A Functional Medicine Protocol for Crohn's Disease

Inflammatory bowel disease is a debilitating and destructive gastrointestinal disease characterized by chronic intestinal inflammation and damage. It affects seven million people worldwide and is thought to result from the interplay of genetics, the immune system, environmental factors, and the gut microbiome. Crohn's disease is one type of inflammatory bowel disease that most commonly affects the last part of the small intestine and the beginning of the colon. Serious complications can occur without proper medical treatment; however, side effects and the cost of conventional therapies deter many from wanting to seek that path. Functional medicine provides alternative and adjunctive treatment options that can improve treatment outcomes, remission rates, and quality of life for patients with Crohn's disease.

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What is Crohn's Disease?

Crohn's disease is an autoimmune inflammatory bowel disease (IBD) subtype characterized by chronic gastrointestinal (GI) tract inflammation. Crohn's disease is differentiated from other forms of IBD by the location of GI inflammation and the type of lesions visualized in the GI tract. Crohn's disease can affect any part of the GI tract from mouth to anus. The inflammation affects the entire thickness of the bowel wall and is visualized in "skip lesions" - areas of patchy inflamed tissue between areas of healthy, unaffected tissue. (1)

Crohn's Disease Symptoms

Crohn's disease symptoms are chronic, with periods of symptom flares in between periods of remission. Intestinal symptoms indicative of active disease include abdominal pain (often in the right lower quadrant), flatulence, bloating, diarrhea with blood and mucus, lack of appetite, and mouth sores. Fatigue, weight loss, and fever are also common. (3)

Crohn's disease is associated with many extraintestinal manifestations, including (1, 4):

• Inflammation and swelling of the eye
• Joint pain and arthritis
• Kidney stones and urinary tract infections
• Skin rashes

Crohn's disease is associated with increased prevalence of the following chronic medical conditions and health complications (2, 4):

• Bowel obstruction and intestinal perforation
• Fistulas: abnormal connections between the intestinal wall and a different body part that can cause infection and abscess
• Anal fissures: small, painful tears in the skin around the anus
• Liver and gallbladder disease
• Colon cancer
• Nutritional deficiencies and anemia
• Skin disorders, including erythema nodosum and pyoderma gangrenosum, that involve painful bumps and ulcers on the skin (commonly the legs)
• Blood clots
• Osteoporosis

What Causes Crohn's Disease?

The exact cause of Crohn's disease is unknown, but it appears to result from exaggerated immune responses triggered by genetic susceptibility and environmental triggers, leading to increased intestinal permeability and chronic GI inflammation.

Genetics

Crohn's disease affects women and men equally and can develop at any age. Most people, however, develop Crohn's disease between the ages of 15-30. (1, 3)

Having a family history of IBD increases the risk of Crohn's disease; up to 20% of people with IBD have a first-degree relative with the disease. People of Eastern European background have the highest risk of developing Crohn's disease, although incidence has increased among African-Americans in recent years. (1, 2)

Over one hundred genes have been associated with IBD. Specific to Crohn's disease, genes related to innate immune function and intestinal barrier integrity and function have been associated with the diagnosis and prognosis of the disease. The NOD2, IL23R, and ATG16L1 genes strongly correlate with Crohn's. (4, 5)

Environmental Factors

People living in a developed country or urban city are at higher risk for developing Crohn's disease than those in undeveloped and rural areas. (2)

Intestinal Permeability

Intestinal hyperpermeability (or "leaky gut") has been demonstrated in most patients with Crohn's disease, especially during active disease flares. Recent research indicates that increased permeability in asymptomatic individuals is significantly associated with the future risk of developing the disease. Bacterial and food antigens are common triggers of leaky gut syndrome.

Infection

Pathogenic bacteria associated with the onset of Crohn's disease include Mycobacterium avium subspecies paratuberculosis, Yersinia enterocolitica, Listeria monocytogenes, and bacteria from the Helicobacter family. Additionally, characteristic dysbiotic findings of the gut microbiome have consistently been documented in patients with Crohn's disease; most notably, decreased abundance of several bacterial species of the Firmicutes and the Bacteroidetes phyla, and an overabundance of Enterobacteriaceae, particularly Escherichia coli species. (6)

Viral agents have also been implicated in Crohn's development. 15% of patients with Crohn's disease have tested positive for Epstein Barr virus (EBV), and gastrointestinal norovirus infection has been associated with worsening IBD symptoms. (6)

Finally, intestinal yeast appears to contribute to the hyperstimulated immune response in Crohn's disease. Anti-Saccharamyces cerevisiae antibodies (ASCA), immune proteins against a non-pathogenic yeast, have been found in up to 70% of Crohn's patients. ASCA is now a serological marker of disease location and progression in Crohn's disease. Research also suggests that Candida yeast species, particularly Candida albicans, are more abundant in patients with Crohn's disease and can induce pro-inflammatory immune responses underlying intestinal inflammation in Crohn's disease. (6)

Lifestyle Factors

Tobacco doubles the risk of Crohn's disease, worsens the severity of illness, and increases the need for steroid and immunosuppressant medications and intestinal operations.

Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin, ibuprofen, and naproxen can exacerbate GI inflammation and bleeding. NSAID use is linked to more symptom flares and higher hospital admission rates, especially at high doses.

A Western diet characterized by a high dietary intake of fat and meat and a low intake of fiber is correlated increased risk of developing Crohn's disease.

Functional Medicine Labs to Test for Crohn's Disease Patients

Imaging

Colonoscopy and endoscopy are required to diagnose Crohn's disease. Direct visualization and biopsy of the lesions allow for identifying and characterizing the lesions, monitoring therapy, and screening for colorectal cancer. In some cases, CT or MRI imaging techniques may be recommended to provide additional information if the diagnosis is unclear or endoscopy is unsafe to perform. (7, 12)

Basic Lab Tests

Initial blood work for suspected Crohn's disease should include a CBC, CMP, CRP, and ESR to support the diagnosis, identify disease severity, and determine alternative pathologies contributing to patient symptoms. (7, 12)

Comprehensive Stool Analysis

A comprehensive stool analysis fulfills the conventional testing requirements for stool studies for culture, ova & parasites, and Clostridium difficile. A comprehensive stool test also measures other markers related to disease severity and contributing factors to disease origin. Biomarkers to pay special attention to include calprotectin, lactoferrin, short-chain fatty acids (SCFAs), and the microbiome analysis.

Anti-Saccharomyces Cerevisiae Antibodies (ASCA)

Serum (ASCA) is often ordered with perinuclear anti-neutrophil cytoplasmic antibody (pANCA) to differentiate between Crohn's disease and ulcerative colitis, another type of IBD. ASCA is more common in Crohn's, while pANCA is more common in ulcerative colitis.

Intestinal Permeability

A serum intestinal permeability screening measures immune proteins against key molecules associated with a leaky gut.

‍Zonulin is currently the only known protein known to reversibly regulate intestinal permeability and can be evaluated through fecal or serum testing methods.

Celiac Disease Screening

Evidence strongly suggests that celiac disease significantly increases the risk of developing IBD. Patients with Crohn's disease can be screened for celiac disease with a serum test. It is recommended that the patient undergo a gluten challenge, in which they incorporate gluten into their diet for at least 4-6 weeks before the test, to improve screening accuracy.

Micronutrient Panel

A micronutrient panel evaluates the nutritional status of vitamins, minerals, and antioxidants that can quickly become depleted in malabsorptive states. Common nutrient deficiencies in patients with Crohn's disease include vitamins B6, B9 (folate), B12, and D, calcium, iron, magnesium, and zinc.

Health Screenings

Nutrient deficiencies, systemic inflammation, and corticosteroids increase the risk of osteoporosis in patients with Crohn's disease. Initial screening for osteoporosis with DEXA at the time of IBD diagnosis is recommended and periodically after, as advised by your doctor. N-telopeptide is also a marker to monitor bone turnover and osteoporotic bone loss. (12)

Screening colonoscopy for colorectal cancer is recommended 8-10 years after initial IBD diagnosis, followed by surveillance colonoscopy at intervals recommended by your doctor.

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Functional Medicine Treatment Protocol for Crohn's Disease

Conventional medical interventions, typically involving some combination of corticosteroids, 5-aminosalicylates, antibiotics, and biologics, may be required to effectively induce disease remission and prevent hospitalization and complication (7). However, a natural approach to Crohn's treatment should be considered, given the safety profile, decreased expense, and efficacy of alternative treatment options.

Nutrition for Crohn's Disease

Balancing bowel rest and maintaining nutrient-dense foods promoting healing can be difficult during active flares. Soft, bland foods, including refined grains, low-fiber fruits, fish, white meat poultry, eggs, and fully-cooked/skinless vegetables, are recommended as foods less likely to aggravate IBD symptoms.

The elemental diet is an alternative well-researched therapeutic intervention for Crohn's disease. This predigested, hypoallergenic formula is a complete meal replacement to fulfill nutritional and caloric needs while providing respite for the gut. Research supports using the elemental diet as a first-line treatment in the induction and maintenance of Crohn's disease remission. (10, 11)

The East Anglian study compared the effects of an elimination-rechallenge diet to oral corticosteroids for maintaining remission of Crohn's disease after an elemental diet. Participants were followed for two years, during which the diet group introduced one new food daily, excluding those that exacerbated GI symptoms. Compared to the steroid group, those in the diet group were shown to have significantly longer periods of disease remission and a lower relapse rate after the two-year study period. Corn, wheat, yeast, dairy, eggs, potatoes, rye, tea, and coffee were documented as the most common food triggers. This study demonstrates that long-term avoidance of food intolerances and sensitivities is essential to Crohn's disease maintenance.

Without food triggers, a whole-food, anti-inflammatory diet (e.g., Mediterranean diet) that emphasizes consuming fruits, vegetables, whole grains, fish, legumes, nuts, and olive oil effectively reduces Crohn's disease symptoms and improves quality of life.

Nutritional Supplements and Herbs for Crohn's Disease

Below are some of the most commonly recommended supplements for Crohn's Disease:

Zinc

There is a significantly higher prevalence of zinc deficiency among patients with Crohn's disease. Consequences of zinc deficiency include frequent infections, poor wound healing, delayed growth, infertility, loss of taste and smell, suppressed appetite, and change in cognitive function. Dietary supplements often are required to optimize zinc status, especially in those with active disease and impaired digestive absorption.

Vitamin D

Vitamin D deficiency is common in IBD patients and is associated with increased flares, hospitalizations, and surgeries; inadequate response to pharmacotherapy; and poorer quality of life. Vitamin D supplementation and the optimization of serum status results in many benefits for patients with Crohn's disease, including the downregulation of pro-inflammatory cytokine TNF-alpha, reduction in serum CRP, and a reduced risk of colorectal cancer and anemia.

Essential Fatty Acids

Given their anti-inflammatory and anticoagulant properties, fish oil supplements have a role in managing IBD. They may be of particular benefit to Crohn's patients at risk for blood clots and heart disease. One study showed that supplementation of omega-3 fatty acids with or without co-administered vitamin D reduced autoimmune disease rate by 15%.

Glutamine

L-glutamine is one of the most popular supplements implemented in functional gut-healing protocols. Glutamine is an amino acid that is the primary fuel source of the cells that line the small intestine. Glutamine depletion can lead to cellular atrophy, decreased expression of cellular tight junctions, and intestinal hyperpermeability. Human studies have concluded that glutamine supplementation decreases intestinal permeability, improves gut barrier function, and reduces cellular inflammation.

Probiotics

Probiotics are live microorganisms that restore the balance of the "good" bacteria in the body. Probiotics have been shown to suppress the growth of unwanted organisms in the GI tract, increase the diversity of function of the gut microbiome, modulate intestinal immunity, and reduce low-grade inflammation (8).

Boswellia serrata

Otherwise known as frankincense, Boswellia is a potent inflammation modulator. Its constituents block key enzymes in pro-inflammatory pathways and exert general antioxidant effects in the body. A 2001 study concluded that an 8-week course of daily dosing of Boswellia resin extract was comparable to standard therapy with mesalamine in treating active Crohn's disease.

Curcumin

Curcumin is a powerful anti-inflammatory compound extracted from the rhizome of turmeric (Curcuma longa). Curcumin is often commonly implemented in IBD treatment protocols because of its proven anti-inflammatory, immunomodulatory, antioxidant, and anticancer effects. Curcumin is not readily absorbed into circulation by the digestive tract. Many companies formulate highly bioavailable curcumin forms for systemic effects, but a less bioavailable form may be preferred for localized impact on the GI tract. (9)

Aloe vera

The juice and gel of Aloe vera exert immunomodulatory and wound-healing effects on the GI tract when taken orally and are commonly recommended for the management of a wide array of digestive disorders, including IBD. Caution should be taken to ensure the latex portion of the plant is not consumed, which has strong laxative effects and can exacerbate diarrhea.

Quercetin

Quercetin is a natural flavonoid in fruits and vegetables that contains anti-inflammatory, antioxidant, and anticancer properties. Quercetin demonstrates anti-IBD effects through its ability to reduce cellular inflammation, promote an intact intestinal barrier, and enhance the diversity of the intestinal microbiome.

Lifestyle Modifications for Crohn's Disease

Cigarette smoking is the most important controllable risk factor for developing and influencing the severity of Crohn's disease. Smoking cessation is paramount, especially in patients experiencing a symptom flare. (2)

NSAIDs should be avoided when possible, given their ability to increase intestinal permeability, induce intestinal ulceration, and exacerbate disease activity and severity (7).

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Summary

Crohn's disease is a severe medical condition of multifactorial origin, leading to a hyperstimulated autoimmune response and chronic inflammation. Specialty testing can help uncover the disease process's root causes to customize treatment to the patient's needs. Utilizing alternative treatment modalities with conventional pharmacotherapy results in better control of Crohn's disease and improved patient outcomes.