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Inflammation & Digestion

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Inflammatory Bowel Disease


Inflammatory bowel disease (IBD) is not a single condition. It is the term for a group of disorders that cause prolonged inflammation of the digestive tract.

The digestive tract is composed of the mouth, esophagus, stomach, small intestine, and large intestine. It is responsible for breaking down food, extracting the nutrients, and removing any unusable material and waste products. Inflammation anywhere along the digestive tract disrupts this normal process. This can be very painful. In some cases, IBD can even be life threatening.


What Are the Main Types of Inflammatory Bowel Disease?


Many diseases are included in this umbrella term. The two most common are ulcerative colitis and Crohn’s disease. Crohn’s disease can cause inflammation in any part of the digestive tract. However, it mostly affects the tail end of the small intestine. Ulcerative colitis is inflammation of the large intestine. It gets its name because the colon is another name for the large intestine. The “itis” suffix means inflammation.


What Causes Inflammatory Bowel Disease?

IBD is a collection of several diseases. Therefore, it does not have a single cause. However, some IBD has been linked to heredity. It can also be caused by problems with the immune system.

Heredity

If you have a sibling or parent with IBD, you are more likely to develop it yourself. Therefore, scientists think IBD may have a genetic component.

The Immune System

The immune system also plays a role in IBD. Normally, the immune system defends the body from pathogens. A bacterial or viral infection of the digestive tract can trigger an immune response. The digestive tract becomes inflamed as the body tries to fight off the invaders. When the infection is gone, the inflammation recedes. That’s a healthy response.

Some people with IBD experience digestive tract inflammation even when there is no infection. The immune system attacks the body’s own cells instead. This is known as an autoimmune response.

Another cause of IBD is inflammation not receding after an infection is cured. In people with IBD, such inflammation is prolonged. It may continue for months or years.


What Are the Risk Factors For Developing Inflammatory Bowel Disease?

The Centers for Disease Control and Prevention (CDC) estimates that 1.4 million people in the U.S. suffer from IBD. Environmental factors have a big impact on the development of Crohn’s disease and ulcerative colitis. Some other risk factors include:

Smoking

Smoking is one of the biggest risk factors for developing Crohn’s disease. Smoking also aggravates pain and other symptoms and increases the risk of complications. However, ulcerative colitis primarily affects non-smokers and ex-smokers.

Ethnicity

IBD occurs in all populations. However, certain ethnic groups such as Caucasians and Ashkenazi Jews have a higher risk.

Age

In most cases, IBD starts before the age of 30. However, it can show up at any age.

Family History

People who have a parent, sibling, or child with IBD have a much higher risk of developing it themselves.

Geographical Region

People in urban areas and industrialized countries have a higher risk of IBD. So do those who work in white-collar jobs. This can partially be explained by lifestyle choices and diet. People who live in industrialized countries consume more fat and processed food. This may also explain the increase in IBD incidence from southern to northern latitudes.

Gender

Overall, IBD affects both genders equally. Ulcerative colitis is more common in men. Crohn’s disease is more common in women.


What Are the Symptoms of Inflammatory Bowel Disease?

Specific symptoms of IBD vary depending on the location and severity of any inflammation.

Diarrhea occurs when affected portions of the bowel can’t reabsorb water.

Bleeding ulcers may cause blood to show up in the stool. This is calledhematochezia.

Inflammation can thicken the wall of the intestine and block the passage of fecal material. This can cause pain, cramping, and bloating.

Problems absorbing essential nutrients can lead to weight loss and anemia. They can also cause delayed growth or development in children.

People with Crohn’s disease may get canker sores in their mouths. Sometimes ulcers and fissures also appear around the genital area or anus.

Finally, IBD can be associated with problems outside the digestive system, such as:

- eye inflammation

- skin disorders

- arthritis


What Are the Possible Complications from Inflammatory Bowel Disease?

Possible complications of IBD include:

- malnutrition

- colon cancer

- fistulas – a fistula is an ulcer that goes through the bowel wall, creating a hole between different parts of the digestive tract

- intestinal rupture

- bowel obstruction


In rare cases, a severe bout of IBD can put you into shock. This can be life threatening. Shock is usually caused by blood loss during a sudden and prolonged episode of bloody diarrhea.


How Is Inflammatory Bowel Disease Diagnosed?

The first step in diagnosing IBD is a thorough medical history. This will include questions about family history as well as information about bowel habits. A physical exam may then be followed by one or more diagnostic tests.  

Stool Sample and Blood Tests

These tests can be used to look for infections and other diseases. Blood tests can also sometimes be used to distinguish between Crohn’s disease and ulcerative colitis. However, blood tests alone cannot be used to diagnose IBD.

Barium Enema

Barium enemas are used to make the colon and small intestine visible by X-ray. Although they used to be done frequently, other tests have largely replaced them.

Flexible Sigmoidoscopy and Colonoscopy

These procedures use a camera on the end of a thin, flexible probe to look at the colon. The camera is inserted through the anus. It allows your doctor to look for ulcers, fistulas, and other damage. Colonoscopy can examine the entire length of the large intestine. Sigmoidoscopy examines only its last third, the sigmoid colon.

Sometimes during these tests a small sample of bowel wall will be taken. This is called a biopsy. Examining this biopsy under the microscope can be used diagnose IBD.

Capsule Endoscopy

The small intestine is much harder to examine than the large intestine. For this test, you swallow a small capsule containing a camera. As it moves through your intestine, it takes pictures. Once you have passed the camera in your stool, the pictures can be seen on a computer.

This test is only used when other tests have failed to find the cause of Crohn’s disease symptoms.

Plain Film or X-Ray

A plain abdominal X-ray is useful in emergency situations when intestine rupture is suspected.

Computer Tomography (CT) and Magnetic Resonance Imaging (MRI)

CT scans are basically computerized X-rays. They create a more detailed image than a standard X-ray. This makes them useful for examining the small intestine. They can also detect complications of IBD.

MRIs use magnetic fields to form images of the body. They are safer than x-rays. MRIs are good for examining soft tissues. They are especially useful in detecting fistulas.

Both MRIs and CT scans can be used to determine how much of the intestine is affected by IBD.


How Is Inflammatory Bowel Disease Treated?

There are a number of different treatments that can be used for IBD.

Anti-inflammatory drugs are the first step in IBD treatment. These drugs decrease inflammation of the digestive tract. However, they have many side effects. Anti-inflammatory drugs used for IBD include sulfasalazine and its derivatives and corticosteroids.

Immune suppressants prevent the immune system from attacking the bowel and causing inflammation. This group includes drugs that block TNF. TNF normally modulates inflammatory activity in the body. These drugs also have many side effects.

Antibiotics are used to kill bacteria that may trigger or aggravate IBD symptoms.

Anti-diarrheal drugs and laxatives can be used to treat IBD symptoms.

Lifestyle choices are important when you have IBD. Drinking plenty of fluids helps to compensate for those lost in stool. Avoiding dairy products and stressful situations also improves symptoms. Exercise can help improve your health, as can stopping smoking.

Vitamin and mineral supplements can help with nutritional deficiencies. For example, iron supplements can treat anemia.

Surgery can sometimes be necessary for people with IBD. Some IBD surgeries include:

- strictureplasty to widen narrowed bowel

- surgery to close or remove fistulas

- removal of affected portions of the intestines, for people with Crohn’s disease

- removal of the entire colon and rectum, for severe cases of ulcerative colitis


Routine colonoscopy is used to monitor your increased risk for colon cancer.

Digestive Inflammation, Ghrelin and Food Cravings


Ghrelin is the hunger hormone made by your stomach; it travels to your brain and impacts your desire to eat. Digestive inflammation elevates ghrelin and increases appetite even when you don’t need food. The more you crave sugar or carbohydrates the greater the problem. The problem can extend to an intense craving for high calorie foods of any type, and a subconscious desire to excessively indulge in the pleasure of eating for pleasure’s sake.

Digestive Inflammation and Appetite

Ghrelin activation is vital for maintaining your blood sugar during calorie restriction or starvation. It is also required for the release of growth hormone that repairs your body and for bowel motility so that your digestive tract moves along in a timely manner and you don’t get heartburn. Ghrelin levels are elevated during digestive distress in an effort to coordinate repair of your digestive tract. If digestive issues persist, ghrelin will remain elevated.

The adverse side effect of elevated ghrelin is that your appetite will increase and you will eat more food, making you gain weight. On the other hand, if you lose your appetite from the digestive inflammation then your body is entering a more serious state of inflammatory-driven malnutrition.

Research pointing out this unique feature of ghrelin comes in part from Celiac research1. Patients with Celiac have highly elevated ghrelin2 that correlates directly to the amount of digestive damage, which lowers when they quit eating gluten for a while. It also comes from research showing that ghrelin is elevated by bacterial endotoxins known as LPS3 (which also inflame your digestive tract). The research shows that ghrelin acts as a powerful repair compound to assist digestive healing4.

It is unfortunate that millions of Americans live with chronic digestive imbalances characterized by an overgrowth of hostile bacteria or candida albicans, resulting in an ongoing overload of LPS toxins and other inflammatory irritants that constantly inflame the GI tract. 

Since elevated ghrelin drives the urge for sugar or carbohydrates, it means that cravings for these concurrent with digestive distress indicates a flare up or problem with an overgrowth of bacteria orcandida albicans. It also means that when you eat better and improve your digestive health that the cravings will go away because your digestive tract is doing better.

How to Improve Digestive Health, Balance Ghrelin, and Reduce Cravings

Friendly flora and fiber - Make sure that you are getting higher levels of fiber, 30 - 60 grams per day. Fiber helps bind LPS and acts as a substrate for the fermentation of friendly flora in your digestive tract. Friendly flora supplements have been shown to lower LPS by promoting a better balance of bacteria in your digestive tract, and would be a basic step in addition to higher fiber intake. Friendly flora has been shown to reduce other types of digestive inflammation as well.

Colostrum and bitter herbs - Colostrum helps improve digestive tract repair. Research shows bovine colostrum taken by humans can lower blood levels of toxic LPS and lower inflammatory markers. It contains unique compounds that help heal an inflamed digestive tract. By protecting against damage to the intestinal linings, colostrum has been shown to prevent bacteria from entering the body. I often combine colostrum with bitter herbs like gymnema sylvestre and inula racemosa to help curb cravings.

Chlorella - Chlorella is a nutrient-dense green algae superfood that has also been shown to lower LPS levels in the blood while repairing the digestive tract, directly offsetting the stress of bacterial imbalance in the digestive tract. Chlorella helps lower high leptin levels, prevent excess new fat cells, and can help lower blood sugar and cholesterol.

If you have digestive distress and excess carbohydrate cravings, at least part of the problem is your digestive system trying to fix itself and repair its lining. Those with a history of digestive issues should recognize increased carbohydrate or sugar cravings as a potential first sign in a flare up of digestive problems. Taking fast action to correct the digestive issue will not only stabilize your health, it may prevent you from gaining weight or gaining back weight after a period of weight loss.

Supplements for Inflammatory Bowel Disease


The use of nutraceutical supplements by patients with gastrointestinal disorders is widespread and growing. Most studies cite that 50% of patients with inflammatory bowel disease use nutraceutical supplements. There is an abundance of clinical trials demonstrating efficacy of nutraceutical supplements for IBD.  Probiotics, prebiotics, butyric acid enemas, Curcuma longa, Boswellia serrata and fish oils have been shown to be superior to placebo and in some cases equal to standard medical therapy in randomized trials.  Thus the nutraceutical supplements that have been shown to have established efficacy for inflammatory bowel disease are reviewed.

Inflammatory Bowel Disease (IBD): The Gut on Fire
Inflammatory bowel disease is a chronic condition characterized by frequent relapses, hospitalizations, diminished quality of life (QOL), complications that require surgery and intestinal cancer.  The pathophysiology of IBD involves an unremitting intestinal inflammation, noninflammatory cytokines, increased reactive oxygen species and tissue injury that is oftentimes triggered by luminal bacteria. Opportunities for natural product therapy include the modulation of mediators involved in the inflammatory process, altering luminal bacteria, modifying the immune response and rejuvenation of intestinal healing.

Usage of supplements for IBD
Surveys of complementary and alternative approaches by patients with gastrointestinal complaints have reported rates of utilization well over 50%. Of all digestive disorders, usage appears to be most common in patients with IBD and IBS.  Table 1 summarizes the latest research on the utilization patterns of complementary and alternative medicine  (CAM) use in IBD.  Surveys have also addressed the reasons why patients used nutraceutical supplements for IBD and which ones they felt to be the most effective.  Given their widespread usage, healthcare practitioners now need to be familiar with the potential benefits of nutraceutical supplements for IBD in an effort to offer superior care to their patients. 

Herbal Therapies

a. Aloe vera
A randomized, double-blind, controlled study showed that aloe vera gel, given for 4 weeks to patients with moderately active UC was superior to placebo . Clinical remission, improvement and response occurred in nine (30%), 11 (37%) and 14 (47%), respectively, of 30 patients given Aloe Vera, compared with one (7%), one (7%) two (14%; P < 0.05), respectively, of 14 patients taking placebo (using a 2:1 A. vera: placebo randomization schedule). The Simple Clinical Colitis Activity Index and histological scores decreased during treatment with A. Vera but not with placebo.

b. Wheat grass juice
In a randomized, double-blind, controlled trial, 23 patients with active distal UC were given oral wheat grass juice or placebo for 4 weeks.Treatment with wheat grass juice was associated with greater reductions in a composite clinical disease activity index, severity of rectal bleeding and physician’s global assessment than occurred in the placebo group. No side-effects were reported.

c. Germinated barley foodstuff
Two open-label Japanese trials suggested efficacy in UC for a germinated barley foodstuff (GBF), which consists mainly of dietary fiber and glutamine-rich protein.  The authors believe this substance acts primarily as a prebiotic.  In the first report, 11 patients given GBF for 4 weeks as adjunctive treatment showed a greater fall in clinical disease activity than nine patients given conventional therapy alone. In a follow-up study, 24 weeks of treatment of 21 patients with GBF together with continuing 5-ASA and steroid therapy reduced rectal bleeding and nocturnal diarrhea. Adjunctive GBF also produced a lower relapse rate over 12 months when given to 22 patients with UC in remission than did conventional therapy in 37 such patients.  GBF was well tolerated and appeared to be safe in all three reports.

d. Polyphenols
Polyphenols are phytochemicals that are found in food substances produced from plants.  Polyphenols are separated from essential micronutrients in that a deficiency state has not been identified; nevertheless, these chemicals are believed to play a biologically-active role and have been shown to be potentially immune-modulating. For IBD, downregulation of inflammatory mediators and nuclear factor kappa beta (NFkB) are broad mechanisms of action for polyphenols’ therapeutic effects.
 
Although numerous polyphenols have been identified, five in particular have evidence of benefit for animal and human studies in IBD including: resveratrol, epigallocatechin, curcumin, quercetin and Boswellia.   Resveratrol, epigallocatechin, curcumin and quercetin have been demonstrated to display both prophylactic and therapeutic effects for colitis in animals; however quercetin was the least effective of the polyphenols studied.   In humans, clinical studies of polyphenols for the treatment of IBD are limited to Boswelia serrata and Curcuma longa. 

Boswellia serrata
Boswellia serrata (‘frankincense’) is a traditional Ayurvedic remedy and a component of incense. In India, the effect of the gum resin from B. serrata in moderately active UC was compared with sulfasalazine. Remission rate in the Boswellia group (82%) resembled that occurring in patients given conventional therapy (75%). The same authors reported a similar study in 2001 resulting in a 70% remission rate in 20 patients taking Boswellia for 6 weeks compared with 40% in 10 on sulfasalazine.  In a randomized, double-blind, controlled 8 week trial, the B. serrata extract, H15, was compared with mesalamine for active CD.  The study included 102 patients and was powered to show non-inferiority. The mean Crohn’s Disease Activity Index (CDAI) fell in both groups and H15 was well tolerated. This result was similar to those in previous trials with 5-ASA preparations.

Curcuma longa
Curcumin is the yellow pigment of turmeric (Curcuma longa), a major ingredient of curry: in animal and in vitro studies, it has a range of immunomodulatory and anti-inflammatory effects. In a recent pilot study, curcumin, when given orally, was reported to benefit five patients with proctitis and five with Crohn’s disease [44]. Hanai and colleagues recently published the results of the first randomized, multicenter, double-blind, placebo-controlled trial from Japan to study the effect of Curcumin on maintenance of UC. All of ninety-seven patients who enrolled and eighty-nine patients who completed the study took a standard dose of mesalamine or sulfasalazine and either 1 gm of Curcumin or placebo twice daily for 6 months and then were followed or another 6 months off study medications.  The relapse rate at 6 months on therapy was greater for the placebo group than for those who took Curcumin (p=049).  Thus, Curcumin may confer some additional therapeutic advantages when used in combination with conventional anti-inflammatory medications in UC.

Prebiotics and Probiotics

a. Probiotics.
As the microbial environment has been shown to play a role in the development and perpetuation of IBD, targeting of the microbiota presents an option for therapeutic intervention. One potential method to manipulate the intestinal microbiota in an attempt to reduce the inflammatory response is via the administration of friendly live bacteria.
Probiotics have been described as, “live micro-organisms which, when consumed in adequate quantities, confer a health benefit on the host”.  They have been used in the treatment of a number of inflammatory conditions including UC, CD and experimental colitis. The mode of action of probiotics is complex and not completely understood, however multiple mechanisms have been described in vitro.   

Based on the success of preventing and treating experimental colitis with VSL#3, Lactobacillus GG and other strains, a number of clinical trials have been executed for both CD and UC.  Overall, the data for CD has shown mixed results regarding benefit as either an induction or maintenance adjunct to standard medical therapy.  In contrast, probiotics have been shown to benefit UC for both induction and for continued remission of disease. Table 2.   

b. Prebiotics
As the intestinal microbiota has been linked to the pathogenesis of IBD, probiotic treatment is an avenue for therapeutic intervention. Another method is via the administration of prebiotics. Prebiotics are described as “non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one, or a limited number of bacteria in the colon, thus improving host health”.   

The rationale behind prebiotic use is to elevate the endogenous numbers of beneficial bacterial strains including lactobacillus and bifidobacterium. This increase then imparts the beneficial effects seen by probiotic administration, including an increase in short chain fatty acid (SCFA) production, particularly butyrate, which is deficient in the colonic mucosa of UC patients.  Butyrate provides fuel for enterocytes, prevents pathogenic adherence and production of anti-bacterial substances, and decreases luminal pH. Based on these protective mechanisms, administration of SCFA enemas have been shown to be effective for left-sided UC that is refractory to medical therapy. 

Common prebiotics include inulin, resistant maltodextrin, oligosaccharides such as fructooligosaccharide (FOS) and galactooligosaccharide (GOS). The body of research involving the use of prebiotics to treat IBD is not currently as extensive as that regarding probiotic therapy.  Overall, the four published studies to date all support the use of prebiotics in the treatment of active UC.

Fish Oil
n–3 Fatty acids have been promoted as conferring broad health benefits by preventing and treating a wide variety of diseases. In cell culture and animal studies, these essential fatty acids have potent immunomodulatory effects that appear to be mediated both through modulation of eicosanoid synthesis and through an eicosanoid-independent inhibitory effect on the proinflammatory cytokines. Thus, it has been proposed that supplemental n–3 fatty acids might be beneficial in treating or preventing relapse in chronic inflammatory diseases. 
For IBD, there are animal in vivo and in vitro studies which all show that n-3 fatty acids can effectively prevent and treat mice-models of colitis.  An early report on the use of enteric coated formulation for CD found a markedly lower relapse rate for the fish oil group than for the control group (28% compared with 69%; P < 0.001). However, on the basis of a comprehensive literature review, the available data are insufficient to draw conclusions about the effects of n–3 fatty acids on clinical, endoscopic, or histologic scores or induced remission or relapse rates.

The data that pertain to the effects of n–3 fatty acids on steroid requirements suggest that n–3 fatty acids may reduce the need for or effective dose of corticosteroids among patients with IBD. Future studies should assess the effects of pharmaceutical grade enteric-coated n–3 fatty acids on clinical outcomes in IBD, including requirements for corticosteroids.

Vitamin D
Vitamin D from sunlight exposure is lower in areas where IBD occurs most often, as IBD is most prevalent in northern climates, such as North America and Northern Europe. Vitamin D deficiency is common in patients with IBD even when the disease is in remission. Several observations in animal models of colitis provide strong evidence that establishes vitamin D and vitamin D receptor (VDR) as a physiologic regulator of intestinal inflammation in IBD.

It is unclear why vitamin D deficiency occurs more frequently in both forms of IBD. It is probably due to the combined effects of low vitamin D intake, malabsorption of many nutrients including vitamin D, and decreased outdoor activities in climates that are not optimal for vitamin D synthesis in the skin.

Since the risk of osteoporosis and Vitamin D deficiency is higher in IBD, every patient should be tested for 25-OH vitamin D3 levels. The accumulating evidence for the immunomodulatory effects of VDR ligands certainly provides a rationale for further investigation of their potential in the treatment of IBD.

There is a further need for clinical trials evaluating the potential efficacy of natural approaches in combination with conventional therapy to achieve better outcomes in IBD. Continued education of health care practitioners about the potential benefits of nutraceutical supplements is essential since these therapies are being increasingly employed by patients with IBD. 



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