Nutritional Deficiencies with IBD

By Amalia


Gastrointestinal disorders appear to be part of an increasing epidemic, especially in developed countries,^1^ particularly in Northern Europe and North America.2 Inflammatory bowel disease (IBD) is a group of chronic, recurrent inflammatory conditions of the gastrointestinal (GI) tract of unknown etiology. 2 Malnutrition is frequently seen in patients with IBD, particularly with CD, 2 and malnutrition can often lead to other complications and diseases. This article will review IBD and its associated nutrient deficiencies, as well as the resulting diseases and the importance of nutritional therapy for IBD patients.


IBD is a group of chronic, debilitating, idiopathic, inflammatory conditions of the gastrointestinal (GI) tract.3 IBD is characterized by severe inflammation of the small bowel and/or colon, leading to recurrent diarrhea and abdominal pain. 3 IBD includes two main clinical subtypes: Crohn’s disease (CD) and ulcerative colitis (UC). 3 However, despite their grouping, the two diseases are traditionally found at opposite ends of the disease spectrum, 4 because they are differentiated by the location of the inflammation in the GI tract and by the occurrence of the histological changes in the intestinal wall. 3

Anatomically, CD can affect the entire GI tract, from the mouth extending to the anus. It commonly affects the terminal ileum and the colon 3 and may also be accompanied by extraintestinal manifestations. 4 While anatomically, UC is exclusive to the large bowel, mainly the rectum, colon and caecum. 3 Microscopically, CD is transmural, affecting the entire thickness of a wall of an organ and often discontinuous. UC affects only the intestinal mucosa in a continuous pattern. 3

IBD is debilitating, due to fatigue accompanying the inflammatory symptoms and due to the prolonged pain suffered by patients. 3 Both diseases encompass change of the immunological tolerance system of the digestive tract mucosa, initiated by a certain factor that gives rise to an anatomically incorrect and prolonged inflammatory response. 4 IBD affects quality of life, but not life span. The mortality rate of patients is not different from the normal population. 3

The ultimate etiology and pathogenesis of IBD has not yet been identified, 4 amidst many studies and hypotheses. Rapid increase in CD and UC has been shown to be more prevalent in developed countries. 1 The highest incidences are reported in northern Europe and North America, ranging from 12 to 19/100,000/year and from 5 to 29/100,000/year, respectively. Nearly 1.4 million Americans and 2.2 million Europeans are affected by IBD. The prevalence of IBD is similar in men and women, and has been shown to peak in young adults. The prevalence also depends on ethnicity, with Caucasians and African-Americans most affected, while IBD is rare among Hispanics and Asians. Ashkenazi Jews have a higher risk of developing IBD, with a 2-4 times higher incidence when compared to non-Jewish Caucasians. There is also evidence to suggest that the prevalence of IBD increases in populations and regions with industrialization. 3

The lower incidence of IBD in Asia and Africa compared to North America and Europe reflects both genetic and environmental factors. The hygiene hypothesis has been invoked to account for the increasing prevalence of various autoimmune and inflammatory conditions, which are thought to result from the lack of early exposure to microbial agents, due to stringent sanitation conditions. Changes in dietary and intestinal microbial milieu may play a key pathogenic role that is common to CD and UC. 3 Childhood infections and poor hygiene could protect one from developing CD by allowing the host to develop a tolerance or immunity to agents that could trigger onset of CD later in life. Additional studies also support the hygiene hypothesis. 1

One important environmental factor is smoking. The effect of smoking is conflicted between CD and UC. Smoking has actually been found to be protective against UC, and may even improve its course, and decrease the need for colectomy (surgical resectioning of the large intestine), after onset of the disease. This is in opposition to CD for which the risk of developing CD is increased and aggravated by nearly twofold in western countries. Furthermore, patients with a higher lifetime exposure to tobacco (i.e. more than 150 cigarettes/year) suffered from small bowel disease more often than non-smokers. Smokers also have increased numbers of fistulae and/or abscesses than non-smokers, and were more vulnerable to CD flare-ups. Particularly with regard to heavy smokers (i.e. more than 10 cigarettes a day), who were more likely to require gastric surgery as a result of IBD and suffer significantly decreased quality of life. 3 Figure 1 shows the positive relationship between smoking and the risk of flare-up for patients with CD. Non-smokers have a significantly decreased risk of flare-up, leveling off to stability. Quitters will show a significant decrease over time, before leveling off to stability. However, active smokers have significantly higher risk of flare-up than both non-smokers and quitters.

Dietary factors have been considered in the role of the origins of IBD. Most case-control studies have determined a significant association between simple sugar consumption and CD. This can be interpreted in two different manners: that simple sugars encourage the onset of CD, or that CD patients consume higher quantities of simple sugars to alleviate their symptoms. Other dietary factors include proteins, fat, margarine, fruit and vegetables, dairy, coffee, soft drinks, and fast food, which have been studied in case-control studies. Methodological problems, however, have prevented any solid conclusion in dietary studies. 1


The earliest descriptions of IBD, especially CD, have been traditionally associated with serious nutritional deficiency. The pattern and severity of malnutrition depends on the duration, activity, and event of the disease. Significant differences are described between CD and UC, due to the small intestine’s involvement accompanying a higher incidence of protein-calorie malnutrition and deficiencies in specific nutrients. CD presents considerable chronic deficiencies, whereas UC tends to have a more preserved nutritional status, except during flares of activity of the diseases, and cases of hospitalization when deficiencies tend to be significant. According to the methods and criteria considered for diagnosis, between 20% and 85% of IBD patients are nutrient deficient, with prominent calorie-protein malnutrition in CD and protein malnutrition in UC. A large proportion of CD patients – between 25% and 80% – and UC patients – between 25% and 50% – present hypoalbuminemia during hospitalization, which may clinically appear as weight loss. 4

Recent studies have shown that most patients in remission are in good nutritional status and some are even overweight, but still have significant abnormalities in body composition. One study reported that the BMI of CD patients overall was lower than of controls. Thirty-two percent of patients with CD had a BMI greater than 25kg/m 2 , but still had lower fat free mass and significantly lower adjusted mean intake of carbohydrates, monosaturated fat, fiber, calcium and vitamins C, D, E and K. Muscle mass depletion was seen in more than half of CD and UC patients, even though they were not malnourished. A second study showed the nutritional status, body composition, muscle strength, and quality of life in patients with IBD in clinical remission. The study observed that despite most of these CD and UC patients were well nourished, both had decreased body cell mass and handgrip strength, when compared to controls. This showed that the most prevalent form of malnutrition in CD patients has changed to one of excess body weight, paired with inadequate dietary intake of micronutrients, secondary to dietary restriction of certain foods. So, despite the appropriate intakes of energy and macronutrients, CD patients in remission have significantly lower plasma concentrations of several vitamins and minerals. 5

Children who suffer from IBD are at risk for malnutrition and growth failure. Similar to adults, recent studies have shown that a significant proportion of children with CD are overweight. In a group of 783 patients with newly diagnosed IBD, low BMI was seen in only 22% to 24% of children with CD and 7% to 9% of children with UC. Ten percent of children with CD and 20% to 30% of children with UC had a BMI consistent with overweight or risk for becoming overweight. However, despite their preserved fat mass, children with CD frequently are observed with low lean body mass. Growth retardation at diagnosis has been reported in 23% to 88% of children with CD. Growth failure not as common in UC compared to CD, but growth impairment is observed in both groups. 5

There are many sources for the beginning of malnutrition in CD, 4 which may cause malnutrition solely or in combination. Factors which may have a major position in one nutritional deficiency may play a minor position in the appearance of a different deficiency in the same patient. 5 The most important causes of malnutrition are reduced food intake, presence of active inflammation, enteric loss of nutrients during periods of disease activity and remission, 5 and the interaction between nutrients and pharmaceuticals. 4 Additionally, the underlying inflammatory mediators of the physiopathology of IBD, including tumor necrosis factor (TNF)- , interleukins- (IL) -1 and -6,4 white adipose tissue adipokines (leptin, adiponectin, resistin) and possible changes in the hypothalamic serotonin levels5 can increase catabolism and lead to anorexia. 4

Likewise, in children, the etiology of growth failure is multiple and not completely understood. Poor nutritional state, systemic consequences of gut inflammation, disturbances of growth hormone/insulin-like growth factor axis, genetic influences and corticosteroid use contribute in different ways. 5 About 30-40% of children continue to have severe linear growth retardation during their disease course and several studies have found that the final height is affected in CD patients who exhibit early onset symptoms. 5 Many of these mechanisms are severe consequences that can lead to further complications to arise.


Bone mineralization in children with inflammatory bowel disease: What is the role of zinc?

Bone demineralization is a significant consequence in pediatric IBD patients. Factors such as inadequate nutrition, corticosteroid therapy and decreased physical activity all contribute. In a study conducted by Saltik-Temizel et al., the aim was to investigate the relation between the serum zinc level and bone mineral indexes of children with IBD. 6 In IBD patients, factors of bone demineralization include vitamin D and calcium deficiency caused by inadequate nutrition, chronic corticosteroid therapy and decreased physical activity. Nutrients and lifestyle affect bone health, and as a nutrient, zinc may have a role in bone development. Zinc is needed for osteoblastic activity, collagen synthesis, and alkaline phosphatase activity. Some studies have shown a positive relationship between zinc intake and bone mineral content in children. The study was conducted on twenty-eight patients with IBD, diagnosed by medical history, clinical, endoscopic, and histological findings, from the ages of 5-18. X-ray measured their lumbar vertebrae. The results were compared to age-and-gender matched 56 healthy children. Serum zinc levels of 28 IBD and 31 healthy children were also determined, with the normal zinc level standard at 70-114µg/dl. 6

The results showed that the mean serum zinc levels of IBD patients and controls were 101.2 ± 28.8 µg/dl and 108.9 ± 15.9 µg/dl, respectively. All controls had normal serum zinc level, but 11 (39.3%) out of 28 IBD patients had low serum zinc level. The difference between bone mineralization indexes also showed a lower level for IBD patients, but the difference was fairly small. 6

Reduction in bone mineral density has been reported in children with IBD. Zinc intake and serum zinc level have been investigated in patients with IBD, notably with CD. A positive relationship has been found between serum zinc and BMD. One main problem with children and adolescent patients is growth failure. Decreased growth velocity, short stature and delayed bone age have been observed in CD patients, particularly. Such factors include inadequate intake, malabsorption, and fecal loss of protein and essential trace elements such as zinc, and corticosteroid therapy. Griffin et al. 6,7 reported that reduced zinc absorption with normal fecal and urinary excretion of zinc caused negative zinc balance in adolescents. Ojuawo et al. 6,8 reported that children with CD had low serum zinc levels. It was also shown that up to 15% of adult IBD patients had subnormal levels of zinc. Zinc is a dietary essential trace mineral necessary for normal collagen synthesis and mineralization of bone, and it is also required for normal growth. 6

As expected in the Saltik-Temizel et al. study, IBD patients had had significantly lower BMD values than the controls. 6 The mean BMC and BMD values were not different between the CD and UC patients, but CD patients had significantly lower BMD values than the controls. Therefore, it is encouraged that zinc supplementation be given to children with IBD and developing growth failure and to prevent osteoporosis. 6

Vitamin D-mediated calcium absorption in patients with clinically stable Crohn’s disease

Vitamin D is important for optimal intestinal absorption of calcium for proper mineralization of bone, and to maintain homeostasis for other cellular processes. The risk of osteoporosis and osteoporotic fractures is associated with impaired intestinal calcium absorption. These conditions are often also associated with increased inflammation. Crohn’s disease (CD) is associated with increased fracture risk, impaired calcium absorption and an increased inflammatory state. 9

Vitamin D regulates intestinal calcium absorption by several proteins expressed in the small intestine. These proteins include calbindin 9K, TRPV6, PMCA1 and NCX1. Vitamin D obtained from diet, as ergocalicferol or cholecalciferol or made in the skin, as vitamin D, is converted to active hormonal form. 9

Calcium absorption in CD may be impaired due to vitamin D deficiency, magnesium deficiency, glucocorticoid use, and/or intestinal resection. CD also may have the potential is inflammation-induced resistance to vitamin D action at the level of the enterocytes. Inflammatory diseases such as CD are characterized by increased systemic and epithelial TNF- and IL-1 concentrations. 9

In a study conducted by Kumari et al., two groups of subjects were recruited into the study, which were diagnosed with stable Crohn’s disease, and did not have any inflammatory disorders of the GI tract, or rheumatoid arthritis. 9 Screening serum and 24 hour urine calcium/creatinine values were collected for all patients. A food diary was also kept for patients, to determine mean daily calcium and vitamin D consumption. Dual isotope FCA testing was performed for each subject at baseline, the morning after completion of a week course of calcitriol 0.25 mcg BID, and the morning after completion of a 7-day course of calcitriol 0.5 mcg BID. A minimum week washout period was required between the two calcitriol treatment courses. Serum was collected on the morning of and prior to each FCA test for determination of calcium and 25(OH)D, and creatinine levels.

The results of Kumari et al. showed that the subjects at baseline in both groups were vitamin D insufficient. 9

Severe metabolic alkalosis and recurrent acute chronic kidney injury in a patient with Crohn’s disease

In a case described by Jacobi et al., a 27-year old male with CD was discussed. 10 The patient was admitted to the hospital with profound diarrhea and hypersecretion, as well as two seizures due to electrolyte disturbances. As was found, severe metabolic alkalosis is a finding of CD patients, albeit rare. The most common disorder is actually an acid-base disorder due to D-Lactate uptake or gastrointestinal bicarbonate loss. The patient suffered metabolic alkalosis due to gastrointestinal losses of volume and chloride, resulting in renal bicarbonate retention. Secondary hyperaldosteronism caused by volume depletion contributed to metabolic alkalosis. However, gastrointestinal chloride loss was particularly prominent. The acidic stool, the short intestinal transit time and the substantial improvement of chloride loss in response to proton pump inhibition all point to gastral HCl secretion. Intestinal inflammation may also lead to chloride secretion directly from the inflamed intestinal mucosa. Thus, inflammation reduces the intestinal expression of SLC26A3, a chloride transporter that is mutated in patients with congenital chloridorrhea. Acquired chloridorrhea has been described in patients with intestinal inflammation due to transplant rejection and may be related to down regulation of SLC26A3.


Maintaining adequate nutrition, not probiotic administration, prevents growth stunting and maintains skeletal muscle protein synthesis rates in a piglet model of colitis

Harding et al. conducted a study on whether probiotic administration or maintaining adequate nutrition actually maintains skeletal muscle protein synthesis. 11 Malnutrition and cytokine-induced catabolism are pervasive in children with IBD, yet the benefits of aggressive nutrition support or of probiotics on nutrient and functional deficiencies and growth remained unclear. Piglets with dextran sulfate-induced colitis consuming a 50% macronutrient restricted diet (C-MR) were compared with those receiving probiotic CFU 450 × 109 VSL#3 [VSL Pharmaceuticals, Gaithersburg, MD, USA) as 1 packet/day in 30 mL of diet, 15 mL twice daily] (C-MRP) or adequate nutrition (C-WN) and with healthy well-nourished controls (REF). The results were that the inflammatory stress of colitis in well nourished piglets (C-WN) resulted in a lower growth rate compared to healthy controls (REF), as manifested by slower gain in weight, chest circumference, and snout to rump length. Probiotic supplementation did not attenuate this reduced weight gain or growth. However, weight did not plateau in either macronutrient restricted group. 11

Probiotic Preparation VSL#3 Induces Remission in Children with Mild to Moderate Acute Ulcerative Colitis

In a study conducted by Huynh et al., 12 eighteen patients between the ages of 13-17 with mild to moderate acute UC received probiotic CFU 450 × 109 VSL#3 [VSL Pharmaceuticals, Gaithersburg, MD, USA) as 1 packet/day in 30 mL of diet, 15 mL twice daily] VSL#3 daily in 2 divided doses for 8 weeks. The disease activity pre- and post-VSL#3 therapy was assessed. Thirteen patients remained in the study for the entire 8 weeks of VSL#3 treatment and 5 patients were withdrawn due to lack of improvement. Remission was achieved in 56% of patients, and no change or worsening in 39%. Post-VSL#3 treatments demonstrated a bacterial taxonomy change in rectal biopsy. DNA was extracted from the collected biopsy tissue samples. This change is associated with progress of the microbial profile in the GI tract, resulting in improvements of a patient’s colitis. The VSL#3 was well tolerated in clinical trials and no biochemical and clinical adverse effects attributed to VSL#3 were identified. In conclusion, treatment of pediatric patients with mild to moderate UC with VSL#3 resulted in remission rate of 56% and a combined remission rate of 61%.

Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis

IBD increases the risk of developing colorectal cancer. Dietary compounds that reduce inflammation are associated with a lower cancer risk. The long chain omega-3 fatty acid docosahexaenoic acid (DHA) is present in fish oil and has potent anti-inflammatory properties. The objective of Woodworth et al. was to determine whether dietary fish oil enriched with DHA could reduce experimentally induced colitis and colon cancer risk in a mouse model.13 The results showed 4 weeks postinfection, mice consuming 6.00% DFO had the highest degree of inflammation and dysplasia compared with three control diets. The observed exacerbation in colitis was dose dependent as 2.25% and 3.75% DFO groups.


IBD has serious nutritional consequences for patients. Studies have shown the consequences of nutritional deficiencies and how IBD disorders can cause nutritional deficiencies. It is important to treat these patients correctly and to prevent further complications, especially those of life-threatening degree.


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11. Harding S, Adegoke O, Fraser K, Marliss E, Chevalier S, Kimball S, Jefferson L, Wykes L. 2010. Maintaining adequate nutrition, not probiotic administration, prevents growth stunting and maintains skeletal muscle protein synthesis rates in a piglet model of colitis. Pediatric Research.
12. Huynh H, deBruyn J, Guan L, Diaz H, Li M, Girgis S, Turner J, Fedorak R, Madsen K. 2009. Probiotic Preparation VSL#3 Induces Remission in Children with Mild to Moderate Acute Ulcerative Colitis: A Pilot Study. Inflammatory Bowel Disease 15 (5): 760-768.
13. Woodworth H, McCaskey S, Duriancik D, et al. 2010. Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis. Cancer Research 70 (20): 7960 – 7969.

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