Fatigue is one of the most crippling symptoms in people with Inflammatory Bowel Disease (IBD).

Yet, it remains consistently under-recognized, under-treated, and, frankly, underestimated by the healthcare system.

It affects up to 50% of people living with IBD — often more disabling than abdominal pain or diarrhea.

Fatigue is not just "feeling tired."

It is a deep, relentless exhaustion that doesn't improve with rest and cuts into every part of life.

Let’s break down what the science actually says about this neglected symptom.

Fatigue in IBD isn’t caused by just one thing.

It is the result of multiple, overlapping problems happening at the same time:

• Active inflammation
   
• Anemia
   
• Micronutrient deficiencies
   
• Medication side effects
   
• Disruption of the gut–brain axis
   
• Sleep disturbances
   
• Psychological distress
   

Ignoring any of these factors means missing the full picture.

The connection between inflammation and fatigue is not speculative — it’s scientifically grounded.

Elevated inflammatory markers like TNFα and IFNγ stimulate the hypothalamic–pituitary–adrenal (HPA) axis.

This triggers cortisol dysregulation and systemic exhaustion.

Studies show that when disease activity is high, fatigue soars.

And when patients achieve deep remission — meaning clinical and endoscopic remission — fatigue significantly drops.

Anemia is rampant in IBD.

Up to 68% of hospitalized patients and 20% of outpatients are affected.

The most common causes are:

• Iron deficiency anemia from chronic blood loss
   
• Vitamin B12 and folate deficiencies from malabsorption or surgeries
   
• Anemia of chronic disease due to ongoing inflammation
   

Anemia is a powerful, correctable driver of fatigue — yet it often slips through the cracks during routine care.

While medications can help to control IBD, they can sometimes worsen fatigue.

Immunomodulators (like azathioprine and methotrexate), biologics (infliximab, vedolizumab), steroids, narcotics, and antidepressants all have fatigue listed among potential side effects.

In some cases, withdrawing or switching medication dramatically improves energy levels.

The gut–brain axis is real, and so is its impact on fatigue.

Dysbiosis — an imbalanced gut microbiome — contributes to systemic inflammation, disrupts the blood–brain barrier, and fuels the sensation of fatigue.

Specific patterns have been identified:

• Loss of beneficial bacteria like Faecalibacterium prausnitzii
   
• Increase in pathobionts like Escherichia coli
   

Despite this knowledge, targeted microbial therapies for fatigue in IBD are still lacking.

Sleep disturbance is not a side story in IBD.

It is a central piece of the puzzle.

Studies consistently show that poor sleep — even in patients with clinically inactive disease — correlates strongly with fatigue, inflammation, and risk of relapse.

This is not about simply "feeling a bit tired."

Sleep deprivation activates pro-inflammatory pathways, increases CRP and IL-6, and worsens immune regulation.

Poor sleep alone can tip someone from remission back into active disease.

Anxiety, depression, and chronic stress are deeply intertwined with fatigue in IBD.

Fatigue persists even in deep remission when psychological health is neglected.

This is a biological reality, not just a "mind over matter" issue.

Neuroinflammation and HPA axis dysfunction underlie this connection.

When no cause can be identified despite exhaustive evaluation, fatigue may need to be seen for what it is:
An extraintestinal manifestation of IBD itself.

Not everything will show up on a blood test, a colonoscopy, or an MRI.

Fatigue, like joint pain, skin disease, and eye inflammation, can exist because of IBD — not despite it.

Recognizing this is crucial for both clinicians and patients.

Fatigue in IBD is real, biological, multifactorial, and devastating.

Why does this happen?

Well it's no coincidence that fatigue and mitochondrial dysfunction co-exist, because these organelles are responsible for producing our energy, in the form of ATP and the deuterium-depleted water that they produce, that forms our water battery. 

Take care of your mitochondria and you might just find that the fatigue resolves! 

Nocerino, A., Nguyen, A., Agrawal, M., Mone, A., Lakhani, K., & Swaminath, A. (2020). Fatigue in Inflammatory Bowel Diseases: Etiologies and Management. Advances in Therapy, 37, 97–112. https://doi.org/10.1007/s12325-019-01138-5