Why Crohn's Disease Is More Likely to Cause Anaemia Than Ulcerative Colitis: What a 2026 Systematic Review Found

Fatigue is one of the most commonly reported symptoms among people living with inflammatory bowel disease, and one of the most frequently overlooked. It is easy to assume tiredness is simply the body responding to chronic illness. But in many cases, there is a specific and treatable cause sitting quietly in the background: anaemia.

What is less widely known is that people with Crohn's disease appear to be substantially more likely to develop anaemia than people with ulcerative colitis, even when the level of disease activity is similar. A 2026 systematic review has taken a closer look at why that difference exists, tracing it back to the distinct ways the two conditions affect the gut and the body's ability to absorb essential nutrients.

The Research

Published in the International Journal of Molecular Sciences, the review by Tesoi DF and colleagues systematically examined the molecular and physiological mechanisms underlying the higher prevalence of anaemia in Crohn's disease compared with ulcerative colitis (Tesoi DF et al., International Journal of Molecular Sciences, 2026 Jun 20). The aim was to understand why the difference exists, because the mechanism determines how the anaemia should be investigated and, critically, how it should be treated.

Why the Location of Disease Matters

The key to understanding the anaemia difference lies in where each condition operates in the digestive tract.

Ulcerative colitis is confined to the large intestine, the colon and rectum. Crohn's disease, by contrast, can affect any part of the digestive tract from mouth to anus, but it most commonly involves the small intestine, and particularly the terminal ileum, the final section of the small bowel.

That distinction matters enormously for anaemia, because the small intestine is where most nutrient absorption takes place.

The Mechanisms That Drive Higher Anaemia in Crohn's Disease

The review identified several overlapping mechanisms that help explain why Crohn's disease is associated with higher rates of anaemia:

Impaired iron absorption. Iron is primarily absorbed in the duodenum and upper small intestine, areas that are frequently inflamed in Crohn's disease. Ongoing inflammation damages the absorptive surface and suppresses the proteins responsible for iron uptake, meaning that even when dietary iron intake is adequate, the gut cannot take it up efficiently. In ulcerative colitis, the duodenum and small bowel are generally unaffected, so this particular route of malabsorption is less common.

Vitamin B12 deficiency. Vitamin B12 can only be absorbed in the terminal ileum, the very section of bowel that Crohn's disease most commonly targets. Active inflammation, strictures (narrowings), surgical resections, or bacterial overgrowth in this area can all impair B12 absorption, leading to a type of anaemia (megaloblastic anaemia) that does not respond to iron supplementation because it has an entirely different cause.

Folate deficiency. Folate is absorbed throughout the small intestine, so Crohn's disease affecting the jejunum or ileum can reduce folate uptake. Some medications used to treat Crohn's disease, notably methotrexate and sulfasalazine, also interfere with folate metabolism, adding a treatment-related layer to the deficiency risk.

Chronic blood loss. Both Crohn's disease and ulcerative colitis can cause intestinal bleeding, but the pattern differs in important ways. In ulcerative colitis, visible rectal bleeding is common and usually prompts investigation. In Crohn's disease, bleeding may be slow and occult, occurring further up the bowel and going unnoticed, quietly depleting iron stores over months or years.

Systemic inflammation and hepcidin. In active IBD of either type, the immune system releases inflammatory cytokines that trigger the liver to produce hepcidin, a hormone that blocks the release of stored iron and reduces iron absorption from food. This produces what is known as anaemia of chronic disease, a type in which iron is present in the body but functionally unavailable to make red blood cells. Crohn's disease often involves a higher systemic inflammatory burden due to its transmural nature, meaning the inflammation goes through the full thickness of the gut wall, which may amplify this mechanism.

Structural complications. Crohn's disease can form strictures, fistulas (abnormal connections between different sections of the bowel), and abscesses, complications that alter the gut environment, promote bacterial overgrowth, and further impair nutrient absorption over time. These complications are not a feature of ulcerative colitis.

What This Means in Practice

Anaemia in Crohn's disease is often multifactorial, meaning several of these mechanisms may be operating simultaneously. A low haemoglobin reading alone does not tell you which type of anaemia is present. Distinguishing between iron-deficiency anaemia, B12-deficiency anaemia, folate-deficiency anaemia, and anaemia of chronic disease requires a blood panel that goes beyond a standard full blood count, typically including serum ferritin, transferrin saturation, serum B12, and serum folate levels.

Treatment depends entirely on the type found. Iron-deficiency anaemia in Crohn's disease is often managed with intravenous iron rather than oral supplements, because oral iron is poorly absorbed in an inflamed small bowel and can worsen gut symptoms. B12 deficiency usually requires intramuscular injections rather than oral tablets, particularly if the terminal ileum is damaged or surgically removed. Folate deficiency responds to supplementation. Anaemia of chronic disease typically improves as IBD inflammation is brought under better control.

The NHS notes that nutritional deficiencies, including anaemia, are recognised features of inflammatory bowel disease that should be monitored and managed as part of routine IBD care (NHS: Inflammatory Bowel Disease, NHS.UK).

If You Are Experiencing Persistent Fatigue

Fatigue that does not improve with rest, or that comes alongside pallor, breathlessness, difficulty concentrating, or heart palpitations, may be a sign of anaemia. These symptoms are worth raising with your IBD care team or GP, not because they are an emergency in most cases, but because they are treatable once the cause is identified.

Anaemia in Crohn's disease is common, frequently underdiagnosed, and very manageable when caught and properly typed. A targeted blood test is the first step.