more, IDA and ACD have significant overlap, making diagnosis difficult. When testing IBD patients, be sure to obtain a full blood count including reticulocytes (12). Also, vitamin B12 and folate levels should be measured.

Generally, IDA will manifest as:

• Low hemoglobin (depends on sex, race, sea level, age)
• Tsf (transferrin saturation) below 20%
• Ferritin below 30 mcg/L when IBD is inactive, or below 100 mcg/L when inflammation signs are present
• Low MCH (mean corpuscular hemoglobin)
• Low CHr (reticulocyte hemoglobin content)

ACD can present with:

• Low hemoglobin (accurately reflecting sex, race, sea level, age)
• Tsf below 20%
• Normal or increased ferritin
• Normal or low MCV (mean corpuscular volume)
• Normal or low reticulocyte

Anemia Screenings Are Often Incomplete in IBD Patients

Despite high prevalence and risk of complications if left untreated, anemia is often poorly handled in IBD patients. In a survey of more than 600 patients, a third of those diagnosed with IBD-associated anemia had received no treatment (13). In 193 cases of anemia in IBD patients from another study, fewer than half had been treated for anemia in the previous six months (14). Anemia is more likely to be treated in severe cases, but it’s very likely that if caught earlier on, mild cases wouldn’t develop into severe ones.

A recent study from 2016 reported that over an eight-year follow-up, 70 percent of the 836 patients diagnosed with UC developed anemia (15). Within this subgroup, 31 percent were not tested for iron-deficiency anemia specifically. Of those who were diagnosed with iron-deficiency anemia, only 76 percent received iron replacement therapy. This means that almost a quarter of those who were deficient in iron were not being properly treated. And possibly many others were iron-deficient but were missed due to incomplete testing.

Unfortunately, this is not uncommon, both in the United States and abroad. In a prospective cohort study that examined lab values from patient records, only 70 percent of IBD-associated anemia cases demonstrated further follow-up to determine the type of anemia (16). Furthermore, fewer than half the patients who were diagnosed with iron-deficiency anemia actually received iron supplements.

Oral or Intravenous Iron Supplements for Iron-Deficiency Anemia?

With IBD-associated anemia, iron deficiency cannot be assumed, but it absolutely must be treated if confirmed. Currently, an iron IV is recommended over oral iron supplements because of the GI-associated side effects associated with oral iron supplements. IBD patients definitely do not need additional GI upsets! One patient survey study reported that two-thirds of patients were dissatisfied with oral iron treatments, while more than 70 percent were satisfied with iron IV (17).

Oral iron supplements can inflict mucosal harm (18) and alter the gut microbiota, at least in an animal model (19).

However, I generally do prefer starting with an oral iron supplement. The heme varieties, like Proferrin ES, are derived from animal products and are less likely to cause GI issues, in my experience. In milder cases of iron deficiency, iron-rich foods like liver and clams are also good choices.

Once iron supplements are started, patients should be monitored every three months for at least a year, and every six to 12 months thereafter, to ensure replete status. Oral iron supplements may not be adequate if the intestines are inflamed to the point of inhibiting iron absorption. In these cases, an IV may be necessary.

Other Support for IBD

Conventional treatment for IBD usually involves steroids to suppress immune function and antibiotics to tame the gut during active flare-ups. A Functional Medicine approach to IBD focuses on the same two cornerstones: gut health and immune function. But instead of suppressing them, my strategies below aim to optimize both:

Remove trigger foods. Up to 65 percent of IBD patients have self-reported food sensitivities (20). Gluten is a common trigger in IBD patients, possibly because it increases gut permeability by modifying tight junctions in the epithelium. A 30-day Paleo Reset, as I outline in The Paleo Cure, can help identify trigger foods if they are currently unknown.

Increase intake of nutrients that promote optimal immune function:

• Glutathione
• Selenium
• Zinc
• Vitamin D
• Vitamin A
• EPA/DHA

Increase intake of foods that support healthy gut microbiota:

• Probiotics – Repopulate the gut with beneficial bacteria from fermented foods and/or probiotic supplements.
• Prebiotics – Maintain the gut flora with the proper fuel from resistant starch, like that found in cooked and cooled potatoes.

Consider the autoimmune protocol (AIP) diet. The AIP diet eschews grains, dairy, refined seed oil, and refined sugar, and, initially, eggs, nightshades, coffee, alcohol, nuts, and seeds. In a remarkable recent study led by a gastroenterologist, 16 patients with IBD adopted the AIP diet (21). In just six weeks, 11 of the 16 went into remission, and four of the participants were able to discontinue all of their prescribed medications. The power of food cannot be overstated.

Low-dose naltrexone (LDN). At a dose an order of magnitude lower than what is prescribed for opiate addiction, LDN (around 2 to 4 mg/day) has shown promising results when administered to people with multiple sclerosis, fibromyalgia, and other immune system-related conditions (22, 23). LDN acts through two routes: regulating the immune system and reducing inflammation.