Diet as treatment for inflammatory bowel disease: is it ready for prime time?

Abstract

Purpose of review.

Diet remains an important topic for patients with inflammatory bowel disease (IBD) yet few guidelines for dietary recommendations exist. There is growing interest in the use of diet as treatment or adjuvant therapy for both ulcerative colitis (UC) and Crohn’s Disease (CD). Here we highlight the latest evidence on the use of diet for treatment of symptoms, active disease, and maintenance of remission in UC and CD.

Recent findings.

The Crohn’s Disease Exclusion Diet (CDED) and the Specific Carbohydrate Diet (SCD) are studied diets that have gained popularity but there is growing interest in the use and efficacy of less restrictive diets like the Mediterranean Diet. Recent data suggests healthful dietary patterns alone, with an emphasis on whole foods that are high in vegetable fiber and that promote less consumption of ultra-processed foods may also help achieve remission in ulcerative colitis and Crohn’s disease patients.

Summary.

In this review, we summarize the literature on diet as treatment for IBD. We highlight the latest clinical dietary studies, randomized clinical trials, as well as new and emerging diets for the treatment of IBD.

INTRODUCTION

Inflammatory bowel diseases (IBD), comprised of Crohn’s disease (CD) and ulcerative colitis (UC), are on the rise globally and affect more than 1.6 million Americans (1–3). This rapid rise in IBD suggests that there are environmental exposures, including diet, that are changing the risk of IBD (4–16). We know that a Western diet, high in animal protein, processed foods, and low in fiber, is associated the development of UC and CD (4–8). Epidemiologic studies also identify that a diet high in a ratio of n-6 to n-3 polyunsaturated fatty acids increases UC risk (6). Similarly, a diet low in fiber, high in saturated fat and processed foods poses an increased risk for CD (17,18). These findings highlight the importance of nutrition and identify potential components in the treatment of ongoing inflammation (6). In the last decade, we have witnessed a greater interest in the development of anti-inflammatory diets. In large part, this movement is driven by patients who identify that food drives their symptoms and food-related quality of life (19–22). Nutrition research in IBD is shifting from case series to controlled clinical studies measuring clinical improvement and objective markers as outcomes. While the future is bright and we anticipate that soon nutrition research in IBD will be strengthened by robust clinical trials that mirror drug studies, providers taking care of IBD patients now face difficult challenges due to limited emphasis on nutrition during training and poor guidance on nutrition.

In this review, we highlight the largest clinical studies by diet focusing on diets with the most evidence and provide practical advice for the practicing gastroenterologist. Exclusive enteral nutrition (EEN) is a well-recognized effective therapy for the treatment of Crohn’s disease (CD) and has received the attention of many prior reviews (23–29). This review will focus instead on whole-food interventions or partial whole-food diets that are more realistic long-term options. Dietary therapies still under investigation are described in Table 1.

Table 1:

Established Diets and Diets under Investigation for Inflammatory Bowel Disease.

Dietary Therapies for Crohn’s Disease and Ulcerative Colitis
Crohn’s Disease Exclusion Diet
	Grains	Fruits	Vegetables	Proteins	Nuts, Seeds	Legumes	Dairy	Oils	Additives	Other
Include (Induction a & b)	Rice b. 1/2 oats, 1/2 whole grain, quinoa	a. Bananas, apples, avocado, strawberries, melon, orange juice, lemon juice b. pears, peaches, kiwis, blueberries, mangos, pineapples, oranges	a. Potatoes, tomatoes, cucumbers, carrot, spinach, lettuce, onion, garlic, ginger b. sweet potatoes, red peppers, corn, green beans, peas, zucchini, mushrooms, broccoli, cauliflower	Eggs, chicken a. one fish/week b. one steak, tuna/week	8 nuts/day, any kind	b. 1/2 beans	None	Olive, canola	None	Honey
Avoid (Induction)	None	No persimmons, pomegranate, passion fruit	Eggplant, turnips, parsnips, Leeks, celery, kale, asparagus, artichokes	Processed meats, all other fish	All seeds	None	All	All others	Preservatives, additives, emulsifiers	Coffee, cocoa, artificial sweeteners
Include (Maintenance)	Rice, oats, whole grain, rice, quinoa	All except below	Starchy and nightshades, corn	Eggs, chicken, one fish, steak, tuna/week	8 nuts/day, any kind	All	one yogurt/day	Olive, canola	None	Honey, coffee, cocoa
Avoid (Maintenance)	None	No persimmons, pomegranate, passion fruit	Leeks, celery, kale	Processed meats	All seeds	None	All others	All others	Preservatives, additives, emulsifiers	Artificial sweeteners
Specific Carbohydrate Diet
	Grains	Fruits	Vegetables	Proteins	Nuts, Seeds	Legumes	Dairy	Oils	Additives	Other
Include	None	All	All except below	All except below	Plain nuts	Lentils, peas	Aged cheeses	Olive Oil		Honey, butter, coffee
Avoid	All cereals, wheat, gluten, oats, rice	Canned, frozen	Potatoes, corn, turnips, parsnips, canned, frozen	Processed, canned, smoked	Roasted with starches, chia, flax	All other	All others	Margarine, soybean, canola	Preservatives, additives, emulsifiers	Chocolate, corn syrup, artificial sweeteners
Mediterranean Diet
	Grains	Fruits	Vegetables	Proteins	Nuts, Seeds	Legumes	Dairy	Oils	Additives	Other
Include	All	All	All	Fish, seafood, some poultry, limit meats	All	All	Cheese, yogurt	Olive oil
Avoid	Refined grains, white flour, white rice	None	None	Red/processed meat, eggs	None	None	Milk, butter	All others	Processed foods	Limit sweets, added sugars
Vegetarian / Plant-Based Diets
	Grains	Fruits	Vegetables	Proteins	Nuts, Seeds	Legumes	Dairy	Oils	Additives	Other
Include (Vegetarian)	All	All	All	Plant protein (eggs optional)	All	All	All	All
Avoid (Vegetarian)	None	None	None	All animal protein	None	None	None	None
Include (Plant Based)	All	All	All	Plant protein	All	All	None	All
Avoid (Plant Based)	Refined grains often avoided	None	None	All animal protein, eggs	None	None	All	In low fat versions, all oils avoided
Diets for Symptom Management
Low FODMAP Diet
	Grains	Fruits	Vegetables	Proteins	Nuts, Seeds	Legumes	Dairy	Oils	Additives	Other
Include	Gluten-free, oats, rice, quinoa	Blueberries, grapes, oranges, banana, cantaloupe, clementine, kiwi, lemon, line, mandarins, melons, oranges, passion fruit, pineapple, raspberry, strawberry	Spinach, spring onion, squash, carrot, corn, cucumber, eggplant, green beans, kale, lettuce, potatoes, alfalfa, bok choy, 1/2 broccoli, 1/2 brussels sprouts, bean sprouts, bell peppers, eggplant, tomato, turnip, zucchini	All	Almonds, chia seeds, macadamia nuts, pecans, nut butters, walnuts, pumpkin seeds	Peanuts	Hard and low-lactose cheese	All	Stevia	Brown sugar, dark chocolate, maple syrup, golden syrup, coconut water, green tea, rum, soft drinks, sports drinks, white tea
Avoid	Wheat, barley, rye	Apples, applesauce, apricot, dates, blackberries, grapefruit, mango, nectarine, pear, peach, plum, prunes, watermelon	Sweet corn, sweet potatoes, peas, onions, garlic, onions, shallots, mushrooms, artichokes, asparagus, avocado, beetroot, cauliflower, leek, cabbage	None	Cashews	Beans, chickpeas, lentils, soybeans, pistachios	Dairy from cow, goat, sheep, buttermilk, soft cheeses and creams	None	High fructose corn syrup	Refined/processed/artificial sugars
Additional Diets under Investigation for Crohn’s Disease and Ulcerative Colitis
Autoimmune Diet *
	Grains	Fruits	Vegetables	Proteins	Nuts, Seeds	Legumes	Dairy	Oils	Additives	Other
Include	None	All	All except below	All except below	None	None	None	None	None
Avoid	All	None	Nightshades, corn	Eggs, processed meat	All	All	All	All	Preservatives, additives, emulsifiers	Coffee, cocoa, refined/processed/artificial sugars
Anti-Inflammatory Diet (IBD-AID) *
	Grains	Fruits	Vegetables	Proteins	Nuts, Seeds	Legumes	Dairy	Oils	Additives	Other
Include	Oat, rice (after 6 months)	Seedless	Cooked	Fish, seafood, lean meat, poultry, red meat, eggs	Flax, chia, nuts	Pureed beans	Aged cheeses, fresh yogurt, cultured cheese	All	None	Honey, coffee, cocoa
Avoid	Gluten	Fruits with seeds	Cruciferous, white potatoes, corn	High fat meats, processed meat	None	Whole beans	All others	None	Preservatives, additives, emulsifiers	Refined/processed/artificial sugars
CD-TREAT *
	Grains	Fruits	Vegetables	Proteins	Nuts, Seeds	Legumes	Dairy	Oils	Additives	Other
Include		All	All	Lean meats			None
Avoid	Gluten	None	None	Processed meats, animal fats			All lactose	Animal Fats	Preservatives, additives, emulsifiers
Low Microparticle Diet *
	Grains	Fruits	Vegetables	Proteins	Nuts, Seeds	Legumes	Dairy	Oils	Additives	Other
Include		Well washed, rinsed, and dewaxed								Calcium, bottle water except hot drinks
Avoid	Premade products with preservatives, whole grain breads	Dried or candied,	Fibrous vegetables	Processed meats, Shellfish, ready meals	seasoned or roasted nuts & seeds		Products with preservatives or flavors, cheese		Preservatives, additives, emulsifiers, sea salt, processed sauces	Titanium dioxide & particulate silicates

The table above presents the various diets that are established for the treatment of IBD, for symptom improvement or diets that are under investigation. The Crohn’s Disease Exclusion diet remains the most studied and includes 3 phases: Phase 1 and Phase 2 make up the induction phase, labeled a & b above for simplicity. Phase 1 or (a) includes weeks 0 – week 6. Phase 2 or (b) includes weeks 7 – week 12. During the second phase, dietary items are slowly added back starting in week 7 so that by week 10, all items listed above are included. A prefix of ½ denotes participants can include this item in their diet, but at ½ portions or limited amounts. Postfix of /week or /day denotes participants should include those items in their diet x number of times per week or day.

Diets that help with inflammation in ulcerative colitis and Crohn’s disease

Crohn’s Disease Exclusion Diet and the Ulcerative Colitis Exclusion Diet

The Crohn’s Disease Exclusion diet (CDED) consists of a three-phase protocol: two induction and one maintenance phase. During the first 6-weeks, participants consume half of their nutrients from partial enteral nutrition (PEN) while abstaining from insoluble fiber, red or processed meat, and more (Table 1). During the second phase, weeks 6–12, participants consume 25% calories from PEN with a phased reintroduction of certain foods. During the third and final phase participants continue phase 2 with flexibility of two free meals two days of the week.

Seven clinical studies have examined the CDED in 318 patients: 218 children, 100 adults (Table 2). We highlight some studies here and their findings. One of the first studies published in 2017 was a retrospective analysis of adults and children failing biological therapy who had been placed on the CDED. This study found that after two weeks of EEN followed by 6 weeks of the CDED, 61.9% achieved clinical remission and reduction in C-reactive protein (CRP) (30). Since then, newer studies examining the CDED compare the efficacy of this diet to EEN. In 2019, Levine et al. published the first randomized clinical trial of 78 children with mild to moderate CD looking at tolerance of the diet (31). Patients on the CDED were 13.92 times more likely to tolerate the diet than patients on EEN (OR 13.92, 95% CI 1.68–115.14, p<.002). By week 12, 75.6% of patients achieved corticosteroid-free remission compared to 45.1% on EEN (31). In 2021, Sigall Boneh et al. published a similar study examining the effect of CDED vs EEN on clinical remission (32). Clinical remission and biochemical response were similar in both arms (32). These results highlight the efficacy of the CDED over EEN with the added benefit of improved adherence and tolerability.

Table 2:

Largest Clinical Studies by Diet.

Diet	Study	Disease	Design	Comparison	Size	Participants	Length	Outcomes
Crohn’s Disease Exclusion Diet (CDED)	Levine (2019) (31)	CD	Randomized, clinical trial	CDED vs EEN/PEN+Free	78	Pediatric	12 weeks	CDED can induce remission
	Yanai (2022) (34)	CD	Open label, pilot randomized trial	CDED+PEN vs CDED	44	Adult	24 weeks	CDED without PEN is effective for induction and maintenance
	Sigall-Boneh (2014) (83)	CD	Clinical Trial		47	Children, young adults	6 weeks	CDED has high remission rates
	Sigall Boneh (2017) (30)	CD	Retrospective analysis		21	Adults, Children	12 weeks	CDED may be a useful salvage regimen after biological failure.
	Szczubelek (2022) (33)	CD	Clinical Trial		32	Adults	12 weeks	CDED can induce remission
	Sigall Boneh (2021) (32)	CD	Multicenter Randomized trial	EEN vs CDED	73	Children	6 weeks	CDED can induce clinical response by week 3
	Sarbagili-Shabat (2021) (35)	UC	Prospective Pilot Study		23	Children	6 weeks	CDED can induce remission in children
Specific Carbohydrate Diet (SCD)	Cohen (2014) (44)	CD	Prospective clinical trial		9	Children	52 weeks	Clinical and mucosal improvements possible with SCD
	Obih (2016) (41)	IBD	Retrospective Review		26 (20 CD & 6 UC)	Children	6 months	SCD can improve clinical and laboratory parameters
	Burgis (2016) (40)	CD	Retrospective Analysis		11	Children	variable	Disease control is possible with the SCD
	Suskind (2018) (45)	IBD	Multicenter Prospective study		12 (CD 9 & 3 UC)	Children	12 weeks	SCD improves clinical findings, laboratory results, and alters the fecal microbiome.
	Wahbeh (2017) (84)	CD	Retrospective Analysis		7	Children	26 months	mSCD does not induce mucosal healing
	Suskind (2014) (39)	CD	Retrospective Analysis		7	Children	30 months	SCD is a good therapeutic option for CD
	Kakodkar (2015) (42)	IBD	Retrospective analysis		50 (36 CD & 9 UC & 5 ID)	Children, adults	Variable	SCD may be effective for colonic and ileocolonic CD
	Suskind (2016) (38)	IBD	Survey		417 (196 CD & 179 UC 42 ID)	Children, Adults	12 months	The SCD can be either a primary or adjunct therapy
	Chutkan (2017) (43)	IBD	Retrospective analysis, abstract		8 (5 CD & 3 UC)	Adults	66 months	SCD can improve symptoms, mucosal healing.
	Suskind (2020) (46)	CD	Randomized Controlled Trial	SCD vs mSCD vs Whole foods	10	Children	12 weeks	SCD, mSCD, and WF diets have positive effect on symptoms and inflammatory burden
Mediterranean Diet (MD)	Lo (2021) (52)	IBD	Observational		828 (363 CD, 465 UC)	Adults		MD adherence may reduce mortality in IBD
	Strisciuglio (2020) (53)	IBD	cross sectional study	MD vs Control	250 (125 C vs 125 IBD (53 CD, 72 UC))	Children		MD decreases intestinal inflammation
	Godny (2020) (54)	UC	Prospective Observational		153	Adults	3–8 years	MD decreases intestinal inflammation
	Chicco (2020) (56)	IBD	Prospective Clinical Trial		142 (58 CD, 84 UC)	Adults	6 months	Improved disease activity and inflammatory markers
MD vs SCD	Lewis (2021) (47)	CD	Randomized Controlled Trial	MD vs SCD	191 (92 MD and 99 SCD)	Adults	12 weeks	SCD was not superior to the MD for remission
Low animal protein, vegetarian, plant-based diets	Albenberg (2019) (61)	CD	Randomized Controlled Trial	low red meat vs high red meat	202 (87 low meat, 115 high)	Adults	49 weeks	Red/processed meat not associated with CD relapse
	Jowett (2004) (59)	UC	Prospective Cohort study		191	Adults	one year	High meat intake increases risk of UC relapse
	Chiba (2010) (60)	CD	Prospective Clinical Trial		22	Adults	2 years	Effective in preventing relapse in CD
	Chiba (2017) (62)	CD	Prospective Clinical Trial		44	Adults, Children	6 weeks	Can induce remission in biologic-naive CD
	Chiba (2019) (63)	UC	Prospective Clinical Trial		92	Adults	6.33 years	PBD reduces relapse risk
	Fritsch (2021) (64)	UC	Cross-over Clinical Trial	iSAD vs LFHF	17	Adults	10 weeks	LFD decreases inflammation and intestinal dysbiosis
Autoimmune Protocol	Lee (2019) (85)	IBD	Retrospective Survey		78	Adults	6 weeks	AIP reduces steroid use
	Konijeti (2017) (86)	IBD	Prospective Clinical Trial		15 (9 CD, 6 UC)	Adults	11 weeks	AIP can improve symptoms and endoscopic inflammation
	Chandrasekaran (2019) (87)	IBD	Prospective Clinical Trial		15 (9 CD, 6 UC)	Adults	11 weeks	AIP can improve quality of life
IBD-AID	Olendzki (2014) (88)	IBD	Case Series		27	Adults	4 weeks	IBD-AID may be an effective adjunct dietary therapy
Low FODMAP Diet	Cox (2020) (65)	IBD	Single-blind Randomized Controlled Trial	Low FODMAP vs control diet	52 (25 control, 27 low FODMAP)	Adults	4 weeks	Low FODMAPS can improve persistent gut symptoms but has no effect on inflammation
	Prince (2016) (68)	IBD	Retrospective analysis		88 (39 CD, 38 UC, 11 ID)	Adults	6 weeks	Low FODMAPS can improve patient-reported satisfactory relief of symptoms
	Gearry (2009) (69)	IBD	Retrospective Case-Control		72 (52 CD, 20 UC)	Adults		LOW FODMAP adherence improves functional gut symptoms
	Halmos (2016) (70)	CD	Randomized Controlled Crossover Trial	Low FODMAP vs typical Australian diet	9	Adults	9 weeks	High fiber diets double IBS-like symptoms in patients with CD
	Pedersen (2017) (71)	IBD	Randomized Controlled Trial	Low FODMAP vs control diet	89 (44 FMD, 45, C) (28 CD, 61 UC)	Adults	6 weeks	Low FODMAP diet reduced IBS symptoms and improved quality of life
	Bodini (2019) (72)	IBD	Randomized Controlled Trial	Low FODMAP vs control diet	55 (35 CD, 20 UC)	Adults	6 weeks	Low FODMAP diet reduces clinical symptoms and decreases fecal calprotectin

A list of all of the major clinical studies and randomized controlled trials on the use of dietary therapy for the treatment of Inflammatory Bowel Disease. The studies are categorized by diet and include studies for the most popular diets that are established or currently under investigation. (IBD = Inflammatory Bowel Disease, CD = Crohn’s disease, UC = Ulcerative Colitis, ID = Indeterminate colitis, EEN = exclusive enteral nutrition, PEN = partial enteral nutrition, mSCD = modified Specific Carbohydrate Diet, WF = whole food, iSAD = improved Standard American Diet, FMD = low FODMAP diet, C = control diet, LFHF = Low fat high fiber, LFD = Low Fat Diet, IBD-AID = IBD Anti-inflammatory diet, PBD = Plant Based diet, AIP = Autoimmune protocol)

More recently, the efficacy of the CDED was tested in adults with CD. In an uncontrolled study, Szczubelek et al. examined the CDED on induction of clinical remission on 32 adults with CD not responding to biologics (33). At 12 weeks, 82.1% of patients achieved clinical remission (33). Following, Yanai et al. published a randomized controlled pilot study of 44 adults with active CD looking at clinical remission without PEN (34). At week 6, 57–68% achieved clinical remission with no difference observed between those on PEN and those on whole food CDED (34). These studies provide evidence that the CDED possibly without PEN, is a promising therapeutic for patients with active disease. Lastly, a variation of the CDED called the ulcerative colitis exclusion diet (UCED) is under investigation for UC and although preliminary, a pilot suggests that it may work in UC (35).

These studies highlight one of the most studied diets available for CD that demonstrates clinical and biochemical response in mostly uncontrolled studies. In some studies, the CDED was used after poor response to biologic therapies providing evidence that we can use diet as an adjunctive therapy to improve medication responsiveness. The CDED and UCED show promise and are particularly attractive if PEN is not necessary (34).

Specific Carbohydrate Diet (SCD)

The Specific Carbohydrate Diet was popularized in 2004 by the book Breaking the Vicious Cycle and it remains a popular diet in IBD (36–38). The diet limits starches, grains, table sugar, additives, and dairy. Participants eat fresh fruit or vegetable and all unprocessed proteins (Table 1).

Nine studies have examined the SCD in both UC and CD in 140 patients: 91 children and 49 adults (Table 2). Most studies available thus far for the SCD are retrospective analyses or case series. To our knowledge, we only have two prospective trials and one small randomized controlled trial for the SCD. Retrospective studies show improvement of symptoms and biochemical markers of inflammation (39–41). In one case study of adults and children with CD and UC with mild symptoms, 66% had symptom resolution with a self-reported effectiveness of 91.3% at controlling flares (42). A recent case series of patients with IBD who followed an SCD for 66 months also reported improvement in quality of life (43).

Since these initial retrospective studies, two prospective, uncontrolled clinical studies examined the effect of the SCD on 21 children with CD (44,45). Both studies reported clinical improvement on the SCD. Similarly, a study by Suskind et al. published in 2020 performed a small, randomized trial comparing three diets following two weeks of an initial SCD trial. The three diets that followed the SCD were the modified SCD (mSCD) (a less restrictive version of the SCD), the SCD, and a whole food (unprocessed diet) for 10 weeks. At 12 weeks, every participant, regardless of diet, had achieved clinical remission and improvement in CRP (46). Of note, because the three diets evaluated provide similar food guidance on avoidance of ultra-processed foods, it could be these shared elements of a “healthful diet” that may be sufficient to improve remission for patients and not necessarily one specific diet over another.

Despite the popularity of the SCD among patients, the limited number of controlled-trials available limit widespread recommendation. A more recent study compared the effectiveness of this diet to the Mediterranean diet and this will be discussed in the next section (47). Larger controlled studies examining the efficacy of the SCD to a sham-diet are also needed.

Mediterranean Diet

The Mediterranean diet (MD), comprised of a diet high in vegetables, fruits, whole grains, and olive oil, is a well-studied diet with an array of health benefits (Table 1) (48,49). Given the benefits of the MD for overall health and given its high tolerability, there is growing interest in the efficacy of this diet for IBD (49–51). To date, there are only a few prospective clinical trials of the MD for IBD.

Several studies discuss adherence to a MD and risk of IBD development, but fewer studies focus on the efficacy of a MD on improving inflammation once disease sets in (Table 2) (15). Three observational studies examine adherence to a MD diet and the effect of this diet on clinical outcomes or biochemical response. In the Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up study, 363 CD patients and 465 UC adult patients were identified (52). IBD patients who adhered to an MD diet and other healthy lifestyle practices had a significant reduction in all-cause mortality (52). Strisciuglio et al. published a cross-sectional diet recall study on pediatric patients and found that patients with IBD who adhered to the MD had lower levels of fecal calprotectin (53). Similar positive results on reduction of fecal calprotectin levels were also found in adult patients with UC after pouch surgery who followed a MD (54). Therefore, these studies provide evidence that the MD may help with improvement of clinical, biochemical remission and quality of life, although they are largely retrospective (54,55).

To our knowledge, there are only two clinical trials published using the MD for IBD patients. In a prospective study by Chicco et al., 142 IBD patients were placed on a MD for six months (56). In this uncontrolled study, patients with both UC and CD reported improvement of clinical symptoms as well as quality of life. The second clinical trial, the Diet to INducE Remission in Crohn’s disease (DINE-CD), included two diets discussed so far, the MD and the SCD. In this study, the MD was compared to the SCD in a head-to-head randomized trial of 191 patients with mild-to-moderate CD symptoms (47). The primary outcome was symptomatic remission at 6 weeks (47). At study completion, both diets had similar rates of symptomatic remission with 46.5% of those on the SCD and 43.5% on the MD, reporting improvement. Researchers saw a similar reduction in fecal calprotectin, and a small but similar CRP response, although the study was not powered to detect changes in biochemical remission.

The results of this study show that the MD, like the SCD, is effective in achieving symptomatic remission but with the added benefit that it is a less restrictive diet. Therefore, based on the latest evidence, in our practice, unless patients prefer the SCD over the MD, we provide guidance on the MD as a method to help induce and maintain clinical remission.

Low Animal Protein, Plant Based, High Fiber Diets

Vegetable-based diets remain popular with IBD patients, though variations exist. Each share similar nutritional components and differs in the degree of consumption of animal protein or animal products (Table 1). Despite their popularity, there are no controlled studies measuring the efficacy of any one vegetarian-based diet in treating IBD (Table 2).

Vegetarian diets, as a whole, are thought to be anti-inflammatory secondary to effects on the gut microbiota and other food component’s impact on the intestinal immune response (57). However, it is important to educate patients that diet quality also matters. Merely focusing on the exclusion of animal protein does not necessarily equate to better health. In fact, a recent study published in The Journal of Nutrition, showed that in some patients consuming a vegetarian diet, there was higher consumption of ultra-processed foods, which has been associated with increased risk of IBD development (18,58).

There are a few studies supporting the premise that diets high in animal protein, primarily diets high in red meat, are associated with worse clinical outcomes in IBD (59,60). However, not all studies support avoidance of animal protein. In the Food and Crohn’s Disease Exacerbation Study (FACES) trial, researchers performed a randomized controlled trial to determine whether reduced consumption of red and processed meat decreased the risk of symptom relapse in patients with quiescent CD (61). Researchers found no difference in time to symptom relapse in those consuming high vs low intake of red meat (61). The caveat however is that it is unclear if patients replaced red meat with more processed foods. This study serves to highlight that a recommendation based on avoidance of food groups may not provide sufficient guidance to patients and global dietary patterns may provide better instruction.

Additionally, there are now a few prospective studies examining the effect of primarily plant-based diets on IBD. In a single arm study in 2017, 44 adults and children received first-line infliximab with a plant-based diet (62). All patients achieved remission defined as improvement of active CD symptoms at week 6 (62). Similarly, in 2019 the same authors published a single-arm study of 92 UC patients who were admitted for induction therapy with medication plus a semi-vegetarian diet and educated to continue the diet at discharge (63). At one and 5-year follow up, relapse rates were far lower than those reported with conventional therapy (63).

These studies and others provide preliminary evidence that diets rich in plant-based, high fiber foods, may help to augment remission in all IBD patients and may help augment response to biologic therapies (64). Except for the FACES study, for which confounders could have been at play, most studies available thus far support that a diet rich in fiber primarily from vegetables and lower in animal protein, may be beneficial long-term for patients with IBD. We therefore recommend to our patients to try to consume less red meat and to try to focus their intake on high fiber plant-based options.

Diets to manage symptoms

A low FODMAP diet

The low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (low FODMAP) diet originally studied for irritable bowel syndrome (IBS) gained interest in the space of IBD as it was recognized that it could also help symptoms in those with quiescent IBD (65). The diet consists of eliminating foods high in FODMAPs for about 2 months followed by a period of slow reintroduction of foods aimed at identifying specific triggers (66) (Table 1). Prior studies highlight that IBS can co-exist in about 39% of IBD patients (67). Three studies have thus far shown that 50 to 78% of IBD patients on a low FODMAP diet can have reduction in their abdominal pain, bloating, flatulence, nausea, and belching (65,68,69).

To date, four randomized controlled trials exist investigating low FODMAP diets for patients with IBD (65,70–72). In a recent clinical trial of 52 patients with quiescent IBD and persistent symptoms of IBS, participants were placed on a low FODMAP or a sham diet for 4 weeks (65). After 4 weeks, patients on the low FODMAP diet had greater improvement of GI symptoms without improvement on inflammatory markers (65). Similarly, Halmos et al. published a cross-over clinical trial using a high vs a low FODMAP diet and found that a high FODMAP diet doubled IBS-like symptoms in CD patients (70).

However, the low FODMAP diet can have several drawbacks. For one, it is a restrictive diet with many limitations on foods during the first six weeks plus little evidence that it ultimately helps gut inflammation. Additionally, studies suggest that patients may be not benefit long-term from a diet low in FODMAP given its association with changes in the gut microbiome, with a greater presence of dysbiosis including a decrease in the abundance of beneficial bacterial species, such as Bifidobacterium (73,74). Therefore, in our practice we only provide guidance on the short-term use of a low FODMAP diet in those patients with persistent symptoms but documented quiescent IBD.

Practical advice for the practicing gastroenterologist

Our goal as treating providers should be to incorporate diet as part of treatment in IBD. Dietary therapy can be envisioned in the future in the following ways: as primary and sole treatment in mild disease, as adjunctive therapy to help induce remission of medications, or to help in maintenance of remission. Until better studies are available for guidance, we provide practical advice here, as seen in Figure 1, on how to discuss diet during busy clinic.

Figure 1: Practical Guidance on Dietary Counseling for Providers.

Advising patients on diet is difficult in a busy clinic setting. Here we present a basic framework for dietary counseling for providers for patients recently diagnosed with inflammatory bowel disease. Highlighted are additional resources available for both providers and patients and appropriate screening recommendations for patients who may meet criteria for malnutrition. (IBD = Inflammatory Bowel Disease, CDED = Crohn’s Disease Exclusion Diet, CD = Crohn’s disease, UC = ulcerative colitis, IBS = irritable bowel syndrome, FODMAP = fermentable oligosaccharides, disaccharides, monosaccharides, and polyols)

First, it is important to screen for malnutrition. The Malnutrition Inflammatory Risk Tool (MIRT) has gained recognition because it is an easy-to-use tool with clinically available variables (75). These include a patient’s BMI, CRP, and asking about weight loss in the past three months. A score of ≥ 3 is associated with a four times greater risk of worse IBD outcomes (RR 4.0, 95% CI 2.4–6.7) (75). If this is the case, a nutrition referral for malnutrition is of utmost importance.

It is also important that providers offer generalized guidance on avoidance of ultra-processed foods and consuming diets high in fruits and vegetables. This guidance may validate the importance of a good diet and also broadly covers the food guidance of all the studied diets (6,64). During clinic time, we also briefly encourage trying more soluble fibers and cooking vegetables so that they may better tolerate more fiber, even during flares (29,76–79). We caution against very restrictive, elimination diet therapies that can lead to malnutrition and encourage to bring in nutritionists on board when that is available.

For further counseling or when no nutritionist is available, we point to fantastic resources available online (80–82). If the opportunity is present to work alongside a nutritionist, we provide more directed guidance. We inform patients of the most studied diets including the CDED, which we reserve for treatment for patients with refractory Crohn’s disease given its use of enteral nutrition. The SCD and MD are offered to all other patients highlighting that the MD is less restrictive and easier to follow. A low FODMAP diet is reserved for patients with IBS symptoms in quiescent IBD and when asked about dietary supplements, we highlight curcumin and vitamin D (Table 3).

Table 3:

Major Trials testing Dietary Supplements for IBD.

Diet	Study	Disease	Design	Size (C/E)	Participants	Intervention	Length	Results
Curcumin	Kedia (2017) (89)	UC	Double Blind RCT	33/29	Mild-Moderate	150 mg TID	8 weeks	Ineffective in inducing remission
	Lang (2015) (90)	UC	Double Blind RCT	24/26	Mild-Moderate	3g daily	1 month	Curcumin + mesalamine superior to placebo + mesalamine for inducing clinical & endoscopic remission
	Sugimoto (2020) (91)	CD	Double Blind RCT	10/20	Mild-Moderate	360mg daily	12 weeks	Theracurmin shows significant clinical and endoscopic efficacy & safety
	Singla (2014) (92)	UC	Double Blind RCT	22/23	Mild-Moderate	140mg enema daily	8 weeks	Enema use resulted in greater improvement in disease activity
	Banerjee (2021) (93)	UC	Triple Blind RCT	25/22	Mild-Moderate	50mg daily	3 months	Add-on therapy superior in inducing clinical & endoscopic remission
	Hanai (2006) (94)	UC	Double Blind RCT	39/43	CAI ≤ 4	2g daily	6 months	Promising for remission maintenance in Pts with quiescent UC
Omega-3 Supplementation	Uchiyama (2010) (95)	UC/CD	Prospective CT	250	Remission	5.1g ALA, EPA, DHA daily	6 months	Improves fatty acid composition of the cells & influences clinical activity
	Scaioli (2018) (96)	UC	RCT	30/30	Mayo < 2	500mg BID	6 months	Reduces fecal levels of calprotectin
	Aslan (1992) (97)	UC	Double Blind RCT	11	Mild-Moderate	2.7g EPA & 1.8g DHA daily	8 months	Fish oil resulted in clinical improvement of UC
	Stenson (1992) (98)	UC	Double Blind cross over RCT	18	active disease	3.2g EPA & 2.2g DHA daily	4 months	Reduces rectal dialysate leukotriene B4 levels & improves histologic findings
	Stack (1997)	UC	Double Blind RCT	53	Not reported	1.5g EPA OR 2.1g GLA OR both	4 months	No effect on steroid use with EPA, GLA, or a combination.
	Almallah (1998) (99)	UC	Double Blind RCT	18	Distal Procto-colitis	3.2g EPA & 2.4g DHA daily	6 months	Suppresses natural cytotoxicity and reduces disease activity
	Dichi (2000) (100)	UC	Crossover RCT	10	Mild-Moderate	3.2g EPA & 2.4g EPA daily	4–6 months	Sulfasalazine treatment superior to EPA treatment
	Varghese (2000) (101)	UC	Double Blind RCT	51	Active, extensive disease	5.6 g PUFA daily	6 months	Supplementation improved clinical score & endoscopic score
	Seidner (2005) (102)	UC	Double Blind RCT	86	Mild-Moderate	2.5g EPA & 1.0g DHA daily	6 months	Improved clinical response & decreased steroid use
	Hawthorne (1992) (103)	UC	Controlled CT	34	Remission	5.0g EPA & 2.1g DHA daily	12 months	Modest steroid sparing effect in active disease, no benefit for maintenance
	Loeschke (1996) (104)	UC	Double Blind RCT	64	Remission	5.1g PUFA daily	24 months	No relapse prevention or improvement in disease clinically or histologically
	Mantzaris (1996) (105)	UC	Controlled CT	40	Remission	3.2g EPA + 2.2g DHA	12 months	No improvement in relapse rate, active symptoms, or endoscopic relapse
	Middleton (2002) (106)	UC	Double Blind RCT	58	Remission	1.62g GLA, 0.27g EPA, 0.05g DHA	12 months	No improvement in remission period or sigmoidoscopic findings
	Nielsen (2005) (107)	CD	Double Blind RCT	31	Mild-Moderate	3.0g EPA, DHA, ALA	9 weeks	May inhibit an increase in proinflammatory cytokines
	Grogan (2011) (108)	CD	Double Blind RCT	41	Moderate-Severe	EN w/ 1.5% ALA & 3% Linoleic	6 weeks	No difference in remission induction
	Belluzzi (1996)	CD	Double Blind RCT	78	Remission	1.8g EPA & 0.9g DHA daily	12 months	Effective in reducing the rate of relapse
	Lorenz-Meyer (1996) (104)	CD	Double Blind RCT	135	Remission	3.3g EPA & 1.8g DHA daily	12 months	No effect on extending remission
	Belluzzi (1997) (109)	CD	Double Blind RCT	50	Remission	1.8g EPA & 0.9g DHA daily	12 months	No side effects noted from supplementation
	Romano (2005) (110)	CD	Double Blind RCT	38	Pediatric, remission	1.2g EPA & 0.6g DHA daily	12 months	Treatment with 5-ASA effective in maintaining remission
	Feagan (2008) EPIC 1 (111)	CD	Double Blind RCT	180/183	Remission	4 grams daily	52 weeks	No effect on prevention of relapse
	Feagan (2008) EPIC 2 (111)	CD	Double Blind RCT	188/187	Remission	4 grams daily	58 weeks	No effect on prevention of relapse
Vitamin D Supplementation	Miheller (2009) (112)	CD	Cohort Study	19/18	Inactive	0.25ug alfacalcidiol BID OR 1000IU D3 daily	12 months	Short-term benefit of active versus plain vitamin D on bone metabolism & disease activity
	Jorgensen (2010) (113)	CD	Double Blind multicenter RCT	48/46	Remission	1200 IU Vit D	12 months	Insignificant reduction in risk of relapse
	Amrousy (2021) (114)	IBD	Double Blind RCT	48/50	Variable	2000 IU D3 daily	6 months	May improve IBD activity score, QOL, & inflammatory markers in children
	Sharifi (2016) (115)	UC	Double Blind RCT	40/46	Remission	300,000 IU D3 injection	90 days	Decreases markers of inflammation
	Garg (2018) (116)	UC	Controlled CT	25	Active	40,000 IU weekly	8 weeks	Reduces intestinal inflammation
Bilberry	Biedermann (2013) (117)	UC	Prospective PT	13	Mild-Moderate	95g dry weight daily	6 weeks	Decreased endoscopic Mayo score & histologic Riley Index
Green Tea	Dryden (2013) (118)	UC	Double Blind RCT	10/10	Mild-Moderate	200mg EGCG or 400mg EGCG	56 days	Improved UCDAI, response rate, & remission rate
Aloe Vera	Langmead (2004) (119)	UC	Double Blind RCT	14/30	Mild-Moderate	100ml BID	4 weeks	Induces clinical response & reduced histologic disease activity
Vitamin E and C	Aghdassi (2003) (120)	CD	RCT	29/28	Inactive to mildly active	E: 800IU / C: 1g Daily	4 weeks	Significantly reduces oxidative stress
Myrrh, chamomile, coffeae carbon	Langhorst (2013) (121)	UC	Double Blind RCT	49/47	Clinical Remission	100mg M, 70mg CB, 50mg CC	12 months	No significant differences in relapse rate, CAI, or fecal biomarkers
Plantago Ovata	Fernandez-Banares (1999) (122)	UC	Multicenter RCT	37/35	Remission	20g daily	12 months	As effective as mesalamine in remission maintenance, results in fecal butyrate level increase

Multiple food components or supplements have been studied for the treatment or improvement of symptoms for patients with inflammatory bowel disease. Listed are the largest clinical studies and randomized controlled trials on frequently consumed, discussed, or studied supplements or food components for inflammatory bowel disease and the studies outcomes. (IBD = Inflammatory Bowel Disease, CD = Crohn’s disease, UC = Ulcerative Colitis, C = Control, E = Experimental, RCT = Randomized Controlled trial, PT = Prospective trial, CT = Cohort Trial, Pts = Patients, UCDAI = Ulcerative Colitis disease activity index, CAI = Colitis activity index, PUFA = Polyunsaturated fatty acids, g = Gram, mg = milligram, CC = Coffee Carbon, CB = Coffee, BID = twice daily, TID = three times daily, QOL = Quality of Life, EGCG = Epigallocatechin Gallate, DHA = Docosahexaenoic acid, EPA = Eicosapentaenoic acid, ALA = Alpha linoleic acid, GHA = Gamma Linolenic Acid)

Conclusion

Diet is an important part of the lives of patients with IBD and can significantly impact quality of life. Although we are still a few years away from precision nutrition approaches, there are now several dietary regimens that may help our patients living with IBD. Ideally in the future, we will be able to tailor personalized dietary therapy based on a patient’s metabolism, intestinal microbiome, and personal food preferences. Future drug trials should also consider dietary regimens embedded within drug efficacy studies.

KEY POINTS.

• New and emerging diets show promise in the treatment of IBD.

• The Crohn’s disease exclusion diet may help induce remission in Crohn’s disease patients who are refractory to medical therapy.

• The Specific Carbohydrate Diet and the Mediterranean diet both help induce clinical remission in patients with Crohn’s disease.

• Diets low in animal protein and high in fiber help induce, maintain remission in patients with ulcerative colitis and Crohn’s disease and may improve quality of life.

• A low FODMAP diet is restrictive but can help in patients with persistent IBS symptoms in the setting of quiescent IBD.