• Crohn’s disease:
Intermittent bouts of diarrhea, low-grade fever, and pain in the lower right abdomen
Loss of appetite, weight loss, flatulence, and malaise
Abdominal tenderness, especially in the lower right part of the abdomen
X-rays show abnormality of the terminal portion of the small intestine
• Ulcerative colitis:
Bloody diarrhea with cramps in the lower abdomen
Mild abdominal tenderness, weight loss, and fever
Rectal examination may show fissures, hemorrhoids, fistulas, and abscesses
Diagnosis confirmed by X-ray and sigmoidoscopy (examination of the colon with a fiber-optic tube)
Inflammatory bowel disease (IBD) is a general term for a group of chronic inflammatory disorders of the intestines. It is divided into two major categories: Crohn’s disease (CD) and ulcerative colitis (UC). Clinically, IBD is characterized by recurrent inflammation of specific intestinal segments. In the United States, about 1.4 million people have IBD, with the number equally split between CD and UC. IBD may occur at any age, but it most often occurs between the ages of 15 and 35. Females are affected slightly more frequently than males. Caucasians have the disease two to five times more often than African-Americans or Asian-Americans, and those with a Jewish heritage have a three- to sixfold higher incidence than non-Jews.
CD is characterized by an inflammatory reaction throughout the entire thickness of the bowel wall. In approximately 40% of cases, however, the inflammatory lesions (granulomas) are either poorly developed or totally absent. The original description in 1932 by Crohn and colleagues localized the disease to segments in the ileum, the terminal portion of the small intestine. However, it is now known that the same granulomatous process may involve the mucosa of the mouth, esophagus, stomach, duodenum, jejunum, and colon.
In UC, there is a nonspecific inflammatory response, limited largely to the lining of the colon. CD and UC do share many common features and, where appropriate, will be discussed together. Otherwise they will be discussed as separate entities.
Features Shared by Crohn’s Disease and Ulcerative Colitis
• The colon is frequently involved in Crohn’s disease and is invariably involved in ulcerative colitis.
• Although this is rare, patients with ulcerative colitis who have total colon involvement may develop so-called backwash ileitis. Thus, both Crohn’s disease and ulcerative colitis may cause changes in the small intestine.
• Patients with Crohn’s disease often have close relatives with ulcerative colitis, and vice versa.
• When there is no granulomatous reaction in Crohn’s disease of the colon, the two lesions may resemble each other in both the clinical picture and the biopsy result.
• The many epidemiological similarities between the two diseases include age, race, sex, and geographic distribution.
• Both conditions are associated with similar manifestations outside the gastrointestinal tract (extraintestinal).
• The causative factors appear to be parallel for the two conditions.
• Both conditions are associated with an increased frequency of colon cancer.
There is a very strong genetic component in IBD.1,2 As already mentioned, IBD is two to four times more common in white than nonwhite people, and about four times more common in those with a Jewish heritage. In addition, multiple members of a family have CD or UC in 15% to 40% of cases. CD is among the best-known of complex genetic disorders. Several genetic pathways involving the maintenance of the integrity and immune function of the lining of the intestinal tract have been found for an increased susceptibility for CD, while only one gene (ECM1) has been reported for UC. Nonetheless, dietary and environmental factors appear to be required for the expression of IBD.
Many microorganisms have been hailed as putative causes of IBD, but in spite of numerous attempts to confirm a bacterial, mycobacterial, fungal, or viral etiology, the idea that a transmissible agent is responsible for IBD is still hotly debated. Viruses—rotavirus, Epstein-Barr virus, cytomegalovirus, measles virus, and an uncharacterized RNA intestinal virus—and mycobacteria continue to be favored candidates. Gastrointestinal infections with various microbes and the yeast Candida albicans can trigger a flare-up of disease, and all patients with IBD should be tested for gastrointestinal infections at the start and during the course of their illness.
The development of IBD probably reflects a nonspecific abnormal host-microbe interaction, rather than infection by any single responsible organism. The ability of microbes to coexist within the human intestinal tract involves host genetic factors, barrier function, and immune function, as well as the number and type of health-promoting gut bacteria. Microbes with virulence factors that allow them to breach the intestinal barrier and induce chronic inflammation are probably responsible for triggering IBD in many cases, hence the long list of implicated microorganisms.3
Exposure to Antibiotics
Exposure to antibiotics is being linked to IBD and probably is a factor in causing disruption of the intestinal lining in some cases. Subjects diagnosed with IBD were more likely to have been prescribed antibiotics two to five years before their diagnosis. A dose-dependent relationship was shown: the more prescriptions for antibiotics, the greater the risk for IBD.4
Before the 1950s, CD was found in selected groups with a strong genetic component. Since this time there has been a rapid climb in incidence in developed countries, particularly the United States, and in countries that previously had virtually no reported cases. In fact, IBD has spread like an epidemic since 1950. Are antibiotics to blame? Penicillin and tetracycline have been available in oral form since 1953. The annual increase in prescriptions of antibiotics parallels the rise in the annual incidence of IBD. Comparative statistics have shown that wherever antibiotics have been used early and in large quantities, the incidence of IBD is now quite high. Considering the critical importance of having the right bacteria in the gut, it is not surprising that the disruption of bacterial balance caused by antibiotics may be a causative factor in IBD.
Over the years researchers have sought to identify IBD as an infectious process. The problem may be that the infectious agent is a component of the normal intestinal flora that suddenly produces immune-stimulatory toxins or becomes invasive as a direct result of sublethal doses of antibiotics. When microbes are not given a full lethal dose, their usual response is to adapt and become even more virulent and numerous. Other medications that have been implicated as well include nonsteroidal anti-inflammatory drugs such as ibuprofen and most recently the acne medication Accutane.
An overwhelming amount of evidence points to an association of immunologic disturbances with IBD, but whether they cause the disease or are the result of it remains unclear. Theories about immune mechanisms as a cause of IBD have been proposed, but the current evidence seems to indicate that the immune system abnormalities seen in IBD are probably secondary to the disease process.
Despite the fact that a dietary cause of CD is barely considered (if mentioned at all) in most standard medical and gastroenterology texts, there is considerable scientific evidence supporting the notion that dietary factors are the most important triggers for IBD.5–7 The incidence of IBD increased in cultures consuming the Western diet, but it is virtually nonexistent in cultures consuming a more primitive diet. Food is the major factor in determining the intestinal environment, so the considerable change in dietary habits over the last century could explain the rising incidence of IBD. Several studies that analyzed the pre-illness diet of patients with IBD have found that they habitually ate more refined sugar, chemically modified fats and fast food, and meat while consuming less raw fruit, vegetables, omega-3 fatty acids, and dietary fiber than healthy people.5–11
Another important dietary factor is the role of food allergies. Studies have shown that an elemental diet or an allergy exclusion diet can be very successful in the treatment of IBD. The role of food allergy is discussed in greater detail later in the chapter, as is the effect of dietary fiber in the etiology and treatment of IBD.
A reduced intake of omega-3 oils and an increased intake of omega-6 oils are also being linked to the growing rise of IBD. Recently this link was shown in a study in Japan. Because the genetic background of the Japanese is relatively homogeneous, this higher incidence is most likely due to the incorporation of Western foods in the diet. The analysis showed that the greater incidence of CD was strongly correlated with increased dietary intake of total fat, animal fat, omega-6 fatty acids, animal protein, milk protein, and the ratio of omega-6 to omega-3 fatty acids.12 Multivariate analysis showed that higher intake of animal protein was the strongest independent factor, followed by an increased ratio of omega-6 to omega-3 fatty acids. Correction of this increased ratio by reduction of omega-6 oil intake and increase of omega-3 oil intake may lead to significant clinical benefit through an effect on eicosanoid metabolism (discussed later).
Inflammatory bowel disease is the end result of a complex interplay of several factors. This section discusses the key nutritional, microbial, and toxic issues that must be addressed for the successful management of this difficult disease.
Little is known about the natural course of CD, because virtually all patients with the disease undergo standard medical care (drugs and/or surgery) or alternative therapy. The only exceptions are patients in clinical trials who are assigned to the placebo group.13,14 However, even these patients do not represent the natural course of the disease, because they are seen frequently by physicians and other members of a health care team and are taking medication, even if it is only in the form of a placebo. If proper evaluation of therapies for IBD is to occur, there must be a greater understanding of its natural history. This is particularly important for natural medicine practitioners, because it is commonly believed that standard medical care often interferes with the normal efforts of the body to restore health. Some aspects of the natural course of CD support this idea, especially when coupled with the limited efficacy of current medications and surgery and their known toxicity. However, conventional measures do have their place in many instances and should be used when appropriate.
Researchers in the National Cooperative Crohn’s Disease Study (NCCDS) reviewed 77 patients who received placebo therapy in part one of the 17-week study.13,14 They all had active disease, as defined by a Crohn’s disease activity index (CDAI) higher than 150. Of the patients completing the study:
• None died.
• Only seven (9%) suffered a major worsening of their disease (i.e., either a major fistula developed or the patient required abdominal surgery).
• Twenty-five (32%) suffered a less serious worsening (increase in the CDAI to >450 or presence of fever of 100°F for two weeks).
• Treatment was considered to have failed in 25 (32%), because their CDAI remained higher than 150.
• Twenty (26%) achieved clinical remission.
On at least one occasion during the 17 weeks of therapy, 49% of the patients on the placebo treatment were found to have a CDAI lower than 150. The patients who showed favorable response to the placebo continued to be observed with placebo therapy for up to two years. It is interesting to note that none of these patients’ intestinal X-rays showed worsening during the study, and 18% showed improvement. Of the patients whose disease responded to the placebo (20 of 77; 26%), the majority (70%) remained in remission at one year, and a fair number (45%) remained in remission at two years. These results indicate that many patients undergo spontaneous remission, approximately 20% at one year and 12% at two years. However, when another factor is considered, the success of placebo therapy rises dramatically. Of patients in the placebo group who had no previous history of steroid therapy, 41% achieved remission after 17 weeks. In addition, 23% of this group continued in remission after two years, compared with only 4% of the group with a history of steroid use.
The European Cooperative Crohn’s Disease Study (ECCDS), although different in some methodological details, is quite similar to the NCCDS.13,15 In the ECCDS, 110 patients constituted the placebo group: 68 patients with prior treatment and 42 patients with no prior treatment. The results of the study showed that 55% of the total placebo group achieved remission by 100 days, 34% remained in remission at 300 days, and 21% remained in remission at 700 days. Like the NCCDS, the ECCDS demonstrated that patients with no prior drug therapy have a greater likelihood of remission.
Although the researchers did not advocate placebo therapy, they did carefully point out that once remission is achieved, 75% of the patients continue in remission at the end of one year and up to 63% at two years, regardless of the maintenance therapy used. These results would suggest that the key is achieving remission, which, once attained, can be maintained by conservative nondrug therapy.13
Eicosanoid Metabolism in Inflammatory Bowel Disease
Patients with IBD show greatly increased levels of inflammatory chemicals in the lining of the intestines, serum, and stool samples. These compounds are produced by white blood cells (neutrophils) to amplify the inflammatory process and cause smooth muscle contraction. The formation of these inflammatory compounds can be decreased by reducing or eliminating consumption of omega-6-rich foods (corn, beef, liver, pork, lamb, milk/dairy products, and soy, safflower, sunflower, and corn oil) and increasing consumption of the longer-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) through higher intake of cold-water fish such as anchovies, sardines, salmon, small mackerel, herring, and halibut as well as fish oil supplements.16
Detailed analyses of double-blind studies with fish oil supplements (2.7 to 5.1 g total omega-3 oils per day) have demonstrated an ability to prevent or delay relapses in both CD and UC.16,17 In one study an omega-3 fatty acid supplement reduced the one-year relapse rate by half with an absolute risk reduction of 31%.18 Much larger studies have asked whether omega-3 fatty acids could sustain remission once it is achieved, but these studies failed to show an advantage of fish oils over a placebo. These results indicate that other factors are not being adequately addressed when fish oils are used as the sole therapy.19
Mucin Defects in Ulcerative Colitis
Mucins are sticky protein compounds that line and protect the intestinal lining. Alterations in mucin composition and content in the colonic mucosa have been reported in patients with UC.20–22 The factors responsible for these changes appear to be a dramatic drop in the mucus content of the goblet cells that produce the mucin (proportional to the severity of the disease) and a decrease of the major sulfomucin subfraction. In contrast, these abnormalities are not found in patients with CD. It is significant that although the mucin content of the goblet cells returns to normal during remission, the sulfomucin deficiency does not. The specific components of the sulfomucin and the cause of its lower concentration have not yet been determined. These mucin abnormalities are also thought to be a major factor in the higher risk of colon cancer in patients with UC. The mucin abnormalities may be the result of lack of dietary fiber.
The intestinal microflora is extraordinarily complex and contains more than 400 distinct microbial species. In an effort to describe a nonspecific alteration (qualitative or quantitative) in the intestinal flora, the term dysbiosis is often used. Dysbiosis is a common feature in many patients with IBD. For example, the fecal flora of many patients with IBD has been found to contain higher numbers of gram-positive anaerobic bacteria and Bacteroides vulgatus, a gram-negative rod bacterium.23 Alterations in the metabolic activity of the various bacteria are thought to be more important than alterations in the number of bacteria per se. In addition, specific bacterial cell components (which vary even within the same species) are thought to be responsible for promoting cell destruction activity against the cells that line the colon (the colonic epithelial cells).3
It is very interesting to note that researchers investigating the intestinal flora of UC often use carrageenan (a sulfated polymer of galactose and d-anhydrogalactose extracted from red seaweed, principally Eucheuma spinosum and Chondrus crispus) to experimentally induce the disease in animals.24 In its natural state, this polymer has a molecular weight of 100,000 to 800,000, but in the studies it was degraded by mild acidic hydrolysis to yield products with weights in the vicinity of 30,000. These smaller molecules are thought to be responsible for inducing the ulcerative damage seen in the animal studies. Carrageenan compounds are used by the food industry as stabilizing and suspending agents (for example, in products that contain milk, such as cottage cheese, ice cream, and milk chocolate), with polymers of different molecular weights being used for a variety of purposes.
As suggestive as the animal studies are in linking UC with carrageenan, no lesions of IBD were observed in healthy human subjects and primates fed enormous quantities of degraded carrageenan.25,26However, differences in intestinal bacterial flora are probably responsible for this discrepancy, as germ-free animals do not display carrageenan-induced damage either.
The bacteria linked to facilitating the carrageenan-induced damage in animals are a strain of Bacteroides vulgatus.23 This organism is found in much higher concentrations (six times as high) in the fecal cultures of patients with UC. The data imply that while carrageenan can be metabolized into nondamaging components in most human subjects, individuals with an overgrowth of Bacteroides vulgatus may be at risk. Strict avoidance of carrageenan appears warranted at this time for individuals with IBD until further research clarifies its safety for them. Read food labels carefully.
Complications of IBD
There are more than 100 systemic complications of IBD (known as extraintestinal lesions, or EILs). The most common EIL in adults is arthritis, which is found in about 25% of patients. Two types are typically described, the more common being peripheral arthritis affecting the knees, ankles, and wrists. Arthritis is more frequently found in patients with colon involvement. Severity of symptoms is typically proportional to disease activity.
Less frequently, the arthritis affects the spine. Symptoms are low back pain and stiffness with eventual limitation of motion. This EIL occurs predominantly in males and is difficult to distinguish from typical ankylosing spondylitis (rheumatoid arthritis of the spine). In fact, it may precede the bowel symptoms by several years. There is probably a consistent underlying factor in both the progression of ankylosing spondylitis and IBD.
Skin lesions are also common, being seen in approximately 15% of patients. The skin lesions can be quite severe, including gangrene and/or painful, red lumps (e.g., erythema nodosum and pyoderma gangrenosum), but are usually simply annoying, like canker sores. In fact, recurrent canker sores occur in approximately 10% of patients with IBD.
Serious liver disease (i.e., sclerosing cholangitis, chronic active hepatitis, cirrhosis, etc.) is also a common EIL, affecting 3 to 7% of people with IBD. Individuals with liver enzyme abnormalities should take silymarin, a group of flavonoid compounds derived from milk thistle (Silybum marianum). These compounds have a tremendous protective effect on the liver and enhance detoxification processes (see the chapter “Hepatitis”).27 The standard dosage for silymarin is 70 to 210 mg three times per day.
Other common EILs are inflammation of blood vessels, impaired blood flow to the fingers or toes, inflammatory eye manifestations (episcleritis, iritis, and uveitis), kidney stones, gallstones, and, in children, failure to grow, thrive, and mature normally.
A decreased food intake is the most significant cause of nutritional deficiency in patients with IBD. It is the most common nutritional deficit in patients who require hospitalization. Often the IBD patient feels pain, diarrhea, nausea, or other symptoms after a meal, resulting in a subtle decrease in dietary intake. Weight loss and protein-calorie malnutrition are prevalent in 65 to 75% of IBD patients.28
Malabsorption—lack of absorption of food and nutrients—can be anticipated in patients with extensive involvement of the small intestine and in patients who have had surgical resection of segments of the small intestine. Particularly common is fat malabsorption, resulting in significant caloric loss as well as loss of fat-soluble vitamins and minerals. Involvement or resection of the ileum of that area typically results in bile acid malabsorption. The laxative effect of bile acids on the colon may result in a chronic watery diarrhea.
Patients with a history of chronic diarrhea may develop electrolyte and trace mineral deficiency, while chronic fat malabsorption (steatorrhea) may result in calcium and magnesium deficiency.
Increased secretion of tissue components and nutrient loss often occur, owing to the inflammatory nature of IBD. In particular, there is a significant loss of blood proteins across the damaged and inflamed mucosa. The loss of protein may exceed the ability of the liver to replace blood proteins, even with a high protein intake. The chronic loss of blood often leads to iron depletion and anemia.
The most common drugs used in the conventional treatment of IBD are corticosteroids (e.g., prednisone) and sulfasalazine, both of which increase nutritional needs. Corticosteroids are known to stimulate protein breakdown (catabolism); depress protein synthesis; decrease the absorption of calcium and phosphorus; increase the urinary excretion of vitamin C, calcium, potassium, and zinc; increase levels of blood glucose, serum triglycerides, and serum cholesterol; increase the requirements for vitamin B6, vitamin C, folate, and vitamin D; decrease bone formation; and impair wound healing. Sulfasalazine inhibits the absorption and transport of folate, decreases serum folate and iron, and increases the urinary excretion of ascorbic acid.
A chronic inflammatory and/or infectious disease such as IBD also leads to nutritional deficiency because of increased nutritional needs. For example, patients with IBD typically require as much as 25% more protein than usual (and sometimes even more), especially if a significant amount of protein is being lost.
Causes of Malnutrition in Inflammatory Bowel Disease
• Decreased oral intake
Disease-induced (pain, diarrhea, nausea, anorexia)
Iatrogenic (restrictive diets without supplementation)
Decreased absorptive surface due to disease or resection
Bile salt deficiency after resection
Drugs (e.g., corticosteroids, sulfasalazine, cholestyramine)
• Increased secretion and nutrient loss
Electrolyte, mineral, and trace mineral loss in diarrhea
• Increased utilization and increased requirements
Inflammation, fever, infection
Increased intestinal cell turnover
The importance of correcting nutritional deficiencies in patients with IBD cannot be overstated. Nutrient deficiencies, both macro and micro, lead to altered gastrointestinal function and structure, which may result in the patient’s entering a vicious circle. That is, the secondary effects of malnutrition on the gastrointestinal tract may lead to a further increase in malabsorption, further decreasing nutrient status.
Frequency of Nutritional Deficiency in Patients with Inflammatory Bowel Disease
Low serum vitamin B12
Low serum folate
Low serum magnesium
Low serum potassium
Low serum retinol
Low serum vitamin C
Low serum vitamin D
Low serum zinc
The majority of individuals with IBD suffer from nutritional deficiencies. Providing adequate caloric intake is the most important aspect of nutritional therapy. The next step in dietary treatment involves the use of either an elemental or an elimination diet.
Elemental and Elimination Diets
An elemental diet is often an effective nontoxic alternative to corticosteroids as the primary treatment of acute IBD. An elemental diet is one that contains all essential nutrients, with protein being provided only in the form of predigested or isolated amino acids. However, the improvements seen in patients on an elemental diet are probably not primarily related to nutritional improvement; rather, the elemental diet is probably serving as an allergen-elimination diet. Some improvement may also be the result of alterations in the fecal flora that have been observed in patients consuming an elemental diet.29,30
Hospitalization is often required for satisfactory administration of elemental diets, and relapse is common when patients resume normal eating. An elimination diet may be a more acceptable alternative in the treatment of IBD, particularly chronic cases.
Elimination (oligoantigenic) diets are described in detail in the chapter “Food Allergy.” Basically they are diets consisting of foods that have a lower tendency to produce allergic reactions.
Food allergy has long been considered an important causative factor in the development of IBD, and studies have shown an elimination diet produces considerable benefit in the treatment of IBD.31–34 In fact, these studies demonstrate that an elimination diet should be the primary therapy in the treatment of chronic IBD. The most common offending foods were found to be wheat and dairy products. Hence, a gluten-free and dairy-free diet may also be effective.
An alternative approach is to determine the actual food allergens by laboratory methods, preferably a method that measures both IgG- and IgE-mediated reactions, such as the ELISA test (see the chapter “Food Allergy”). The allergens can then be avoided, or a diversified rotation diet may be appropriate.
Treatment with a high-fiber diet has been shown to have a favorable effect on the course of CD and UC.35 This is in direct contrast to one of the oldest conventional medical dietary treatments of IBD: a low-fiber diet. Although some foods, such as wheat bran, may be too difficult to handle, the dietary treatment of IBD should involve foods rich in fiber and unrefined carbohydrates, combined with a diet that avoids known food allergens or a diversified rotation diet. The combination is much more effective than a high-fiber diet alone.
Dietary fiber has a profound effect on the intestinal environment and is thought to promote a more optimal intestinal flora composition. However, considering the high degree of intolerance to wheat found in patients with IBD and the known roughness of wheat bran, supplemental wheat bran is not a good choice for these patients.
Multiple Vitamin and Mineral Formula
It is absolutely essential that patients with IBD take a high-quality multiple vitamin and mineral supplement that provides all of the known vitamins and minerals. Use the recommendations in the chapter “Supplementary Measures” to select a high-quality multiple.
Along with taking a high-potency multiple vitamin and mineral formula, individuals with IBD will need to take additional antioxidants, especially vitamin C and either grape seed, pine bark, or green tea extract, as individuals with IBD show increased oxidative stress and decreased antioxidant defenses in the lining of the intestines.36 Flavonoid-rich extracts such as grape seed, pine bark, and green tea are showing considerable benefits in preliminary studies and animal models of IBD.37
Zinc, Folic Acid, and Vitamin B12 in IBD
Three nutrients deserve special mention in the treatment of IBD: zinc, folic acid, and vitamin B12. Zinc deficiency is a well-known complication of CD, due to low dietary intake, poor absorption, and excess fecal losses.38 Evidence of zinc deficiency occurs in approximately 45% of CD patients, and in similar proportions of patients with UC. Low zinc concentrations in the blood, low zinc levels in the hair, malabsorption of zinc, altered urinary excretion of zinc, and impaired taste acuity are commonly found in CD patients. In addition, many of the complications of the disease may be a direct result of zinc deficiency: poor healing of fissures and fistulas, skin lesions, decreased sexual development (hypogonadism), growth retardation, retinal dysfunction, depressed immunity, and loss of appetite.39
Many IBD patients may not respond to oral or even intravenous zinc supplementation; there appears to be a defect in tissue transport. Supplying zinc in the form of zinc picolinate may be more advantageous, possibly improving both intestinal absorption and tissue transport. Picolinate is a zinc-binding molecule secreted by the pancreas and appears to be better absorbed and utilized than other forms of zinc in certain situations.
Like zinc deficiency, folic acid deficiency is quite common in IBD. The reason for this deficiency, in many cases, is the drug sulfasalazine.40 Correction of folate deficiency is absolutely essential because folate deficiency promotes further malabsorption and diarrhea due to altered structure of the intestinal mucosal cells.41 These cells have a very rapid turnover (one to four days) and need to have a constant supply of folic acid.
Since vitamin B12 is absorbed at the portion of the intestine most commonly affected with CD (the terminal ileum), deficiency of this vitamin is also quite common. Overall, abnormal B12 absorption is found in almost half of patients with CD.42 Often the terminal ileum of a CD patient has been surgically removed (resected). If the length of the resection is less than 60 cm, or the extent of the inflammatory lesion is less than 60 cm, adequate absorption may occur. Otherwise, intake of active vitamin B12 (methylcobalamin) in a daily sublingual tablet or a monthly injection (1,000 mcg intramuscularly) is recommended.
There is evidence that vitamin D deficiency is quite common in IBD, with laboratory evidence in 75% of CD and 35% of UC patients.43 This is probably a result of decreased absorption of vitamin D. Patients with IBD are at an increased risk for the development of metabolic bone diseases such as osteoporosis and osteomalacia. Vitamin D plays an important role is supporting proper immune regulation and has also been shown to dampen pro-inflammatory cytokines produced in animal models of IBD. Early research with supplemental vitamin D is encouraging, with 1,200 IU per day resulting in a reduction of relapse rate from 29 to 13% in one study after a year of treatment.44
Prebiotics are non-digestible food ingredients that stimulate the growth or modify the metabolic activity of intestinal bacterial species that have the potential to improve the health of their human host. Prebiotic food ingredients include bran, psyllium husk, resistant (high-amylose) starch, inulin (a polymer of fructofuranose), lactulose, and various natural or synthetic oligosaccharides, which consist of short-chain complexes of sucrose, galactose, fructose, glucose, maltose, or xylose. Bacterial fermentation of prebiotics yields short-chain fatty acids such as butyrate. Several studies have shown significant benefits of various prebiotics for the treatment of patients with UC. When oat bran at 60 g per day (supplying 20 g dietary fiber) was given to UC patients, fecal butyrate increased by 36% and abdominal pain improved.45
A dietary supplement containing fish oil and two types of indigestible carbohydrate, FOS and xanthan gum, allowed reduction of glucocorticoid dosage when compared with a placebo, in patients with steroid-dependent UC.46 In a trial, a Japanese germinated barley foodstuff containing hemicellulose-rich fiber at a dose of 20 to 30 g per day was found to increase stool butyrate concentration,47 decrease the clinical activity index of patients with active disease,48and induce prolonged remission in patients with inactive disease.49 In another trial, a mixture of Bifidobacterium longum and inulin-derived FOS administered for one month as monotherapy to patients with UC produced improvement in sigmoidscopic appearance and several biochemical indices of tissue inflammation when compared with a placebo.50
Probiotics are the beneficial bacteria and yeast that can be administered orally to achieve a therapeutic benefit. Over the last 20 years there have been numerous studies demonstrating the benefits of probiotic supplementation. For the most part, they are of little if any benefit during an active flare-up of disease; however there is significant benefit of probiotics for maintaining remissions. Several different probiotic organisms have shown benefit, including the beneficial yeast Saccharomyces boulardii and the bacteria Lactobacillus rhamnosus and Bifidobacterium species.50–58
Mental and emotional stress can promote exacerbation of IBD, so stress management techniques may prove useful for some patients. Psychological counseling to help deal with the stress of IBD was shown to also help reduce recurrences.59
Turmeric (Curcuma longa) contains the active anti-inflammatory compound curcumin. Studies have demonstrated that curcumin administration in animal models of IBD produced significant improvement and decreased inflammatory cytokine production.60–63
In a pilot study involving open-label administration of curcumin preparation to five patients with UC and five patients with CD, 9 of the 10 patients reported improvement at the conclusion of the two-month study.64 Four of the five patients with UC were able to decrease or eliminate their medications. In a larger, randomized, double-blind multicenter trial involving 89 patients with UC, administration of 1 g curcumin twice per day resulted in both clinical improvement and a statistically significant decrease in the rate of relapse.65 Given its excellent safety profile, its defined mechanism for affecting inflammation, and the results above, curcumin appears to have an important role in the management of IBD.
The ayurvedic herb Boswellia serrata (Indian frankincense) contains boswellic acids, which inhibit the production of inflammatory compounds involved in IBD.66 During a small six-week trial, 350 mg three times a day of boswellia gum resin was as effective as the drug sulfasalazine (1,000 mg three times a day) in reducing symptoms or laboratory abnormalities of patients with active UC.67 The rate of remission was 82% with boswellia and 75% with sulfasalazine.68 In another double-blind study, boswellia extract was found to be as effective as mesalazine is improving symptoms of active CD.69
Aloe vera gel inhibits the production of reactive oxygen metabolites and inflammatory mediators by human colon epithelial cells grown in tissue culture.70 When administered orally, aloe vera gel at 100 ml twice a day for four weeks produced a clinical response significantly more often than a placebo in patients with UC.71 Remission occurred in 30% of patients taking aloe vera gel and 7% of patients receiving the placebo. In this clinical trial, aloe also reduced objective measures of disease activity, whereas the placebo did not. Acemannan, an extract of aloe vera, at a mucopolysaccharide concentration of 30% of solid weight, has also been demonstrated to reduce symptoms and indices of inflammation in controlled studies of patients with UC.72
Calprotectin is a protein secreted into the intestinal lumen in direct proportion to inflammation. Measurement of calprotectin in stool samples has been shown to be a sensitive and specific noninvasive assessment for inflammation in patients with IBD, and the test is helpful for distinguishing IBD from other, noninflammatory gastrointestinal conditions, such as irritable bowel syndrome.73
Crohn’s Disease Activity Index (CDAI)
The CDAI provides a consistent numerical index for monitoring IBD.74 The CDAI is calculated by adding together eight variables (see the table below). It incorporates both subjective and objective information in determining relative disease activity. In general, CDAI scores below 150 indicate a better prognosis than higher scores. The CDAI is a very useful way to monitor progress of therapy.
Monitoring of the Pediatric Patient
Pediatric patients with IBD present a particularly difficult problem, in that it is often very difficult for them to achieve normal growth and development. Growth failure occurs in 75% of children with CD and in 25% of children with UC. The pediatric patient with IBD should receive an evaluation at least twice yearly by a knowledgeable physician, including detailed body and weight measurements and appropriate laboratory testing.
The list below outlines the necessary components of a comprehensive twice-yearly nutritional evaluation of pediatric patients with IBD. An aggressive nutritional program should be instituted, including supplements (it may be necessary to use injectable methods for some patients), that is similar to the approach outlined for the adult patient, with the doses adjusted as appropriate.
Parents of children who have IBD need to know the components necessary to monitor their children. They need not understand the significance of each component, but they do need to make sure that their children are being properly evaluated.
Independent Variables and Formula Used to Calculate the Crohn’s Disease Activity Index (CDAI)*
Number of liquid or very soft stools in 1 week
Sum of seven per day abdominal pain ratings:
0 = none 1 = mild 2 = moderate 3 = severe
Sum of seven per day ratings of general well-being:
0 = well 1 = slightly below par 2 = poor 3 = very poor 4 = terrible
Symptoms or findings presumed related to Crohn’s disease. Add 1 point for each category corresponding to patient’s symptoms:
• Arthritis or arthralgia • Iritis or uveitis • Erythema nodosum, pyoderma gangrenosum, aphthous stomatitis • Anal fissure, fistula, or perirectal abscess • Other bowel-related fistula • Episode of fever >100°F during past week
Taking diphenoxylate HCl/atropine sulfate tablets (Lomotil) or opiates for diarrhea:
0 = no 1 = yes
0 = none 0.4 = questionable 1 = present
47—hematocrit value, males 42—hematocrit value, females
100 (standard weight—body weight) ∏ standard weight
* CDAI = 2¥X1 + 5¥X2 + 7¥X3 + 20¥X4 + 30¥X5 + 10¥X6 + 6¥X7 + X8.
Source: Adapted from Ford-Hutchinson AW. J Allergy Clin Immunol 1984;74:437–440.
Monitoring of the Pediatric Patient with Inflammatory Bowel Disease
• Appetite, extracurricular activities
• Type and duration of inflammatory bowel disease, frequency of relapses
• Severity and extent of ongoing symptoms
• Medication history
• Three-day diet diary
• Height, weight, arm circumference, triceps skinfold measurements
• Loss of subcutaneous fat, muscle wasting, edema, pallor, skin rash, hepatomegaly
• Complete blood count and differential, reticulocyte and platelet count, sedimentation rate, urinalysis
• Serum total proteins, albumin, globulin, retinol-binding protein
• Serum electrolytes, calcium, phosphate, ferritin, folate, carotenes, tocopherol, vitamin B12
• Leukocyte ascorbate, magnesium, and zinc
• Creatinine height index, blood urea nitrogen/creatinine ratio
• Antibiotic exposure is being linked to Crohn’s disease.
• Over 100 disorders, known as extraintestinal lesions (EIL), constitute a diverse group of systemic complications of IBD.
• Clinical studies that have utilized an elemental diet, intravenous nutrition, or an exclusion diet have produced great success in the treatment of Crohn’s disease and ulcerative colitis.
• Treatment with a high-fiber diet has been shown to have a favorable effect on the course of CD and UC.
• Nutritional complications occur during the course of IBD.
• Foremost in nutritional therapy is providing adequate caloric intake.
• Elemental and elimination diets have been shown to be an effective nontoxic primary treatment of acute and chronic IBD.
• Treatment with a high-fiber diet has been shown to have a favorable effect on the course of Crohn’s disease.
• The majority of individuals with IBD suffer from nutritional deficiencies.
It is important to recognize that in some patients CD and UC are life-threatening diseases that at times require emergency treatment. A small percentage of patients who have severe UC may experience exacerbations requiring hospitalization.
Typically, IBD is a chronic disease requiring long-term therapy and follow-up. The first step is to identify and remove all factors that may be initiating or aggravating the inflammatory reaction, such as food allergens and low levels of omega-3 fatty acids or dietary antioxidants.
A broad-based nutritional supplementation plan is necessary for all patients with IBD. Particularly important are the nutrients zinc, folic acid, vitamin B12, magnesium, vitamin A, and possibly vitamin D. Nutritional supplements are used as appropriate to correct deficiencies, normalize the inflammatory process, and promote healing of the damaged mucosa. Botanical medicines are used to promote healing and normalize the intestinal flora.
The recommendations given in the chapter “A Health-Promoting Diet” are appropriate in IBD. All allergens, wheat, corn, and dairy products, and carrageenan-containing foods should be eliminated. The diet should be high in dietary fiber and low in sugar and refined carbohydrates.
• A high-potency multiple vitamin and mineral formula as described in the chapter “Supplementary Measures”
• Key individual nutrients:
Vitamin A: 2,500 to 5,000 IU per day (Note: dosages in excess of 3,000 IU per day should not be used in women who are or may become pregnant.)
Vitamin B6:25 to 50 mg per day
Folic acid: 800 mcg per day
Vitamin B12: 800 mcg per day
Vitamin C: 500 to 1,000 mg two to three times per day
Vitamin E (mixed tocopherols): 100 to 200 IU per day
Selenium: 100 to 200 mcg per day
Zinc (picolinate form recommended): 30 to 45 mg per day
Vitamin D3: 2,000 to 4,000 IU per day (ideally, measure blood levels and adjust dosage accordingly)
Fish oils: 1,000 mg EPA + DHA per day
• One of the following:
Grape seed extract (>95% procyanidolic oligomers): 100 to 300 mg per day
Pine bark extract (>95% procyanidolic oligomers): 100 to 300 mg per day
Green tea extract (>90% polyphenol content): 300 to 450 mg per day
Some other flavonoid-rich extract with a similar flavonoid content, super greens formula, or another plant-based antioxidant that can provide an oxygen radical absorption capacity (ORAC) of 3,000 to 6,000 units or more per day
• Probiotic (active lactobacillus and bifidobacteria cultures): a minimum of 5 billion to 10 billion colony-forming units per day
• Prebiotics (inulin, fructose oligosaccharides, etc.): 5 g per day
• Curcumin (Curcuma longa): 1,000 mg two to three times per day before meals
• Boswellia extract: equivalent of 400 mg boswellic acids three times per day
• Aloe vera, one of the following:
Aloe vera gel: 100 ml per day orally
Aloe vera juice: a variety of different preparation types and concentrations make accurate dosage recommendations difficult, but it can be consumed orally as a beverage or tonic
Acemannan: 400 to 800 mg per day