Download Micronutrient deficiencies in Inflammatory Bowel Disease (IBD)

Micronutrient deficiencies in Inflammatory Bowel Disease (IBD)
Overview:
Inflammatory bowel disease (IBD) is an idiopathic disease characterized by dysregulated immune
response to commensal intestinal microflora. 1 Two types of IBD are ulcerative colitis, inflammation of
colon, and Crohn’s disease, inflammation of one or more sections of the gastrointestinal tract. 2
Malnutrition in IBD patients can be divided into protein-energy malnutrition and micronutrient
deficiency. 3 Although micronutrient deficiencies are caused by multiple mechanisms the four key
causes are:
a) Reduced food intake: A study of IBD patients in remission found avoidance of major food
groups - ⅓ avoided grains, ⅓ avoided dairy, 18% avoided vegetables and 11% avoided
fruits. 4 IBD cohorts have been reported to have inadequate intake of iron, Vitamin D, Vitamin
C and calcium, folate, Vitamin B1 and B6, beta-carotene, Vitamin K, and Vitamin E. 5,6
b) Enteric loss of nutrients: Chronic diarrhea and fistula leads to wasting of zinc, potassium and
calcium while gastrointestinal bleeding might cause iron deficiency. 7,8
c) Malabsorption: Inflammation and resection of the small bowel >40-60 cm can lead to Vitamin
B 12 deficiency and bile-salt wasting leading to impaired fat soluble vitamin absorption. 9
d) Drug interaction: Medications used by IBD patients can interfere with nutrient absorption. For
example, sulfasalazine is a folate antagonists, cholestyramine impairs absorption of fat
soluble vitamins, and glucocorticoids might impair absorption of calcium, phosphorus and
zinc and alter metabolism of calcium and Vitamin D. While parenteral nutrition can also lead
to deficiencies of micronutrients not included in sufficient quantity. 10
e) Other causes include - anorexia secondary to inflammation, steatorrhea which leads to
malabsorption of fat soluble vitamins and divalent cations and hypermetabolic state which
alters the resting energy expenditure. 11
1
Podolsky, Daniel K. Inflammatory bowel disease. New England Journal of Medicine 325.14 (1991): 10081016.
2
http://www.crohnscolitisfoundation.org/assets/pdfs/updatedibdfactbook.pdf accessed Feburary 27, 2017
3
Harries, A. D., and R. V. Heatley. Nutritional disturbances in Crohn's disease. Postgraduate medical journal
59.697 (1983): 690-697.
4
Guerreiro, Catarina Sousa, et al. A comprehensive approach to evaluate nutritional status in Crohn's patients
in the era of biologic therapy: a case-control study. The American journal of gastroenterology 102.11 (2007):
2551-2556.
5
Filippi, Jérôme, et al. Nutritional deficiencies in patients with Crohn's disease in remission. Inflammatory
bowel diseases 12.3 (2006): 185-191.
6
Vidarsdottir, Jona B., et al. A cross-sectional study on nutrient intake and-status in inflammatory bowel
disease patients. Nutrition journal 15.1 (2016): 61.
7
Harries, A. D., and R. V. Heatley. Nutritional disturbances in Crohn's disease. Postgraduate medical journal
59.697 (1983): 690-697.
8
Weiss, Günter, and Christoph Gasche. Pathogenesis and treatment of anemia in inflammatory bowel
disease. (2010): 175-178.
9
Duerksen, Donald R., Glen Fallows, and Charles N. Bernstein. Vitamin B12 malabsorption in patients with
limited ileal resection. Nutrition 22.11 (2006): 1210-1213.
10
Irving, Peter M., Fergus Shanahan, and David S. Rampton. Drug interactions in inflammatory bowel
disease. The American journal of gastroenterology 103.1 (2008): 207-219.
11
Hartman, Corina, Rami Eliakim, and Raanan Shamir. Nutritional status and nutritional therapy in
inflammatory bowel diseases. World J Gastroenterol 15.21 (2009): 2570-2578.
Here is a summary of common micronutrient deficiencies in IBD patients:
Micronutrients
Site of Absorption
Prevalence of deficiencies
based on serum levels
Thiamine (B 1 )
Jejunum/ileum
32% 5
Niacin (B 3 )
Jejunum
77% 5
Folate
Jejunum/ileum
19 % 5
B6
Jejunum
B 12
Terminal ileum
18.4% 12
C
Jejunum/ileum
84% 5
A
Ileum
23.4% 12
D
Ileum
17.6% 12
E
Ileum
Water Soluble Vitamins
29%
12
Fat Soluble Vitamins
16%
13
Macrominerals
Calcium
Duodenum/ Jejunum
80-86% 5
Iron
Duodenum
39.2% 12
Zinc
Jejunum
15.2% 12
Copper
Duodenum
84% 5
Microminerals
Selenium
Ileum
82% 5
Anemia:
The most common complication of IBD is anemia which is associated with impaired quality of life.
Although there is guidelines on how to care for anemia in patients with IBD, there are gaps in clinical
12
Vagianos, Kathy, et al. Nutrition assessment of patients with inflammatory bowel disease. Journal of
Parenteral and Enteral Nutrition 31.4 (2007): 311-319.
13
Guerreiro, Catarina Sousa, et al. A comprehensive approach to evaluate nutritional status in Crohn's
patients in the era of biologic therapy: a case-control study. The American journal of gastroenterology 102.11
(2007): 2551-2556.
practice. 14 The leading cause of anemia in IBD patients is iron deficiency. Iron deficiency is caused
predominantly by impaired metabolism. There is increased retention of iron in enterocytes,
macrophages and monocytes due to pro-inflammatory cytokines stimulated upregulation of hepcidin,
a regulator of iron homeostasis. Reduced circulating iron levels decreases plasma ferritin levels, an
indicator of iron status. However, ferritin is an acute phase reactant, whose levels are elevated in
inflammation, making the diagnosis of iron deficiency in IBD patients challenging. Per the guidelines
for diagnosis and treatment of iron deficiency anemia in IBD patients,c-reactive protein (CRP) levels
should also be considered. 15 The guidelines state that the goal of iron supplementation should be
achieve ferritin >100 mcg/L, hemoglobin (12g/dL in women and 13 g/dL in men) and transferrin
saturation (16-50%).15
Folate deficiency causes macrocytic megaloblastic anemia. Without folate intake of 400- 1000
mcg/day, folic acid stores are readily depleted. 16 In IBD patients, there are no clear guidelines for
screening for folate deficiency, although measuring serum and RBC folate levels is indicated.
Vitamin B 12 deficiency is also associated with megaloblastic anemia. Evaluating Vitamin B 12 status
is indicated for patients with macrocytic anemia or anemia not corrected by iron. If serum Vitamin
B 12 levels are normal then levels of Vitamin B 12 metabolites, methylmalonic acid and homocysteine,
should be checked as these metabolites are more sensitive markers of B 12 deficiency than serum
B 12 levels. 17
Bone Metabolism:
Bone disease, osteopenia and osteoporosis, occur in 22- 77% and 17- 41% of IBD patients,
respectively. 18 Although malnutrition and malabsorption plays an important in pathogenesis of bone
disease, other risk factors include inflammation, corticosteroid use, and reduced physical activity.18
Calcium supplementation at doses of 1000–1500 mg/day (1000 mg for women age 25 until
menopause and men <65 years old; 1300 mg for women between 18–25 years; 1500 mg for
postmenopausal women, and men >65 years old), is recommended in IBD patients. 19 In bone
metabolism, calcium works in concert with Vitamin D thus, Vitamin D status should be measured
and monitored in all IBD patients. If a patient is Vitamin D deficient (<15 ng/mL) various regimens
can be employed. Supplementation with 6000 IU/day till serum 25-OHD levels of >30 ng/mL are
achieved followed by a maintenance dose of 1500-2000 IU/day is recommended. However, for
obese patients or patients on glucocorticosteroids, Vitamin D dose should be two -three times
greater than the recommended amount for their age group. 20
14
Hou, Jason K., et al. Assessment of Gaps in Care and the Development of a Care Pathway for Anemia in
Patients with Inflammatory Bowel Diseases. Inflammatory Bowel Diseases 23.1 (2017): 35-43.
15
Gasche, Christoph, et al. Guidelines on the diagnosis and management of iron deficiency and anemia in
inflammatory bowel diseases. Inflammatory bowel diseases 13.12 (2007): 1545-1553.
16
https://www.ncbi.nlm.nih.gov/books/NBK114318/ accessed on February 27, 2017.
17
Savage, David G., et al. "Sensitivity of serum methylmalonic acid and total homocysteine determinations for
diagnosing cobalamin and folate deficiencies." The American journal of medicine 96.3 (1994): 239-246.
18
Ali, Tauseef, et al. "Osteoporosis in inflammatory bowel disease." The American journal of medicine 122.7
(2009): 599-604.
19
British Society of Gastroenterology, N. R. Lewis, and Brian B. Scott. Guidelines for osteoporosis in
inflammatory bowel disease and coeliac disease. British Society of Gastroenterology, 2008.
20
Holick, Michael F., et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society
clinical practice guideline.The Journal of Clinical Endocrinology & Metabolism 96.7 (2011): 1911-1930.
Hyperhomocysteinemia:
The prevalence of hyperhomocysteinemia is higher in patients with IBD. 21 Hyperhomocysteinemia is
a risk factor for venous thrombosis and other atherosclerotic cardiovascular diseases. Folate status
is the strongest determinant of homocysteine levels along with Vitamin B 6 and Vitamin B 12 . Once
folate and Vitamin B 12 deficiencies are addressed, serum pyridoxal phosphate levels should be
evaluated to ascertain Vitamin B 6 deficiency. Homocysteine levels can be lowered by 7.6 - 51.7%
with folic acid, Vitamin B 12 and Vitamin B 6 supplementation in healthy subjects. The effect of Vitamin
B supplementation has not been studied in IBD patients. 22
Wound healing:
Wound healing is important for IBD patients. Micronutrients - Vitamin A, Vitamin C, and zinc play an
important role in wound healing. To support wound healing in patients on corticosteroids 10,00015,000 IU/day of Vitamin A is recommended. 23 For patients with Vitamin C deficiency,
supplementation at 100- 200 mg/d is recommended for acute wound healing. Also, 40 mg of
elemental zinc (176 mg of zinc sulfate) for 10 days is recommended to enhance wound healing for
patients with zinc deficiency. 24
Conclusion:
Micronutrient deficiencies are common in IBD and its’ mechanism is multifactorial. There are no
guidelines for micronutrient deficiencies assessment in patients with IBD. Micronutrient deficiencies
are associated with complications. Anemia in IBD patients is precipitated due to iron deficiency
caused by inadequate intake, impaired absorption and utilization, and chronic gastrointestinal
bleeding; folate deficiency due to medication interaction, inadequate intake, and malabsorption; and
Vitamin B12 deficiency due to ileal resection or ileocolonic resection. Altered bone metabolism due
to calcium deficiency caused by inadequate intake, diarrhea, and malabsorption and Vitamin D
deficiency due to insufficient intake, small bowel resection or steatorrhea. IBD patients have
hyperhomocysteinemia due to Vitamin B12, Vitamin B6 and folic acid deficiencies. It is highly
recommended to determine micronutrient status in IBD patients on certain medications, long term
total parenteral nutrition, diarrhea, and fistula or non-healing wounds and provide them with
adequate micronutrient supplementation for repletion and maintenance of their micronutrient and
overall health status.