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Curcumin for Inflammatory Bowel Disease: A Review of Human Studies

Posted By Administration, Friday, July 8, 2011
Updated: Friday, April 18, 2014


Case study from the Alternative Medicine Review (AMR) - the official journal of the American College for Advancement in Medicine (ACAM)

by Rebecca A. Taylor, PharmD, MBA, BCPS and Mandy C. Leonard, PharmD, BCPS


OBJECTIVE: To evaluate the use of curcumin in inflammatory bowel disease. DATA SOURCES: ALTMEDEX, Comprehensive Database of Natural Medicines, MEDLINE/PubMed were searched from January 1980 through May 2009 using the terms curcumin, turmeric, ulcerative colitis, Crohn’s disease,
Curcuma longa, Curcuma domestica, Indian saffron, inflammatory bowel disease. Data was limited to human trials. References of identified articles were reviewed. DATA SYNTHESIS: Data evaluating the use of curcumin in inflammatory bowel disease (including ulcerative colitis and Crohn’s disease) is limited to two studies comprising data for only 99 patients. Curcumin in conjunction with mainstream therapy, consisting of sulfasalazine (SZ) or mesalamine (5-aminosalicylic acid [5-ASA] derivatives) or corticosteroids was shown to improve patient symptoms and allow for a decrease in the dosage of corticosteroids or 5-ASA derivatives. In one small study of 10 patients, some patients even stopped taking corticosteroids or 5-ASA. CONCLUSIONS: Although two small studies have shown promising results, all authors conclude
that larger-scale, double-blind trials need to be conducted to establish a role for curcumin in the treatment of ulcerative colitis. In addition to improving results when used in conjunction with conventional medications for UC, curcumin may pose a less-expensive alternative. (Altern Med Rev 2011;16(2):152-156)


Turmeric, used as a spice in curry powders and mustard, is known scientifically as Curcuma longa or Curcuma domestica. The perennial herb has multiple ingredients, including curcuminoids, the most active ingredients for medicinal use. These curcuminoids, comprising the yellow-pigmented fractions of turmeric, include diferuloylmethane (curcumin I), demethoxycurcumin (curcumin II), bisdemethoxycurcumin (curcumin III), and the recently discovered cyclocurcumin. The major components of commercial curcumin are curcumin I (77%), curcumin II (~17%), and curcumin III (~3%). Curcumin is also known by many synonyms and translated into various languages around the world; in Tibetan language it is known
as Gaser, in Swahili it is known as Manjano.

Curcumin has well-documented historical use in Chinese, Hindu, and Ayurvedic medicine. Curcumin has been used for a variety of disorders, from respiratory conditions to dyspepsia to malignancy. To date, no studies in animals or humans have discovered significant toxicity related to curcumin, even at very high doses.

Mechanisms of Action

Much is known about the molecular targets and interactions of curcumin with receptors, growth and transcription factors, cytokines, enzymes, and genes. Curcumin is often cited as pleiotropic, meaning it has the ability to interact with many cell targets. For the purposes of this discussion, curcumin’s molecular targets will be confined to those involved in gastrointestinal inflammation. Curcumin has been shown to inhibit the activity of lipoxygenase4 or binding to phosphatidylcholine micelles, thereby inhibiting lipoxygenase I. Of note in gastrointestinal disorders, curcumin has been found to inhibit the activation of various transcription factors that play a key role in inflammation, cell survival and proliferation, and
angiogenesis. These include nuclear factor-kappaB (NF-kB), activated protein-1 (AP-1), signal transducer and activator of transcription (STAT) proteins, peroxisome proliferator-activated receptor-gamma (PPAR-γ), and β-catenin. Inflammatory stimuli activate one of three independent mitogen-activated protein kinase (MAPK) pathways leading to activation of the p44/42 MAPK, JNK, or p38 MAPK pathway.
Cyclooxygenase-2 (COX-2) proteins are crucial to the inflammation cascade and have been linked to
certain cancers. There are several ways in which curcumin inhibits COX-2, both directly and indirectly. Curcumin downregulates the expression of COX-2, most likely through the downregulation of NF-kB that is required for COX-2 activation. In cancer cells, curcumin exerts anti-inflammatory and growth-inhibition by inhibiting expression of interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α).


Curcumin studies in animals show it is rapidly metabolized, conjugated in the liver, and excreted in the feces with minimal amounts found in the urine. A 40 mg/kg intravenous dose of curcumin given to rats resulted in complete plasma clearance at one hour post-dose, showing its rapid metabolism; data in humans is inconclusive. A phase I clinical trial conducted on 25 patients with precancerous lesions showed oral doses of 4, 6, and 8 g curcumin daily for three months yielded serum curcumin concentrations of only 0.51 ± 0.11, 0.63 ± 0.06, and 1.77 ± 1.87 µM respectively, indicating poor absorption of straight curcumin. In this study serum levels peaked one and two hours post-dose and declined rapidly.

Inflammatory Bowel Disease (IBD)

Inflammatory bowel disease is a chronic immune disorder that involves an overactive immune component in the intestinal mucosa. IBD is divided into two major categories, ulcerative colitis (UC) and Crohn’s disease (CD). The two diseases have a fair amount of overlap, including presenting symptoms, quality of life issues, and treatments. Patients with IBD often have symptoms of abdominal pain, cramping, diarrhea, rectal bleeding, urgency, nausea, fever, and weight loss. Major differences of the two types of IBD are listed in Table 1.11 Proctitis is ulcerative colitis confined to the rectal area.

Certain cytokines have been associated with IBD, including TNF-α, IL-1, IL-6, IL-8, and others. Targeted drug therapies, specifically infliximab, have been successful in treating IBD. Infliximab is an anti-TNF-α monoclonal antibody that has been extensively studied in myriad inflammatory disorders, including CD and UC. Widespread use of infliximab is limited because of adverse effects, cost, and the emergence of antibodies that result after multiple administrations.

Most recently, the role of NF-kB in IBD has been elucidated. Colon biopsies in IBD patients with active disease show increased levels of NF-kB p65 protein (a member of the NF-kB family of proteins). The amount of NF-kB p65 in the tissue samples correlated with the severity of intestinal inflammation. This increased expression of NF-kB results in an increased ability to secrete inflammatory cytokines, such as
TNF-α, IL-1, IL-6, IL-12, and IL-23, the latter of which are directly responsible for mucosal damage in IBD. TNF-α is also able to up-regulate the production of NF-kB, resulting in a cyclical feedback loop of inflammation.

Table 1. Differential Diagnosis of Ulcerative Colitis and Crohn's Disease


 Diagnosis and Staging of IBD in Clinical Studies

Ulcerative colitis is diagnosed through a colonoscopy, while the severity of symptoms can be rated on a number of severity index scales. Although several endoscopic indices are available to characterize the severity of ulcerative colitis, those currently used in clinical trials are not uniform. Hanai and colleagues, in the double-blind study discussed below, did not disclose their specific methodology for endoscopic index. The Clinical Activity Index (CAI) was used to assess UC severity in this same study. A CAI of ≤4
indicated remission, whereas a CAI ≥5 indicated relapse. A Crohn’s disease activity index (CDAI) is
often used to evaluate disease severity in CD – as was the case in the small pilot study discussed below.

Clinical IBD Studies
Small Pilot Study

Holt and colleagues conducted a small, open-label, pilot study of curcumin in five patients with ulcerative colitis/proctitis and five patients with Crohn’s disease. Five patients with ulcerative proctitis, who were currently using 5-aminosalicylic acid (5-ASA) compounds and corticosteroids (four of five patients were on corticosteroids + 5-ASA compounds), were given 550 mg curcumin twice daily for one month, then 550 mg three times daily for the second month. The five patients with Crohn’s disease received curcumin at a dose of 360 mg orally three times daily for one month and then 360 mg four times daily for an additional two months. Patient characteristics and demographics are reported in Table 2.

Patients were assessed at baseline and after two months of curcumin via hematological, biochemical, and inflammatory analysis (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) as well as sigmoidoscopy and biopsy. Subjective analysis was via a self-reported symptom diary. In the ulcerative
proctitis group, all five patients had significant improvement. Two patients stopped taking 5-ASA compounds, two reduced 5-ASA dosages, and one stopped corticosteroids entirely. Although only four of five CD patients completed the study, they also experienced a reduction in CDAI scores, ESR, and CRP. The Crohn’s disease group also reported symptomatic improvements of fewer bowel movements, less diarrhea, and less abdominal pain and cramping. In the absence of a clearly stated primary endpoint, it was considered to be the symptom diary. Based on the symptom diary (p<0.02), all patients improved from baseline after two months and inflammatory markers decreased to normal limits. The authors recommended larger scale, double-blinded, placebo-controlled trials in the future.

Table 2. Patient Characteristics and Medications at Study Entry


Adapted from: Holt PR, Katz S, Kirschoff R Curcumin therapy in inflammatory bowel disease; a pilot study. Dig Dis Sci 2005;50:2191-2193.

5-ASA = 5-aminosalicyllic acid

SZ = sulfasalazine

6-MP = 6-mercaptopurine

Double-blind, Placebo-controlled Trial

Hanai and colleagues conducted a randomized, multicenter, double-blind, placebo-controlled trial of curcumin plus sulfasalazine (SZ) or mesalamine compared to placebo plus SZ or mesalamine in 89
patients with UC. After a four-week washout period, subjects were randomly assigned to a six-month regimen of either placebo (n=44) or curcumin 1,000 mg after breakfast and 1,000 mg after dinner (n=45) in combination with SZ (1-3 g/ day; median 2 g/day) or mesalamine (1.5-3 g/day; median 2.25 g/day). The inclusion and exclusion criteria were extensive (Table 3).

Patients were followed during treatment and for six months after the treatment ended; patients received only SZ or mesalamine during the six-month follow-up. Seven patients requested to be excluded, leaving 82 evaluable patients. The relapse rate was significantly higher in the placebo group (20.5% [8/39]) than in the curcumin-treated group (4.7% [2/43]). Curcumin also suppressed disease-associated CAI and endoscopic index (EI) scores. The mean CAI in the curcumin group was improved from 1.3 to 1.0 at six months (p=0.38), while CAI in the placebo group increased from 1.0 to 2.2 (p=0.0003). Patients in the curcumin group also had significantly improved EI (1.3 to 0.8 [p=0.0001]), while EI values in the placebo group showed no significant improvement. The authors provided only before- and after-treatment data,
despite assessments every two months. There was a statistically significant (p=0.049) difference between the percentage of patients with recurrence at six months in the curcumin (4.44 [95% confidence interval (CI) 0.54-15.15]) compared to the placebo (15.15 [CI 8.18-32.71]) group. This difference was not significant at 12 months.

Side effects reported by study subjects included abdominal bloating, nausea, hypertension (one patient), diarrhea, and elevated γ-guanosine triphosphate (GGTP) levels (one patient). This latter patient was a heavy drinker. With the exception of the patient that experienced hypertension, no patient discontinued curcumin therapy due to side effects.

Only two of 43 patients treated with curcumin in combination with SZ or mesalamine relapsed during six months of therapy; whereas, eight of 39 patients who received placebo with SZ or mesalamine relapsed during the same period. Although this difference was not statistically significant, the authors postulate curcumin may have an effect on suppressing relapse. The authors drew three major conclusions: (1) curcumin had better clinical efficacy over placebo in the prevention of relapse, (2) curcumin significantly improved the CAI and EI, and (3) curcumin was well-tolerated. The authors, stating their results might have
been better had they used a higher dose of curcumin, recommend that future studies use dosages greater than 2 g/day.

Table 3. Inclusion and Exclusion Criteria in Hanai Study


Precautions and Contraindications

Patients with gallstones or bile duct obstructions should use curcumin with caution, primarily due to curcumin’s ability to cause gallbladder contractions. In a randomized, double-blind, cross- over study involving 12 healthy volunteers, 20 mg curcumin produced as much as 29-percent reduction in gallbladder size, indicating gallbladder contraction (statistically different than placebo). A subsequent study indicated
that doses of 40 and 80 mg curcumin produced 50- and 72-percent decreases in gallbladder volume, respectively.

Because curcumin inhibits platelet aggregation in vitro and in animal studies, it is theorized it could be additive in effect to antiplatelet medications such as aspirin, clopidogrel, and non-steroidal anti-inflammatories (NSAIDS).18,19 In a mouse model, 100 mg/kg curcumin or 25 mg/kg aspirin resulted in 60- or 61.1-percent protection from thrombosis, respectively. The concomitant use of curcumin and
anticoagulant or antiplatelet medications should be approached with caution.


Although this review discusses just two clinical studies of inflammatory bowel disease, the uses of curcumin far exceed the scope of this article. Curcumin shows promise in treating myriad disorders. It has recently been studied, at wide-ranging daily dosages of as little as 20 mg and as much as 12 g, for ailments such as psoriasis, colorectal cancer, renal graft function, pancreatitis, dyspepsia, and chronic anterior uveitis, to name a few. Larger-scale, prospective studies are needed to confirm its effect for IBD. Curcumin has an advantageous safety profile as well as low relative cost, making it an attractive option for IBD patients.

1. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “curecumin”: from kitchen to clinic. Biochem Pharmacol 2008;75:787-809.
2. Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review
of preclinical and clinical research. Altern Med Rev 2009;14:141-153.
3. Hanai H, Sugimoto K. Curcumin has bright prospects for the treatment of inflammatory bowel disease. Curr Pharm Des 2009;15:2087-2094.
4. Skrzypczak-Jankun E, Zhou K, McCabe NP, et al. Structure of curcumin in complex with lipoxygenase and its significance in cancer. Int J Mol Med 2003;12:17-24.
5. Began G, Sudharshan E, Appu Rao AG. Inhibition of lipoxygenase 1 by phosphatidylcholine micelles-bound curcumin. Lipids 1998;33:1223-1228.
6. Shishodia S, Singh T, Chaturvedi MM.  Modulation of transcription factors by curcumin. Adv Exp Med Biol 2007;595:127-148.
7. Cho JW, Lee KS, Kim CW. Curcumin attenuates the expression of IL-1beta, IL-6, and TNF-alpha as well as cyclin E in TNF-alpha-treated HaCaT cells; NF-kappaB and MAPKs as potential upstream targets. Int J Mol Med 2007;19:469-474.
8. Sharma RA, Steward WP, Gescher AJ. Pharmacokinetics and pharmacodynamics of curcumin. Adv Exp Med Biol 2007;595:453-470.
9. Ireson C, Orr S, Jones DJ, et al. Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol esterinduced prostaglandin E2 production. Cancer Res 2001;61:1058-1064.
10. Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001;21:2985-2900.
11. Friedman S, Blumberg RS. inflammatory bowel disease. In: Fauci AS, Braunwald E, Kasper DL, Hauser SL, eds. Harrison’s Principles of Internal Medicine. 17th ed. Columbus, OH: McGraw-Hill Professional; 2008:1886- 1898. content.aspx?aID=2883197
12. Papadakis KA, Targan SR. Role of cytokines in the pathogenesis of inflammatory bowel disease. Annu Rev Med 2000;51:289-298.
13. Atreya I, Atreya R, Neurath MF. NF-kappaB in inflammatory bowel disease. J Intern Med 2008;263:591-596.
14. Hanai H, Iida T, Takeuchi K, et al. Curcumin maintenance therapy for ulcerative colitis: randomized, multi- center, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol 2006;4:1502-1506.
15. Holt PR, Katz S, Kirschoff R. Curcumin therapy in inflammatory bowel disease: a pilot study. Dig Dis Sci
16. Rasyid A, Lelo A. The effect of curcumin and placebo on human gall-bladder function: an ultrasound study. Aliment Pharmacol Ther 1999;13:245-249.
17. Rasyid A, Rahman AR, Jaalam K, Lelo A. Effect of different curcumin dosages on human gall bladder. Asia Pac J Clin Nutr 2002;11:314-318.
18. Srivastava KC, Bordia A, Verma SK. Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. Prostaglandins Leukot Essent Fatty Acids 1995;52:223-227.
19. Srivastava R, Dikshit M, Srimal RC, Dhawan BN. Anti-thrombotic effect of curcumin. Thromb Res 1985;40:413-417.
20. Srivastava R, Puri V, Srimal RC, Dhawan BN. Effect of curcumin on platelet aggregation and vascular prostacyclin synthesis. Arzneimittelforschung 1986;36:715-717.

Tags:  inflammatory bowel disease 

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The Second Brain: The Gut and Serotonin

Posted By Administration, Thursday, May 6, 2010
Updated: Friday, April 18, 2014



by Zina Kroner, DO

This is not the “shock and awe” study of the year, but it elucidates an excellent medical phenomenon.  A recent study in the American Journal of Gastroenterology showed that St. John’s Wort, an herb used to treat mild depression, was less effective than placebo at treating irritable bowel syndrome (IBS).  Improvements in quality of life were similar in both placebo and the herb treated groups.  Gastroenterologists have been treating IBS with anti-depressants for quite some time.   I would like to bring to light the theory behind it, as this may have clinical implications beyond the use of medication.

The gut, often referred to as the second brain due to the powerful enteric nervous system that it houses, is tightly connected to serotonin, the feel good neurotransmitter.   Dr. Michael D. Gershon, the chairman of the department of anatomy and cell biology at Columbia has brought this to light in his book entitled “The Second Brain.” 

We have all felt a twinge in the stomach prior to a major exam or a public speaking event.  It is quite common for my patients with a psychiatric disorder to have a concomitant gastrointestinal issue. 

There are several reasons why stress or anxiety can cause irritable bowel syndrome.  First, with any fight or flight response, cortisol, a stress hormone, is released. Cortisol fires up the sympathetic nervous system and makes the parasympathetic nervous system less efficient.  It is the parasympathetic nervous system that we need in order to maintain bodily homeostasis, such as breathing, digestion,etc.  Therefore, with a cortisol surge, digestion becomes ineffective and irritable bowel syndrome can kick in.

Second, it is important to note that serotonin has a profound effect on gastrointestinal function, being that 95% of the body’s serotonin is cradled in the gut.  At the start of digestion, it is the enterochromaffin cells that release serotonin into the gastrointestinal tract, which houses many serotonin receptors.  The receptors then initiate a process via nerve cells that starts the flow of digestive enzymes. 

Serotonin then relays messages up to the brain, letting it know what is happening.  Therefore, certain foods may elicit a feeling of nausea, etc.  Once serotonin is released in the gastrointestinal tract and the process of digestion is stimulated, normally, it is cleared out of the way by SERT, a serotonin transporter. 

These transporters are found in the gut walls.   Often, those with IBS, may not have an appropriate level of functioning SERTs, and they are therefore unable to clear out the serotonin cells.  This can stimulate diarrhea. Once the serotonin receptors are supersaturated, the effect is constipation, thus the infamous Irritable Bowel Syndrome.  Therefore, medications as well as supplements such as St. Johns Wort which manipulate the serotonin may potentially help IBS symptoms. It is no wonder that in this recent study, placebo was quite beneficial in IBS.  This shows how much mind and body are connected.  Focusing on stress management is key as well. 

A third contributor to IBS as it related to the enteric nervous system is allergens.  Often, the barrier of the gut becomes damaged and certain allergens, etc, may enter the bloodstream, triggering the brain to send a message to the gut to increase the production of histamines and other inflammatory cells in order to try to get rid of the allergens.  This inflammatory process may trigger the neurons in the enteric nervous system (in the gut) to become hyperactive and therefore contribute to diarrhea. 

The challenge now is to optimize the efficiency of the gastrointestinal tract by preventing unnecessary cortisol surges so not to disrupt the sympathetic and parasympathetic nervous system harmony, to maintain a healthy serotonin and SERT level, and to prevent unnecessary allergens from entering the GI tract so not to trigger the inflammatory process involved in diarrhea.  The gut really is the Second Brain! 

Citation:  Saito YA et al. A randomized, double-blind, placebo-controlled trial of St John's wort for treating irritable bowel syndrome. Am J Gastroenterol 2010 Jan; 105:170.

Tags:  gut health  inflammatory bowel disease 

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Role of Diet in the Management of Inflammatory Bowel Disease

Posted By Administration, Friday, April 30, 2010
Updated: Friday, April 18, 2014


Many studies have looked at connections between diet, etiology, signs and symptoms associated with inflammatory bowel disease (IBD). Although these connections are apparent to clinicians, they are difficult to prove qualitatively or quantitatively. Enteral feeding and polymeric diets are equally effective at bringing about remission in Crohn’s disease (CD). Parenteral feeding is also effective, although none of these methods is as effective as corticosteroid therapy. However, enteral feeding is preferred in the pediatric population because linear growth is more adequately maintained via this route. Exclusion diets in patients brought into remission using an elemental diet have been shown to maintain remission for longer periods. Studies that aim to isolate culpable food groups have shown that individuals react differently on exposure to or exclusion of various foods. The commonly identified food sensitivities are cereals, milk, eggs, vegetables and citrus fruits. Studies that have looked at gut mucosal antigen behavior have shown higher rectal blood flow, in response to specific food antigens, in those with CD over healthy subjects. Exclusion of sugar shows little evidence of amelioration in CD. Omega 3 fatty acids show promise in the treatment of IBD but await larger randomized controlled trials. Patients frequently notice that specific foods cause aggravation of their symptoms. Whilst it has been difficult to pinpoint specific foods, with advances in the laboratory tests and food supplements available, the aim is to prolong remission in these patients using dietary measures, and reduce the need for pharmacotherapy and surgical intervention.


The etiology of inflammatory bowel disease (IBD) is considered multifactorial. Genetic, infective and environmental theories exist, as well as those centered around host immunity, intraluminal gut flora, food allergies and hypersensitivity.

Whilst pharmacological therapy plays a major role, many patients prefer to control their symptoms by the most conservative means possible. Our aims in IBD therapy are to downregulate inflammation, and reduce the incidence of relapse and the healing time.

Dietary therapy encompasses dietary modifications suggested by physicians and those that patients make autonomously. The putative mechanisms of action are due to bowel rest, provision of nutrients, alteration of bowel flora or alteration of antigenic stimuli. The gastrointestinal flora and its interaction with nutritional factors has a huge impact on the environment, especially in genetically predisposed individuals. Nutrients as components of cell structure or antigens can induce inflammatory mediator expression and suboptimal levels of nutrients, which may have an impact on tissue repair and other cellular processes. Other reviews have concluded that nutrients that tend to affect the immune responses of the host (n-3 fatty acids, antioxidants) are likely to play a role in the treatment of IBD.

In this review, we examine the literature for dietary interventions in IBD, such as exclusion/elimination diets, enteral nutrition and total parenteral nutrition (TPN), and review the evidence that they induce and/or maintain remission in patients with IBD.


Elemental/polymeric diets

Elemental diets were chanced upon as a therapeutic option for CD patients when they were used to bolster their nutritional status and reduce inflammation. Liquid feeds are thought to work by reducing mucosal antigen exposure, partly due to the nature of the feed and partly to faster transit times. They also alter the fecal flora, which causes local immunomodulation downscaling, which enhances nutritional status and allows relative bowel rest.

Compliance may be poor as elemental diets are not known for their palatability and are often delivered via a nasogastric tube, whereas the polymeric drinks are far more palatable. Several trials and meta-analyses have shown no significant difference in the efficacy of elemental diets over polymeric diets.

Elemental diets offer a cheaper way of bringing about remission and without the side effect profile of TPN. In both adult and pediatric populations, elemental and polymeric feeds have been shown to be as effective as corticosteroid therapy in treating active CD. However, a Cochrane review by Zachos et al has shown, in a meta-analysis, that enteral nutrition is not as effective as steroid therapy for inducing remission.

However, enteral therapy for CD has its role in selected cases, in particular, in children in whom steroids may cause growth retardation. Food exclusion with liquid diet is very difficult to maintain, therefore, these are rarely long-term solutions. Unfortunately, a staged return to normal feeding often leads to relapse.

Exclusion diets

The East Anglia Multicentre Controlled Trial showed that various food intolerances were perceived in individual patients, and among the more common were cereals, dairy produce and yeast. This work looked at the use of exclusion diets as an intervention in active CD. The exclusion diet was based around daily reintroduction of a single food type. If it caused diarrhea or pain, it was eliminated. All patients were treated initially with an elemental diet, and those who attained remission followed a reduced prednisolone course or the exclusion diet pathway. Jones et al have shown that maintenance of remission, by identification and avoidance of food intolerances, is possible, often without pharmaceutical adjuncts. Testing for these sensitivities has proven difficult, because testing shows a large number of sensitivities in unselected populations, which are of doubtful clinical significance. Jones et al have tested a diet rich in unrefined carbohydrate against an exclusion diet. Seven out of 10 patients on the exclusion diet stayed in remission for 6 mo, while none of those on the carbohydrate-rich diet remained in remission. Pearson et al have conducted a study of 42 CD patients after induction of remission by elemental diet. Single foods were investigated using open and double blind rechallenge over 5 d. Fourteen patients dropped out due to flare-ups that were thought to be unrelated to food, and caused by inability to comply with the regimen. Twenty of the remaining patients identified food intolerances and eight did not. This research group has concluded that food intolerance is not as frequent as claimed in other studies, and that it is variable in its intensity and occurrence.

Parenteral feeding in CD

TPN allows bowel rest while supplying adequate calorific intake and essential nutrients, and removes antigenic mucosal stimuli. However, TPN is expensive, invasive and has a number of side effects. TPN has been shown to bring about remission in CD. Müller et al have found that, in 30 consecutive complicated CD patients, 3 wk of TPN as an inpatient followed by an additional 9 wk at home, during which time, no medication or oral intake was allowed, 25 patients avoided surgery. These patients returned to work and needed no further medication and ate normal meals subsequently. In a prospective randomized controlled trial (RCT), 51 patients with active CD refractory to medical treatment were treated with TPN and nil by mouth, defined formula diet via a nasogastric tube, or partial parenteral nutrition. Clinical remission was obtained in 71% of the patients on TPN, 58% on enteral feeding, and 60% on partial parenteral feed.

Enteral vs parenteral feeding

There has been controversy regarding the enteral vs parenteral route for feeding in patients with IBD. Comparison of TPN against elemental diet in a group of 36 patients showed no significant difference in the number of days to remission, the drop in Crohn’s disease activity index (CDAI) score, the erythrocyte sedimentation rate (ESR), or albumin. However, in other studies that have agreed with this finding, neither was proven to be as beneficial as corticosteroids, except one study in a pediatric population. In that study, Sanderson et al entered 17 children into an RCT, in which eight were given an elemental diet for 6 wk via a nasogastric tube, and seven were given adrenocorticotrophic hormone injections and oral prednisolone and sulfasalazine. The elemental diet was equally effective at improving the Lloyd-Still disease activity index scores, C-reactive protein (CRP), ESR and albumin. The elemental diet was markedly better at maintaining linear growth. Whilst strong evidence exists supporting the primary use of enteral feeding in children with CD, it is not commonplace in the treatment of adults.

Omega-3 fatty acids

Shoda et al have noted that the gradual replacement of n-3 polyunsaturated fatty acids with n-6 polyunsaturated fatty acids results in an increased incidence of CD. This implies that there is the potential to modulate immune responses by altering the ratio of polyunsaturated fatty acids in favor of n-3 rather than n-6. Meister and Ghosh have shown that fish-oil-enriched enteral diet, when incubated with intestinal tissue from 11 subjects with IBD and four controls, reduced inflammation modestly in CD and significantly in UC. Inflammatory improvement was assessed by analyzing the interleukin (IL)-1 receptor antagonist/IL-1β ratio. The greater the ratio, the less inflamed the tissue. A systematic review of the effects of n-3 fatty acids in IBD by MacLean et al has identified 13 controlled trials that investigated the effects of n-3 fatty acids. The results were mixed but in the three studies that looked at steroid requirements, this was found to be reduced. However, this was statistically significant in just one of these studies.



Exclusion diets

Jones has looked at exclusion diets for the maintenance of remission of CD and has shown that, in personalized exclusion diets, 62% of the patients maintained remission at 2 years and 45% at 5 years, with no other medical intervention. This was compared to the European Cooperative Crohn’s Disease Study in 1984 in which the placebo arm of the study had no patient who maintained remission after 2 years of follow-up.

A Cochrane review of the maintenance of remission in CD has suggested that larger, high-powered controlled trials are required to confirm current hypotheses relating to diet and maintenance of remission. Trials of diet against azathioprine and infliximab also have been suggested to investigate quantitative effects of nutritional supplements and their impact on cost-effectiveness and quality of life.

Enteral feeding

Enteral feeding has been shown to have a role in preventing relapse in inactive CD patients (predominantly in children), but the effect has also been observed in a Japanese study of adult CD patients. Esaki et al have demonstrated in a trial of 145 patients with CD (mostly induced into remission with TPN) that, under maintenance with elemental/polymeric nutrition, the risk of recurrence was lower in those with small bowel rather than large bowel involvement.



Maintenance of remission in UC

UC does not seem to be ameliorated by bowel rest and elemental diets in the same way as CD is. However, patients still express concern about specific food types, and there does appear to be an association with a western diet. In a study that has investigated self-reported food intolerance in chronic IBD, patients with CD and UC have reported that they felt intolerant to specific dietary triggers and restricted their diet accordingly. The same study has shown that the pattern and frequency of food intolerance did not differ between CD and UC patients. This has been reinforced by work from our own group that has investigated food intolerances detected by measuring IgG4 antibodies to specific food antigens. There is no evidence to support the use of elemental/polymeric feeding in the treatment of UC.

Omega-3 fatty acids

Omega-3 fatty acids derived from fish oils have been shown to be of benefit in a double-blind RCT that looked at patients with distal UC. That study found that the group treated with 3.2 g eicosapentaenoic acid or 2.4 g docosahexaenoic acid daily had significantly better clinical and sigmoidoscopic scores compared with the control group who took sunflower oil, after 3 and 6 mo. This supports the idea that omega-3 oils suppress natural cytotoxicity.




Dietary fiber has been investigated as a means of increasing short-chain fatty acid (SCFA) production. IBD has been linked with impaired SCFA production. SCFAs are mainly produced by the anaerobic bacterial fermentation of undigested carbohydrates and fiber polysaccharides. In 1995, Galvez et al reviewed a number of studies that concluded that dietary fiber confers clinical benefits in patients with IBD because it maintains remission and reduces colonic damage. This is thought to occur by increasing SCFA production and by altering the gut flora towards predominantly non-pathogenic bacteria.


The properties of omega-3 fatty acids have been discussed elsewhere in this review. Other studies have revealed an inverse correlation between the percentage of energy derived from long-chain triglycerides and the efficacy of enteral feeds in achieving remission.


A high intake of sugar has been shown to be linked to CD in a number of trials, hence its possible etiological role has led to therapeutic trials of sugar avoidance. Most of these trials also have promoted a high fiber intake. The only trial to look solely at sugar avoidance has shown no statistically significant benefit.




Van den Bogaerde et al have published a trial in which the reactivity of peripheral lymphocytes to food, yeast and bacterial antigens was studied. They found that 23 out of 31 patients with CD responded to one or more antigens, compared to five out of 22 in the control group. They also correlated in vitro sensitization and in vivochanges with histological and blood flow changes. Skin testing and rectal exposure to six food antigens and saline were tested in 10 patients and 10 controls. The results showed that CD patients demonstrated in vitro and in vivo sensitization to food antigens and this was gut specific.

Levo et al have shown that patients with IBD have higher serum concentrations of IgE. They also have shown that the levels are higher still in those with active disease over those in remission. However, this difference is not statistically significant. In 1998, another study was performed to investigate food-specific IgE as well as IgG, and IgE anti-IgE autoantibodies using serum from normal subjects, patients with CD and those with food allergies. They found that food-specific IgE was not detected at all in the CD group but they did have higher levels of IgG and IgE anti-IgE autoantibodies. They concluded that, even if IgE is an autoantigen in CD, it is not thought to take part in the pathophysiology of the adverse food reactions commonly reported by the patients.

Western diets are more strongly associated with CD. There are several theories as to whether this may relate to the increased intake of sucrose, refined carbohydrate, and omega-6 fatty acids, and reduced intake of fruit and vegetables. Urban diets contain large quantities of microparticles such as natural contaminants like dust, and food additives which may be antigenic. CD patients allocated to a low microparticle diet experienced a reduction in disease activity and in steroid requirement compared to a control group on a normal diet.


Although many studies have looked at diet therapy and IBD, mixed opinions exists as to the importance that food intolerance plays in the pathophysiology of IBD. In those that have looked at food sensitivity, this was done using different methods. Riordan et al have observed sensitivity to corn in seven patients; wheat, milk and yeast in six; egg, potato, rye, tea and, coffee in four; and apples, mushrooms, oats and chocolate in three. Ballegaard et al have found sensitivity, using questionnaires, to vegetables (particularly onions and cabbage), fruits (apples, strawberries, and citrus fruits) and to meat (especially beef). Van den Bogaerde et al have shown in a case-control study using lymphocyte proliferation that, out of 31 CD patients, 16 reacted to cabbage and peanuts, 14 to cereals, 13 to milk, and nine to citrus fruits.

As observed by Hunter, epidemiologists tend to look at statistical relationships that lead to studies of sugar, sweet, coke and chocolate intake because patients with CD eat and drink more of these substances than control subjects. Clinicians focus on the foods that patients associate with their symptoms and therefore avoid. As a result, exclusion diets have tended to concentrate more on dairy products, cereals and yeast. Other work is being carried out on polyunsaturated fatty acids, especially omega-3 oils, and their anti-inflammatory effects.

Current elemental and polymeric diets have a role to play in the management of CD, particularly in children. Exclusion diets are of use particularly for maintenance of remission. TPN is of value and has been shown to be as effective as elemental diets, but none have proven as effective as corticosteroid therapy. However, TPN remains a crucial method for administering nutrition in patients with severe disease, who are not able to tolerate enteral feeding.

Despite early ideas about the involvement of sugars in the etiology of CD, the omission of sugar has not been found to be of benefit. Omega oil has shown promising results, particularly in reducing inflammation in UC, and to a lesser degree, in CD.


IBD has a multifactorial etiology but food sensitivity/intolerance appears to play a role, and the culpable foods vary on an individual basis. Techniques to identify food intolerance require refining. Progress has been made by looking at factors such as IgG4 responses to food antigens, but a large expanse of work exists in trying to determine people’s food sensitivities and the degree to which these affect disease activity. Without further research, it remains unclear whether dietary manipulation will continue to have a role solely in symptom control, or whether complete remission may be possible using these methods in combination with pharmacological agents.




Peer reviewer: Wallace F Berman, MD, Professor, Division of Pediatric GI/Nutrition, Department of Pediatrics, Duke University Medical Center, Duke University School of Medicine, Durham, Box 3009, NC 27710, United States

S- Editor Tian L L- Editor Kerr C E- Editor Ma WH



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Source: Nirooshun Rajendran and Devinder Kumar. 

World J Gastroenterol. 2010 March 28; 16(12): 1442–1448.

Published online 2010 March 28. doi: 10.3748/wjg.v16.i12.1442





Tags:  diet  inflammatory bowel disease 

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