Nutrition in Crohn’s Disease

• Sources:
  • Donnellan CF, Yann LH, Lal S. Nutritional management of Crohn’s disease. Therap Adv Gastroenterol. 2013 May; 6(3): 231–242.
  • Hwang C, Ross V, Mahadevan U. Micronutrient deficiencies in inflammatory bowel disease: from A to zinc. Inflamm Bowel Dis. 2012 Oct;18(10):1961-81.

Protein energy malnutrition

• Contributing factors include:
  • Poor oral intake
  • Malabsorption due to active disease
  • Malabsorption following surgery
  • Hypercatabolism due to active inflammation
  • Side effects from treatment

Micronutrient deficiency

• Multiple simultaneous deficiencies in micronutrients more common in Crohns, esp. if:
  • Fistulas
  • Strictures
  • Prior small bowel resections
• 95% of vitamins and minerals are absorbed in proximal small bowel, usually by mid-jejunum except B12, which, bound to intrinsic factor, is absorbed in the terminal ileum
• Distal ileum absorbs bile acids, which are critical for absorption of fat and fat-soluble vitamins

Pathogenesis of Micronutrient Deficiency in IBD

• Decreased food intake
  • Anorexia (due to cytokines, e.g. IL-1, IL-6, TNF-alpha)
  • Mechanical (fistulas, post-op)
  • Avoidance of high-residue food (as it can worsen pain/diarrhoea)
  • Avoidance of lactose-containing foods (high rates of concomitant lactose intolerance)
• Increased intestinal loss
  • Diarrhoea (increased loss of Zn2+, K+, Mg2+)
  • Fistula disease
  • Occult/overt blood loss (Fe deficiency)
  • Exudative enteropathy (protein loss, decrease in albumin-binding proteins, e.g. Vit D binding protein)
• Malabsorption
  • Loss of intestinal surface area from active inflammation, resection, bypass or fistula
  • Terminal ileal disease associated with deficiencies in B12 and fat-soluble vitamins
  • PSC can lead to biliary strictures of the main branches of the biliary tract which could lead to bile-salt insufficiency and impaired absorption of fat-soluble vitamins
• Hypermetabolic state
  • Alterations of resting energy expenditure
• Drug interactions
  • Sulfasalazine and Methotrexate inhibit Folate absorption
  • Glucocorticoids impair Ca2+, Zn, and Phosphorus absorption
  • Glucocorticoids causes Vitamin C loss and Vitamin D resistance
  • Cholestyramine impairs absorption of fat- soluble vitamins, Vit B12 and Iron
• Long-term TPN
  • Can occur with any micronutrient not added to TPN

Iron Deficiency

• Most common extra-intestinal manifestation of IBD
• Due to:
  • Inadequate oral intake, e.g. avoidance of green leafy vegetables and/or vegetarian diets
  • Chronic GI blood loss
  • Impaired absorption and utilization
    • Normal iron absorption occurs in duodenum and proximal jejunum
  • Pro-inflammatory stimuli, e.g. lipopolysaccharide, IL-6, TNF-alpha, cause upregulation of hepcidin that blocks iron from being exported from enterocytes into the blood stream and causes iron retention in macrophages and monocytes

Folate (Vit B9) Deficiency

• Inadequate dietary intake – likely the most important cause
• Malabsorption
• Medication interactions – both sulfasalazine and methotrexate cause folate deficiency as both are inhibitors of dihydrofolate reductase and cellular uptake of folate

Vitamin B12 (cobalamin) Deficiency

• Usual absorption process complicated:
  • Dietary cobalamin cleaved from R-factor by pancreatic proteases
  • Bind to intrinsic factor produced in the stomach
  • IF-cobalamin compound travels to ileum where it binds to a specific receptor and is then absorbed through the distal ileal mucosa Thus, abnormality anywhere along pathway can lead to deficiency
• Deficiency is thought to occur in all patients after resection of > 60cm of terminal ileum
• British Society of Gastroenterology guidelines: give B12 replacement in all patients with ileal resections > 20 cm and yearly B12 measurements if < 20cm

Calcium Deficiency

• Usual absorption:
  • Primarily in duodenum and proximal jejunum
• Two mechanisms – paracellular route which largely depends on dietary intake and luminal calcium concentration AND active intra-cellular route via calcium channels – transcription of these channels depend on 1,25-Vit D
• Calcium is secreted in the distal jejunum and ileum as well as in colon
• Intestinal losses likely aggravated by diarrhoea and malabsorption
• Deficiency due to:
  • Malabsorption secondary to magnesium deficiency (from diarrhoea)
  • Malabsorption due to glucocorticoids
  • Inadequate oral intake – avoidance of milk and dairy products common due to high rates of concomitant lactose intolerance

Vitamin D Deficiency

• Usual absorption:
  • Occurs mainly in jejunum and requires presence of bile acids for emulsification prior to binding to plasma vitamin D- binding protein
• Deficiency due to:
  • Significant small bowel resection (> 2- 3m)
  • Steatorrhoea
  • Protein-losing enteropathy
  • Systemic inflammation
  • Glucocorticoids (causes Vit D resistance)

Magnesium Deficiency

• Due to:
  • Inadequate oral intake
  • Losses from chronic diarrhoea
  • Losses from fistula output
  • Malabsorption
• Contributing factors include:
  • Poor oral intake of dietary vitamins and micronutrients
  • Underlying causes: loss of appetite, hunger, and depressed mood