A Functional Medicine Crohn's Disease Protocol: Specialty Testing, Nutrition, and Supplements

Crohn's disease has a profound impact on affected individuals and their loved ones. Prevalence trends indicate a rising number of diagnosed cases in the United States, with over half a million Americans currently grappling with this condition. Grappling with the daily realities of chronic disease, the emotional toll of managing symptoms, and navigating treatment options are some of the obstacles these patients encounter on their road to wellness. Integrative and personalized treatment strategies aim to offer hope and guidance for those living with this inflammatory bowel disease.

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What Is Crohn's Disease?

Crohn's disease (CD) is a chronic inflammatory condition that primarily affects the gastrointestinal (GI) tract. It belongs to a group of conditions known as inflammatory bowel diseases (IBD). 

The hallmark feature of CD is inflammation that can occur anywhere along the GI tract, from the mouth to the anus. This inflammation arises from an abnormal immune response, where the immune system mistakenly attacks healthy cells in the GI tract. It occurs in patches (called "skip lesions") and extends through multiple layers of the intestinal wall.

Crohn's Disease Signs & Symptoms

Crohn's disease can manifest with a variety of signs and symptoms, which can vary in severity and may fluctuate over time, influenced by factors such as disease activity, diet, stress, and medication use. Classic symptoms of CD flares include: 

• Abdominal pain, often occurring in the lower right abdomen
• Diarrhea, which may contain blood and mucus
• Nausea and vomiting
• Bloating
• Mouth sores
• Loss of appetite
• Fever
• Weight loss 
• Fatigue

CD may also involve other parts of the body beyond the GI tract, such as the joints, skin, and eyes, leading to systemic manifestations: 

• Eye pain, swelling, and inflammation
• Joint pain and arthritis
• Kidney stones and urinary tract infections
• Skin rashes and lesions

Root Causes of Crohn's Disease

While the exact cause of Crohn's disease remains unclear, it's believed to involve a complex interplay of genetic, environmental, and immunological factors. 

Genetic predisposition plays a significant role in the development of Crohn's disease. Individuals with a family history of the condition are at a higher risk of developing it themselves. Up to 20% of patients with CD have a first-degree relative with IBD. Over one hundred genes have been implicated in CD susceptibility, including those responsible for immune regulation and response to fungal and bacterial pathogens. (29) 

However, no single gene determines the risk of developing CD. Instead, the interaction of genetic variants with environmental factors influences disease susceptibility and expression. These environmental factors include: 

• Western dietary patterns, including a high intake of processed foods, sugar, and saturated fats and a low intake of fiber, fruits, and vegetables, have been associated with an increased risk of CD. 
• Alterations in the composition and function of the gut microbiota, collectively known as dysbiosis, can contribute to GI inflammation and immune dysregulation. 
• Cigarette smoking is a well-established environmental risk factor for Crohn's disease. Tobacco use doubles the risk of CD and increases the likelihood of having a more severe form of the disease.
• Psychological stress is believed to influence disease activity and symptom severity by affecting the immune system and gut function.
• Regular use of non-steroidal anti-inflammatory drugs (NSAIDs), defined as at least five times per month, is associated with increased CD activity and less robust disease remission.

How to Diagnose Crohn's Disease

A Crohn's disease diagnosis requires the integration of medical history, physical exam, laboratory tests, endoscopy and radiographic results, and GI pathology findings (27).

Step 1: Narrow the Differential

CD should be suspected in patients with cardinal clinical symptoms (chronic diarrhea and abdominal pain) and laboratory signs of inflammation. 

Inflammatory bowel markers are nonspecific markers of inflammation; elevations are likely in IBD but unlikely in functional gastrointestinal conditions like irritable bowel syndrome (IBS), which can cause similar GI symptoms. For example, patients with a normal CRP or fecal calprotectin less than 40 μg/g have less than a 1% chance of having IBD.

The following inflammatory markers can help narrow the differential diagnosis:

• ESR
• CRP
• Fecal calprotectin
• Lactoferrin

Step 2: Order Colonoscopy

Patients with suspected CD should be referred to a gastroenterologist for ileocolonoscopy with biopsy. Mucosal changes suggestive of a CD diagnosis include mucosal nodularity, swelling, ulceration, easy bleeding, and intestinal narrowing. Upper endoscopy can be performed at the same time in patients presenting with upper GI symptoms. (27)

Computed tomography (CT) and magnetic resonance imaging (MRI) can complement endoscopic techniques. They aid in assessing the extent and severity of intra- and extraintestinal manifestations of disease, such as bowel wall thickening, strictures, fistulas, and abscesses. (40) 

Step 3: Labs That Can Individualize a Crohn's Disease Treatment Plan

Specialty tests aid in the personalization of effective treatment plans that target the root cause of disease and monitor patient progress through time. 

Comprehensive Stool Analysis

Comprehensive stool tests are an all-encompassing way to assess for malabsorption, intestinal inflammation, and dysbiotic patterns that can cause or result from CD. The following results are correlated to increased disease and symptom severity:

• Elevations in calprotectin, fecal secretory IgA, lactoferrin
• Dysbiotic patterns: infection with Mycobacterium avium subspecies paratuberculosis, Yersinia enterocolitica, Listeria monocytogenes, and Helicobacter spp.; decreased abundance of Firmicutes and Bacteroidetes, and an overgrowth of Enterbacteriaceae and Candida albicans (4) 

Popular comprehensive stool tests that help in assessing the general health of the GI tract include: 

• GI-MAP by Diagnostic Solutions
• GI360 by Doctor's Data
• GI Effects Comprehensive Profile - 3 day by Genova Diagnostics

Intestinal Permeability 

Increased intestinal permeability ("leaky gut") in asymptomatic individuals has been identified as a risk factor for future risk of disease development and is observed in most patients with active disease flares. 

Labs that measure zonulin and antibodies to zonulin, actin, and lipopolysaccharide can help quantify the degree and give clues to the underlying reason for leaky gut: 

• Array 2 by Cyrex Laboratories
• Zonulin by Diagnostic Solutions
• Gut Barrier Panel by KBMO Diagnostics

Food Sensitivities

According to one study, 66% of patients with CD report food intolerances that exacerbate diarrhea and abdominal pain. Unidentified food sensitivities may trigger leaky gut and autoimmune reactions, exacerbating CD's GI and extraintestinal symptoms. Because physical symptoms associated with food sensitivities can occur up to days after ingesting the trigger food, they can be challenging to identify. Food sensitivity tests help in their identification so that patients can successfully eliminate them from their diet. 

Popular food sensitivity panels available through Rupa Health include: 

• 96 IgG Food Sensitivity Panel by Alletess Medical Laboratory
• foodANALYZER IgG Food Sensitivity by Access Med Labs
• Basic Food Sensitivity Panel - 96 Foods by Ayumetrix

Nutritional Assessment

Due to structural changes in the small intestine's absorptive surface, individuals with IBD are at increased risk for nutritional deficiencies. Patients with CD are at high risk for nutritional deficiencies in iron, vitamin B12, vitamin D, folate, and vitamin K.

Micronutrient panels screen for common nutritional deficiencies and help doctors tailor their dietary and supplemental recommendations based on the individual's nutritional needs:

• Micronutrient Test by SpectraCell
• Cellular Micronutrient Assay by Cell Science Systems 
• NutrEva FMV by Genova Diagnostics

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Treatment Plan for Crohn's Disease

An integrative treatment protocol for Crohn's disease merges conventional medical treatments with complementary therapies, offering a holistic framework to manage symptoms, enhance overall well-being, and improve long-term health outcomes.

1. Reduce Inflammation

Here's Why This Is Important: 

Inflammation is central to CD pathogenesis and symptomatology. Targeting and reducing inflammation puts the disease into remission, mitigates tissue damage, alleviates the patient's symptoms, and minimizes the risk of complications associated with chronic inflammation.

How Do You Do This?

Conventional treatment guidelines propose the use of various classes of medications that target GI inflammation, including:

• Aminosalicylates, such as mesalamine and sulfasalzine
• Corticosteroids
• Immunomodulators
• Biologic agents

There are cases where medications may be non-negotiable to prevent poor health outcomes. However, given their expense and associated side effects, many people seek alternative avenues to induce and retain disease remission and reduce their reliance on pharmacotherapy for disease management. 

Diet is an excellent place to start reducing systemic inflammation, with studies supporting dietary interventions as effective means to induce and maintain disease remission. Examples include: 

• Elemental diet reduces the rate of CD relapse by 50%
• The Specific-Carbohydrate Diet (SCD) has been shown to induce clinical remission in 
• 33% and 42% of patients with IBD in two and six months, respectively.
• Increasing the dietary omega-3:omega-6 ratio by following a Mediterranean-like diet, reducing intake of ultra-processed foods, and eating fatty fish and olive oil regularly 

Many supplements are also effective in quelling inflammation. For example, with or without pharmacotherapy, curcumin at 2-3 grams daily is superior to placebo at inducing and maintaining clinical remission and reducing intestinal inflammation (as assessed by endoscopy) in patients with IBD. Vitamin D3 in doses as low as 1,200 IU daily has also been shown to reduce rates of CD relapse from 29% to 13%. (25) 

2. Correct Nutritional Deficiencies

Here's Why This Is Important:

Deficiencies in essential nutrients can exacerbate symptoms and contribute to disease progression. Correcting these deficiencies, therefore, is important to support general wellness, prevent further complications, and enhance treatment efficacy. Optimizing nutritional status can improve energy levels, weight management, immune function, and GI health.

How Do You Do This?

Dietary supplements should be selected based on identified vitamin and mineral deficiencies and dosed accordingly, depending on the severity of the deficiency.

Diet will also play an important role in correcting deficiencies and maintaining nutritional adequacy. Outlined below are foods rich in some of the most common nutrients commonly deficient in CD patients:

• Vitamin D: cod liver oil, fatty fish, beef liver, egg yolks, mushrooms
• Iron: meat, seafood, fortified cereals, spinach
• Vitamin B12: beef liver, meat, seafood, nutritional yeast, eggs, yogurt
• Folate: fruits, vegetables, grains, beans
• Vitamin K: green leafy vegetables, meat, dairy, eggs, natto

3. Address Autoimmune Triggers

Here's Why This Is Important:

Identifying and managing autoimmune triggers leads to long-term success in reducing disease activity, preventing flares, and maintaining remission.  

How Do You Do This?

Factors contributing to immune dysregulation in autoimmune disease include exposure to environmental toxins, physical and emotional stress, increased intestinal permeability and dysbiosis, and hormonal imbalances. Not everyone will have each of these playing into their CD, so patient history and laboratory results will be enormously helpful in guiding doctors in making appropriate treatment recommendations. 

Here are some examples of treatment recommendations that could be implemented to address each of these factors:

• Support the gut microbiome by eradicating GI infections and using probiotic supplements to reinoculate the colon with beneficial Lactobacillus and Bifidobacterium.
• Balance thyroid, stress, and reproductive hormones with mind-body therapies, a healthy diet, liver support, and regular exercise.
• Reduce exposure to environmental toxins by using air and water filters, buying natural household cleaners and cosmetic products, avoiding the use of plastics, and eating organic when possible. 
• Quit smoking

4. Heal the Gut

Here's Why This Is Important:

The gut will inherently begin to heal itself as patients follow recommendations outlined in the first few steps of this treatment protocol. However, doctors will often recommend additional supplements to expedite this process. 

How Do You Do This?

Evidence-based supplements that have proven efficacy in treating CD include: 

• Resveratrol 50 mg twice daily
• L-Glutamine 10-20 grams daily
• Lactoferrin 100-400 mg daily

The Risks of Untreated Crohn's Disease

Without proper management, ongoing inflammation in the GI tract can lead to complications such as strictures, fistulas, abscesses, and bowel obstructions, increasing the risk of bowel perforation and sepsis that require surgical intervention and bowel resection. (9) 

Crohn's disease can affect organs outside the digestive system, resulting in extraintestinal manifestations such as arthritis, skin disorders, eye inflammation, and liver complications. Chronic inflammation may also contribute to long-term complications such as malnutrition, osteoporosis, colorectal cancer, and heart disease. (9) 

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Key Takeaways:

• Crohn's disease is a manifestation of the complex interplay of genetic predisposition, environmental factors, and immune dysregulation, which underscores the importance of individualized care for effective treatment outcomes.
• Through comprehensive evaluation, including medical history, specialized testing, and dietary assessment, practitioners can uncover underlying triggers and imbalances contributing to CD pathogenesis. 
• A holistic protocol addresses inflammation, corrects nutritional deficiencies, modulates the immune response, and promotes gut healing. It offers a framework for managing CD symptoms, achieving remission, and enhancing long-term health outcomes. 
• Integrating conventional therapies with evidence-based complementary interventions empowers patients to actively participate in their health journey, fostering a collaborative partnership between them and their healthcare providers.