In: Vitamin B: New Research ISBN 978-1-60021-782-1
Editor: Charlyn M. Elliot, pp. 57-80 © 2008 Nova Science Publishers, Inc.
INFLAMMATORY BOWEL DISEASE: FOCUS ON
THE VITAMIN B COMPLEX DEFICIENCIES AND
Petros Zezos1,∗ and Georgios Kouklakis2
Gastroenterology & Hepatology Department, Military General Hospital of
Alexandroupolis, Alexandroupolis, Greece;
Endoscopy Unit, University General Hospital of Alexandroupolis, Democritus
University of Thrace, Alexandroupolis, Greece.
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.
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
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
Keywords: Aetiology; Crohn’s disease; complications; inflammatory bowel disease; therapy;
ulcerative colitis; vitamin B complex.
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
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
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
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
Table 1. Prevalence of nutritional deficiencies in inflammatory bowel disease
Deficiency Crohn’s disease Ulcerative colitis
Negative nitrogen balance 69 R
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
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
Intake-associated pain or discomfort
Iatrogenic dietary restrictions
(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
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
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
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.
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