Nutrition Assessment in Crohn’s Disease using Anthropometric, Biochemical, and Dietary Indexes: A Narrative Review

      Abstract

      Malnutrition is common in patients with Crohn’s disease and negatively influences immunity and quality of life. The optimal tools for nutrition assessment in patients with Crohn’s disease are not clearly defined and lead to variations in practice. With this review, we aimed to appraise the existing evidence for nutrition assessment of patients with Crohn’s disease compared with healthy controls and provide a comprehensive guide with relevant measures applicable to clinical practice. A literature search using Medline, Embase, and Scopus from inception to October 1, 2018, was conducted. Forty-one articles that assessed body composition, muscle strength, micronutrient status and/or dietary intake in adults with Crohn’s disease compared with an age- and sex-matched healthy individuals were included. There were heterogeneous findings on nutritional status in patients with Crohn’s disease compared with healthy controls. Only one article reported a clinically significant difference for body mass index; however, significant deficits in fat mass, fat-free mass, and muscle strength were observed in patients with Crohn’s disease compared with healthy controls, with more pronounced differences with increasing disease activity and length of diagnosis. Most research reported significantly lower serum micronutrients in patients with Crohn’s disease compared with healthy controls. Half of studies measuring micronutrient intake reported lower intakes in patients with Crohn’s disease compared with healthy controls. Fruit and vegetable intake was also lower in patients with Crohn’s disease. Difficulties characterizing the type and prevalence of malnutrition exist due to the heterogeneous nature of Crohn’s disease and warrants continued investigation. As a result of this review, we advocate that a nutrition assessment should include more parameters than weight and body mass index.

      Keywords

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      Research Question: What is the existing evidence to inform a comprehensive nutrition assessment of patients with Crohn’s disease?
      Key Findings: There were heterogeneous findings on nutritional status in Crohn’s disease. Significant deficits in fat mass, fat-free mass, and muscle strength were observed. Lower serum micronutrient levels, micronutrient intakes, and fruit and vegetable intakes were reported in patients with Crohn’s disease compared with healthy controls. The findings from this narrative review have informed the development of a practical clinical guide for comprehensive nutrition assessment of patients with Crohn’s disease.
      Malnutrition is a significant issue in patients with Crohn’s disease with an estimated prevalence between 20% and 85%, depending on the criteria used.
      • Donnellan C.F.
      • Yann L.H.
      • Lal S.
      Nutritional management of Crohn’s disease.
      It is associated with increased susceptibility to infections, gastrointestinal barrier dysfunction, postoperative complications, and reduced quality of life.
      • Burnham J.M.
      • Shults J.
      • Semeao E.
      • et al.
      Body-composition alterations consistent with cachexia in children and young adults with Crohn disease.
      • Alves A.
      • Panis Y.
      • Bouhnik Y.
      • Pocard M.
      • Vicaut E.
      • Valleur P.
      Risk factors for intra-abdominal septic complications after a first ileocecal resection for Crohn's disease: A multivariate analysis in 161 consecutive patients.
      • Makela J.T.
      • Kiviniemi H.
      • Laitinen S.
      Risk factors for anastomotic leakage after left-sided colorectal resection with rectal anastomosis.
      Reasons for malnutrition in patients with Crohn’s disease are multifactorial. More than 80% of people with Crohn’s disease experience problems with food
      • Prince A.
      • Whelan K.
      • Moosa A.
      • Lomer M.C.
      • Reidlinger D.P.
      Nutritional problems in inflammatory bowel disease: The patient perspective.
      and 72% alter their diet as a result,
      • Vidarsdottir J.B.
      • Johannsdottir S.E.
      • Thorsdottir I.
      • Bjornsson E.
      • Ramel A.
      A cross-sectional study on nutrient intake and -status in inflammatory bowel disease patients.
      often leading to insufficient nutrient intakes.
      • Casanova M.J.
      • Chaparro M.
      • Molina B.
      • et al.
      Prevalence of malnutrition and nutritional characteristics of patients with inflammatory bowel disease.
      Active disease is associated with reduced appetite, low mood, and abdominal pain
      • Donnellan C.F.
      • Yann L.H.
      • Lal S.
      Nutritional management of Crohn’s disease.
      ; furthermore, mucosal inflammation causes malabsorption due to damaged intestinal microvilli
      • Vitek L.
      Bile acid malabsorption in inflammatory bowel disease.
      and increased diarrhea, leading to a loss of electrolytes and fluids.
      • Barkas F.
      • Liberopoulos E.
      • Kei A.
      • Elisaf M.
      Electrolyte and acid-base disorders in inflammatory bowel disease.
      Systemic inflammation elevates nutrient requirements due to catabolism causing weight loss.
      • Donnellan C.F.
      • Yann L.H.
      • Lal S.
      Nutritional management of Crohn’s disease.
      The inflammatory response produces cell-damaging free radicals; micronutrients act as antioxidants to reduce damage; therefore, prolonged inflammation eliminates micronutrients via excessive utilization.
      • Krzystek-Korpacka M.
      • Neubauer K.
      • Berdowska I.
      • Zielinski B.
      • Paradowski L.
      • Gamian A.
      Impaired erythrocyte antioxidant defense in active inflammatory bowel disease: Impact of anemia and treatment.
      Pharmacologic side effects also contribute to malnutrition. Corticosteroids increase adiposity and are associated with reduced bone mineral density.
      • Jahnsen J.
      • Falch J.A.
      • Mowinckel P.
      • Aadland E.
      Body composition in patients with inflammatory bowel disease: A population-based study.
      Micronutrient deficiencies in patients with Crohn’s disease are a further health care burden. Inflammation and suboptimal vitamin D levels are associated with impaired bone mineral density, making osteoporosis common in patients with Crohn’s disease.
      • Lima C.A.
      • Lyra A.C.
      • Rocha R.
      • Santana G.O.
      Risk factors for osteoporosis in inflammatory bowel disease patients.
      Dietary deficits in zinc reduce muscle mass and strength,
      • Wiroth J.B.
      • Filippi J.
      • Schneider S.M.
      • et al.
      Muscle performance in patients with Crohn's disease in clinical remission.
      which has deleterious consequences on functional ability and activities of daily living.
      • Vaapio S.
      • Salminen M.
      • Vahlberg T.
      • Kivela S.L.
      Increased muscle strength improves managing in activities of daily living in fall-prone community-dwelling older women.
      Suboptimal circulating concentrations of folic acid, vitamin B-12, vitamin C, and selenium have also been reported.
      • Filippi J.
      • Al-Jaouni R.
      • Wiroth J.B.
      • Hebuterne X.
      • Schneider S.M.
      Nutritional deficiencies in patients with Crohn's disease in remission.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      The risk of malnutrition persists during the remission phase of the disease; whilst 86% of patients with active disease avoid certain foods during flare-ups, 77% of patients continue to avoid certain foods during remission to prevent disease relapse.
      • Casanova M.J.
      • Chaparro M.
      • Molina B.
      • et al.
      Prevalence of malnutrition and nutritional characteristics of patients with inflammatory bowel disease.
      In clinical practice, nutrition assessment in patients with Crohn’s disease remains challenging and most frequently is measured using weight and body mass index (BMI).
      • Lomer M.C.E.
      • Gourgey R.
      • Whelan K.
      Current practice in relation to nutritional assessment and dietary management of enteral nutrition in adults with Crohn's disease.
      Weight and BMI are inadequate measures of malnutrition in Crohn’s disease as systemic inflammation alters body composition, meaning BMI may mask deficits in lean mass due to increased fat mass.
      • Bryant R.V.
      • Trott M.J.
      • Bartholomeusz F.D.
      • Andrews J.M.
      Systematic review: Body composition in adults with inflammatory bowel disease.
      However, there are no guidelines on what components should be included in a comprehensive nutrition assessment for patients with Crohn’s disease.
      Accurate quantification of nutritional status in Crohn’s disease is essential to enable diet and nutrition therapy to be targeted to address specific deficits. However, in a study on nutrition assessment in patients with Crohn’s disease, body composition was measured in only 3%, handgrip strength in only 4%, and dietary micronutrient intake in 16% of patients, suggesting that current assessments are limited.
      • Lomer M.C.E.
      • Gourgey R.
      • Whelan K.
      Current practice in relation to nutritional assessment and dietary management of enteral nutrition in adults with Crohn's disease.
      This narrative review comprehensively appraised the existing evidence for nutrition assessment of patients with Crohn’s disease in comparison to a healthy population. It aims to provide a comprehensive guide with relevant measures applicable to clinical practice.

      Methods

      Search Strategy and Study Selection

      The population, intervention, comparison, outcomes, and type of study framework
      • Aslam S.
      • Emmanuel P.
      Formulating a researchable question: A critical step for facilitating good clinical research.
      was used to inform the criteria needed to answer the research question, What evidence exists on the nutritional status of patients with Crohn’s disease and how can this evidence inform nutrition assessment in clinical practice? The search strategy included studies of patients with Crohn’s disease aged 18 to 64 years using validated assessment methods available in clinical practice to establish nutritional status compared with a healthy age- and sex-matched control group (HC) sampled from the same population as those with Crohn’s disease. Studies that reported nutritional status outcomes, including body composition, muscle strength and function, micronutrient status, and/or dietary intake were included in the case that they were in the English language and primary research or systematic reviews.
      Limiting the search in this way allowed the literature review to establish a typical nutritional status in healthy people without Crohn’s disease and facilitated the comparative quantification of nutritional status in Crohn’s disease. Whilst anthropometric reference ranges for the healthy population have been developed, these vary depending on assessment methods used.
      • Kyle U.G.
      • Genton L.
      • Karsegard L.
      • Slosman D.O.
      • Pichard C.
      Single prediction equation for bioelectrical impedance analysis in adults aged 20-94 years.
      Recruiting a HC group ensured comparisons were made using identical methods to those used with patients with Crohn’s disease. Three databases were searched (Medline, Embase, and Scopus) on October 1, 2018. Multiple search terms were combined with the Boolean functions and and or to focus the search.
      • Harvard L.
      How to conduct an effective and valid literature search.
      The medical library subject heading terms or keywords included were [Crohn’s disease OR inflammatory bowel disease] AND [nutrition* assessment, body composition, body fat, fat mass, anthropometry, lean body weight, malnutrition, protein energy malnutrition, muscle strength, hand grip, grip strength, trace element, nutrition* status, nutrition* deficiency, vitamin deficiency, mineral deficiency, dietary intake, diet OR micronutrient]. Filters (English, human, and adults aged 18 to 64 years) were applied to target the search results.
      Following removal of duplicates, the titles, and where applicable abstracts, were screened for relevance. Abstracts of relevant titles were reviewed and in the case that an HC group was described the full text was examined against the inclusion and exclusion criteria.

      Data Extraction and Synthesis

      Eligible studies for data synthesis were critically appraised using the Critically Appraising Papers process in Hickson
      • Hickson M.
      Critically appraising papers.
      and the Assessing Methodological Quality question checklist in Greenhalgh
      • Greenhalgh T.
      Assessing methodological quality.
      to assess quality of individual studies. Data were summarized in a data extraction spreadsheet according to anthropometric, biochemical, and dietary assessment techniques (per the Nutrition Care Process structure
      Writing Group of the Nutrition Care Process/Standardized Language Committee
      Nutrition care process and model part I: The 2008 update.
      ). The Nutrition Care Process was developed by the Academy of Nutrition and Dietetics and is used by members of the dietetics profession to ensure systematic, evidence-based nutrition care.
      Writing Group of the Nutrition Care Process/Standardized Language Committee
      Nutrition care process and model part I: The 2008 update.
      Outcome data were only extracted when they were available and clinically relevant. Anthropometric outcomes included assessment of body composition using direct anthropometry, bioelectrical impedance analysis (BIA), dual energy x-ray absorptiometry (DEXA), computed tomography (CT) or magnetic resonance imaging (MRI), and muscle strength or function measurements. Biochemical outcomes included plasma or serum markers of nutritional status such as folic acid, vitamin B-12, vitamin C, vitamin D, zinc, copper, and selenium. Iron status and albumin were not collected because these are acute phase reactants and results are difficult to compare with an HC population. Dietary intake outcomes included macronutrient and micronutrient intake, food group intake, or exclusions of specific food groups. Where possible the anthropometric, biochemical, and dietary assessment methods and results were compared and critiqued across studies.

      Discussion

      To our knowledge, this is the first review appraising the evidence for methods of nutrition assessment in patients with Crohn’s disease relevant to clinical practice. There were 41 eligible papers (Figure 1), including 2,370 patients with Crohn’s disease and 4,450 HC. All studies were cross-sectional in design. The Crohn’s disease cohorts included patients with active disease and/or disease in remission. Most studies included men and women with the exception of two studies that reported body composition data of only men
      • Katznelson L.
      • Fairfield W.P.
      • Zeizafoun N.
      • et al.
      Effects of growth hormone secretion on body composition in patients with Crohn's disease.
      or only women.
      • Buning C.
      • Von Kraft C.
      • Hermsdorf M.
      • et al.
      Visceral adipose tissue in patients with Crohn's disease correlates with disease activity, inflammatory markers, and outcome.
      Nevertheless, compared with HC, there were significant differences in body composition and dietary intake as well as deficits in muscle strength and serum micronutrients. The findings follow the Nutrition Care Process (anthropometric, biochemical, and dietary assessment structure) and include recommendations for clinical practice (Figure 2).
      Figure thumbnail gr1
      Figure 1Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram for studies included in the narrative review on nutrition assessment in patients with Crohn’s disease.
      Figure thumbnail gr2a
      Figure 2Components of a comprehensive nutrition assessment tool for patients with Crohn’s disease. Components are based on evidence from studies included in the narrative review.
      • Norman K.
      • Stobaus N.
      • Gonzalez M.C.
      • Schulzke J.D.
      • Pirlich M.
      Hand grip strength: Outcome predictor and marker of nutritional status.
      British Assocation for Parenteral and Enteral Nutrition
      Malnutrition Universal Screening Tool (MUST).
      • Burden S.T.
      • Stoppard E.
      • Shaffer J.
      • Makin A.
      • Todd C.
      Can we use mid upper arm anthropometry to detect malnutrition in medical inpatients? A validation study.
      • Noori N.
      • Kopple J.D.
      • Kovesdy C.P.
      • et al.
      Mid-arm muscle circumference and quality of life and survival in maintenance hemodialysis patients.
      • Houtkooper L.B.
      • Lohman T.G.
      • Going S.B.
      • Howell W.H.
      Why bioelectrical impedance analysis should be used for estimating adiposity.
      • Kyle U.G.
      • Bosaeus I.
      • De Lorenzo A.D.
      • et al.
      Bioelectrical impedance analysis—part I: Review of principles and methods.
      • Kyle U.G.
      • Bosaeus I.
      • De Lorenzo A.D.
      • et al.
      Bioelectrical impedance analysis-part II: Uutilization in clinical practice.
      • Klidjian A.M.
      • Foster K.J.
      • Kammerling R.M.
      • Cooper A.
      • Karran S.J.
      Relation of anthropometric and dynamometric variables to serious postoperative complications.
      • Bishop C.W.
      • Bowen P.E.
      • Ritchey S.J.
      Norms for nutritional assessment of American adults by upper arm anthropometry.
      • Miazgowski T.
      • Kucharski R.
      • Soltysiak M.
      • Taszarek A.
      • Miazgowski B.
      • Widecka K.
      Visceral fat reference values derived from healthy European men and women aged 20-30 years using GE Healthcare dual-energy x-ray absorptiometry.
      • Welch A.
      Dietary assessment. In: Gandy J. Manual of Dietetic Practice.
      • Lof M.
      • Forsum E.
      Validation of energy intake by dietary recall against different methods to assess energy expenditure.
      • Johnson R.K.
      Dietary intake—how do we measure what people are really eating?.
      • Ma Y.S.
      • Olendzki B.C.
      • Pagoto S.L.
      • et al.
      Number of 24-hour diet recalls needed to estimate energy intake.
      • Smith A.F.
      Cognitive psychological issues of relevance to the validity of dietary reports.
      Figure thumbnail gr2b
      Figure 2Components of a comprehensive nutrition assessment tool for patients with Crohn’s disease. Components are based on evidence from studies included in the narrative review.
      • Norman K.
      • Stobaus N.
      • Gonzalez M.C.
      • Schulzke J.D.
      • Pirlich M.
      Hand grip strength: Outcome predictor and marker of nutritional status.
      British Assocation for Parenteral and Enteral Nutrition
      Malnutrition Universal Screening Tool (MUST).
      • Burden S.T.
      • Stoppard E.
      • Shaffer J.
      • Makin A.
      • Todd C.
      Can we use mid upper arm anthropometry to detect malnutrition in medical inpatients? A validation study.
      • Noori N.
      • Kopple J.D.
      • Kovesdy C.P.
      • et al.
      Mid-arm muscle circumference and quality of life and survival in maintenance hemodialysis patients.
      • Houtkooper L.B.
      • Lohman T.G.
      • Going S.B.
      • Howell W.H.
      Why bioelectrical impedance analysis should be used for estimating adiposity.
      • Kyle U.G.
      • Bosaeus I.
      • De Lorenzo A.D.
      • et al.
      Bioelectrical impedance analysis—part I: Review of principles and methods.
      • Kyle U.G.
      • Bosaeus I.
      • De Lorenzo A.D.
      • et al.
      Bioelectrical impedance analysis-part II: Uutilization in clinical practice.
      • Klidjian A.M.
      • Foster K.J.
      • Kammerling R.M.
      • Cooper A.
      • Karran S.J.
      Relation of anthropometric and dynamometric variables to serious postoperative complications.
      • Bishop C.W.
      • Bowen P.E.
      • Ritchey S.J.
      Norms for nutritional assessment of American adults by upper arm anthropometry.
      • Miazgowski T.
      • Kucharski R.
      • Soltysiak M.
      • Taszarek A.
      • Miazgowski B.
      • Widecka K.
      Visceral fat reference values derived from healthy European men and women aged 20-30 years using GE Healthcare dual-energy x-ray absorptiometry.
      • Welch A.
      Dietary assessment. In: Gandy J. Manual of Dietetic Practice.
      • Lof M.
      • Forsum E.
      Validation of energy intake by dietary recall against different methods to assess energy expenditure.
      • Johnson R.K.
      Dietary intake—how do we measure what people are really eating?.
      • Ma Y.S.
      • Olendzki B.C.
      • Pagoto S.L.
      • et al.
      Number of 24-hour diet recalls needed to estimate energy intake.
      • Smith A.F.
      Cognitive psychological issues of relevance to the validity of dietary reports.

      Anthropometric Outcomes

      Clinically relevant and commonly available anthropometric assessments methods were reviewed.

      BMI

      In the majority of studies (n=18), BMI was not significantly different between patients with Crohn’s disease and HC (Table 1),
      • Jahnsen J.
      • Falch J.A.
      • Mowinckel P.
      • Aadland E.
      Body composition in patients with inflammatory bowel disease: A population-based study.
      • Wiroth J.B.
      • Filippi J.
      • Schneider S.M.
      • et al.
      Muscle performance in patients with Crohn's disease in clinical remission.
      • Filippi J.
      • Al-Jaouni R.
      • Wiroth J.B.
      • Hebuterne X.
      • Schneider S.M.
      Nutritional deficiencies in patients with Crohn's disease in remission.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      • Katznelson L.
      • Fairfield W.P.
      • Zeizafoun N.
      • et al.
      Effects of growth hormone secretion on body composition in patients with Crohn's disease.
      • Duggan P.
      • O'Brien M.
      • Kiely M.
      • McCarthy J.
      • Shanahan F.
      • Cashman K.D.
      Vitamin K status in patients with Crohn's disease and relationship to bone turnover.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      • Geerling B.J.
      • Lichtenbelt W.D.
      • Stockbrugger R.W.
      • Brummer R.J.
      Gender specific alterations of body composition in patients with inflammatory bowel disease compared with controls.
      • Gilman J.
      • Shanahan F.
      • Cashman K.D.
      Altered levels of biochemical indices of bone turnover and bone-related vitamins in patients with Crohn's disease and ulcerative colitis.
      • Grunbaum A.
      • Holcroft C.
      • Heilpern D.
      • et al.
      Dynamics of vitamin D in patients with mild or inactive inflammatory bowel disease and their families.
      • Suibhne T.N.
      • Cox G.
      • Healy M.
      • O'Morain C.
      • O'Sullivan M.
      Vitamin D deficiency in Crohn's disease: Prevalence, risk factors and supplement use in an outpatient setting.
      • Tjellesen L.
      • Nielsen P.K.
      • Staun M.
      Body composition by dual-energy X-ray absorptiometry in patients with Crohn's disease.
      • Turk N.
      • Turk Z.
      Prevalent hypovitaminosis D in Crohn's disease correlates highly with mediators of osteoimmunology.
      • Van Langenberg D.R.
      • Della Gatta P.
      • Warmington S.A.
      • Kidgell D.J.
      • Gibson P.R.
      • Russell A.P.
      Objectively measured muscle fatigue in Crohn's disease: Correlation with self-reported fatigue and associated factors for clinical application.
      • van Langenberg D.R.
      • Della Gatta P.
      • Hill B.
      • Zacharewicz E.
      • Gibson P.R.
      • Russell A.P.
      Delving into disability in Crohn's disease: Dysregulation of molecular pathways may explain skeletal muscle loss in Crohn's disease.
      • Lomer M.C.E.
      • Kodjabashia K.
      • Hutchinson C.
      • Greenfield S.M.
      • Thompson R.P.H.
      • Powell J.J.
      Intake of dietary iron is low in patients with Crohn's disease: A case-control study.
      • Rizzi M.
      • Mazzulo S.
      • Fregnan S.
      • et al.
      Energy balance and muscle function in patients with Crohn's disease: relationship with nutritional state and disease activity.
      but in eight of these studies, significant differences in body composition were observed.
      • Jahnsen J.
      • Falch J.A.
      • Mowinckel P.
      • Aadland E.
      Body composition in patients with inflammatory bowel disease: A population-based study.
      • Filippi J.
      • Al-Jaouni R.
      • Wiroth J.B.
      • Hebuterne X.
      • Schneider S.M.
      Nutritional deficiencies in patients with Crohn's disease in remission.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      • Katznelson L.
      • Fairfield W.P.
      • Zeizafoun N.
      • et al.
      Effects of growth hormone secretion on body composition in patients with Crohn's disease.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      • Geerling B.J.
      • Lichtenbelt W.D.
      • Stockbrugger R.W.
      • Brummer R.J.
      Gender specific alterations of body composition in patients with inflammatory bowel disease compared with controls.
      • Tjellesen L.
      • Nielsen P.K.
      • Staun M.
      Body composition by dual-energy X-ray absorptiometry in patients with Crohn's disease.
      • Rizzi M.
      • Mazzulo S.
      • Fregnan S.
      • et al.
      Energy balance and muscle function in patients with Crohn's disease: relationship with nutritional state and disease activity.
      Where significant differences in BMI existed (n=12), it was always lower in patients with Crohn’s disease compared with HC.
      • Guerreiro C.S.
      • Cravo M.
      • Costa A.R.
      • et al.
      A comprehensive approach to evaluate nutritional status in Crohn's patients in the era of biologic therapy: A case-control study.
      • Mingrone G.
      • Benedetti G.
      • Capristo E.
      • et al.
      Twenty-four-hour energy balance in Crohn disease patients: metabolic implications of steroid treatment.
      • Molnar A.
      • Csontos A.A.
      • Kovacs I.
      • Anton A.D.
      • Palfi E.
      • Miheller P.
      Body composition assessment of Crohn's outpatients and comparison with gender- and age-specific multiple matched control pairs.
      • Schneider S.M.
      • Al-Jaouni R.
      • Filippi J.
      • et al.
      Sarcopenia is prevalent in patients with Crohn's disease in clinical remission.
      • Lu Z.L.
      • Wang T.R.
      • Qiao Y.Q.
      • et al.
      Handgrip strength index predicts nutritional status as a complement to body mass index in Crohn's disease.
      • Benjamin J.
      • Makharia G.
      • Ahuja V.
      • Joshi Y.K.
      Body composition in Indian patients with Crohn's disease during active and remission phase.
      • Capristo E.
      • Addolorato G.
      • Mingrone G.
      • Greco A.V.
      • Gasbarrini G.
      Effect of disease localization on the anthropometric and metabolic features of Crohn's disease.
      • Capristo E.
      • Mingrone G.
      • Addolorato G.
      • Greco A.V.
      • Gasbarrini G.
      Metabolic features of inflammatory bowel disease in a remission phase of the disease activity.
      • Cuoco L.
      • Vescovo G.
      • Castaman R.
      • et al.
      Skeletal muscle wastage in Crohn's disease: A pathway shared with heart failure?.
      • Joseph A.J.
      • George B.
      • Pulimood A.B.
      • Seshadri M.S.
      • Chacko A.
      25(OH) vitamin D level in Crohn's disease: Association with sun exposure & disease activity.
      • Kallel L.
      • Feki M.
      • Sekri W.
      • et al.
      Prevalence and risk factors of hyperhomocysteinemia in Tunisian patients with Crohn's disease.
      • Tajika M.
      • Matsuura A.
      • Nakamura T.
      • et al.
      Risk factors for vitamin D deficiency in patients with Crohn's disease.
      However, studies rarely assessed clinically significant differences in BMI, because BMI tended to be reported as a mean rather than as the proportion of patients who had a clinically underweight BMI (<18.5).
      Physical Status: The Use and Interpretation of Anthropometry
      Report of a WHO Expert Committee.
      Only one study assessed this, and the prevalence of underweight BMI was 21% in patients with Crohn’s disease and 2% to 4% in HC.
      • Lomer M.C.E.
      • Kodjabashia K.
      • Hutchinson C.
      • Greenfield S.M.
      • Thompson R.P.H.
      • Powell J.J.
      Intake of dietary iron is low in patients with Crohn's disease: A case-control study.
      Table 1Assessment of body composition in patients with Crohn’s disease (CD) compared with an age- and sex-matched healthy control group (HC)
      Author(s), year, countryParticipantsDisease activityTechniqueBMI
      BMI=body mass index.
      Fat Mass (kg)% Fat MassFat-Free Mass (kg)Visceral Adipose Tissue (cm2 or mL)
      CDHCCDHCCDHCCDHCCDHCCDHC
      nmean±standard deviation
      Only mean is provided where standard deviation was absent in the original reference.
      Capristo and colleagues,
      • Capristo E.
      • Addolorato G.
      • Mingrone G.
      • Greco A.V.
      • Gasbarrini G.
      Effect of disease localization on the anthropometric and metabolic features of Crohn's disease.
      1998, Italy
      4360RemissionBIA
      BIA=bioelectrical impedance analysis.
      21.5
      P<0.05 for CD vs HC.
      23.712.2
      P<0.05 for CD vs HC.
      17.020.4
      P<0.001 for CD vs HC.
      25.549.250.4
      Capristo and colleagues,
      • Capristo E.
      • Mingrone G.
      • Addolorato G.
      • Greco A.V.
      • Gasbarrini G.
      Metabolic features of inflammatory bowel disease in a remission phase of the disease activity.
      1998, Italy
      1820RemissionBIA20.5
      P<0.05 for CD vs HC.
      23.612.6
      P<0.05 for CD vs HC.
      17.422.0
      P<0.05 for CD vs HC.
      26.445.649.5
      Mingrone and colleagues,
      • Mingrone G.
      • Capristo E.
      • Greco A.V.
      • et al.
      Elevated diet-induced thermogenesis and lipid oxidation rate in Crohn disease.
      1999, Italy
      1812MixedBIA21.6±2.9
      P<0.05 for CD vs HC.
      23.8±1.813.8±5.6
      P<0.001 for CD vs HC.
      19.0±3.548.0±7.147.7±6.1
      Wiroth and colleagues,
      • Wiroth J.B.
      • Filippi J.
      • Schneider S.M.
      • et al.
      Muscle performance in patients with Crohn's disease in clinical remission.
      2005, France
      41

      17 M
      M=men.


      24 W
      W=women.
      25

      10 M

      15 W
      RemissionBIA22.1±3.5

      22.1±3.7
      24.0±2.4

      21.4±1.6
      13.0±5.1

      15.3±4.8
      16.4±5.4

      16.0±4.2
      18.3±6.0

      25.8±4.5
      21.7±5.6

      27.5±5.5
      56.2±6.4

      42.9±6.5
      58.0±4.5

      41.0±4.4
      Filippi and colleagues,
      • Filippi J.
      • Al-Jaouni R.
      • Wiroth J.B.
      • Hebuterne X.
      • Schneider S.M.
      Nutritional deficiencies in patients with Crohn's disease in remission.
      2006, France
      5425RemissionBIA22.122.114.4
      P<0.05 for CD vs HC.
      16.649.246.7
      Valentini and colleagues,
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      2008, Austria, Germany, and Italy
      94

      33 M

      61 W
      61

      20 M

      41 W
      RemissionBIA22.3

      22.1
      23.7

      21.8
      12.7

      18.1
      15.2

      16.6
      58.5
      P<0.001 for CD vs HC.


      43.9
      67.4

      44.1
      Benjamin and colleagues,
      • Benjamin J.
      • Makharia G.
      • Ahuja V.
      • Joshi Y.K.
      Body composition in Indian patients with Crohn's disease during active and remission phase.
      2011, India
      80100RemissionBIA21.6±5.0
      P<0.01 for CD vs HC.
      23.9±4.013.4±10.614.1±7.521.9±11.321.5±9.143.3±10.4
      P<0.01 for CD vs HC.
      48.9±7.4
      43Active18.8±3.6
      P<0.05 for CD vs HC.
      23.9±4.08.2±5.9
      P<0.05 for CD vs HC.
      14.1±7.515.7±9.3
      P<0.05 for CD vs HC.
      21.5±9.140.7±8.5
      P<0.05 for CD vs HC.
      48.9±7.4
      Rizzi and colleagues,
      • Rizzi M.
      • Mazzulo S.
      • Fregnan S.
      • et al.
      Energy balance and muscle function in patients with Crohn's disease: relationship with nutritional state and disease activity.
      2012, Italy
      78

      42 M

      36 W
      75

      41 M

      34 W
      MixedBIA22±2

      21±3
      22±1

      22±2
      12±6
      P<0.01 for CD vs HC.


      15±4
      P<0.05 for CD vs HC.
      22±4

      21±4
      53±4

      37±3
      49±7

      40±3
      Lu and colleagues,
      • Lu Z.L.
      • Wang T.R.
      • Qiao Y.Q.
      • et al.
      Handgrip strength index predicts nutritional status as a complement to body mass index in Crohn's disease.
      2016, China
      150

      109 M

      41 W
      256

      115 M

      139 W
      MixedBIA19.8±3.6
      P<0.001 for CD vs HC.


      19.1±3.2
      P<0.001 for CD vs HC.
      23.9±3.0

      22.1±2.9
      9.9±6.0
      P<0.001 for CD vs HC.


      12.7±5.0
      P<0.001 for CD vs HC.
      16.8±6.4

      17.2±5.5
      Katznelson and colleagues,
      • Katznelson L.
      • Fairfield W.P.
      • Zeizafoun N.
      • et al.
      Effects of growth hormone secretion on body composition in patients with Crohn's disease.
      2003, United States
      20 M20 MMixedBIA and CT
      CT=computed tomography.
      24.223.321.0
      P<0.05 for CD vs HC.
      17.7115±11
      P<0.001 for CD vs HC.
      69±7
      Buning and colleagues,
      • Buning C.
      • Von Kraft C.
      • Hermsdorf M.
      • et al.
      Visceral adipose tissue in patients with Crohn's disease correlates with disease activity, inflammatory markers, and outcome.
      2015, Germany
      31 W19 WMixedMRI
      MRI=magnetic resonance imaging.
      25.923.81,185±1,403
      P<0.05 for CD vs HC.
      941±988
      nmean±standard deviation
      Only mean is provided where standard deviation was absent in the original reference.
      Geerling and colleagues,
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      1998, The Netherlands
      32

      14 M

      18 W
      32

      14 M

      18 W
      RemissionDEXA
      DEXA=dual energy x-ray absorptiometry.
      23.2±3.7

      22.8±4.1

      23.4±3.5
      24.6±3.6

      26.4±3.5

      23.3±3.2
      17.6±7.9

      13.2±7.0

      20.9±7.1
      19.7±6.3

      18.4±5.0

      20.7±7.2
      26.1±9.4

      18.4±6.3
      P<0.05 for CD vs HC.


      32.1±6.5
      28.7±7.5

      23.5±5.3

      32.7±16.45
      48.6±9.3

      56.4±7.1

      42.6±5.5
      49.7±11.6

      60.5±8.9

      41.2±2.9
      Tjellesen and colleagues,
      • Tjellesen L.
      • Nielsen P.K.
      • Staun M.
      Body composition by dual-energy X-ray absorptiometry in patients with Crohn's disease.
      1998, Denmark
      31

      13 M

      18 W
      Weighted mean reported.
      88

      19 M

      69 W
      RemissionDEXA23.5

      21.1
      23.9

      22.0
      20.3

      21.6
      19.2

      21.3
      27.8
      P<0.05 for CD vs HC.


      38.8
      P<0.05 for CD vs HC.
      23.1

      32.8
      51.8
      P<0.05 for CD vs HC.


      34.9
      P<0.05 for CD vs HC.
      62.2

      42.4
      Geerling and colleagues,
      • Geerling B.J.
      • Lichtenbelt W.D.
      • Stockbrugger R.W.
      • Brummer R.J.
      Gender specific alterations of body composition in patients with inflammatory bowel disease compared with controls.
      1999, The Netherlands
      20
      Newly diagnosed.


      40
      Longstanding disease >5 years.
      20

      40
      Mixed

      Mixed
      DEXA22.7±2.5

      22.8±4.0
      23.0±2.8

      24.0±3.3
      19.4±6.3

      17.7±8.7
      19.5±7.0

      18.9±4.9
      28.3±8.3

      26.7±10.6
      29.2±8.6

      27.7±6.3
      49.2±9.9
      P<0.05 for CD vs HC.


      47.1±8.7
      P<0.05 for CD vs HC.
      46.8±8.9

      49.9±11.0
      Geerling and colleagues,
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      2000, The Netherlands
      2323MixedDEXA22.2±2.722.7±2.718.5±6.519.0±6.827.5±8.428.7±8.748.9±9.8
      P<0.05 for CD vs HC.
      46.9±8.9
      Jahnsen and colleagues,
      • Jahnsen J.
      • Falch J.A.
      • Mowinckel P.
      • Aadland E.
      Body composition in patients with inflammatory bowel disease: A population-based study.
      2003, Norway
      60

      24 M

      36 W
      60

      24 M

      36 W
      MixedDEXA23.3

      23.2
      P<0.05 for CD vs HC.


      23.4
      23.4

      24.8

      22.5
      20.8

      16.7

      23.5
      20.0

      18.1

      21.3
      31.4

      23.1

      37.0
      29.2

      22.6

      33.6
      44.5
      P<0.05 for CD vs HC.


      54.2
      P<0.001 for CD vs HC.


      38.0
      P<0.01 for CD vs HC.
      48.8

      61.0

      40.7
      Cuoco and colleagues,
      • Cuoco L.
      • Vescovo G.
      • Castaman R.
      • et al.
      Skeletal muscle wastage in Crohn's disease: A pathway shared with heart failure?.
      2008, Italy
      1320ActiveDEXA19.8±1.2
      P<0.01 for CD vs HC.
      23.4±1.121.1±1.419.6±2.435.8±4.1
      P<0.001 for CD vs HC.
      49.6±4.4
      Schneider and colleagues,
      • Schneider S.M.
      • Al-Jaouni R.
      • Filippi J.
      • et al.
      Sarcopenia is prevalent in patients with Crohn's disease in clinical remission.
      2008, France
      8250RemissionDEXA21.1±3.4
      P<0.05 for CD vs HC.
      22.2±2.516.2±8.916.1±4.925.7±10.025.9±7.743.8±9.446.7±10.1
      a BMI=body mass index.
      b Only mean is provided where standard deviation was absent in the original reference.
      c BIA=bioelectrical impedance analysis.
      d M=men.
      e W=women.
      f CT=computed tomography.
      g MRI=magnetic resonance imaging.
      h DEXA=dual energy x-ray absorptiometry.
      i Weighted mean reported.
      j Newly diagnosed.
      k Longstanding disease >5 years.
      P<0.05 for CD vs HC.
      ∗∗ P<0.01 for CD vs HC.
      ∗∗∗ P<0.001 for CD vs HC.

      DEXA

      Seven studies used DEXA to determine body composition (Table 1).
      • Jahnsen J.
      • Falch J.A.
      • Mowinckel P.
      • Aadland E.
      Body composition in patients with inflammatory bowel disease: A population-based study.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      • Geerling B.J.
      • Lichtenbelt W.D.
      • Stockbrugger R.W.
      • Brummer R.J.
      Gender specific alterations of body composition in patients with inflammatory bowel disease compared with controls.
      • Tjellesen L.
      • Nielsen P.K.
      • Staun M.
      Body composition by dual-energy X-ray absorptiometry in patients with Crohn's disease.
      • Schneider S.M.
      • Al-Jaouni R.
      • Filippi J.
      • et al.
      Sarcopenia is prevalent in patients with Crohn's disease in clinical remission.
      • Cuoco L.
      • Vescovo G.
      • Castaman R.
      • et al.
      Skeletal muscle wastage in Crohn's disease: A pathway shared with heart failure?.
      DEXA studies most frequently found no difference in fat mass (FM) between patients with Crohn’s disease and HC,
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      • Tjellesen L.
      • Nielsen P.K.
      • Staun M.
      Body composition by dual-energy X-ray absorptiometry in patients with Crohn's disease.
      • Schneider S.M.
      • Al-Jaouni R.
      • Filippi J.
      • et al.
      Sarcopenia is prevalent in patients with Crohn's disease in clinical remission.
      • Cuoco L.
      • Vescovo G.
      • Castaman R.
      • et al.
      Skeletal muscle wastage in Crohn's disease: A pathway shared with heart failure?.
      but a trend of fat-free mass (FFM) depletion in patients with Crohn’s disease.
      • Jahnsen J.
      • Falch J.A.
      • Mowinckel P.
      • Aadland E.
      Body composition in patients with inflammatory bowel disease: A population-based study.
      • Tjellesen L.
      • Nielsen P.K.
      • Staun M.
      Body composition by dual-energy X-ray absorptiometry in patients with Crohn's disease.
      • Cuoco L.
      • Vescovo G.
      • Castaman R.
      • et al.
      Skeletal muscle wastage in Crohn's disease: A pathway shared with heart failure?.
      Superior FFM was observed in patients with newly diagnosed Crohn’s disease compared with HC.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      The only study to include patients with longstanding Crohn’s disease (>5 years) found they had significantly lower FFM compared with HC.
      • Geerling B.J.
      • Lichtenbelt W.D.
      • Stockbrugger R.W.
      • Brummer R.J.
      Gender specific alterations of body composition in patients with inflammatory bowel disease compared with controls.
      These findings suggest that lean mass depletion in patients with Crohn’s disease occurs over time. One study recruited patients with active Crohn’s disease and showed that BMI was significantly lower in the active disease group as was FFM, and FM was nonsignificantly different when compared with HC.
      • Cuoco L.
      • Vescovo G.
      • Castaman R.
      • et al.
      Skeletal muscle wastage in Crohn's disease: A pathway shared with heart failure?.
      DEXA scans have ethical and practical limitations. Small amounts of radiation are absorbed by bone and tissue and increasing exposure to radiation is linked to an increased cancer risk.
      • Damilakis J.
      • Adams J.E.
      • Guglielmi G.
      • Link T.M.
      Radiation exposure in X-ray-based imaging techniques used in osteoporosis.
      In addition, whole-body DEXA scans are conducted by specialist radiographers,
      • Van Loan M.D.
      • Mayclin P.L.
      Body composition assessment: Dual-energy X-ray absorptiometry (DEXA) compared to reference methods.
      which presents a practical barrier for routine clinical use.

      BIA

      Eleven studies used BIA to determine body composition (Table 1).
      • Wiroth J.B.
      • Filippi J.
      • Schneider S.M.
      • et al.
      Muscle performance in patients with Crohn's disease in clinical remission.
      • Filippi J.
      • Al-Jaouni R.
      • Wiroth J.B.
      • Hebuterne X.
      • Schneider S.M.
      Nutritional deficiencies in patients with Crohn's disease in remission.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      • Katznelson L.
      • Fairfield W.P.
      • Zeizafoun N.
      • et al.
      Effects of growth hormone secretion on body composition in patients with Crohn's disease.
      • Rizzi M.
      • Mazzulo S.
      • Fregnan S.
      • et al.
      Energy balance and muscle function in patients with Crohn's disease: relationship with nutritional state and disease activity.
      • Mingrone G.
      • Benedetti G.
      • Capristo E.
      • et al.
      Twenty-four-hour energy balance in Crohn disease patients: metabolic implications of steroid treatment.
      • Molnar A.
      • Csontos A.A.
      • Kovacs I.
      • Anton A.D.
      • Palfi E.
      • Miheller P.
      Body composition assessment of Crohn's outpatients and comparison with gender- and age-specific multiple matched control pairs.
      • Lu Z.L.
      • Wang T.R.
      • Qiao Y.Q.
      • et al.
      Handgrip strength index predicts nutritional status as a complement to body mass index in Crohn's disease.
      • Benjamin J.
      • Makharia G.
      • Ahuja V.
      • Joshi Y.K.
      Body composition in Indian patients with Crohn's disease during active and remission phase.
      • Capristo E.
      • Addolorato G.
      • Mingrone G.
      • Greco A.V.
      • Gasbarrini G.
      Effect of disease localization on the anthropometric and metabolic features of Crohn's disease.
      • Capristo E.
      • Mingrone G.
      • Addolorato G.
      • Greco A.V.
      • Gasbarrini G.
      Metabolic features of inflammatory bowel disease in a remission phase of the disease activity.
      In contrast to DEXA, the majority of BIA studies observed a lower FM in patients with Crohn’s disease compared with HC
      • Filippi J.
      • Al-Jaouni R.
      • Wiroth J.B.
      • Hebuterne X.
      • Schneider S.M.
      Nutritional deficiencies in patients with Crohn's disease in remission.
      • Rizzi M.
      • Mazzulo S.
      • Fregnan S.
      • et al.
      Energy balance and muscle function in patients with Crohn's disease: relationship with nutritional state and disease activity.
      • Benjamin J.
      • Makharia G.
      • Ahuja V.
      • Joshi Y.K.
      Body composition in Indian patients with Crohn's disease during active and remission phase.
      • Capristo E.
      • Addolorato G.
      • Mingrone G.
      • Greco A.V.
      • Gasbarrini G.
      Effect of disease localization on the anthropometric and metabolic features of Crohn's disease.
      • Capristo E.
      • Mingrone G.
      • Addolorato G.
      • Greco A.V.
      • Gasbarrini G.
      Metabolic features of inflammatory bowel disease in a remission phase of the disease activity.
      • Mingrone G.
      • Capristo E.
      • Greco A.V.
      • et al.
      Elevated diet-induced thermogenesis and lipid oxidation rate in Crohn disease.
      but, as shown in Table 1, the results were not consistent.
      • Wiroth J.B.
      • Filippi J.
      • Schneider S.M.
      • et al.
      Muscle performance in patients with Crohn's disease in clinical remission.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      • Katznelson L.
      • Fairfield W.P.
      • Zeizafoun N.
      • et al.
      Effects of growth hormone secretion on body composition in patients with Crohn's disease.
      For FFM, there were no consistent differences between groups.
      A study from India in patients with active Crohn’s disease detected significant deficits in FM and FFM.
      • Benjamin J.
      • Makharia G.
      • Ahuja V.
      • Joshi Y.K.
      Body composition in Indian patients with Crohn's disease during active and remission phase.
      However, it lacks external validity to non-Indian populations because recent data demonstrate significant ethnic disparities in body composition, especially in South Asians.
      • Shah A.D.
      • Kandula N.R.
      • Lin F.
      • et al.
      Less favorable body composition and adipokines in South Asians compared with other US ethnic groups: Results from the MASALA and MESA studies.
      Another study in patients with active Crohn’s disease reported lower FM compared with HC.
      • Rizzi M.
      • Mazzulo S.
      • Fregnan S.
      • et al.
      Energy balance and muscle function in patients with Crohn's disease: relationship with nutritional state and disease activity.
      Thus, there are body composition deficits in patients with active Crohn’s disease, highlighting the importance of considering disease activity in the clinical assessment section of the Nutrition Care Process.

      CT and MRI

      Three studies used medical imaging techniques to further explore body composition.
      • Katznelson L.
      • Fairfield W.P.
      • Zeizafoun N.
      • et al.
      Effects of growth hormone secretion on body composition in patients with Crohn's disease.
      • Buning C.
      • Von Kraft C.
      • Hermsdorf M.
      • et al.
      Visceral adipose tissue in patients with Crohn's disease correlates with disease activity, inflammatory markers, and outcome.
      • van Langenberg D.R.
      • Della Gatta P.
      • Hill B.
      • Zacharewicz E.
      • Gibson P.R.
      • Russell A.P.
      Delving into disability in Crohn's disease: Dysregulation of molecular pathways may explain skeletal muscle loss in Crohn's disease.
      One study undertook umbilicus CT scanning to determine body fat distribution alongside BIA.
      • Katznelson L.
      • Fairfield W.P.
      • Zeizafoun N.
      • et al.
      Effects of growth hormone secretion on body composition in patients with Crohn's disease.
      The researchers found intra-abdominal fat was significantly higher in patients with Crohn’s disease vs HC. Furthermore, using MRI, visceral adipose tissue was significantly higher in patients with Crohn’s disease in remission compared with HC.
      • Buning C.
      • Von Kraft C.
      • Hermsdorf M.
      • et al.
      Visceral adipose tissue in patients with Crohn's disease correlates with disease activity, inflammatory markers, and outcome.
      In another study, CT scans were used to characterize muscle size.
      • van Langenberg D.R.
      • Della Gatta P.
      • Hill B.
      • Zacharewicz E.
      • Gibson P.R.
      • Russell A.P.
      Delving into disability in Crohn's disease: Dysregulation of molecular pathways may explain skeletal muscle loss in Crohn's disease.
      Quadricep muscle cross-sectional area was 14% lower in patients with Crohn’s disease compared with HC; however, this was not statistically significant.

      Muscle Strength and Function

      Eight studies assessed muscle strength and function.
      • Wiroth J.B.
      • Filippi J.
      • Schneider S.M.
      • et al.
      Muscle performance in patients with Crohn's disease in clinical remission.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      • Van Langenberg D.R.
      • Della Gatta P.
      • Warmington S.A.
      • Kidgell D.J.
      • Gibson P.R.
      • Russell A.P.
      Objectively measured muscle fatigue in Crohn's disease: Correlation with self-reported fatigue and associated factors for clinical application.
      • Rizzi M.
      • Mazzulo S.
      • Fregnan S.
      • et al.
      Energy balance and muscle function in patients with Crohn's disease: relationship with nutritional state and disease activity.
      • Lu Z.L.
      • Wang T.R.
      • Qiao Y.Q.
      • et al.
      Handgrip strength index predicts nutritional status as a complement to body mass index in Crohn's disease.
      • Salacinski A.J.
      • Regueiro M.D.
      • Broeder C.E.
      • McCrory J.L.
      Decreased neuromuscular function in Crohn's disease patients is not associated with low serum vitamin D levels.
      Limited studies have reported the potential effect of disease duration on muscle strength or function.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      • Van Langenberg D.R.
      • Della Gatta P.
      • Warmington S.A.
      • Kidgell D.J.
      • Gibson P.R.
      • Russell A.P.
      Objectively measured muscle fatigue in Crohn's disease: Correlation with self-reported fatigue and associated factors for clinical application.
      In patients with newly diagnosed Crohn’s disease, muscle strength is similar to HC,
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      whereas at least 5 years after diagnosis, the literature suggests a reduction in muscle strength and increased muscle fatigue in active disease or disease in remission.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Van Langenberg D.R.
      • Della Gatta P.
      • Warmington S.A.
      • Kidgell D.J.
      • Gibson P.R.
      • Russell A.P.
      Objectively measured muscle fatigue in Crohn's disease: Correlation with self-reported fatigue and associated factors for clinical application.
      • Salacinski A.J.
      • Regueiro M.D.
      • Broeder C.E.
      • McCrory J.L.
      Decreased neuromuscular function in Crohn's disease patients is not associated with low serum vitamin D levels.
      However, disease activity may influence muscle strength.
      • Rizzi M.
      • Mazzulo S.
      • Fregnan S.
      • et al.
      Energy balance and muscle function in patients with Crohn's disease: relationship with nutritional state and disease activity.
      • Lu Z.L.
      • Wang T.R.
      • Qiao Y.Q.
      • et al.
      Handgrip strength index predicts nutritional status as a complement to body mass index in Crohn's disease.
      There are no reports of change in muscle strength over time in patients with Crohn’s disease compared with HC. It is unknown whether reduced muscle strength during active disease is a temporary reduction in strength associated with a disease flare and if, or how quickly, muscle strength improves once the disease is in remission. One study found no difference in handgrip strength but reduced muscle endurance between patients with Crohn’s disease in remission for at least 3 months compared with HC.
      • Wiroth J.B.
      • Filippi J.
      • Schneider S.M.
      • et al.
      Muscle performance in patients with Crohn's disease in clinical remission.
      Longitudinal research on muscle strength during periods of active disease and disease remission would provide further understanding on the effects of acute and chronic inflammation on muscle strength and function. Muscle wasting and weakness results in fatigue and reduced quality of life,
      • Wiroth J.B.
      • Filippi J.
      • Schneider S.M.
      • et al.
      Muscle performance in patients with Crohn's disease in clinical remission.
      both of which are prevalent in people living with Crohn’s disease.
      • Grimstad T.
      • Norheim K.B.
      Fatigue in inflammatory bowel disease.
      • Huppertz-Hauss G.
      • Hoivik M.L.
      • Langholz E.
      • et al.
      Health-related quality of life in inflammatory bowel disease in a European-wide population-based cohort 10 years after diagnosis.

      Direct Anthropometry

      Five studies report the use of direct anthropometry in their methods
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Guerreiro C.S.
      • Cravo M.
      • Costa A.R.
      • et al.
      A comprehensive approach to evaluate nutritional status in Crohn's patients in the era of biologic therapy: A case-control study.
      • Capristo E.
      • Addolorato G.
      • Mingrone G.
      • Greco A.V.
      • Gasbarrini G.
      Effect of disease localization on the anthropometric and metabolic features of Crohn's disease.
      • Capristo E.
      • Mingrone G.
      • Addolorato G.
      • Greco A.V.
      • Gasbarrini G.
      Metabolic features of inflammatory bowel disease in a remission phase of the disease activity.
      ; however, three do not report their data.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      • Capristo E.
      • Addolorato G.
      • Mingrone G.
      • Greco A.V.
      • Gasbarrini G.
      Effect of disease localization on the anthropometric and metabolic features of Crohn's disease.
      • Capristo E.
      • Mingrone G.
      • Addolorato G.
      • Greco A.V.
      • Gasbarrini G.
      Metabolic features of inflammatory bowel disease in a remission phase of the disease activity.
      The authors cite strong correlations between their direct anthropometry results and BIA/DEXA as a justification for presenting only the results of the latter. However, critics may argue this preferential inclusion of BIA/DEXA results at the expense of omitting anthropometric data represents reporting bias.
      • Schulz K.F.
      • Altman D.G.
      • Moher D.
      CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials.
      Direct anthropometry is the most frequently used body composition assessment method in clinical practice because of its low cost and feasibility.
      • Lee S.Y.
      • Gallagher D.
      Assessment methods in human body composition.
      Therefore, there is a missed opportunity for these unreported anthropometric data to be available to clinicians.
      One study calculated body FM percentage using composite measures of skinfold thickness from the bicep, tricep, subscapular, and suprailiac.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      FM percentage and muscle mass did not differ significantly between patients with Crohn’s disease and HC. This finding that the body composition of Crohn’s disease patients is not inferior to HC is surprising; especially considering 47% of the group had active disease (Crohn's disease activity index [CDAI] >150). In another study, lower tricep skinfold thickness was reported in men with Crohn’s disease compared with HC men, whilst there was no difference between women, suggesting there may be sex differences.
      • Guerreiro C.S.
      • Cravo M.
      • Costa A.R.
      • et al.
      A comprehensive approach to evaluate nutritional status in Crohn's patients in the era of biologic therapy: A case-control study.

      Summary for Anthropometric Outcomes

      The majority of studies found no significant difference in BMI between Crohn’s disease and HC groups,
      • Jahnsen J.
      • Falch J.A.
      • Mowinckel P.
      • Aadland E.
      Body composition in patients with inflammatory bowel disease: A population-based study.
      • Wiroth J.B.
      • Filippi J.
      • Schneider S.M.
      • et al.
      Muscle performance in patients with Crohn's disease in clinical remission.
      • Filippi J.
      • Al-Jaouni R.
      • Wiroth J.B.
      • Hebuterne X.
      • Schneider S.M.
      Nutritional deficiencies in patients with Crohn's disease in remission.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      • Lomer M.C.E.
      • Gourgey R.
      • Whelan K.
      Current practice in relation to nutritional assessment and dietary management of enteral nutrition in adults with Crohn's disease.
      • Katznelson L.
      • Fairfield W.P.
      • Zeizafoun N.
      • et al.
      Effects of growth hormone secretion on body composition in patients with Crohn's disease.
      • Duggan P.
      • O'Brien M.
      • Kiely M.
      • McCarthy J.
      • Shanahan F.
      • Cashman K.D.
      Vitamin K status in patients with Crohn's disease and relationship to bone turnover.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      • Geerling B.J.
      • Lichtenbelt W.D.
      • Stockbrugger R.W.
      • Brummer R.J.
      Gender specific alterations of body composition in patients with inflammatory bowel disease compared with controls.
      • Gilman J.
      • Shanahan F.
      • Cashman K.D.
      Altered levels of biochemical indices of bone turnover and bone-related vitamins in patients with Crohn's disease and ulcerative colitis.
      • Grunbaum A.
      • Holcroft C.
      • Heilpern D.
      • et al.
      Dynamics of vitamin D in patients with mild or inactive inflammatory bowel disease and their families.
      • Suibhne T.N.
      • Cox G.
      • Healy M.
      • O'Morain C.
      • O'Sullivan M.
      Vitamin D deficiency in Crohn's disease: Prevalence, risk factors and supplement use in an outpatient setting.
      • Tjellesen L.
      • Nielsen P.K.
      • Staun M.
      Body composition by dual-energy X-ray absorptiometry in patients with Crohn's disease.
      • Van Langenberg D.R.
      • Della Gatta P.
      • Warmington S.A.
      • Kidgell D.J.
      • Gibson P.R.
      • Russell A.P.
      Objectively measured muscle fatigue in Crohn's disease: Correlation with self-reported fatigue and associated factors for clinical application.
      • van Langenberg D.R.
      • Della Gatta P.
      • Hill B.
      • Zacharewicz E.
      • Gibson P.R.
      • Russell A.P.
      Delving into disability in Crohn's disease: Dysregulation of molecular pathways may explain skeletal muscle loss in Crohn's disease.
      • Rizzi M.
      • Mazzulo S.
      • Fregnan S.
      • et al.
      Energy balance and muscle function in patients with Crohn's disease: relationship with nutritional state and disease activity.
      • Mingrone G.
      • Benedetti G.
      • Capristo E.
      • et al.
      Twenty-four-hour energy balance in Crohn disease patients: metabolic implications of steroid treatment.
      confirming that using BMI alone provide limited data for an optimal nutrition assessment. Only 14 studies examined FFM and FM, half of which suggest that FFM is decreased in Crohn’s disease
      • Jahnsen J.
      • Falch J.A.
      • Mowinckel P.
      • Aadland E.
      Body composition in patients with inflammatory bowel disease: A population-based study.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      • Geerling B.J.
      • Lichtenbelt W.D.
      • Stockbrugger R.W.
      • Brummer R.J.
      Gender specific alterations of body composition in patients with inflammatory bowel disease compared with controls.
      • Tjellesen L.
      • Nielsen P.K.
      • Staun M.
      Body composition by dual-energy X-ray absorptiometry in patients with Crohn's disease.
      • Benjamin J.
      • Makharia G.
      • Ahuja V.
      • Joshi Y.K.
      Body composition in Indian patients with Crohn's disease during active and remission phase.
      • Cuoco L.
      • Vescovo G.
      • Castaman R.
      • et al.
      Skeletal muscle wastage in Crohn's disease: A pathway shared with heart failure?.
      and two studies suggests that intra-abdominal FM is greater in Crohn’s disease than HC.
      • Katznelson L.
      • Fairfield W.P.
      • Zeizafoun N.
      • et al.
      Effects of growth hormone secretion on body composition in patients with Crohn's disease.
      • Buning C.
      • Von Kraft C.
      • Hermsdorf M.
      • et al.
      Visceral adipose tissue in patients with Crohn's disease correlates with disease activity, inflammatory markers, and outcome.
      A reduction in muscle endurance in Crohn’s disease, and reduced muscle strength during active or longstanding Crohn’s disease has been reported.
      • Wiroth J.B.
      • Filippi J.
      • Schneider S.M.
      • et al.
      Muscle performance in patients with Crohn's disease in clinical remission.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Van Langenberg D.R.
      • Della Gatta P.
      • Warmington S.A.
      • Kidgell D.J.
      • Gibson P.R.
      • Russell A.P.
      Objectively measured muscle fatigue in Crohn's disease: Correlation with self-reported fatigue and associated factors for clinical application.
      • Rizzi M.
      • Mazzulo S.
      • Fregnan S.
      • et al.
      Energy balance and muscle function in patients with Crohn's disease: relationship with nutritional state and disease activity.
      • Lu Z.L.
      • Wang T.R.
      • Qiao Y.Q.
      • et al.
      Handgrip strength index predicts nutritional status as a complement to body mass index in Crohn's disease.
      • Salacinski A.J.
      • Regueiro M.D.
      • Broeder C.E.
      • McCrory J.L.
      Decreased neuromuscular function in Crohn's disease patients is not associated with low serum vitamin D levels.
      BIA is a more feasible and less invasive measure of body composition than CT or DEXA scans.
      • Lee S.Y.
      • Gallagher D.
      Assessment methods in human body composition.
      However, the routine use of BIA in clinical practice may be time intensive and financially challenging; thus, mid-arm anthropometry and handgrip strength (HGS) are measures that can be readily and cheaply assimilated into clinical practice
      • Lee S.Y.
      • Gallagher D.
      Assessment methods in human body composition.
      (Figure 2). Because body composition fluctuates over the disease course, anthropometric assessments should be repeated to monitor change.

      Biochemical Outcomes

      Comprehensive plasma micronutrient studies are arguably lacking, with most articles only quantifying two or three micronutrients.
      • Kallel L.
      • Feki M.
      • Sekri W.
      • et al.
      Prevalence and risk factors of hyperhomocysteinemia in Tunisian patients with Crohn's disease.
      • Geerling B.J.
      • v Houwelingen A.C.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn's disease, compared with controls.
      • Gentschew L.
      • Bishop K.S.
      • Han D.Y.
      • et al.
      Selenium, selenoprotein genes and Crohn's disease in a case-control population from Auckland, New Zealand.
      • Hinks L.J.
      • Inwards K.D.
      • Lloyd B.
      • Clayton B.
      Reduced concentrations of selenium in mild Crohn's disease.
      • Ringstad J.
      • Kildebo S.
      • Thomassen Y.
      Serum selenium, copper, and zinc concentrations in Crohn's disease and ulcerative colitis.
      • Wendland B.E.
      • Aghdassi E.
      • Tam C.
      • et al.
      Lipid peroxidation and plasma antioxidant micronutrients in Crohn disease.
      • Yakut M.
      • Ustun Y.
      • Kabacam G.
      • Soykan I.
      Serum vitamin B12 and folate status in patients with inflammatory bowel diseases.
      Geerling and colleagues
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      are the only research group to measure an extensive range of micronutrients.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      A major limitation of the 18 micronutrient studies (Table 2 and Table 3)
      • Duggan P.
      • O'Brien M.
      • Kiely M.
      • McCarthy J.
      • Shanahan F.
      • Cashman K.D.
      Vitamin K status in patients with Crohn's disease and relationship to bone turnover.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      • Gilman J.
      • Shanahan F.
      • Cashman K.D.
      Altered levels of biochemical indices of bone turnover and bone-related vitamins in patients with Crohn's disease and ulcerative colitis.
      • Grunbaum A.
      • Holcroft C.
      • Heilpern D.
      • et al.
      Dynamics of vitamin D in patients with mild or inactive inflammatory bowel disease and their families.
      • Suibhne T.N.
      • Cox G.
      • Healy M.
      • O'Morain C.
      • O'Sullivan M.
      Vitamin D deficiency in Crohn's disease: Prevalence, risk factors and supplement use in an outpatient setting.
      • Joseph A.J.
      • George B.
      • Pulimood A.B.
      • Seshadri M.S.
      • Chacko A.
      25(OH) vitamin D level in Crohn's disease: Association with sun exposure & disease activity.
      • Kallel L.
      • Feki M.
      • Sekri W.
      • et al.
      Prevalence and risk factors of hyperhomocysteinemia in Tunisian patients with Crohn's disease.
      • Tajika M.
      • Matsuura A.
      • Nakamura T.
      • et al.
      Risk factors for vitamin D deficiency in patients with Crohn's disease.
      • Salacinski A.J.
      • Regueiro M.D.
      • Broeder C.E.
      • McCrory J.L.
      Decreased neuromuscular function in Crohn's disease patients is not associated with low serum vitamin D levels.
      • Geerling B.J.
      • v Houwelingen A.C.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn's disease, compared with controls.
      • Gentschew L.
      • Bishop K.S.
      • Han D.Y.
      • et al.
      Selenium, selenoprotein genes and Crohn's disease in a case-control population from Auckland, New Zealand.
      • Hinks L.J.
      • Inwards K.D.
      • Lloyd B.
      • Clayton B.
      Reduced concentrations of selenium in mild Crohn's disease.
      • Ringstad J.
      • Kildebo S.
      • Thomassen Y.
      Serum selenium, copper, and zinc concentrations in Crohn's disease and ulcerative colitis.
      • Wendland B.E.
      • Aghdassi E.
      • Tam C.
      • et al.
      Lipid peroxidation and plasma antioxidant micronutrients in Crohn disease.
      • Yakut M.
      • Ustun Y.
      • Kabacam G.
      • Soykan I.
      Serum vitamin B12 and folate status in patients with inflammatory bowel diseases.
      • Ardizzone S.
      • Bollani S.
      • Bettica P.
      • Bevilacqua M.
      • Molteni P.
      • Bianchi Porro G.
      Altered bone metabolism in inflammatory bowel disease: There is a difference between Crohn's disease and ulcerative colitis.
      • Dumitrescu G.
      • Mihai C.
      • Dranga M.
      • Prelipcean C.C.
      Serum 25-hydroxyvitamin D concentration and inflammatory bowel disease characteristics in Romania.
      • Tan B.
      • Li P.
      • Lv H.
      • et al.
      Vitamin D levels and bone metabolism in Chinese adult patients with inflammatory bowel disease.
      is that only two
      • Filippi J.
      • Al-Jaouni R.
      • Wiroth J.B.
      • Hebuterne X.
      • Schneider S.M.
      Nutritional deficiencies in patients with Crohn's disease in remission.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      report deficiency prevalence for micronutrients other than vitamin D. In clinical practice, patients are not treated for low micronutrient levels unless they are deficient,
      Joint Formulary Committee
      British National Formulary.
      thus it would be more clinically relevant to report the prevalence of micronutrient deficiency rather than mean micronutrient levels.
      Table 2Blood markers of nutritional status in patients with Crohn’s disease (CD) compared with an age- and sex-matched healthy control group (HC)
      Author(s), year, countryParticipantsDisease activityFolic Acid (nmol/L)Vitamin B-12 (pmol/L)Vitamin C (μmol/L)Zinc (μmol/L)Copper (μmol/L)Selenium (μmol/L)
      CDHCCDHCCDHCCDHCCDHCCDHCCDHC
      nmean±standard deviation
      Only mean is provided where standard deviation was absent in the original reference.
      Kallel and colleagues,
      • Kallel L.
      • Feki M.
      • Sekri W.
      • et al.
      Prevalence and risk factors of hyperhomocysteinemia in Tunisian patients with Crohn's disease.
      2011, Tunisia
      89103Mixed19.3±6.918.4±7.0218
      P<0.001 CD vs HC.
      ±118
      279±125
      Yakut and colleagues,
      • Yakut M.
      • Ustun Y.
      • Kabacam G.
      • Soykan I.
      Serum vitamin B12 and folate status in patients with inflammatory bowel diseases.
      2010, Turkey
      4553Mixed17.4±12.022.4±7.5207±122252±132
      Geerling and colleagues,
      • Geerling B.J.
      • v Houwelingen A.C.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn's disease, compared with controls.
      1999, The Netherlands
      20
      Newly diagnosed Crohn’s disease.


      32
      Diagnosed Crohn’s disease for more than 5 years.
      20

      32
      Remission

      Mixed
      12.4

      12.0
      P<0.05 CD vs HC.
      13.0

      13.1
      Geerling and colleagues,
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      2000, The Netherlands
      23
      Newly diagnosed Crohn’s disease.
      23Mixed10.7±9.112.4±5.6225
      P<0.05 CD vs HC.
      ±60.7
      270±88.247.6±17.754.5±22.912.3±3.012.9±1.323.6±8.922.2±7.40.92±0.160.99±0.16
      Geerling and colleagues,
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      1998, The Netherlands
      3232Remission14.4±13.413.4±5.88403±282263±91.535.3
      P<0.001 CD vs HC.
      ±25.8
      57.8±22.312.0
      P<0.01 CD vs HC.
      ±1.7
      13.4±2.219.1±4.620.1±6.90.86
      P<0.001 CD vs HC.
      ±0.14
      1.30±0.15
      Hinks and colleagues,
      • Hinks L.J.
      • Inwards K.D.
      • Lloyd B.
      • Clayton B.
      Reduced concentrations of selenium in mild Crohn's disease.
      1988, United Kingdom
      1122Active12.7±1.812.9±1.717.3±3.316.3±2.6
      Ringstad and colleagues,
      • Ringstad J.
      • Kildebo S.
      • Thomassen Y.
      Serum selenium, copper, and zinc concentrations in Crohn's disease and ulcerative colitis.
      1993, Norway
      47
      Newly diagnosed Crohn’s disease.


      27
      Men.


      20
      Women.
      123

      76
      Men.


      47
      Women.
      Not stated14.4

      13.5
      12.7

      12.9
      20.8
      P<0.001 CD vs HC.


      23.8
      P<0.01 CD vs HC.
      15.8

      18.1
      1.31
      P<0.001 CD vs HC.


      1.24
      P<0.01 CD vs HC.
      1.45

      1.37
      Gentschew and colleagues,
      • Gentschew L.
      • Bishop K.S.
      • Han D.Y.
      • et al.
      Selenium, selenoprotein genes and Crohn's disease in a case-control population from Auckland, New Zealand.
      2012, New Zealand
      351853Not stated1.37
      P<0.001 CD vs HC.
      ±0.01
      1.41±0.01
      Wendland and colleagues,
      • Wendland B.E.
      • Aghdassi E.
      • Tam C.
      • et al.
      Lipid peroxidation and plasma antioxidant micronutrients in Crohn disease.
      2001, Canada
      3737Mixed64.0
      P<0.01 CD vs HC.
      ±4.6
      78.4±2.90.81±0.040.80±0.04
      a Only mean is provided where standard deviation was absent in the original reference.
      b Newly diagnosed Crohn’s disease.
      c Diagnosed Crohn’s disease for more than 5 years.
      d Men.
      e Women.
      P<0.05 CD vs HC.
      ∗∗ P<0.01 CD vs HC.
      ∗∗∗ P<0.001 CD vs HC.
      Table 3Vitamin D concentration and prevalence of deficiency in patients with Crohn’s disease (CD) compared with an age- and sex-matched healthy control group (HC)
      Author(s), year, countryParticipantsDisease activityVitamin D (nmol/L
      To convert nmol/L vitamin D to ng/mL, multiply nmol/L by 0.4006. To convert ng/mL vitamin D to nmol/L, multiply ng/mL by 2.496. Vitamin D of 70 nmol/L=28.042 ng/mL.
      )
      Vitamin D 25(OH)D3 (ng/mL
      To convert nmol/L vitamin D to ng/mL, multiply nmol/L by 0.4006. To convert ng/mL vitamin D to nmol/L, multiply ng/mL by 2.496. Vitamin D of 70 nmol/L=28.042 ng/mL.
      )
      Suboptimal micronutrient levelSuboptimal criteria
      CDHCCDHCCDHCCDHC
      nmean±standard deviationn (%)
      Geerling and colleagues,
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      1998, The Netherlands
      3232Remission18
      P<0.01 for CD vs HC.
      (56.0)
      9 (28.0)<70 nmol/L
      To convert nmol/L vitamin D to ng/mL, multiply nmol/L by 0.4006. To convert ng/mL vitamin D to nmol/L, multiply ng/mL by 2.496. Vitamin D of 70 nmol/L=28.042 ng/mL.
      (summer and autumn) or < 25 nmol/L
      To convert nmol/L vitamin D to ng/mL, multiply nmol/L by 0.4006. To convert ng/mL vitamin D to nmol/L, multiply ng/mL by 2.496. Vitamin D of 70 nmol/L=28.042 ng/mL.
      (winter)
      Ardizzone and colleagues,
      • Ardizzone S.
      • Bollani S.
      • Bettica P.
      • Bevilacqua M.
      • Molteni P.
      • Bianchi Porro G.
      Altered bone metabolism in inflammatory bowel disease: There is a difference between Crohn's disease and ulcerative colitis.
      2000, Italy
      5130Mixed19.5±7.518.1±7.9
      Duggan and colleagues,
      • Duggan P.
      • O'Brien M.
      • Kiely M.
      • McCarthy J.
      • Shanahan F.
      • Cashman K.D.
      Vitamin K status in patients with Crohn's disease and relationship to bone turnover.
      2004, Ireland
      4444Remission75.0
      P<0.05 for CD vs HC.
      ±28.7
      105.3±55.53
      No statistical test reported comparing CD and HC.
      (6.8)
      2 (4.5)<40 nmol/L
      To convert nmol/L vitamin D to ng/mL, multiply nmol/L by 0.4006. To convert ng/mL vitamin D to nmol/L, multiply ng/mL by 2.496. Vitamin D of 70 nmol/L=28.042 ng/mL.
      Tajika and colleagues
      • Tajika M.
      • Matsuura A.
      • Nakamura T.
      • et al.
      Risk factors for vitamin D deficiency in patients with Crohn's disease.
      2004, Japan
      3315Mixed15.2±6.516.9±5.29 (27.3)1 (6.7)<10 ng/mL
      To convert nmol/L vitamin D to ng/mL, multiply nmol/L by 0.4006. To convert ng/mL vitamin D to nmol/L, multiply ng/mL by 2.496. Vitamin D of 70 nmol/L=28.042 ng/mL.
      Gilman and colleagues,
      • Gilman J.
      • Shanahan F.
      • Cashman K.D.
      Altered levels of biochemical indices of bone turnover and bone-related vitamins in patients with Crohn's disease and ulcerative colitis.
      2006, Ireland
      4747Remission71.6
      P<0.001 for CD vs HC.
      ±33.0
      113±69.29
      P<0.05 for CD vs HC.
      (19.1)
      2 (4.3)<40 nmol/L
      To convert nmol/L vitamin D to ng/mL, multiply nmol/L by 0.4006. To convert ng/mL vitamin D to nmol/L, multiply ng/mL by 2.496. Vitamin D of 70 nmol/L=28.042 ng/mL.
      Joseph and colleagues,
      • Joseph A.J.
      • George B.
      • Pulimood A.B.
      • Seshadri M.S.
      • Chacko A.
      25(OH) vitamin D level in Crohn's disease: Association with sun exposure & disease activity.
      2009, India
      3434Mixed16.3
      P<0.05 for CD vs HC.
      ±10.8
      22.8±11.927
      P<0.05 for CD vs HC.
      (79.0)
      17 (50.0)<20 ng/mL
      To convert nmol/L vitamin D to ng/mL, multiply nmol/L by 0.4006. To convert ng/mL vitamin D to nmol/L, multiply ng/mL by 2.496. Vitamin D of 70 nmol/L=28.042 ng/mL.
      Suibhne and colleagues,
      • Suibhne T.N.
      • Cox G.
      • Healy M.
      • O'Morain C.
      • O'Sullivan M.
      Vitamin D deficiency in Crohn's disease: Prevalence, risk factors and supplement use in an outpatient setting.
      2012, Ireland
      8170Mixed47.8±27.351.9±24.551 (63.0)36 (51.0)<50 nmol/L
      To convert nmol/L vitamin D to ng/mL, multiply nmol/L by 0.4006. To convert ng/mL vitamin D to nmol/L, multiply ng/mL by 2.496. Vitamin D of 70 nmol/L=28.042 ng/mL.
      Grunbaum and colleagues,
      • Grunbaum A.
      • Holcroft C.
      • Heilpern D.
      • et al.
      Dynamics of vitamin D in patients with mild or inactive inflammatory bowel disease and their families.
      2013, Canada
      3448Remission71.1±31.168.3±26.210
      No statistical test reported comparing CD and HC.
      (29.4)
      11 (22.9)<50 nmol/L
      To convert nmol/L vitamin D to ng/mL, multiply nmol/L by 0.4006. To convert ng/mL vitamin D to nmol/L, multiply ng/mL by 2.496. Vitamin D of 70 nmol/L=28.042 ng/mL.
      Salacinski and colleagues,
      • Salacinski A.J.
      • Regueiro M.D.
      • Broeder C.E.
      • McCrory J.L.
      Decreased neuromuscular function in Crohn's disease patients is not associated with low serum vitamin D levels.
      2013, United States
      1919Remission32.0±9.135.3±11.12
      No statistical test reported comparing CD and HC.
      (10.5)
      1 (5.3)<20 ng/mL
      To convert nmol/L vitamin D to ng/mL, multiply nmol/L by 0.4006. To convert ng/mL vitamin D to nmol/L, multiply ng/mL by 2.496. Vitamin D of 70 nmol/L=28.042 ng/mL.
      Dumitrescu and colleagues,
      • Dumitrescu G.
      • Mihai C.
      • Dranga M.
      • Prelipcean C.C.
      Serum 25-hydroxyvitamin D concentration and inflammatory bowel disease characteristics in Romania.
      2014, Romania
      1494Mixed23.0
      P<0.05 for CD vs HC.
      ±10.0
      31.0±13.05
      No statistical test reported comparing CD and HC.
      (36.0)
      19 (20.0)<20 ng/mL
      To convert nmol/L vitamin D to ng/mL, multiply nmol/L by 0.4006. To convert ng/mL vitamin D to nmol/L, multiply ng/mL by 2.496. Vitamin D of 70 nmol/L=28.042 ng/mL.
      Tan and colleagues,
      • Tan B.
      • Li P.
      • Lv H.
      • et al.
      Vitamin D levels and bone metabolism in Chinese adult patients with inflammatory bowel disease.
      2014, China
      107122Mixed11.6
      P<0.05 for CD vs HC.
      ±5.0
      12.9±4.4
      a To convert nmol/L vitamin D to ng/mL, multiply nmol/L by 0.4006. To convert ng/mL vitamin D to nmol/L, multiply ng/mL by 2.496. Vitamin D of 70 nmol/L=28.042 ng/mL.
      b No statistical test reported comparing CD and HC.
      P<0.05 for CD vs HC.
      ∗∗ P<0.01 for CD vs HC.
      ∗∗∗ P<0.001 for CD vs HC.
      Disease activity was reported in all but three of the studies.
      • Gentschew L.
      • Bishop K.S.
      • Han D.Y.
      • et al.
      Selenium, selenoprotein genes and Crohn's disease in a case-control population from Auckland, New Zealand.
      • Ringstad J.
      • Kildebo S.
      • Thomassen Y.
      Serum selenium, copper, and zinc concentrations in Crohn's disease and ulcerative colitis.
      • Wendland B.E.
      • Aghdassi E.
      • Tam C.
      • et al.
      Lipid peroxidation and plasma antioxidant micronutrients in Crohn disease.
      The remaining studies reported micronutrient concentrations in either patients with Crohn’s disease in remission
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • v Houwelingen A.C.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn's disease, compared with controls.
      or in a heterogeneous patient group.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      • Kallel L.
      • Feki M.
      • Sekri W.
      • et al.
      Prevalence and risk factors of hyperhomocysteinemia in Tunisian patients with Crohn's disease.
      • Geerling B.J.
      • v Houwelingen A.C.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn's disease, compared with controls.
      • Gentschew L.
      • Bishop K.S.
      • Han D.Y.
      • et al.
      Selenium, selenoprotein genes and Crohn's disease in a case-control population from Auckland, New Zealand.
      • Ringstad J.
      • Kildebo S.
      • Thomassen Y.
      Serum selenium, copper, and zinc concentrations in Crohn's disease and ulcerative colitis.
      • Wendland B.E.
      • Aghdassi E.
      • Tam C.
      • et al.
      Lipid peroxidation and plasma antioxidant micronutrients in Crohn disease.
      • Yakut M.
      • Ustun Y.
      • Kabacam G.
      • Soykan I.
      Serum vitamin B12 and folate status in patients with inflammatory bowel diseases.
      There were no studies comparing micronutrient differences between active and remission Crohn’s disease, although the validity of measuring micronutrients in active disease is questionable. In clinical practice, and in the included studies, micronutrients are quantified in the plasma fraction of blood. However, inflammatory responses in patients with active Crohn’s disease have been found to decrease plasma micronutrient concentrations by decreasing albumin, independent of their actual body stores.
      • Gerasimidis K.
      • Talwar D.
      • Duncan A.
      • et al.
      Impact of exclusive enteral nutrition on body composition and circulating micronutrients in plasma and erythrocytes of children with active Crohn's disease.
      Micronutrients on circulating erythrocytes provide a more accurate marker of micronutrient stores, particularly for zinc, copper, selenium, riboflavin and vitamin B-6, but this analysis is not available in routine clinical practice. Indeed, the transport protein for copper increases in the acute phase response, which may explain one study’s finding of significantly higher serum levels of copper in patients with Crohn’s disease compared with HC.
      • Ringstad J.
      • Kildebo S.
      • Thomassen Y.
      Serum selenium, copper, and zinc concentrations in Crohn's disease and ulcerative colitis.
      In summary, the majority of studies reported lower mean levels of circulating micronutrients in patients with Crohn’s disease compared with HC, including folic acid, vitamin B-12, vitamin C, vitamin D, zinc, and selenium.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      • Kallel L.
      • Feki M.
      • Sekri W.
      • et al.
      Prevalence and risk factors of hyperhomocysteinemia in Tunisian patients with Crohn's disease.
      • Geerling B.J.
      • v Houwelingen A.C.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn's disease, compared with controls.
      • Gentschew L.
      • Bishop K.S.
      • Han D.Y.
      • et al.
      Selenium, selenoprotein genes and Crohn's disease in a case-control population from Auckland, New Zealand.
      • Ringstad J.
      • Kildebo S.
      • Thomassen Y.
      Serum selenium, copper, and zinc concentrations in Crohn's disease and ulcerative colitis.
      • Wendland B.E.
      • Aghdassi E.
      • Tam C.
      • et al.
      Lipid peroxidation and plasma antioxidant micronutrients in Crohn disease.
      The majority of studies reported higher prevalence of vitamin D deficiency in patients with Crohn’s disease compared with HC.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Gilman J.
      • Shanahan F.
      • Cashman K.D.
      Altered levels of biochemical indices of bone turnover and bone-related vitamins in patients with Crohn's disease and ulcerative colitis.
      • Suibhne T.N.
      • Cox G.
      • Healy M.
      • O'Morain C.
      • O'Sullivan M.
      Vitamin D deficiency in Crohn's disease: Prevalence, risk factors and supplement use in an outpatient setting.
      • Joseph A.J.
      • George B.
      • Pulimood A.B.
      • Seshadri M.S.
      • Chacko A.
      25(OH) vitamin D level in Crohn's disease: Association with sun exposure & disease activity.
      • Tajika M.
      • Matsuura A.
      • Nakamura T.
      • et al.
      Risk factors for vitamin D deficiency in patients with Crohn's disease.
      • Dumitrescu G.
      • Mihai C.
      • Dranga M.
      • Prelipcean C.C.
      Serum 25-hydroxyvitamin D concentration and inflammatory bowel disease characteristics in Romania.
      Whilst the review findings do not support the routine measurement of vitamin B-6 and thiamine in all Crohn’s disease patients, consideration must be given to their jejunal absorption site. For patients with small bowel disease or previous resection, it is common practice to measure micronutrients absorbed at the jejunum every 3 to 6 months.
      • Maaser C.
      • Sturm A.
      • Vavricka S.R.
      • et al.
      ECCO-ESGAR guideline for diagnostic assessment in IBD part 1: Initial diagnosis, monitoring of known IBD, detection of complications.
      See Figure 2 for key micronutrients that should be measured in Crohn’s disease in clinical practice, and their accuracy in reflecting body stores during the acute phase response.

      Dietary Assessment Outcomes

      Eleven studies assessed dietary intake and the main findings are summarized in Table 4.
      • Filippi J.
      • Al-Jaouni R.
      • Wiroth J.B.
      • Hebuterne X.
      • Schneider S.M.
      Nutritional deficiencies in patients with Crohn's disease in remission.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      • Katznelson L.
      • Fairfield W.P.
      • Zeizafoun N.
      • et al.
      Effects of growth hormone secretion on body composition in patients with Crohn's disease.
      • Duggan P.
      • O'Brien M.
      • Kiely M.
      • McCarthy J.
      • Shanahan F.
      • Cashman K.D.
      Vitamin K status in patients with Crohn's disease and relationship to bone turnover.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      • Lomer M.C.E.
      • Kodjabashia K.
      • Hutchinson C.
      • Greenfield S.M.
      • Thompson R.P.H.
      • Powell J.J.
      Intake of dietary iron is low in patients with Crohn's disease: A case-control study.
      • Guerreiro C.S.
      • Cravo M.
      • Costa A.R.
      • et al.
      A comprehensive approach to evaluate nutritional status in Crohn's patients in the era of biologic therapy: A case-control study.
      • Benjamin J.
      • Makharia G.
      • Ahuja V.
      • Joshi Y.K.
      Body composition in Indian patients with Crohn's disease during active and remission phase.
      • Capristo E.
      • Addolorato G.
      • Mingrone G.
      • Greco A.V.
      • Gasbarrini G.
      Effect of disease localization on the anthropometric and metabolic features of Crohn's disease.
      • Geerling B.J.
      • v Houwelingen A.C.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn's disease, compared with controls.
      Energy intake was similar between patients with Crohn’s disease and HC in eight studies
      • Filippi J.
      • Al-Jaouni R.
      • Wiroth J.B.
      • Hebuterne X.
      • Schneider S.M.
      Nutritional deficiencies in patients with Crohn's disease in remission.
      • Valentini L.
      • Schaper L.
      • Buning C.
      • et al.
      Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.
      • Lomer M.C.E.
      • Gourgey R.
      • Whelan K.
      Current practice in relation to nutritional assessment and dietary management of enteral nutrition in adults with Crohn's disease.
      • Katznelson L.
      • Fairfield W.P.
      • Zeizafoun N.
      • et al.
      Effects of growth hormone secretion on body composition in patients with Crohn's disease.
      • Duggan P.
      • O'Brien M.
      • Kiely M.
      • McCarthy J.
      • Shanahan F.
      • Cashman K.D.
      Vitamin K status in patients with Crohn's disease and relationship to bone turnover.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      • Geerling B.J.
      • v Houwelingen A.C.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn's disease, compared with controls.
      and lower in the other three studies,
      • Guerreiro C.S.
      • Cravo M.
      • Costa A.R.
      • et al.
      A comprehensive approach to evaluate nutritional status in Crohn's patients in the era of biologic therapy: A case-control study.
      • Benjamin J.
      • Makharia G.
      • Ahuja V.
      • Joshi Y.K.
      Body composition in Indian patients with Crohn's disease during active and remission phase.
      • Capristo E.
      • Addolorato G.
      • Mingrone G.
      • Greco A.V.
      • Gasbarrini G.
      Effect of disease localization on the anthropometric and metabolic features of Crohn's disease.
      especially in patients with a lower BMI.
      • Guerreiro C.S.
      • Cravo M.
      • Costa A.R.
      • et al.
      A comprehensive approach to evaluate nutritional status in Crohn's patients in the era of biologic therapy: A case-control study.
      • Benjamin J.
      • Makharia G.
      • Ahuja V.
      • Joshi Y.K.
      Body composition in Indian patients with Crohn's disease during active and remission phase.
      Although nine studies
      • Filippi J.
      • Al-Jaouni R.
      • Wiroth J.B.
      • Hebuterne X.
      • Schneider S.M.
      Nutritional deficiencies in patients with Crohn's disease in remission.
      • Katznelson L.
      • Fairfield W.P.
      • Zeizafoun N.
      • et al.
      Effects of growth hormone secretion on body composition in patients with Crohn's disease.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.
      • Lomer M.C.E.
      • Kodjabashia K.
      • Hutchinson C.
      • Greenfield S.M.
      • Thompson R.P.H.
      • Powell J.J.
      Intake of dietary iron is low in patients with Crohn's disease: A case-control study.
      • Guerreiro C.S.
      • Cravo M.
      • Costa A.R.
      • et al.
      A comprehensive approach to evaluate nutritional status in Crohn's patients in the era of biologic therapy: A case-control study.
      • Benjamin J.
      • Makharia G.
      • Ahuja V.
      • Joshi Y.K.
      Body composition in Indian patients with Crohn's disease during active and remission phase.
      • Capristo E.
      • Addolorato G.
      • Mingrone G.
      • Greco A.V.
      • Gasbarrini G.
      Effect of disease localization on the anthropometric and metabolic features of Crohn's disease.
      • Geerling B.J.
      • v Houwelingen A.C.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn's disease, compared with controls.
      measured protein intake, seven of these found no significant differences in intakes between groups (Table 4).
      • Filippi J.
      • Al-Jaouni R.
      • Wiroth J.B.
      • Hebuterne X.
      • Schneider S.M.
      Nutritional deficiencies in patients with Crohn's disease in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission.
      • Geerling B.J.
      • Badart-Smook A.
      • Stockbrugger R.W.
      • Brummer R.J.
      Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls.