Functional Nutrition for Crohn’s Disease

What is Crohn’s disease?

A chronic inflammatory disease of the gastrointestinal tract characterized by inflammation that affects all layers of the gut and the formation of granulomas (small masses of immune cells) (1). 

Although it mainly affects the end of the small intestine and the anus, it can occur in any part of the gastrointestinal tract (1). 

Crohn’s is a type of inflammatory bowel disease (IBD), a term that encompasses diseases of chronic intestinal inflammation, along with ulcerative colitis (1). 

How common is Crohn’s disease?

According to the CDC, approximately 3.1 million people living in the United States (1.3%) have been diagnosed with inflammatory bowel disease (2).

Crohn’s disease is more common in northern Europe and North America, but it is increasing in Asia and Africa as well (3).

Research regarding the prevalence of Crohn’s disease in the United States is limited, but one study in Minnesota found that there were 10.7 cases per 100,000 people (4).

What are the signs and symptoms?

Patients with Crohn’s disease may experience any of the following symptoms (15):

  • Abdominal pain
  • Bloody stool
  • Cramping
  • Diarrhea
  • Fatigue
  • Fever (low-grade)
  • Perianal lesions
  • Weight loss

What causes Crohn’s disease?

The following may contribute to the development of Crohn’s disease:

1. Immune dysfunction

Crohn’s disease is characterized by chronic inflammation caused by abnormal immune responses (5).

The innate immune system is the body’s first-line defense against pathogens, such as bacteria and viruses (6).

In Crohn’s disease, alterations in the innate immune response cause the immune system to attack healthy cells in the intestinal lining (5).

This inflammation is then upregulated by the adaptive immune system, which takes over for the innate immune system and contributes to chronic inflammation (78).

Over time, inflammation damages the lining of the intestines and produces skip lesions (patchy areas of inflammation), which are a key feature of Crohn’s (9).

2. Genetics

Studies show that 15% of people with Crohn’s disease have a family member who also has IBD, suggesting that genetics play a small role in the development of Crohn’s disease (1011).

Approximately one-third of patients have a mutation in the nucleotide-binding oligomerization domain 2 (NOD2) gene (10). 

NOD2 plays a key role in the regulation of the ileal microbiota and mediates innate immune responses (1213).

3. Leaky gut

Increased intestinal permeability allows food particles and other molecules to pass through the lining of the intestines and activate an immune response (14). 

Studies suggest that altered intestinal permeability (aka “leaky gut”) plays a role early on in the development of Crohn’s disease (15).

However, more research is needed to determine whether this is a cause or a consequence of the disease (15).

4. Gut dysbiosis

It is thought that altered intestinal bacteria can contribute to inflammation and may play a role in the pathogenesis of inflammatory bowel disease (16). 

Studies have shown increased levels of Escherichia coli and Clostridium difficile, and decreased levels of Faecalibacterium prausnitizii in patients with Crohn’s disease (10).

However, more research is needed to determine whether dysbiosis is a cause or a consequence of the disease (17).

5. Dietary factors

Diet can contribute to the development of intestinal inflammation and Crohn’s disease by altering the gut microbiome and increasing intestinal permeability (18).

Crohn’s disease has been linked with Western diets, which are known to cause gut dysbiosis due to the lack of plant-based foods and fiber (19).

In general, higher intake of meat, sugar, and omega-6 fatty acids may increase risk, while fruits and vegetables may decrease risk (20).

6. Nutrient deficiencies

Vitamin D is an important regulator of innate immunity, the body’s first line of defense against pathogens (621).

Vitamin D deficiency may lead to dysregulated intestinal innate immunity, which is thought to be one of the causes of Crohn’s disease (21).

A 2019 meta-analysis found that vitamin D levels were inversely related to Crohn’s disease, and more than half of the patients had insufficient vitamin D levels (22).

7. Smoking

Studies show that people who smoke are nearly twice as likely to develop Crohn’s disease compared to non-smokers (23).

The underlying mechanism isn’t entirely clear, but it is known that smoking causes alterations in immunity and the gut microbiota (2425).

8. Medications

NSAIDs have been linked with a higher risk of Crohn’s disease, but more research is needed because studies are conflicting (1826). 

Antibiotics are associated with Crohn’s disease, especially among children, possibly due to their effects on the gut microbiota (2728). 

Oral contraceptives, which have been shown to increase intestinal permeability, increase Crohn’s risk by 24% (2930). 

9. Poor sleep

Sleep deprivation can lead to increased inflammation and may play a role in the development of Crohn’s disease (1831).

There is also some evidence that poor sleep may increase disease activity in those who already have Crohn’s. A study of people in remission found that those with impaired sleep had a 2-fold increased risk of developing active Crohn’s disease 6 months later (32).

What are the potential health consequences of Crohn’s disease?

The following conditions may co-occur in people with Crohn’s disease:

1. Intestinal complications

Anal fissures are small tears in the lining of the anus that can cause severe pain during bowel movements (33).

Approximately 4% of Crohn’s patients develop chronic anal fissures, although it’s unknown why this occurs (34).

Fissures that don’t heal on their own may require treatment with medication and/or surgery (34).

Intestinal strictures occur when the accumulation of scar tissue causes a narrowing in the intestines (35).

About 25% of patients with Crohn’s disease have had at least one small bowel stricture, which can eventually lead to a bowel obstruction and require surgery (36). 

Intra-abdominal abscesses (pockets of pus and infected fluid within the abdominal cavity) form in about 10% of patients with Crohns’ (37).

They’re treated with antibiotics (to control the infection) and surgery (to drain the abscess) (38).

Fistulas (abnormal connections between two or more body parts) occur in 50% of patients within 20 years of initial diagnosis (3940).

The most common type is an anal fistula, which is formed when an abscess in the anus drains, leaving behind a small tunnel from the anal canal to an opening in the skin near the anus (41).

Surgery is typically required to help drain any infection and allow the fistula to heal properly (41).

2. Malnutrition

An estimated 65-75% of patients with Crohn’s are malnourished and micronutrient deficiencies are common (42).

This is caused by many different factors, including inadequate caloric intake, malabsorption of nutrients, increased energy expenditure, and medications (42).

3. Anemia

In Crohn’s disease, nearly 30% of patients have anemia, which can be caused by nutrient deficiencies (iron, folate, vitamin B12) and anemia of inflammation (43).

This occurs when the body sequesters iron in response to inflammation, making it unavailable for red blood cell production (44).

4. Arthritis

Arthritis is one of the most common extraintestinal complications of Crohn’s disease, affecting between 17% and 39% of patients (45).

The most prevalent form of arthritis in these patients is spondyloarthritis, which refers to a group of inflammatory rheumatic diseases that cause arthritis, mainly in the spine (46).

It’s still unclear why this occurs, but some believe the gut-joint axis is involved, allowing inflammation in the gut to travel to the joints (47).

5. Kidney stones and gallstones

A recent study found that gallstones and kidney stones were diagnosed in 8% and 5% of patients with Crohn’s disease, respectively (48).

It has been hypothesized that bile acid malabsorption in patients with inflammation of the ileum may result in bile that contains too much cholesterol, which can cause the bile to harden into gallstones (4950).

The higher risk of kidney stones in these patients may be due to chronic inflammation or intestinal malabsorption (51).

6. Anxiety and depression

Patients with Crohn’s disease must cope with the stress of frequent symptom recurrence, the high cost of medical care, and the side effects from medical and surgical treatments (52).

Ultimately, these factors can contribute to a lower health-related quality of life and can increase the risk for depression and anxiety (53).

About 20% and 15% of these patients are diagnosed with anxiety or depression, respectively (54).

During disease flare-ups, the prevalence increases dramatically to 40% for depression and 75% for anxiety (54). 

7. Colon cancer

Colorectal cancer accounts for 10-15% of all deaths among patients with inflammatory bowel disease (55). 

Patients who have disease activity in the colon are at a higher risk than those with only small intestine involvement (56).

This increase in cancer risk is caused by chronic inflammation and depends on the duration, extent, and severity of the disease (56). 

8. Osteoporosis

One common cause of reduced bone mineral density is chronic systemic inflammation, such as that seen in Crohn’s disease (57).

A recent study found that among patients with Crohn’s, 40% were diagnosed with osteopenia and 20% with osteoporosis (58).

Those who had previously undergone a bowel resection were at a higher risk for osteoporosis (58). 

How is Crohn’s diagnosed?

Crohn’s disease is diagnosed based on symptoms and a combination of the following (59):

1. Blood tests

Doctors typically order several of the following blood tests to evaluate patients with suspected Crohn’s disease (60):

  • C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are used to measure inflammation. 
  • To check for anemia and infection, a complete blood count (CBC) is often ordered.
  • Nutritional markers (serum iron, ferritin, serum B12, etc.) identify nutrient deficiencies and malnutrition caused by the disease.
  • The presence of anti-Saccharomyces cerevisiae antibodies can differentiate Crohn’s from ulcerative colitis.

2. Stool testing

Often, stool samples are collected to test for the presence of white blood cells (a sign of infection), bacterial or viral pathogens, and parasites (60).

Fecal calprotectin and lactoferrin (markers of intestinal inflammation) may also be evaluated to help differentiate inflammatory bowel disease from irritable bowel syndrome (60).

3. Imaging

Several types of imaging can be used to check for intestinal inflammation and help diagnose Crohn’s disease.

Computer tomography enterography is a type of CT scan in which patients must first drink a contrast solution in order to produce a better image of the intestines (6162).

Magnetic resonance (MR) enterography is similar, but it uses magnetic resonance imaging (MRI) instead of radiation to provide a detailed picture of the GI tract (6263).

4. Endoscopy and biopsy

Endoscopy is used to examine the GI tract in order to check for key features of Crohn’s disease (inflammation, lesions, etc.) (62). 

During this procedure, a long, thin tube with a light and camera at the end is inserted into the mouth or anus and guided through the intestines.

Capsule endoscopy is another method, in which the patient is asked to swallow a capsule containing a tiny camera that takes pictures of the intestines as it passes through (64).

In addition, doctors will often perform a biopsy (tissue sample collection) of the intestines during endoscopic procedures of patients with suspected Crohn’s disease (62).

A biopsy can confirm a diagnosis of Crohn’s disease if abnormalities, such as granulomas, are present in the sample tissue (6566).

How do doctors typically treat Crohn’s disease?

The two main goals of medical treatment are to achieve remission (by controlling inflammation and resolving symptoms) and then maintain remission using the following (67):

1. Medications

There are five classes of medications commonly prescribed for Crohn’s disease (67):

  • Aminosalicylates are used to reduce mild inflammation in the intestines and can be delivered orally or rectally (via suppository or enema). Examples include sulfasalazine, olsalazine, and mesalamine.
  • Corticosteroids are used to reduce inflammation and induce remission when aminosalicylates have been ineffective. Examples include cortisone, prednisone, and hydrocortisone.
  • Immunosuppressive agents are used to prevent flare-ups and avoid the need for corticosteroids. Examples include azathioprine and methotrexate.
  • Antibody agents (also called biologics) are used to reduce tumor necrosis factor-alpha (TNF-alpha), a protein that helps regulate immune cells and increases inflammation, when other drugs have failed to induce or maintain remission. Examples include infliximab and adalimumab.
  • Antibiotics are used for patients with mild to moderate disease who have fistulas and/or abscesses. Examples include metronidazole and ciprofloxacin.
  • Low-dose naltrexone (a drug typically used to manage alcohol or opioid dependence) is currently being studied as a potential treatment to induce remission in CD (68).

2. Surgery

When medications fail to control inflammation and maintain remission, surgery may be considered as a last resort (5969).

Many patients (about 70%) eventually require surgery (typically bowel resection) (5969).

During a bowel resection, the section of the intestines that is inflamed, damaged, or blocked is removed (70).

In other cases, emergency operations are required due to life-threatening complications, such as bowel obstructions (71).

However, surgery does not cure the disease, so further treatment is typically needed to maintain remission (59).

What diets are recommended for Crohn’s disease?

Several types of diets may be recommended for people with Crohn’s disease:

1. Enteral nutrition

Enteral nutrition (EN) involves the delivery of liquid nutrients to the digestive tract via a tube placed in the nose, stomach, or intestines (72).

It is thought that EN might induce remission by restoring the gut barrier and correcting dysbiosis (73).

The use of EN to induce or maintain remission in patients with active Crohn’s disease is controversial, and guidelines differ between countries (17475).

European guidelines recommend enteral nutrition as a first choice therapy in children and adolescents with Crohn’s (75). 

A recent Cochrane review found enteral nutrition was more effective than steroids for inducing remission in children (76). 

However, the authors concluded that EN wasn’t any more effective than treatment with steroids in adults (76). 

2. Specific carbohydrate diet (SCD)

The specific carbohydrate diet (SCD) is an elimination diet that restricts grains, starches, processed meats, and most dairy products (77).

Some of these foods can be reintroduced in the later phases of the diet, but many are excluded indefinitely (77).

It was designed by gastroenterologist Sidney Haas in the 1920s for people with IBD and other gastrointestinal disorders (77).

In the 1980s, the diet was popularized by biochemist Elaine Gottschall and her book Breaking the Vicious Cycle: Intestinal Health through Diet (7378).

According to Gotschall, undigested carbohydrates in the intestines promote bacterial overgrowth, which then damages the lining of the intestines (73).

A small number of studies have shown improvements in Crohn’s symptoms and inflammatory markers in patients (mainly children) following the Specific Carbohydrate Diet (798081828384)

According to one survey, 33% of patients reported remission after just 2 months on the SCD diet (85).

Unfortunately, there haven’t been any randomized controlled trials to confirm these results.

3. Mediterranean diet

Due to its anti-inflammatory and antioxidant effects, the Mediterranean diet may be beneficial for patients with Crohn’s disease (86).

A recent study found that patients with Crohn’s disease had less active disease and lower levels of inflammatory markers after 6 months on a Mediterranean diet (87).

However, there are very few studies available, so more research is needed.

4. Low-FODMAP diet

Several studies have shown significant improvements in stool frequency and diarrhea in participants with IBD who followed a low-FODMAP diet (88899091).

Unfortunately, there is also evidence that beneficial gut bacteria are reduced after several weeks on the diet, although taking a daily probiotic might help protect against these effects (899293). 

So far, studies haven’t shown that reducing FODMAPs actually lowers inflammation in the intestines (8994). 

More research is needed to determine whether this diet could be helpful in the long-term for people with Crohn’s (9194).

5. Elimination diets

Inflammation plays a large role in the development of Crohn’s disease, and food sensitivities may contribute to this (5795).

A 2014 study found that an exclusion diet based on food-specific IgG antibodies significantly improved symptoms and quality of life in patients with Crohn’s disease (96).

However, IgG testing is not considered a reliable marker for diagnosing adverse food reactions (979899100).

It’s possible that participants in the studies actually DID have inflammatory hypersensitivity reactions to some of the eliminated foods.

But it’s also possible that some foods were eliminated unnecessarily, because they weren’t actually causing symptoms, despite the presence of IgG antibodies.

What nutrient deficiencies are common with Crohn’s?

The following nutrients should be monitored by a doctor and dietitian:

1. Iron

An estimated 36-90% of patients with Crohn’s disease have iron deficiency (101).

This can be caused by reduced iron intake, impaired iron absorption due to intestinal inflammation, blood loss from intestinal ulcers, and sequestering of iron due to inflammation (102103104).

Every patient with Crohn’s should be screened for iron deficiency and anemia on a regular basis, and those who have iron deficiency anemia should be treated with supplements (105). 

Patients with inactive disease are typically treated with oral iron supplements (no more than 100 mg/day elemental iron), while patients with active disease may need intravenous iron (106).

2. Calcium

It is estimated that one third of patients with IBD have inadequate calcium intake (107).

Many patients exclude dairy products, which are some of the best sources of calcium, because they believe they have lactose intolerance (107).

Calcium absorption may also be impaired in Crohn’s disease due to ongoing inflammation, intestinal damage, and vitamin D deficiency (108).

3. Zinc

Evidence suggests that zinc deficiency increases intestinal permeability and promotes gut inflammation (109).

Among patients with Crohn’s disease, approximately 8.5% don’t consume enough zinc and 20% have low serum zinc levels (110).

Patients with zinc deficiency are more likely to have increased hospitalizations, surgeries, and disease-related complications (111).

An older study from 2001 found that patients who received oral zinc sulfate supplementation (110 mg three times/day) for 8 weeks had improved intestinal barrier function and reduced risk of relapse (112). 

However, there was no control group, and the study’s methodology has been criticized by some experts (112113).

4. Magnesium

It is estimated that 13-88% of patients with IBD have low magnesium levels, likely due to decreased intake and malabsorption (114).

Magnesium deficiency may increase inflammation, which could aggravate symptoms in Crohn’s disease (115).

5. Vitamin A

It is thought that vitamin A needs may be higher in patients with Crohn’s disease, because it is used as an antioxidant to combat oxidative stress (116).

A recent study showed that nearly 30% of patients with Crohn’s disease were deficient in vitamin A (116).

6. Vitamin D

Nearly 60% of patients with Crohn’s disease are deficient in vitamin D (117).

Vitamin D is important for immune functioning, and having lower levels has been associated with increased Crohn’s disease severity (117).

Studies have found that supplementation with vitamin D (2000-5000 IU/day) for up to 6 months effectively raises serum vitamin D levels and reduces inflammatory markers (118119). 

7. Vitamin B12

Evidence regarding the prevalence of vitamin B12 deficiency in Crohn’s disease is mixed, although most of these studies have looked at serum B12, a less accurate marker (120121122).

A recent study used MMA (methylmalonic acid) and holoTC (holotranscobalamin), which are more reliable markers for B12, and found that 33% of participants with Crohn’s were deficient (123).

Patients who have had an ileal resection or who have active inflammation in the ileum are at a higher risk for deficiency (123).

Research has found that treatment with oral B12 (1 mg/day cyanocobalamin) is typically required indefinitely to restore and maintain B12 status in these patients (124).

8. Fiber

Many patients with Crohn’s disease choose to avoid dietary fiber because they believe it will cause flare-ups (125).

Fiber may actually help reduce inflammation in Crohn’s disease by altering the gut microbiota and correcting dysbiosis, although more research is needed (126).

A 2016 study found that participants who reported that they did not avoid high fiber foods were about 40% less likely to have a disease flare than those who avoided high fiber foods (127). 

9. Protein

Patients with IBD are at risk of losing muscle mass over time due to poor dietary intake, malabsorption of nutrients, and the effects of medical treatments (74).

In particular, corticosteroids are known to alter protein metabolism and increase muscle loss, which can cause muscle weakness (128).

During flare-ups, protein intake should be increased to 1.2-1.5 grams/kg of body weight per day in adults (74).

Protein requirements in remission are lower, around 1 g/kg (74).

10. Omega-3s?

Omega-3 fatty acids may be beneficial for patients with Crohn’s disease because of their ability to combat inflammation (129).

Studies have linked diets low in omega-3s and high in omega-6s to a higher risk of developing IBD (20).

However, studies evaluating the effects of omega-3 supplements on remission rates in Crohn’s have reported conflicting results (130).

A 2014 review of 6 studies concluded that supplementation with omega-3s is probably ineffective for maintaining remission (130).

Are any other supplements beneficial for Crohn’s?

The following supplements have some research to support their use for people with Crohn’s disease:

1. Wormwood

Artemisia absinthium (also known as wormwood) is a shrub that has been used in herbal medicine to treat many conditions, including IBD (131).

It has been shown to have beneficial effects on immunity and reduces TNF-alpha, which may aid healing in Crohn’s disease (131132).

Several small trials suggest that wormwood supplementation (500-750 mg, 3x/day) decreased symptoms and disease severity in patients with Crohn’s disease (132133)

2. Tripterygium wilfordii Hook F 

Tripterygium wilfordii Hook F (TwHF) is a woody vine that has been widely used in traditional Chinese medicine (134).

It contains a large number of chemical components with anti-inflammatory and immune-altering properties (134).

One trial found that patients who received high-dose TwHF supplements (2 mg/kg of body weight per day) were significantly more likely to maintain remission after one year (135). 

However, studies using lower doses (1.5 mg/kg/day) of TwHF haven’t shown any significant effects (135136).

3. Prebiotics

Fructooligosaccharides (FOS) and inulin are two types of prebiotic fiber that may be beneficial for Crohn’s disease (137138).

They are found in many foods, including onions, garlic, asparagus, Jerusalem artichokes, bananas, and oats (139140).

Limited research suggests that supplementation with these fibers (10-15 g/day) improves the gut microbiota and may decrease disease activity in patients with Crohn’s disease (137138).

More research is needed to support these results.

4. Probiotics?

It is thought that probiotics might improve symptoms of Crohn’s disease by strengthening the intestinal barrier, inhibiting the growth of pathogens, and decreasing inflammatory cytokines (141). 

Unfortunately, research hasn’t shown probiotic supplements to have any significant effects on Crohn’s disease in adults (142143).

One meta-analysis did find that a combination of Saccharomyces boulardii, Lactobacillus, and VSL#3 probiotics showed some benefit, although it wasn’t statistically significant (p = 0.057) (143).

More evidence from randomized controlled trials is needed before the efficacy of probiotics can be determined (142).

5. Other

  • Aloe vera 
    • Although oral aloe vera supplementation has shown promise for ulcerative colitis, there are no studies evaluating its effects in Crohn’s disease (144).
  • Boswellia 
    • A 2011 trial found that boswellia supplementation (2400 mg/day) for one year was no more effective than placebo for maintaining remission (145).
  • Curcumin
    • Research is limited, but a 2020 trial was discontinued after 55% of patients who received curcumin (3 g/day) experienced a severe recurrence of disease, compared to only 24% of the placebo group (146).
  • Green tea polyphenols
    • Research in animals shows that green tea polyphenols (such as epigallocatechin) improve antioxidant levels and reduce intestinal inflammation, but there haven’t been any human studies to evaluate their effect on Crohn’s disease (147148).
  • Serum-derived bovine immunoglobulin (SBI)
    • SBIs bind to bacterial antigens in the intestines, which may help inhibit the inflammatory reactions that are responsible for IBD (149).
    • Evidence from animal and observational studies suggests SBI supplementation (5g/day) may be helpful in patients with Crohn’s disease that hasn’t responded to other treatments (149150151152).
    • There haven’t been any clinical trials.

Are there any other interventions to try?

The following complimentary therapies have been studied for their use in Crohn’s disease:

1. Acupuncture with herb-partitioned moxibustion

Moxibustion is a type of heat therapy that involves burning cones or sticks made from dried mugwort leaves (called “moxa”) on certain parts of the body (153).

In particular, herb-partitioned moxibustion is performed by placing a cake of herbs on each of the patient’s acupoints, then covering each cake with a moxa cone (154). 

Research shows that patients with Crohn’s disease who are treated with a combination of herb-partitioned moxibustion and acupuncture (2-3 times/week) experience significant improvements in symptoms and quality of life (154155156). 

This technique may work by regulating the balance of certain immune cells in the intestines, which in turn reduces levels of proinflammatory cytokines (157). 

2. Cannabis?

An estimated 15% of IBD patients use cannabis to manage their symptoms (158).

The two main components of cannabis are tetrahydrocannabinol (THC), known for causing the sensation of being “high”, and cannabidiol (CBD), which has anti-inflammatory properties (158).

So far, only two small peer-reviewed placebo-controlled studies have evaluated the effects of cannabis in active Crohn’s disease (158).

One study found a significant decrease in disease activity but no changes in remission rates of patients who smoked cannabis containing 115 mg tetrahydrocannabinol (THC) twice daily (159).

Another study showed no beneficial effects of cannabidiol (CBD) supplementation (10 mg twice daily) on disease activity (160). 

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