Inflammatory Bowel Disease

Supplements for Healthy Digestion

The following supplements can promote a healthy digestive system:

Antioxidants. Normal digestion produces a host of reactive oxygen and nitrogen species (also known as free radicals), against which the intestinal mucosa maintains an extensive system of antioxidants. When presented with excessive oxidant stress, however, the mucosal barrier can sustain damage and become leaky, setting the stage for inflammation.

Inflammation itself produces large quantities of reactive species, and a destructive cycle can be perpetuated. In patients who have inflammatory bowel disease, there are high levels of reactive oxygen species in the intestines, which contributes to the damage caused by the disease. Oxidative damage is emerging as a key factor in the disease process (Koutroubakis IE et al 2004). The levels and the balance of important antioxidants are impaired within intestinal mucosa in inflammatory bowel disease (Kruidenier L et al 2003). Studies have shown that antioxidant combinations, including vitamin A, vitamin C, vitamin E, and selenium, can reduce the symptoms associated with inflammatory bowel disease (Trebble TM et al 2004, 2005).

Butyrate. Butyrate (also known as butyric acid) is a short-chain fatty acid produced when intestinal fiber is metabolized by bacteria. Butyrate ameliorates inflammation in ulcerative colitis and Crohn’s disease, but the mechanism is not known. One mechanism by which butyrate may function is to inhibit the activation of a proinflammatory cell–signaling component called nuclear factor kappa B (NF-kappa B). This inhibition makes cells less responsive to proinflammatory cytokines (Segain JP et al 2000). Butyrate is often administered as an enema twice daily. The turmeric extract known as curcumin also inhibits NF-kappa B and can be taken orally.

Selenium. Selenium is a potent antioxidant necessary for metabolism of calcium and vitamin C, conversion of blood sugar into energy, reduction of platelet aggregation, and promotion of cardiovascular health. Selenium deficiency is common in people who have inflammatory bowel disease (Ishida T et al 2003; Kuroki F et al 2003). Supplementation may alleviate this problem.

Omega-3 fatty acids. Omega-3 fatty acids are well-known anti-inflammatories. They can be found in cold-water fish such as salmon, halibut, sardines, trout, or herring. Precursors to the most active omega-3s (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) can be obtained in walnut oil, flaxseed oil, perilla oil, and canola oil. Omega-3 fatty acids have been shown to reduce inflammation in inflammatory bowel disease by reducing the production of inflammatory cytokines (Almallah YZ 1998; Hillier K 1991; Ross E 1993; Steinhart AH 1997). They may also reduce the dosage of corticosteroid drugs needed to cause a remission (Grimminger F 1993; Hawthorne AB et al 1992). Gamma linolenic acid (GLA), an omega-6 fatty acid found in evening primose oil, borage seed oil, and blackcurrant oil, is also showing promise in ulcerative colitis (Burke A et al 1997).

Similarly, a ginger extract called zerumbone has been shown to reduce inflammatory biomarkers in animals that have inflammatory bowel disease (Murakami A et al 2003).

Glutamine. Glutamine is an amino acid that is frequently used as a sports and fitness supplement. It has been found to help modulate the immune system and protect the mucosal protective layer in the intestine. Studies have demonstrated that glutamine can help improve blood flow in inflamed segments of the colon in patients who have ulcerative colitis, although its benefits did not extend to the most seriously affected portion of the colon (Kruschewski M et al 1998). Glutamine is also able to reduce leakiness of the intestine, which may help to reduce symptoms of inflammatory bowel disease.

Arginine. Research has suggested that arginine suppresses the growth of some strains of unfavorable bacteria and inhibits bacterial toxin release, a common problem in people who have chronic intestinal inflammation (Karasawa T 1997). Dietary supplementation of RNA and arginine promote healing of small-bowel ulcers in experimental ulcerative ileitis. Rats with experimental ileitis that received yeast RNA and/or arginine showed a significant decrease in the number of their ulcers compared to control rats. Scientists concluded that diets that were supplemented with yeast RNA, alone or in combination with arginine, accelerated ulcer healing by promoting increased cell proliferation (Sukumar P 1997; Vardareli E et al 2003).

Other studies, however, raise questions about the use of arginine for some models of colitis. Arginine promotes nitric oxide synthesis, and excess nitric oxide production may be detrimental to patients with colitis. Although many people benefit from the healthy effects of arginine-induced nitric oxide synthesis, some patients with colitis may not.

Dehydroepiandrosterone (DHEA). DHEA plays an important role in preventing chronic inflammation and provides signals needed to maintain healthy immune function. DHEA is a vitally important hormone. In fact, published studies link low levels of DHEA to aging and diseased states. Specifically, a deficiency of DHEA has been found to correlate with chronic inflammation. Excess levels of one or more of the inflammatory cytokines (TNF-alpha, IL-6, IL-1b, or LTB4) are usually found when a cytokine blood profile is conducted. DHEA has been shown to lower these proinflammatory cytokines and protect against their toxic effects (Haden ST et al 2000; Kipper-Galperin M et al 1999; Straub RH et al 1998). These proinflammatory cytokines rise with age and are especially high in patients who have inflammatory diseases. DHEA has consistently been shown to boost beneficial interleukin-2 (IL-2) and suppress damaging IL-6 levels.

The deficiency of DHEA in inflammatory diseases also implies a deficiency in peripheral tissue of various sex hormones for which DHEA serves as a precursor. These hormones, both estrogenic and androgenic, are known to have beneficial effects on muscle, bone, and blood vessels. Mainstream therapy with corticosteroids is also known to lower androgen levels. Consequently, researchers argue that hormone replacement for patients who have chronic inflammatory diseases should include not only corticosteroids but also DHEA (Andus T et al 2003; Straub RH et al 2000).

Probiotics. With more than 400 microorganism species in the human gastrointestinal tract, the overall balance can profoundly influence intestinal health. Intestinal bacteria produce toxins and antitoxins, alter chemical composition of foods and drugs, produce and degrade vitamins, degrade dietary toxins, and inhibit the growth of certain pathogens. Intestine-derived bacterial products play a role in the systemic immune inflammatory response (Chin J 2004). Several probiotic mechanisms of action have been elucidated. Probiotics compete with microbial pathogens for a limited number of receptors present on the surface epithelium, have antimicrobial activity, suppress pathogen growth, and enhance barrier function (Fedorak RN et al 2004; Furrie E et al 2004).

Vitamin K. Vitamin K is used by the body to regulate blood clotting. A deficiency in vitamin K can result in bruising or bleeding. Patients with ulcerative colitis are frequently deficient in vitamin K. One study showed that 31 percent of patients who had chronic gastrointestinal disease had a vitamin K deficiency, and all of them had either ulcerative colitis or Crohn’s disease (Krasinski SD et al 1985).

Fiber

Dietary fiber is essential to good health and is found in many plant foods, such as fruits, vegetables, beans, nuts, and whole grains. Insoluble fiber found in such foods as fruit pulp, vegetable peels and skins, and grain brans adds bulk to stool and hastens the movement of food through the digestive tract, helping to prevent constipation and diarrhea. Soluble fiber found in fruits, vegetables, grains, oatmeal, and dried beans helps to lower cholesterol and prevent such diseases as colon cancer and diabetes.

A high-fiber diet may be helpful in reducing flare-ups of colitis. However, during active cases of colitis, fiber should be avoided because of its harshness to the walls of the intestinal tract. Juice from green leafy vegetables is a better alternative. After healing occurs, soluble fibers can be reintroduced into the diet.

Surgery: A Last Resort

In severe or advanced cases of Crohn’s disease, abscesses can develop in chronically inflamed tissues. These abscesses can grow and tunnel through tissue barriers to produce fistulas, or channels between organs. More than one third of patients who have Crohn’s disease develop perianal disease involving anal fissures and perianal abscesses and fistulas. These symptoms seldom respond well to conventional therapies (Braunwald E 2001; McNamara DA et al 2004). Surgery may be required to drain abscesses or remove and close fistulas (Danelli P et al 2003). Surgery on inflamed tissue is itself potentially dangerous, and complications are frequent.

Surgery may also be recommended to remove severely inflamed portions of the intestinal tract. The goal of surgery is to preserve as much of the intestine as possible. Surgery commonly involves the colon or small intestine. Occasionally, the end of the intestine that has been left in place will need to be brought to the skin's surface. When this procedure involves the small intestine, it is called an ileostomy. If the procedure involves the colon, it is called a colostomy. Although Crohn's disease may recur after surgery, the symptoms are likely to be less severe and less debilitating than they were previously. However, when the disease does recur, it usually does so at the site of the last surgery.

In patients with ulcerative colitis, surgery is indicated for up to half of patients in the first decade of their illness. At one time, the surgery of choice was removal of the anus and a portion of the lower colon, which resulted in lifelong incontinence and an ileostomy. Newer surgeries, however, have been developed that can preserve fecal continence by using part of the ileum to create a pouch that is connected to the intact rectal sphincter.

The Protective Effect of Folate on Colon Cancer in Ulcerative Colitis

Evidence suggests that people with ulcerative colitis are at increased risk of colon cancer (Mitamura T et al 2002). About 5 percent of people with ulcerative colitis develop colon cancer. The risk of cancer increases with the duration and the extent of involvement of the colon. For people with ulcerative colitis, there are two factors affecting the risk of developing colon cancer. The first factor is that risk increases after 8 to 10 years of having ulcerative colitis. The second is the extent of the disease in the colon. Patients who have ulcerative colitis only in the rectum have the lowest risk. Having the disease in only part of the colon carries an intermediate risk. The greatest risk is for people whose entire colon is diseased (called pancolitis) (Itzkowitz SH et al 2004). It is assumed that chronic inflammation is what causes cancer in ulcerative colitis. This is supported by the fact that colon cancer risk increases with longer duration of colitis, greater anatomic extent of colitis, and the concomitant presence of other inflammatory manifestations (Itzkowitz SH et al 2004).

Two case-control studies have shown that folate may protect against the development of colon cancer caused by ulcerative colitis. The most recent study showed that folate use for at least 6 months reduced the risk of colon cancer by 28 percent in 98 patients who had ulcerative colitis for at least 8 years. Of the patients with ulcerative colitis, 29.6 percent developed cancerous lesions. The greater the dose of supplemental folate consumed, the lower the rate of colon cancer. Scientists concluded that “daily folate supplementation may protect against the development of neoplasia in ulcerative colitis” (Lashner BA et al 1997). Supplementing the diet with vitamin B12 enables the body to metabolize folate better and avoids masking a vitamin B12 deficiency. Vitamin B12 supplementation is important, particularly for older people (when it is less effectively absorbed) and for vegetarians (because vitamin B12 is found only in red meat).

Inflammatory Bowel Disease Raises Homocysteine Levels

A number of studies have shown that patients with inflammatory bowel disease are more likely to have elevated homocysteine levels. In one study, more than 55 percent of patients with inflammatory bowel disease had elevated homocysteine levels (Roblin X et al 2006). The greatest risk factor for elevated homocysteine in patients with inflammatory bowel disease is reduced folate levels (Zezos P et al 2005). Vitamin B12 deficiencies are also frequently encountered (Mahmood A et al 2005). Certain drugs used to treat inflammatory bowel disease, such as methotextrate, are antimetabolites for folic acid, which may help explain why so many patients are deficient in this vital nutrient.

The elevated homocysteine level that is typical in patients with inflammatory bowel disease accounts for a 3-fold higher risk of blood clots and vascular disease (Fernandez-Miranda C et al 2005; Srirajaskanthan R et al 2005). It also helps explain why patients with inflammatory bowel disease are more likely to have early atherosclerosis (Papa A et al 2005). Based on these findings, it is logical that patients with inflammatory bowel disease should take a prophylactic B complex vitamin, with adequate folic acid and vitamin B12.

Inflammatory Bowel Disease and Bone Loss

Osteoporosis is a serious complication of inflammatory bowel disease that has not received adequate recognition despite its high prevalence and potentially devastating clinical effects (Compston JE 1995; Harpavat M et al 2004; Scharla SH et al 1994). Osteoporosis can be caused by inflammatory bowel disease itself or it can be an adverse effect of corticosteroid treatment. Data derived from a retrospective survey of 245 patients with inflammatory bowel disease suggest that the prevalence of bone fractures in people with ulcerative colitis and Crohn’s disease is unexpectedly high, particularly in patients who have a long duration of disease, frequent active phases, and high cumulative doses of corticosteroid intake (Bischoff SC et al 1997; Gassull MA 2003; Vanis N et al 2003). Recent advances in the diagnosis and management of osteoporosis have facilitated early detection of bone loss and identified means by which it may be prevented. Bone-density measurements to predict fracture risk and define thresholds for prevention and treatment should be performed routinely in patients with inflammatory bowel disease (Rogler G et al 2004). For more information, see the chapter Osteoporosis.

Corticosteroids can also contribute to the risk of osteoporosis because of their effects on calcium and bone metabolism. Corticosteroids suppress calcium absorption in the small intestine, increase calcium excretion by the kidneys, and alter protein metabolism. Patients with inflammatory bowel disease who are taking corticosteroids experience a 6.2 percent annual loss of total bone mass compared with only a 0.9 percent annual loss of total bone mass in patients who are not taking corticosteroids. Nutrients that can help protect bone loss include calcium, vitamin D, and vitamin K.