In: Vitamin B: New Research ISBN 978-1-60021-782-1

Editor: Charlyn M. Elliot, pp. 57-80 © 2008 Nova Science Publishers, Inc.

Chapter IV

NUTRITIONAL ISSUES IN

INFLAMMATORY BOWEL DISEASE: FOCUS ON

THE VITAMIN B COMPLEX DEFICIENCIES AND

THEIR CLINICAL IMPACT

Petros Zezos1,∗ and Georgios Kouklakis2

1

Gastroenterology & Hepatology Department, Military General Hospital of

Alexandroupolis, Alexandroupolis, Greece;

2

Endoscopy Unit, University General Hospital of Alexandroupolis, Democritus

University of Thrace, Alexandroupolis, Greece.

ABSTRACT

Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory

condition of unknown cause, which manifests with two major forms: as Crohn’s disease

(CD), affecting any part of the gastrointestinal tract and as ulcerative colitis (UC),

affecting the colon. Medical management with aminosalicylates (5-ASA), steroids, and

immunomodulating or immunosuppressive agents is the mainstay of therapy for most

IBD patients. Surgery is reserved for patients with severe disease refractory to medical

management or for patients with complications.

Nutrition plays an important role in pathogenesis, management and treatment of

IBD. Malnutrition is a common problem in patients with IBD, especially in those

suffering from Crohn’s disease (CD). A wide array of vitamin and mineral deficiencies

has been described in patients with IBD. Nutritional abnormalities are often overlooked

in the management of IBD patients, despite their pathogenic role in clinical

manifestations and complications of IBD. The causes of malnutrition in IBD are

multiple, including decreased oral nutrient intake, malabsorption, excessive nutrient

losses, increased nutrient requirements, and iatrogenic due to surgery or medications.

∗

 Correspondence concerning this article should be addressed to: Petros Zezos, MD, 40 Venizelou Str., 68100

Alexandroupolis, Greece. Tel.: +30-25510-84166; Fax: +30-25510-84168; Email: zezosp@hol.gr.

58 Petros Zezos and Georgios Kouklakis

Thiamin (B1), riboflavin (B2), niacin, pyridoxine (B6), pantothenic acid, biotin, folic

acid (B9) and vitamin B12 are referred to as members of the “vitamin B complex”. These

are water-soluble factors, playing an essential role in the metabolic processes of living

cells, functioning as coenzymes or as prosthetic groups bound to apoenzymes. These

vitamins are closely interrelated and impaired intake of one may impair the utilization of

others.

Folate and vitamin B12 deficiencies are frequently described in IBD patients and are

implicated in anemia, thrombophilia and carcinogenesis associated with IBD. Low serum

concentrations of other members of the “vitamin B complex” have also been described in

IBD patients, producing the syndromes due to their deficiency.

This article focuses on the recent research for the aetiology, the clinical

consequences and the management of the vitamin B complex deficiencies in patients with

inflammatory bowel disease.

Keywords: Aetiology; Crohn’s disease; complications; inflammatory bowel disease; therapy;

ulcerative colitis; vitamin B complex.

INTRODUCTION

Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory

process, which manifests with two major forms: as Crohn’s disease (CD), affecting any part

of the gastrointestinal tract and as ulcerative colitis (UC), affecting the colon. The aetiology

and pathogenesis of IBD are still unclear. Medical management with aminosalicylates (5-

ASA), steroids, and immunomodulating or immuno-suppressive agents is the mainstay of

therapy for most IBD patients, while surgery is reserved for patients with severe disease

refractory to medical management or for patients with disease complications.

Nutrition plays an important role in IBD pathogenesis, management and treatment. The

epidemiological observation that populations with different dietary habits may have different

incidences of IBD suggests that some nutrients may play a pathogenic role in the disease

process. On the other hand, malnutrition is a common problem in patients with established

IBD, especially in those suffering from Crohn’s disease (CD). Besides protein-energy

malnutrition, a wide array of vitamin and mineral deficiencies has been described in patients

with IBD. Nutritional abnormalities are often overlooked in the management of IBD patients,

despite their impact in clinical manifestations and complications of IBD. Finally, nutritional

therapy in IBD can be considered in two ways, as supportive and as primary treatment.

Supportive nutritional therapy aims to correct malnutrition and its metabolic consequences,

while nutritional primary therapy (in the form of enteral diet) may be effective in specific

subgroups of patients with Crohn’s disease, especially in children with poor nutritional status

or growth impairment.

Thiamin (B1), riboflavin (B2), niacin (nicotinic acid), pyridoxine (B6), pantothenic acid,

biotin, folic acid (B9) and vitamin B12 are referred to as members of the “vitamin B complex”.

These are water-soluble factors, playing an essential role in the metabolic processes of living

cells, functioning as coenzymes or as prosthetic groups bound to apoenzymes. These vitamins

are closely interrelated and impaired intake of one may impair the utilization of others.

Nutritional Issues in Inflammatory Bowel Disease… 59

This article focuses on the recent research for the aetiopathogenesis, the clinical

consequences and the management of the vitamin B complex deficiencies in patients with

inflammatory bowel disease.

1. Vitamin B Complex and the Aetiopathogenesis of IBD

The aetiopathogenesis of IBD is poorly understood. The role of genetic factors in IBD

pathogenesis is well established in previous studies and much progress has been achieved in

recent research to identify susceptibility genes for IBD. However, the geographic variation of

IBD incidence and the rising incidence of IBD in developed countries, while the genetic

background remained stable, indicates that environmental factors also play an important role

in IBD pathogenesis. The interaction between environmental factors (bacteria, viruses and

antigens) and predisposing genes results in chronic inflammatory process and tissue injury

mediated by the immune and non-immune cellular systems in the gut microenvironment

[1,2]. In addition, many epidemiological studies have revealed possibly important

associations between dietary factors and IBD, but there is still no conclusive evidence about

the role of specific dietary components in IBD pathogenesis [3]. Low fiber and fruit, high

sugar, high animal fat westernized diets have been proposed as risk factors for the

development of IBD [4].

There is limited data about of the role of “vitamin B complex” members in IBD

pathogenesis. In a recent study, Geerling et al. found that high intakes of vitamin B6 and fat

(mono- and polyunsaturated) may enhance the risk of developing ulcerative colitis [5]. The

authors could not explain the mechanisms responsible for the increased risk for UC with high

consumption of vitamin B6 and stated that they are uncertain whether this observation reflects

a true causal relationship or rather a certain dietary lifestyle in UC patients.

2. Malnutrition in IBD: Vitamin B Complex Deficiencies in IBD Patients

Malnutrition is a common feature in IBD patients with active disease, but is also

observed in patients with disease in remission. Nutrient deficiencies are more frequent in

Crohn’s disease of the small bowel compared to UC or Crohn’s disease limited to the colon.

Weight loss occurs in approximately 65-75% of CD patients [6] and 20-60% of UC patients

[6-9]. Besides weight loss, deficiencies in macronutrients and micronutrients may develop in

IBD patients during the disease course (Table 1). Patients with CD develop malnutrition

slowly and may present with multiple severe nutritional deficiencies, whereas patients with

UC are often well nourished, and develop acute nutritional deficiencies rapidly during acute

flare-ups of the disease [10].

Multiple factors are involved in the development of malnutrition and include poor dietary

intake, impaired nutrient digestion and absorption, increased nutrient requirements and

iatrogenic complications or drug effects (Table 2). In most patients, more than one factor is

responsible for the malnutrition. Decreased oral intake is one of the most important factors

for malnutrition development in IBD patients. The decreased intake can be due to a

60 Petros Zezos and Georgios Kouklakis

combination of anorexia, abdominal pain, nausea, vomiting, or dietary restrictions, either

iatrogenic or self-imposed. In Crohn’s disease, extensive inflammation or resection of the

small bowel is another important cause of malnutrition due to malabsorption. Moreover, in

CD patients bypassed loops of bowel, coloenteric fistulas and strictures may result in

bacterial overgrowth and malabsorption. Finally, drugs used in IBD patients may inhibit the

absorption of specific nutrients. Sulfasalazine decreases folate absorption and corticosteroids

inhibit calcium absorption.

Table 1. Prevalence of nutritional deficiencies in inflammatory bowel disease

 Prevalence (%)

Deficiency Crohn’s disease Ulcerative colitis

Weight loss 65-75 18-62

Hypoalbuminemia 25-80 25-50

Intestinal protein loss 75 R

Negative nitrogen balance 69 R

Anemia

 Iron deficiency

 Folic acid deficiency

 Vitamin B12 deficiency

25-85

39

67

48

66

81

30-40

5

Calcium deficiency 13 R

Magnesium deficiency 14-33 R

Potassium deficiency 5-20 R

Vitamin A deficiency 11 NR

Vitamin K deficiency R NR

Vitamin C deficiency R NR

Vitamin D deficiency 75 35

Zinc deficiency 50 R

Selenium deficiency 35-40 NR

R= reported but prevalence not described; NR= not reported

(Adapted from Dieleman LA, Heizer WD. Nutritional issues in inflammatory bowel disease.

Gastroenterol Clin North Am 1998;27:435-451 and Han PD, Burke A, Baldassano RN, Rombeau JL,

Lichtenstein GR. Nutrition and inflammatory bowel disease. Gastroenterol Clin North Am

1999;28:423-443)

Several vitamin deficiencies have been reported in IBD patients. With regard to watersoluble B vitamins, the vast majority of data refer to folate and B12, while there are a few

studies that have investigated the serum concentrations of thiamin (B1), riboflavin (B2),

niacin, biotin, pantothenic acid and pyridoxine (B6) in IBD patients.

Fernandes-Banares et al. evaluated the status of water-soluble and fat-soluble vitamins in

23 IBD patients with active disease and found that, among other nutrients, biotin, riboflavin,

folate, vitamin B1 and vitamin B12 serum levels were decreased in IBD patients compared to

89 healthy subjects. Although some patients had extremely low vitamin values, in no case

were clinical symptoms or syndromes due to the vitamin deficiency observed [11].

Nutritional Issues in Inflammatory Bowel Disease… 61

In another study, Kuroki et al. investigated the status of various vitamins in 24 patients

with Crohn’s disease. They found that vitamin B1, vitamin B2, and folate levels were

decreased in CD patients compared to control subjects. They also found that vitamin B2 and

niacin levels showed a negative correlation with disease severity [12].

Table 2. Causes of malnutrition in inflammatory bowel disease

1. Decreased nutrient intake

 Anorexia

 Altered taste

 Intake-associated pain or discomfort

 Iatrogenic dietary restrictions

2. Malabsorption

 Mucosal abnormalities

 Diminished absorptive surface

 Surgery

 Extensive disease

 Bacterial overgrowth

3. Excessive losses

 Protein-losing enteropathy

 Bleeding

 Fistula outputs

4. Increased requirements

 Hypercatabolic states

 Fever

 Sepsis

 Growth in children

5. Iatrogenic

 Surgical complications

 Drugs

 Corticosteroids

 Sulfasalazine

 Cholestyramine

 5-aminosalicylic acid

 Metronidazole

 Methotrexate

(Adapted from Graham TO, Kandil HM. Nutritional factors in inflammatory bowel disease.

Gastroenterol Clin North Am. 2002;31:203-18)

In addition, Geerling et al. assessed the nutritional status in 69 recently diagnosed IBD

patients and found that although nutritional intake of riboflavin was lower in UC patients

compared to controls, no significant difference in serum concentrations between the two

groups was noted, while serum concentration of vitamin B12 in CD patients was significantly

lower [13].

62 Petros Zezos and Georgios Kouklakis

Furthermore, Filippi et al. observed multiple nutritional deficiencies, including vitamin

B1, vitamin B6 and niacin, in patients with Crohn’s disease in remission [14]. On the contrary,

Geerling et al. although found significant low serum concentrations of several nutrients in

CD patients with disease in remission, they did not noticed deficiencies of the “vitamin B

complex” members [15].

Moreover, in a recent study Magee et al. analyzed the dietary intake of 81 UC patients

and found that endoscopic severity was positively related with the anti-thiamin additive

sulfite in food like white wine, burgers, sausages, lager and red wine [16]. Sulfite is a

precursor of sulfate that can potentially be reduced to sulfide by sulfate reducing bacteria in

the colon. Sulfide may a metabolic toxin in UC. Alternatively, the association of sulfite with

UC activity may be due to its ability to degrade thiamin, particularly in colonic pH,

promoting a metabolic disturbance to the gut microflora, since thiamin is a requirement for

the metabolism of the probiotic bacteria (lactobacilli).

Finally, Saibeni et al. investigated the vitamin B6 status in 61 IBD patients and found

that low vitamin B6 plasma levels, an independent risk factor for thrombosis, are frequent in

IBD patients, especially in those with active disease [17].

Folate and vitamin B12 nutritional status has been investigated more extensively in IBD

patients. Vitamin B12 deficiency is more frequently found in CD patients than UC patients

(Table 1). Although most vitamins and minerals are absorbed throughout the small intestine,

vitamin B12 is unique in that it is actively absorbed specifically in the terminal ileum [18].

Only a small amount is passively absorbed throughout the small bowel.

In patients with Crohn’s disease, besides decreased oral intake, resection or disease of the

terminal ileum can cause vitamin B12 malabsorption and deficiency. Many studies showed

impaired vitamin B12 absorption and decreased vitamin B12 serum levels in CD patients. Most

of them have studied the vitamin B12 absorption in operated CD patients, although there are

some studies that assessed the vitamin B12 status in patients with Crohn’s disease that have

not been operated.

Fernandes-Banares et al. [11] and Chowers et al. [19] found decreased vitamin B12 serum

levels in CD patients with small bowel or ileocecal disease and not in CD patients with

colitis. Geerling et al. [13] found that recently diagnosed CD patients had significantly lower

vitamin B12 levels compared to healthy controls, although other studies [12,20-22] did not

find any difference in vitamin B12 levels between CD patients and controls.

Ileal resection of more than 60 cm results in vitamin B12 malabsorption and decreased

vitamin B12 serum levels [23,24]. Behrend et al. [25] found that most Crohn’s disease patients

with ileal resection and ileorectal anastomosis had vitamin B12 malabsorption. Individuals

with more than 60 cm of ileal loss are particularly affected (100%), but approximately 50%

of patients with 10-60 cm ileal resection and 40% of patients with less than 10 cm ileal

resection also malabsorbed vitamin B12. On the contrary, in a recent study Duerksen et al.

investigated the vitamin B12 malabsorption in Crohn’s disease patients with limited ileal

resection and found that terminal ileal resections less than 20 cm were not at risk for vitamin

B12 deficiency [26]. Impaired vitamin B12 absorption after significant (more than 60 cm) ileal

resection may be permanent in adults, whereas in children adaptation of the remaining small

bowel may result in restoration of B12 absorption years after ileal resection [27].

Nutritional Issues in Inflammatory Bowel Disease… 63

Vitamin B12 deficiency is also known to occur in a small percentage of patients with

continent/pouch ileostomy [28,29]. In a series of 235 patients with IBD and continent

ileostomies, 27% of patients with CD were found to have subnormal or borderline

concentrations of vitamin B12 [30].

Kennedy et al. [31] observed that 12 CD patients with end ileostomies for at least 1 year

and variable lengths of ileal resection had lower vitamin B12 serum concentrations compared

to healthy controls. In a recent study, Jayaprakash et al. [32] stated that vitamin B12

deficiency in patients who have undergone end ileostomy is not very common, since it was

observed only in one patient out of 39 studied.

Ileal pouch–anal anastomosis (IPAA) has become the operation of choice for the surgical

management of ulcerative colitis (UC). Pouchitis is a potential complication in the ileal

pouch after restorative proctocolectomy. The etiology of pouchitis is unknown, but fecal

stasis and bacterial overgrowth play a major role in development of pouchitis. Anaerobic

organisms bind both vitamin B12 and the vitamin B12–intrinsic factor complex, and as a result

deficiency in vitamin B12 may be demonstrated in pouch patients [33]. Reduced vitamin B12

absorption (Schilling test) has been shown in 10–30% of patients with IPAA, and clinically

significant vitamin B12 deficiency has been documented in 3–9% of patients [29,34-36]. In a

recent study Kuisma et al. evaluated the long term metabolic consequences at least 5 years

after IPAA and the influence of pouchitis on pouch histology and on bile acid, lipid, and

vitamins B12, A, D and E metabolism, in 104 UC patients with a J-pouch [37]. Vitamin B12

malabsorption of ileal type was seen in 20% of patients with IPAA and vitamin B12

deficiency was observed in approximately 5% of IPAA patients.