Inflammatory Bowel Disease

Inflammatory bowel disease is a common cause of discomfort and misery for tens of thousands of people in the United States. The two major types of inflammatory bowel disease are Crohn’s disease and ulcerative colitis. Because Crohn’s disease and ulcerative colitis are comparable and treated similarly, they have been combined in this chapter.

As the name implies, inflammatory bowel disease is characterized by inflammation within the gastrointestinal tract. In Crohn’s disease, the inflammation can extend to any part of the gastrointestinal tract, from the mouth to the anus. Up to 55 percent of people have Crohn’s disease that affects both the small and large intestines. In Crohn’s disease, diseased portions of the intestine often alternate with healthy intestinal areas. By contrast, ulcerative colitis is limited to the colon.

Both Crohn’s disease and ulcerative colitis typically have active periods followed by periods of remission. Conventional medical therapy relies on anti-inflammatories to provoke a remission and for remission maintenance. In serious cases, surgery may be necessary.

Fortunately, both diseases offer excellent opportunities for nutritional therapy. It is important that patients with these diseases pay careful attention to their nutritional intake, making sure to maintain healthy levels of nutrients. Many people with inflammatory bowel disease almost completely stop eating during flare-ups. Also, malabsorption of nutrients is a significant problem (especially in Crohn’s disease), making it doubly important to use supplements. Finally, a number of nutrients have been shown to reduce inflammation and possibly reduce symptoms associated with these difficult conditions.

No definitive cause has been uncovered for inflammatory bowel disease, although there is clearly an interaction among genetic, environmental, nutritional, and inflammatory factors (Marteau P et al 2004; Prehn JL et al 2004; Soderholm JD et al 2004).

Crohn’s Disease: Background and Diagnosis

Because of the nature of Crohn’s disease, nutritional supplementation is extremely important. The Life Extension Foundation advocates the 4-R Program (described later in this chapter) for people who have Crohn’s disease. This program of lifestyle changes and nutritional supplementation works to provide healthy digestion and absorption, while simultaneously reducing the inflammation and damage associated with Crohn’s disease.

Crohn’s disease can attack any portion of the digestive tract, although inflammation most commonly occurs in the lower portion of the small intestine, known as the ileum. The disease can cause ulcerations within the intestine that can erode into surrounding tissues such as the bladder (Sato S et al 1999), vagina (Feller ER et al 2001), or even the surface of the skin (Tavarela VF 2004). Inflammation in Crohn’s disease is not limited to the intestine—some people who have Crohn’s disease have inflammation of the eyes and joints as well.

The most common symptoms of the disease include severe abdominal pain with or without diarrhea. Diarrheal stool may be mixed with blood and often with mucus or pus. Bowel movements are often painful. Cramping in the right lower side of the abdomen is common, especially after meals. People with Crohn’s disease often have chronic low-grade fever, poor appetite, fatigue, and weight loss. Symptoms outside the gastrointestinal tract include joint pain and swelling, and occasionally eye pain and vision disturbances. Skin rashes may also occur. People who have Crohn’s disease almost always have some degree of anemia, related both to poor iron absorption and to chronic blood loss from inflamed tissue.

Guidelines produced by the American Society of Gastroenterology classify patients into mild-moderate, moderate-severe, or severe-fulminant disease categories. Those at the milder end of the spectrum can eat and function reasonably normally, while those at the severe end fail to respond to treatment and have persistent symptoms, fevers, and infections.

Diagnosis of Crohn’s disease is usually based on a patient’s medical history and symptoms. Diagnostic tests may be used to confirm the disease and to distinguish it from ulcerative colitis. Such tests include x-rays (with contrast material such as barium) and endoscopy, in which a fiber-optic telescope is passed into the intestines. Endoscopy allows specimens to be taken for culture and microscopic examination.

No blood test can diagnose Crohn’s disease, but routine testing is usually done to detect anemia, infection, and degree of inflammation, and to determine liver function. Certain markers of inflammation, such as erythrocyte sedimentation rate and C-reactive protein, may be used to follow a patient’s course over time.

Depending on the severity of the symptoms, medical treatment of Crohn’s disease involves a three-pronged approach: first, drug therapy and a restricted diet; second (if necessary), hospital treatment; and third, the last resort of surgery to remove the affected sections of the intestine. Some patients with Crohn's disease may be prescribed high-protein, high-calorie liquid supplements. Children may require these supplements to maintain growth and development (Gupta SK et al 2004).

Ulcerative Colitis: Background and Diagnosis

Ulcerative colitis is characterized by inflammation of the large intestine (colon) that leads to episodes of bloody diarrhea, abdominal cramping, and even fever. Unlike Crohn’s disease, ulcerative colitis usually doesn’t affect the full thickness of the intestine and never affects the small intestine. The disease usually begins in the rectum or sigmoid colon and spreads partially or completely through the large intestine.

Ulcerative colitis typically begins gradually, with abdominal pain and diarrhea that is sometimes bloody. In more serious cases, diarrhea is severe and frequent. Fever, loss of appetite, and weight loss occur. The severity of the disease depends on how much of the colon is involved. In about half of patients, the disease is limited to the rectum and rectosigmoid. In about 30 percent of patients, the disease extends beyond the sigmoid but does not involve the whole colon. In about 20 percent of people, the disease involves the entire colon (Kasper DL et al 2005).

The symptoms caused by ulcerative colitis tend to come and go. There may be long periods with no symptoms at all, followed by flare-ups. Approximately 70 percent of patients will have complete remissions between attacks. Ten percent of patients will have an initial attack and experience no subsequent attacks, and 15 percent to 20 percent will be troubled by continuous symptoms that occur without remission.

A definitive diagnosis can be made by direct examination of the colon by sigmoidoscopy (examination of the lower portion only) or colonoscopy (examination of the entire colon, the preferred approach). Both procedures can be used to take a biopsy of intestinal tissue, which can reveal important information about the degree and extent of inflammation and help rule out other causes of symptoms. Small, painless biopsies that reveal certain features of ulcerative colitis are sometimes taken. A barium enema x-ray of the colon will also be required at some point in the course of colitis. Once diagnosed, ulcerative colitis can be categorized based on the following disease severity:

• Severe. Severe ulcerative colitis, which involves the whole colon, is the least common form of the disease. Symptoms consist of profuse diarrhea (occurring six or more times per day), with constant and severe rectal bleeding. There is a sustained fever (up to 104°) and tachycardia greater than 90 beats per minute. Severe anemia, increased white blood cell count, and decreased serum albumin levels are also characteristic symptoms.
• Moderate. Symptoms consist of diarrhea that occurs less than five times a day, small amounts of blood in the stool, no fever or tachycardia, mild anemia, and minimal signs of inflammation. Moderate ulcerative colitis responds quickly to appropriate therapies. However, repeated attacks of equal or increased severity can occur, which can significantly increase the risk of developing colon cancer later.
• Mild. Mild ulcerative colitis is the most common form of the disorder, occurring in about 50 percent of patients. In most cases, ulcerative colitis will be limited to the lower portion of the colon and the rectum. Most often the disease will remain in this area, although in 10 percent of patients it will eventually involve the whole colon (Paterson WG et al 2000).

People who have colitis should consider having cytokine blood tests to measure autoimmune cytokine activity. These tests are simple and effective ways of monitoring cytokine levels and can be used as a measure of the effectiveness of any other therapies. Cytokine blood profiles measure tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (beta) (IL-1b), interleukin-6 (IL-6), leukotriene-B4 (LTB4), and leukotriene-C4 (LTC4).

Drug Treatments

Traditional treatments for inflammatory bowel disease depend on the disease’s location and severity, complications, and response to prior treatments. The goals of therapy are to control inflammation, correct nutritional deficiencies, and relieve symptoms such as abdominal pain, diarrhea, and rectal bleeding. Therapy may include drugs, nutritional supplementation, surgery, or a combination of approaches.

The following drugs are used to treat inflammatory bowel disease:

• Aminosalicylates. Aminosalicylates are drugs that contain 5-aminosalicyclic acid (5-ASA) and help control inflammation. These drugs are primarily used to treat mild to moderate inflammatory bowel disease, as well as to help with remission maintenance (Bebb JR et al 2004). Adverse effects include nausea, vomiting, heartburn, diarrhea, and headache. 5-ASA agents such as olsalazine, mesalamine, and balsalazide have a different carrier and fewer adverse effects and may be used by people who cannot take sulfasalazine. Balsalazide is one of the newest drug therapies and has the advantage of slow release. It is converted in the body to mesalamine and has been shown to reduce bowel inflammation, diarrhea, rectal bleeding, and stomach pain (Muijsers RB et al 2002). 5-ASA agents are given orally or rectally (through an enema or in a suppository), depending on the location of the inflammation.
• Corticosteroids. Corticosteroids (such as prednisone and hydrocortisone) reduce inflammation. They are used to treat more severe cases of inflammatory bowel disease and to induce remission. Corticosteroids can be given orally, intravenously, or rectally (through an enema or in a suppository), depending on the location of the inflammation. These drugs can cause serious adverse effects, including increased risk of infection, high blood pressure, bone loss, kidney suppression, and ulcers. Less serious adverse effects include weight gain, acne, facial hair, and mood swings. They are not recommended for long-term use and are typically replaced with 5-ASA drugs once remission has been induced.
• Antimetabolites. Antimetabolites (such as azathioprine and mercaptopurine) reduce inflammation by preventing replication of inflammatory cell lines. They are used to treat people with inflammatory bowel disease who have not responded to 5-ASAs or corticosteroids or who are dependent on corticosteroids. However, antimetabolites are slow acting; it may take up to 6 months before their full benefit is seen. Anyone taking these drugs should be monitored for complications such as pancreatitis, hepatitis, a reduced white blood cell count, and an increased risk of infection.
• Methotrexate. The cancer chemotherapy drug methotrexate can promote remission in approximately 50 percent of patients with inflammatory bowel disease but it is less effective in maintaining remission (Harrell LE et al 2004, Xu CT et al 2004). Methotrexate has been effective in treating patients who have moderate to severe ulcerative colitis and in patients with Crohn’s disease who are not responding to corticosteroids, mercaptopurine, or azathioprine. It can be given orally or by weekly injections under the skin or into the muscles (Xu CT et al 2004). Methotrexate is most reliably absorbed by injection.
• Infliximab. During flare-ups, levels of the inflammatory cytokine TNF-alpha become elevated. This has led to interest in drugs such as infliximab that suppress TNF-alpha. In early experiments, infliximab has shown clinical promise in treating inflammatory bowel disease and offers a good, although very expensive, therapy option. Its use is generally limited to severe cases of Crohn’s disease.
• Cyclosporine. This drug inhibits T cell-mediated immune responses, thus reducing the immune reaction that underlies inflammation. It blocks a number of inflammatory cytokines, including TNF-alpha and various interleukins. Because cyclosporine is associated with significant risk of toxicity, its use is limited to severe ulcerative colitis or Crohn’s disease.
• Pentoxifylline. Pentoxifylline is an inexpensive prescription drug that has been shown to lower TNF-alpha. This drug was approved to reduce blood viscosity and treat occlusive arterial disease, but a beneficial side effect is its ability to down-regulate the release of TNF-alpha, IL-1b, and IL-6. Pentoxifylline is well tolerated. It has very low toxicity and minimal adverse effects associated with chronic use. This makes it a very desirable drug for treatment of chronic conditions. The suggested dose of pentoxifylline to reduce these inflammatory cytokines is 400 milligrams (mg) twice a day.

Other drugs that may be considered include immunosuppressive agents such as tacrolimus, mycophenolate mofetil and thalidomide. Each of these drugs acts to reduce the immune response.

Nutrient and Supplement Therapy

Because most medications for inflammatory bowel disease have substantial adverse effects, people who have inflammatory bowel disease may want to seek additional or alternative treatments. Attention to nutrition and diet can reduce dependence on medications to stave off active disease or induce remission. Intolerance to certain foods and other nutritional factors can be causes of exacerbations, so elimination of these is important to avoid flare-ups.

In people who have Crohn’s disease, elemental diets (in which nutrients have been reduced to simple molecules) have been shown to be as effective as corticosteroids at inducing remission (Ogata H et al 2003; O'Keefe SJ 1996). In patients already taking prednisone, the drug could be reduced or eliminated in 50 percent of patients who follow an elemental diet. While on an elemental diet, inflammatory parameters and intestinal permeability decrease (Meister D et al 2002; Teahon K et al 1991). This diet does not work for ulcerative colitis.

The 4-R Program for Crohn’s Disease

The following steps are recommended to help patients with Crohn's disease first reduce their symptoms and then begin long-term repair of the damage caused by their disease:

• Remove. Remove all suspicious foods from the patient's diet that precipitate inflammation. The following are the most likely to be troublesome: dairy, eggs, nuts, fruit, tomatoes, corn, wheat (or gluten), and red meat. All refined carbohydrates should be removed. All fats except for essential fatty acids should be eliminated, because hard or trans fats are detrimental to people with Crohn's disease (Heckers H et al 1988; Lorenz-Meyer H et al 1996). Products such as Vivonex®, UltraMaintain®, or UltraClear® can be used at the outset. UltraClear® is preferable because it contains sufficient fiber to maintain regular bowel evacuation. Removal of gastrointestinal parasites, undesirable bacteria, or fungal elements is important.
• Replace. The diets of most patients who have inflammatory bowel disease are nutritionally imbalanced. Replacement of vital nutrients consists of a good multivitamin, together with minerals that are lacking. The vitamins that most patients with inflammatory bowel disease lack are the B-complex vitamins such as folic acid and vitamin B6, and particularly vitamin B12 (Rogler G et al 2004). Iron and calcium deficiencies are frequently found in patients with Crohn's disease (Capurso G et al 2002; Lomer MC et al 2004; Siffledeen JS et al 2003), as well as deficiencies in zinc, protein, vitamin D, and folic acid (Rath HC et al 1998; Siffledeen JS et al 2003). Patients with Crohn’s disease are usually under increased oxidative stress and have lower levels of antioxidant vitamins. Supplementation with vitamins C and E reduces oxidative stress (Aghdassi E et al 2003). Long-term use of corticosteroids warrants the inclusion of supplemental calcium and vitamin D to prevent corticosteroid-induced osteoporosis.
• Reinoculate. A normal healthy intestine contains 5 to 7 pounds of friendly bacteria, the good bacteria that are responsible for manufacturing some vitamins and cell food in the intestine. In a diseased intestine, these bacteria are not present in adequate amounts or are absent, having been replaced by pathogenic organisms or yeast overgrowth. Reinoculation consists of taking mixtures of the friendly bacteria Lactobacillus acidophilus and Lactobacillus bulgaricus along with fructose oligosaccharides to promote continued repopulation with these beneficial bacteria (Fedorak RN et al 2004). Inhibition of pathogens by lactobacilli follows the lowering of pH through liberation of acids, resulting in an antimicrobial action. Stool samples provide information regarding these overgrowth factors, pH, and the balance of fatty acids.
• Repair. Frequently the lining of the small intestine becomes permeable, allowing antigens and other incompletely digested products to pass through the bowel wall. Repair of the protective layer consists of adding nutrients such as pantothenic acid (vitamin B5), zinc (Cario E et al 2000; Kapp A et al 1991; Weimann BI et al 1999), fructose oligosaccharides, and vitamin C to build up the integrity of the intestinal wall itself.

In a study of patients who had Crohn’s disease with “leaky gut” (increased intestinal permeability as measured by a lactose/mannitol challenge), patients who did not have their small bowel mucosal integrity restored (those who still had a leaky gut), relapsed within 1 year (76 percent to 81 percent of the patients). Patients with normal intestinal mucosal integrity and healing had less than a 5 percent probability of relapse (Wyatt J et al 1993).