British Dietetic Association consensus guidelines on the nutritional assessment and dietary management of patients with inflammatory bowel disease

Search strategy

Systematic reviews for each topic were undertaken in line with recommendations of the Cochrane Handbook for Systematic Reviews of Interventions³ and reported in line with the guidelines of Preferred Reporting Items for Systematic reviews and Meta-Analyses.⁴ A Population, Intervention, Comparison and Outcomes framework and literature search strategy criteria were developed (see Supporting information, Tables S2 and S3) to search Cochrane, Embase®, Medline® and Scopus® electronic databases for topics on nutritional assessment and dietary management of IBD up until March 2022. Identification, screening, eligibility and inclusion of eligible papers were agreed between the researchers in advance and published prior to the literature searches being conducted (PROSPERO 2018 CRD42018096818; PROSPERO 2019 CRD42019138650).

References were imported into a bibliographic database and duplicates were removed automatically (EndNote X9; Thomson Reuters). Titles and abstracts were screened against the PICO eligibility criteria and potentially eligible full text articles were then obtained and screened against the eligibility criteria by two researchers independently. Reference lists of potential studies were cross-referenced for other studies of potential relevance. The percentage agreement in study eligibility and a kappa statistic were calculated to check concordance between reviewers.³ Disparities in study eligibility were resolved through discussion with a third researcher.

Reasons for excluding studies are provided (see Supporting information, Table S4).

Data extraction and risk of bias

Data were extracted from each eligible study relating to the patient or group, the intervention, the comparator, outcomes measured and the study design. A standardised data extraction sheet was developed, and two reviewers extracted the data from eligible papers. Discrepancies were reviewed and resolved.

Risk of bias tools appropriate to the study design were used. Two reviewers independently assessed risk of bias using seven domains: adequacy of randomisation, allocation concealment, blinding methods, complete outcome data, selective reporting and other sources of bias.³ Any disparities were resolved through discussion with a third reviewer.

Where data were available from randomised controlled trials (RCTs), this was used to answer the research question and lower quality studies were not considered when developing evidence statements. Where no RCT data were available lower quality studies were considered when developing evidence statements.

GRADE approach

Research papers were critically appraised using the GRADE tool.⁵ GRADE analysis of the evidence was performed where two or more studies reported data for the same outcome. For dichotomous outcomes (e.g., remission), frequencies were entered to obtain an odds ratio (OR). For continuous outcomes (e.g., disease activity score), standardised mean differences were calculated.

To address the research questions where data were expected to be available for a range of interventions, dietary interventions were categorised and each of these were separately assessed for available outcomes using the GRADE approach. The categories of nutrition outcome were; complementary alternative medicine, elimination diets, enteral nutrition, fibre (including prebiotics), nutrients, probiotics and whole diets.

Where a recently published systematic review was available, data from this were combined with data from studies published subsequent to the last search date of the systematic review.

Furthermore, where evidence was of low quality and GRADE Statements were not possible, recommendations to inform clinical practice were developed as Practice Statements.

Consensus

GRADE Statements and Practice Statements underwent consensus voting using an eDelphi online platform. IBD experts from British Dietetic Association Gastroenterology Specialist Group, British Society of Gastroenterology, Crohn's and Colitis UK and patients with IBD were invited to vote anonymously on the statements.

Three rounds of voting took place. Participants used a five-point Likert scale to vote (strongly disagree, disagree, neutral, agree, strongly agree). After each voting round, statements that did not reach 80% consensus were reformulated and taken to the next round of voting or removed. In rounds 2 and 3, updated iterations of the statements were voted on and evaluative text based on feedback from the previous round was available.

BMI

Thirty studies reported BMI, 11 studies matched healthy controls and IBD patients for BMI so were excluded from the GRADE analysis.^7-17 The remaining 19 studies included 1077 patients with Crohn's disease (CD), 426 patients with UC and 4255 healthy controls.^18-36

Fat mass

Seventeen studies assessed fat mass in 920 CD patients, 195 UC patients and 983 healthy controls.^{8, 14-24, 27, 33, 35-37}

Percentage fat mass

Fifteen studies assessed percentage fat mass in IBD with 664 CD patients, 190 UC patients and 675 healthy controls.^{7, 12, 13, 17-20, 22-24, 27, 29, 33, 35, 38}

Fat free mass

Fat free mass was measured in 18 studies ^{8, 9, 14-24, 27, 33, 35, 37, 38} in 836 CD patients, 210 UC patients and 814 healthy controls and analysis demonstrated inconsistent findings.

Percentage fat free mass

Two studies assessed percentage fat free mass in 61 CD patients in remission, 16 UC patients in remission and 75 healthy controls.^{19, 20} One study showed that percentage fat free mass was lower in patients (n = 43) compared to healthy controls (n = 55),¹⁹ whereas the other study showed similar percentage fat free mass between groups: patients (n = 18) and health controls (n = 20).²⁰

No studies in UC were identified.

Visceral adipose tissue

Three studies assessed visceral adipose tissue in a mixed population of active CD and CD in remission with 101 CD patients and 67 healthy controls.^{7, 12, 13} All studies found visceral adipose tissue was higher in patients compared to healthy controls.

No studies in UC were identified.

Waist to hip ratio

Two studies assessed waist to hip ratio, one in CD in remission²² and the other in a mixed population of active CD and CD in remission.¹² Fifty patients with CD and 52 healthy controls were included in the analysis. Both studies found no difference in waist to hip ratio between patients and healthy controls.^{12, 22}

Muscle strength

In health, muscle mass is a strong predictor of muscle strength. In IBD, muscle strength is likely to be affected by disease activity. Longitudinal assessment of muscle function can be useful for assessing long-term effects of disease activity on muscle strength and endurance.

Handgrip and lower limb strength are reliable measures of muscle function; however, in clinical practice, handgrip strength is more practical, quicker and cheap assessment tool compared to assessment of lower limb strength.

Muscle strength was assessed in seven studies.^{15-17, 22, 24, 36, 39} There were 437 patients with CD, 96 patients with UC and 491 healthy controls with inconsistent results.

Folic acid

Five studies assessed serum folic acid and/or folic acid deficiency rates.^{16, 22, 24, 51, 52}

The studies included 283 patients with CD, 189 patients with UC and 272 healthy controls. One study reported that they excluded patients who were receiving folic acid supplementation within the previous 6 months,⁵² two studies included patients who took folic acid supplements ^{16, 22} and two studies did not describe whether patients received folic acid supplementation or not.^{24, 51}

Vitamin B₁₂

Five studies assessed serum vitamin B₁₂ and/or vitamin B₁₂ deficiency rates.^{16, 22, 24, 51, 52}

Micronutrient deficiency rates were reported in CD patients and healthy controls in two studies.^{16, 51}

The studies included 283 patients with CD, 189 patients with UC and 272 healthy controls. One study reported that they excluded patients who had received vitamin B₁₂ supplementation within the previous 6 months,⁵² two studies included patients who had received intramuscular vitamin B₁₂ ^{16, 22} and two studies did not report whether patients did or did not receive vitamin B₁₂ supplementation.^{24, 51}

Vitamin D

There are 11 studies (five in remission and six in mixed IBD) measuring vitamin D status.

Zinc

Ten studies assessed serum zinc or zinc deficiency rates.^{11, 16, 22-24, 60-64} There were 375 CD patients, 398 UC patients and 451 healthy controls.

Zinc is mostly intracellular and disease activity and CRP > 20 mg L^–1 will limit interpretation in IBD.

Copper

Four studies assessed serum copper levels.^{22, 24, 61, 63} There were 113 CD patients, 163 UC patients and 200 healthy controls.

Magnesium

Three studies assessed serum magnesium levels or magnesium deficiency rates.^{16, 22, 24} There were 149 CD patients, 96 UC patients and 126 healthy controls included in the analysis.

Selenium

Eight studies assessed serum selenium levels or selenium deficiency rates.^{11, 16, 22, 24, 61, 64-66} There were 684 CD patients, 328 UC patients and 1214 healthy controls.

Iron

Use serum ferritin, CRP, transferrin saturation and serum iron to assess presence of iron deficiency and haemoglobin, blood count and other micronutrients when diagnosing iron deficiency anaemia.

Three studies assessed serum iron levels.^{29, 64, 67} The analysis included 191 patients with CD, 287 patients with UC and 280 healthy controls. No studies assessed iron deficiency rates in IBD compared to healthy controls.

Energy

Similar energy intakes compared to healthy controls (n = 1940) were observed in eight of 15 studies in CD patients (n = 572)^{12, 21-24, 31, 69, 72} and four of seven studies in UC patients (n = 258) compared to 1607 healthy controls.^{24, 31, 34, 72} Lower energy intakes compared to healthy controls (n = 767) were found in six of 14 studies in CD patients (n = 381)^{18, 19, 25, 32, 70, 71} and three of six studies in UC patients (n = 167) compared to healthy controls (n = 527).^{25, 32, 70} One study found that CD patients (n = 20) had significantly higher energy intake compared to healthy controls (n = 31) but this study had a small sample size and these patients also had significantly higher protein and carbohydrate intakes.³⁴

Protein

Fourteen studies assessed protein intake^{12, 18, 19, 21-25, 31, 34, 69-72} with 725 patients with CD, 359 patients with UC and 2474 healthy controls.

Eight of studies showed there was no difference in protein intakes between patients with CD (n = 539) and healthy controls (n = 487),^{19, 21-24, 69, 71} and patients with UC (n = 161)²⁴ and healthy controls (n = 107). Four studies showed significantly lower intakes for patients with CD (n = 187) compared to healthy controls (n = 547),^{12, 18, 25, 70} two studies showed significantly lower intakes for UC patients (n = 101) compared to healthy controls (n = 427)^{25, 70} and two studies showed a higher percentage of total energy from protein for CD (n = 111) and UC (n = 97) patients compared to healthy controls (n = 1500).^{31, 34}

Fat

There were 15 studies that assessed fat intake^{12, 18, 19, 21-24, 28, 31, 32, 34, 69-72} with 849 patients with CD, 400 patients with UC and 2525 healthy controls. Fourteen studies included patients with CD and seven studies included patients with UC. Active IBD and IBD in remission were included in eight studies and seven studies included patients only in remission.

Fat intake was significantly lower in CD patients (n = 154) compared to healthy controls (n = 1560) in three of 13 studies^{19, 31, 34} and in three of six studies in UC patients (n = 109) compared to healthy controls (n = 1512).^{28, 31, 34}

Fat intake was significantly higher in CD patients (n = 121) compared to healthy controls (n = 486) in two of 13 studies^{32, 70} and in one of six studies in UC patients (n = 66) compared to healthy controls (n = 100).³²

Fat intake was similar between CD patients (n = 607) and healthy controls (n = 515) in nine of 14 studies^{12, 18, 21-24, 69, 71, 72} and three of seven studies in UC patients (n = 175) compared to healthy controls (n = 493).^{24, 70, 72}

Carbohydrate

There were 15 studies that assessed carbohydrate intake^{12, 18, 19, 21-24, 28, 31, 32, 34, 69-72} with 849 patients with CD, 400 patients with UC and 2525 healthy controls. Fourteen studies included patients with CD and seven studies included patients with UC. Active IBD and IBD in remission were included in eight studies and seven studies included patients only in remission.

There were no differences in carbohydrate intake between CD (n = 483) and healthy controls (n = 806) in nine of 14 studies^{12, 18, 19, 21, 22, 32, 69, 70, 72} and UC (n = 227) and healthy controls (n = 207) in three of seven studies.^{24, 32, 72} Compared with healthy controls (n = 1643), higher carbohydrate intake was found in five of 13 studies for CD patients (n = 261)^{23, 24, 31, 34, 71} and four of six studies for UC patients (n = 155) compared to healthy controls (n = 1898).^{28, 31, 34, 70}

Fibre

Seven studies assessed fibre intake, three had a low risk of bias^{22, 24, 32} and four had unclear risk of bias ^{31, 70-72} in 471 CD patients, 226 UC patients and 2142 healthy controls.

Fibre intake was significantly lower in patients with CD (n = 439) compared to healthy controls (n = 2142) in six of seven studies^{22, 31, 32, 70-72} and patients with UC (n = 341) compared to healthy controls (n = 2062) in four of five studies.^{31, 32, 70, 72}

Calcium

Ten studies assessed calcium intake, three had a low risk of bias,^{22, 24, 53} four had an unclear risk of bias^71-74 and three had high risk of bias^{25, 28, 75} in 906 IBD patients (CD, n = 425; UC, n = 329; unknown, n = 152) and 837 healthy controls.

Four studies included patients in remission^{22, 53, 71, 73} and six studies included patients with active disease or disease in remission.^{24, 25, 28, 72, 74, 75}

Six of nine studies found no significant difference in calcium intake between CD (n = 381) and healthy controls (n = 708)^{22, 24, 25, 72-74} and four of six studies between UC (n = 278) and healthy controls (n = 557).^{25, 28, 72, 74} Two studies found lower intakes compared to healthy controls, one in UC (n = 46) compared to healthy controls (n = 23)²⁴ and one in mixed IBD (n = 152) compared to healthy controls (n = 73).⁷⁵

Self-screening

Four recent studies from Canada^{81, 87} and the UK^{77, 78} have found that patients can accurately self-screen for risk of malnutrition using MUST^{77, 78, 81, 87} IBD-NST,⁷⁸ SaskIBD-NR⁸⁷ or abridged patient-generated SGA.⁸⁷ The use of self-screening may be a more cost-effective method of identifying patients who are likely to benefit from further nutritional assessment and dietetic input.

Enteral nutrition

A recent systematic literature review of exclusive enteral nutrition (EEN) to induce disease remission in adults with Crohn's disease reviewed literature published from inception to July 2017.⁹² No further studies in adults were identified after this date. Six RCT published from 1985 to 2002 were included in an intention to treat and per protocol meta-analysis of EEN versus corticosteroids to induce remission.^93-98 The intention to treat meta-analysis found 87 of 194 (45%) patients on EEN and 116 of 158 (73%) patients on corticosteroids achieved disease remission with risk ratio of 0.65 (95% CI = 0.52–0.82) favouring corticosteroids. The per protocol meta-analysis induction of remission results also favoured corticosteroids with 87 of 149 (58%) patients on EEN and 116 of 158 (73%) on corticosteroids with a risk ratio of 0.82 (95% CI = 0.70–0.95). These RCTs were reported between 1985 and 2002. The palatability of and methods used to administer current enteral nutrition formula have significantly improved since then. In addition, evidence from recent paediatric RCTs suggest that EEN is equivalent to corticosteroids at inducing disease remission.^{92, 99, 100} Recent guidelines suggest that EEN may be considered as an alternative to corticosteroids in patients with mildly active CD.^{47, 101}

Two case series reported improvement in CRP and disease activity in patients with active Crohn's disease treated with exclusive enteral nutrition as an adjuvant to aminosalicylates, immunosuppressive and/or biologic therapy.^{102, 103} One case series in 16 adults with active Crohn's disease treated with exclusive enteral nutrition as an adjuvant to existing Crohn's disease medications (details not provided)¹⁰² showed significant reductions in Harvey Bradshaw index (6.5 ± 5.8 to 2.4 ± 3.3) (p = 0.001) and CRP (3.5–0.88 mg dl^–1) (p = 0.023). Another case series in 25 patients with active Crohn's disease treated with EEN included 13 patients on stable doses of mesalazine (n = 9), immunosuppressants (n = 3) or biologic (n = 1) medications. Only 14 of 25 (56%) patients completed EEN and achieved disease remission (Harvey Bradshaw Index < 5).¹⁰³ The outcomes of patients on concurrent medications were not reported separately. The two case series suggest that remission may be induced in patients with active Crohn's disease treated with EEN in addition to concurrent medications but this needs to be confirmed in controlled studies. The use of exclusive enteral nutrition to induce disease remission in patients with active disease on an optimised regimen of immunosuppressant and/or biologic medication has not been described in the literature.

A recent open label RCT of 7 days of EEN in acute severe UC has investigated whether EEN can improve the response to intravenous corticosteroids.¹⁰⁴ On an intention-to-treat analysis, corticosteroid treatment failed in eight of 32 (25%) patients who received EEN versus 13 of 30 (43%) who ate a normal diet (p = 0.051). Larger high-quality studies are warranted to confirm whether EEN can augment the effectiveness of corticosteroids in acute severe UC.

Access to dietetic expertise and use of a defined pathway are essential for successful use of exclusive enteral nutrition.^{47, 105} Practical guidance is provided in Table 6.

Whole food or elimination diets

Practical dietary advice for IBD is provided in Table 7. Ten whole food dietary exclusion interventions to induce remission in adults with active IBD were reviewed. These are anti-inflammatory IBD diet, low FODMAP (i.e., fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, Crohn's disease exclusion diet (CDED), IgG4, Western diet, low microparticle diet, semi-vegetarian plant-based diet, Mediterranean diet, specific carbohydrate diet (SCD) and Crohn's disease TReatment with EATing diet (CD-TREAT).^109-112 The results of a feasibility study of a low emulsifier diet in adults with active IBD are also promising.¹¹³ However, high quality evidence is needed for most of these whole food interventions before they may be recommended as alternative treatments to current management strategies recommended as primary treatment for active disease.

A 2019 Cochrane review concluded that there is insufficient evidence to determine whether exclusion diets induce disease remission in Crohn's disease or ulcerative colitis.¹¹⁴ Some of their reviewed studies did not meet our inclusion criteria.^115-117 Subsequent to this review, new evidence from RCTs in adults with IBD has been published. Below is a summary of the evidence for each whole food dietary exclusion intervention.

Fibre

Two systematic reviews of fibre (supplement or whole diet intervention) as a treatment to induce remission in IBD were performed.^{129, 130} Five RCTs were identified that included 114 patients with active UC.^131-135 All studies assessed the effects of a prebiotic, two of which were combined with a probiotic compared with a placebo. Study duration varied from 2 weeks to 12 months and there was no homogeneity of outcomes to which GRADE criteria could be applied. Compared with placebo the findings from these studies are summarised below.

Germinated barley fibre (20–30 g day^–1) led to lower overall disease score at 4 weeks (p = 0.045), mainly driven by reduced frequency of diarrhoea.¹³⁴

Fructo-oligosaccharide (12 g day^–1) plus probiotic led to greater reduction in sigmoidoscopy score at 4 weeks but failed to reach significance (p = 0.06) and there was no difference in clinical disease activity score.¹³¹

Oligofructose inulin (12 g day^–1) alongside mesalamine (3 g day^–1) for 2 weeks had no effect on clinical outcomes compared to placebo alongside mesalamine (3 g day^–1), although faecal calprotectin was lower than baseline in the prebiotic group only (p < 0.05).¹³²

Galacto-oligosaccharide (5.5 g day^–1) with a probiotic led to similar endoscopic score at 1 year compared with placebo. However, there was a significant reduction in faecal myeloperoxidase for the intervention arm compared to placebo (p < 0.05).¹³³

Oligosaccharide inulin (7 g day^–1) with a probiotic and micronutrients for 2 months led to lower interleukin (IL)-6 (p < 0.05), IL-8 (p < 0.01) and lymphocyte expression (p < 0.05) but clinical outcomes were not reported.¹³⁵

No further RCTs in UC patients have been identified subsequent to the 2014 systematic review of fibre by Wedlake et al.¹²⁹

Three studies that measured the effect of prebiotic fibre on clinical outcomes in 156 patients with active CD ^{124, 136, 137} have been systematically reviewed.^{124, 129, 136, 137}

An organic high-fibre diet (n = 8; mean fibre content 46 g day^–1) was compared with a control low-fibre diet (n = 10; mean fibre content 16 g day^–1).¹²⁴ There was no difference between groups for remission rates and on an intention to treat basis, with three of eight patients achieving mucosal healing in the high fibre group compared to one of 10 in the control group.

Oligofructose inulin (12 g day^–1) alongside a probiotic showed no difference in remission rates at 6 months in patients with active CD (n = 19) compared to placebo (n = 16); however, the treatment group had a significant improvement in histological scores from baseline but the control did not. There were no changes in either group in bowel habit, biochemical markers or IBD questionnaire scores.¹³⁷

Oligofructose inulin (15 g day^–1, n = 54) compared to placebo (n = 49) for 4 weeks in active CD patients demonstrated no improvement in clinical outcomes and worse flatulence and abdominal pain and rumbling after prebiotic, although lower numbers of IL-6 and higher numbers of IL-10 expressing dendritic cells in the prebiotic group were reported.¹³⁶

No further randomised controlled trial were identified after the publication of the systematic review by Wedlake et al.¹²⁹

Vitamin D

Low serum vitamin D is common in IBD. Adjuvant high dose vitamin D supplementation improves serum vitamin D concentrations but there is conflicting evidence on the effect of vitamin D supplementation on disease activity.^{138, 139}

Public Health England recommend that all adults should consider taking a daily vitamin D supplement of 10 μg from October to March to improve their vitamin D status.

Fish oil

An RCT in patients with mild to moderately active UC (n = 121) found that partial enteral nutrition (33% of energy) supplemented with fish oil (2.5 g day^–1 eicosapentaenoic acid and 1 g day^–1 docosahexaenoic acid) and fructo-oligosaccharide (6.5 g day^–1) had no effect on clinical outcomes or histology after 6 months compared TO a carbohydrate-based placebo.¹⁴⁰ At baseline, 50% of patients were taking prednisone and/or sulfasalazine and medication doses could be adjusted based on patient symptoms. The effect of the fish oil could not be extrapolated from the mixed enteral nutrition and drug therapy; however, there were no differences between the intervention and placebo in reduction in disease activity.

An open label study in mild to moderately active CD (n = 20) using partial enteral nutrition (33% of energy) supplemented with fish oil (2.5 g day^–1 eicosapentaenoic acid and 1 g day^–1 docosahexaenoic acid) and fructo-oligosaccharide (6.5 g day^–1) was conducted.¹⁴¹ At baseline, 50% of patients were taking corticosteroids. A number of adverse effects were attributed to the intervention in active CD including nausea, excessive flatulence, faecal incontinence, hot flushes and abdominal pain, although it would be difficult to determine the ingredient that induced the effects. Half of the patients achieved 85% compliance with the nutrition intervention associated with a >2% increase in plasma phospholipid eicosapentaenoic acid (n = 10). This group showed a significant improvement in CDAI change (−47.8 [−65 to −37]) (p = 0.049), whereas patients with 54% compliance (n = 10) had no change in CDAI (−8.1 [−54.6 to 40.1]) (p = 0.99). At 4 months, CDAI was significantly less for the 85% compliance patients (116 ± 95) compared with the 54% compliance patients (262 ± 87) (p < 0.005). The number of patients who achieved disease remission was not reported. These results need to be interpreted with caution as a result of the study being open label with small numbers, the use of corticosteroids and the inability to extrapolate the effect of the fish oil from the enteral nutrition.

Complementary and alternative medicine

A systematic review of complementary and alternative medicines to improve disease activity and markers of inflammation in IBD was published in 2015.¹⁴² The systematic review concluded that there was a lack of homogeneity in the literature and that complementary and alternatives therapies may be effective, although further research is required to confirm their efficacy. Subsequent to this systematic review, nine further RCTs to improve disease activity in active IBD have been published: seven using a curcumin supplement^143-149 and two using cannabidiol-rich botanical extract.^{150, 151} The evidence and recommendation for curcumin supplementation in active UC is described below. Two RCTs showed cannabidiol-rich botanical extract versus placebo improved disease activity^{150, 151} but not endoscopic healing.¹⁵¹ Further details are available in recent reviews and guidelines.^{47, 152}

Probiotics

Eight systematic reviews of probiotics in active IBD were reviewed for RCTs that met the inclusion criteria.^154-161 One further study also met the inclusion criteria.¹⁶²

Ten RCTs assessed the effect of probiotics in active UC alongside usual medication, mostly 5-aminosalicylic acid. One study had low risk of bias,¹⁶³ five studies had unclear risk of bias ^{162, 164-167} and four studies had high risk of bias.^168-171 The analysis included 356 patients randomised to a probiotic and 311 randomised to placebo. Different probiotics were used across studies. Seven studies showed more patients achieved remission with probiotics (124/272 [46%]) compared to placebo (75/277 [27%]). The probiotics were: De Simone Formulation in three studies^{166, 167, 169}; Yakult Bifidobacterium breve strain Yakult, Bifidobacterium bifidum strain Yakult and a Lactobacillus acidophillus strain in one study¹⁶⁴; Bifidobacterium longum 536 (BB-536) in one study¹⁷⁰; Profermin Lactobacillus plantarum 299v in one study ¹⁶⁸; and Lactobacillus casei Zhang, Lactobacillus. plantarum P-8 and Bifidobacterium animalis subsp. lactis V9 in one study.¹⁶² Three studies showed similar remission rates between probiotics (53/112 [47%]) and placebo (40/62 [65%]) with these probiotics: Escherichia coli nissle in two studies,^{163, 165} and Lactobacillus. casei strain ATCC PTA‑3945 in one study.¹⁷¹

In practice, if patients want to try a probiotic, they should be given the evidence highlighting which ones have been shown to be beneficial in ulcerative colitis (for practical guidance, see Table 8).

Three studies have assessed probiotics versus placebo to induce remission in 54 patients with CD.^178-180 One study demonstrated improvement in Crohn's disease activity index for the probiotic Saccharomyces boulardii (n = 10)¹⁷⁸ compared to placebo (n = 7) and two showed no difference between probiotics Lactobacillus rhamnosus GG and E. coli Nissle 1917 (6/19 [32%]) compared to placebo (6/18 [33%]).^{179, 180}

Whole food or elimination diets

There is much interest in aspects of the modern Western lifestyle that may contribute to intestinal inflammation in IBD. From a dietary perspective, processed foods and the use of preservatives and emulsifiers may be important and studies are underway to evaluate these dietary components.

In a retrospective case–control study, a diet that excluded immunoreactive foods was compared to a control diet to maintain Crohn's disease remission for 3 months following EEN to induce disease remission.¹⁸¹ Disease relapse was similar between groups (p = 0.337) with relapse in four of 32 in the exclusion diet group and eight of 32 in the control diet group after 3 months.

In a prospective pilot RCT, CDED with partial enteral nutrition was compared to CDED without partial enteral nutrition.¹¹² The CDED is described as a progressive high protein, low animal fat, low haem, low gluten, and low additive diet with exposure to fibre. Remission maintenance was compared at 24 weeks in the intention to treat group (n = 40). In the CDED with partial enteral nutrition group, from week 13, patients did not have to include any enteral nutrition and were only allowed to eat foods from CDED, which is the same intervention as CDED without partial enteral nutrition. At 6 weeks, 25 patients were in remission and, at 24 weeks, 20 remained in remission, 12 of 19 patients from the CDED with partial enteral nutrition group and eight of 21 patients from the CDED without partial enteral nutrition group (p = 0.113).¹¹²

Further trials are awaited; however, no recommendations can be made on the use of such diets at this time.^{114, 125, 182}

Enteral nutrition

Three RCTs addressed the efficacy of partial enteral nutrition (oral nutritional supplementation) (420–1200 kcal day^–1) for maintaining remission in CD.^184-186 One had low risk of bias,¹⁸⁵ one had unclear risk of bias¹⁸⁴ and one had high risk of bias.¹⁸⁶ Combining the data from these three studies was possible for the outcome of remission maintenance. More patients who received partial enteral nutrition 56 of 94 (60%) maintained remission compared to patients who did not (34/88 [39%]) (OR = 2.34, 95% CI = 1.29–4.24).

Low quality observation studies have investigated the use of partial enteral nutrition (300–900 kcal day^–1) to prevent loss of response to biologic anti-tumour necrosis factor α therapy.^187-193 However, it is unclear whether there is a beneficial effect compared with no enteral nutrition.

There is no evidence to recommend partial or exclusive enteral nutrition for maintaining remission in patients with UC.

Complementary and alternative medicine

There is a lack of evidence to recommend complementary and alternative medicines to maintain disease remission in IBD.^{142, 152} One RCT investigated 2 g day^–1 curcumin compared to placebo for 6 months in patients with quiescent UC and reported significantly fewer patients relapsed following supplementation with curcumin (2/43 [5%]) compared to placebo (8/39 [21%]) (p = 0.04). Curcumin was given in addition to standard medication (sulfasalazine or mesalamine).¹⁹⁴ In another RCT in 62 post-operative patients with Crohn's disease receiving azathioprine, curcumin was no more effective than placebo in preventing endoscopic or clinical recurrence in Crohn's disease at 6 months.¹⁹⁵

Fibre

The recommended intake of fibre is 30 g day^–1; however, most patients with IBD do not meet this level.^{22, 72} Patients perceive that fibre exacerbates symptoms¹⁹⁶ and therefore often avoid it during a disease flare. However, in stable disease without strictures, there is no research evidence to support restriction of fibre.¹⁹⁷

In patients with UC in remission, psyllium appears safe to use and could be used alongside standard medication should patients wish to try it.^{198, 199}

Two systematic reviews of fibre (supplement or whole diet intervention) as a treatment to maintain remission in IBD were performed^{129, 130} and, despite identifying five studies including 232 patients with quiescent UC^198-202 and four studies including 465 patients with quiescent CD,^203-206 there was high heterogeneity among studies with varied criteria for assessing outcome and neither meta-analysis, nor GRADE summary of the evidence was possible.^{198-201, 203-206} The largest trial of 105 patients compared remission maintenance over 12 months for 1.5 g day^–1 mesalamine (24/37 [65%]) with 20 g day^–1 psyllium fibre (21/35 [60%]) or a combination of both treatments (21/30 [70%]) (p = 0.67) and concluded that the treatments were equivalent for remission maintenance.¹⁹⁸ For the other four studies,^199-202 either clinical outcomes were not reported or the results were reported as percentages without the data to ascertain the number of patients in each group; therefore, the outcome of remission maintenance in UC could not be analysed using GRADE. One further RCT conducted subsequent to these systematic reviews compared prebiotics (15 g day^–1 oligofructose and inulin) with placebo for 6 months and showed no difference in relapse rates for prebiotics (11/35) and control (10/41).²⁰⁷

Four studies of CD in remission including 465 patients were identified, and all four studies reported disease outcomes.¹²⁹ However, the interventions were heterogenous and the evidence could not be analysed using GRADE. One study of 20 patients showed that a low fibre exclusion diet led to increased remission maintenance rates compared to a ‘fibre-rich’ refined carbohydrate diet²⁰⁵; however, the other three studies of 445 patients showed no difference between placebo and fibre intervention in clinical outcomes.^203-206

One study compared the effect of an anti-IBD diet (a diet low in animal fat, grains, additives, and high in monounsaturated and ω-3 fatty acids) with fructooligosaccharides or placebo and reported that relapse occurred more frequently in the fructooligosaccharides group (6/19 [32%]) than the anti-IBD diet group (0/16 [0%]) (p = 0.035), although neither group was significantly different to the placebo group with respect to the rate of relapse (4/19 [21%]).²⁰⁸

An RCT in 32 quiescent IBD patients with functional gut symptoms demonstrated that 12 g day^–1 fructans exacerbated abdominal pain, bloating, flatulence and urgency compared to a placebo (12 g day^–1 glucose) after 3 days of supplementation.²⁰⁹

Nutrients

Probiotics

Six systematic reviews of probiotics to maintain remission were assessed for RCTs that met the inclusion criteria.^{154, 155, 158, 159, 161, 212} Three studies have assessed probiotics versus placebo to maintain disease remission for 4 weeks to 12 months in CD.^213-215 None of the studies demonstrated lower relapse rates for probiotic (52/133 [39%]) compared to placebo (50/125 [40%]).

Four studies have assessed probiotics versus placebo to maintain disease remission in UC.^{172, 214, 216, 217} One study showed that probiotics (3/15 [20%]) had a lower relapse rate compared to placebo (14/15 [93%]) following 8 weeks,¹⁷² whereas the other studies showed similar rates between probiotics (29/83 [35%]) and placebo (32/61 [52%]) at 4 weeks²¹⁴ and 12 months.^{216, 217}

Extra-intestinal manifestations

Refer to BSG guidelines and ECCO guidelines on how to manage extra-intestinal manifestations of IBD.^{47, 274, 275}

OFG

One case series met the inclusion criteria and reported on either clinical response in patients with OFG following a nutrition intervention.

Patients with OFG (n = 32) received dietary advice on a cinnamon and benzoate free diet for 8 weeks. Only 25 patients completed the study and nine patients had gut involvement. A clinical response was reported in 18 of 25 (72%) patients.²⁷⁶ A cinnamon and benzoate free diet is a first-line treatment option for patients with OFG; however, the mechanisms are not understood. Dietary resources on a cinnamon and benzoate free diet are available online (www.kcl.ac.uk/ofg) for healthcare professionals working with patients with OFG.

Upper gastrointestinal Crohn's disease

Proton pump inhibitors are often used to treat upper gastrointestinal Crohn's disease and may affect iron, vitamin B₁₂, vitamin C and vitamin D, and possibly magnesium status, as well as bone mineral density. Refer to BSG guidelines and ECCO guidelines on how to manage upper gastrointestinal Crohn's disease.^{47, 101, 274}

Perianal IBD

Refer to BSG guidelines and ECCO guidelines on how to manage perianal IBD.^{47, 274, 277}