Central Journal of Human Nutrition & Food Science

Cite this article: Penagini F, Dilillo D, Zuin G, Brunetti D, Zuccotti GV (2015) Dietary Intakes in Children and Adolescents with Inflammatory Bowel Disease: A Case-Control Study. J Hum Nutr Food Sci 3(2): 1061.

*Corresponding authorFrancesca Penagini, Ospedale dei Bambini V. Buzzi, University of Milan, via Castelvetro 32, Milan, Italy, Tel: 39-02-57995349; Fax: 39-02-50319801; E-mail:

Submitted: 12 November 2014

Accepted: 23 March 2015

Published: 26 March 2015

ISSN: 2333-6706

Copyright© 2015 Penagini et al.

OPEN ACCESS

Short Communication

Dietary Intakes in Children and Adolescents with Inflammatory Bowel Disease: A Case-Control StudyFrancesca Penagini*, Dario Dilillo, Giovanna Zuin, Domenica Brunetti and Gian Vincenzo ZuccottiDepartment of Pediatrics, University of Milan, Italy

ABBREVIATIONSIBD: Inflammatory Bowel Disease; CD: Crohn’s Disease; UC:

Ulcerative Colitis; HCs: Healthy Controls; PUFAs: Polyunsaturated Fatty Acids; RDI: Recommended Dietary Intakes; LARN: Livelli di Assunzione di Riferimento di Nutrienti ed Energia per la Popolazione Italiana; EER: Estimated Energy Requirements; RI: Refernce Intake; ROS: Reactive Oxygen Species; DSS: Dextran Sulphate Sodium.

INTRODUCTIONNutrition is involved in many aspects of inflammatory bowel

disease (IBD), from disease pathogenesis, diagnosis and treatment to prognosis. Several epidemiological studies conducted in IBD subjects in adults have focused on diet and IBD risk, identifying

specific nutrients that are likely to play a role as risk factors or protective factors for the development of disease [1,2]. Shoda et al. examined the correlation between the incidence of Crohn’s disease (CD) and dietary change over a period of time of 19 years in Japan. The analysis showed that the increased incidence of CD was strongly correlated with increased dietary intake of animal fat (r =0.880), polyunsaturated fatty acids (PUFAs) Omega 6 (r =0.883), animal protein (r =0.908) and the ratio of PUFA Omega6/Omega3 fatty acid intake (r =0.792) [3]. Tjonneland et al. conducted a large multicenter prospective cohort study in Europe to assess the association between diet and risk of developing Ulcerative Colitis (UC). The study found a correlation between high intake of PUFAs Omega 6 and the development of UC [4]. On the contrary, a high dietary intake of PUFAs Omega 3 has been identified as a protective factor for the development

Abstract

Background: Nutrition is involved in many aspects of inflammatory bowel disease (IBD), including pathogenesis. Adult IBD studies have identified animal protein and Omega 6 lipids as risk factors for Crohn’s Disease (CD) and Omega 3 lipids as protective factors for Ulcerative Colitis (UC). Data in paediatric IBD is scanty.

Objectives: To compare pre-illness dietary intakes of paediatric IBD patients with those of healthy controls, to identify nutrients which could be potentially involved in disease pathogenesis?

Methods: Pre-illness dietary intakes were investigated in 25 subjects aged 6-17 years with newly diagnosed IBD and dietary intakes were assessed in 25 healthy controls (HCs) matched for age and gender, by means of a dietary recall performed by a skilled dietician. Calculation of average nutrient intakes was done with the software MètaDieta. Between group (IBD vs HCs) and within IBD group (CD vs UC) comparison of nutrient intakes was performed.

Results: Energy, protein and iron intakes were higher in IBD vs HC group (p =0,017, p=0, 0001 and p=0, 0286). The ratio of Animal /Vegetable protein and Omega 6 /Omega 3 lipid intakes were higher in IBD vs HC group (p=0, 0225 and p=0, 0523). Intake of vitamin E was lower in IBD vs HC group, with values close to statistical significance (p=0, 0752).

Conclusions. High intakes of animal protein, Omega 6 lipids and iron are likely to be involved in pathogenesis of paediatric IBD. High vitamin E intake could be protective for development of IBD in consideration of the antioxidant properties of this vitamin.

Keywords•Inflammatoryboweldisease•Diet•Etiology•Children•Adolescents

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of Ulcerative Colitis (UC) [5]. Data in paediatric age is lacking, only few studies have been performed. Amre et al. examined the impact of diet on new onset of CD in children aged < 20 years using a food-frequency questionnaire (FFQ) and comparing the intakes with a group of healthy controls. The study found that imbalances of fatty acids, vegetables and fruits were associated with an increased risk for CD among Canadian children [6]. D’Souza et al. identified specific dietary patterns associated with higher or lower risk for CD in children. For example a dietary pattern characterized by high intake of vegetables, fruit, olive oil, fish, grains and nuts was negatively associated with development of CD in children [7]. The above mentioned paediatric studies have not included children with UC. The objective of our study was to compare pre-illness dietary intakes of paediatric IBD patients, including both CD and UC cases, with those of a healthy control group in order to identify nutrients which could be potentially involved in disease pathogenesis as risk or protective factors.

MATERIALS AND METHODSA case-control study was prospectively carried out. Twenty-

five children and adolescents aged 6-17 years with newly diagnosed IBD (Crohn’s Disease n=13, Ulcerative colitis n=10, Undetermined Colitis n=2) were enrolled from January 2014 to July 2014 in our Paediatric Inflammatory Bowel Disease Clinic. Over the same period of time 25 healthy controls (HCs) matched for age and gender were also enrolled. Pre-illness dietary consumption, at least 12 months prior to symptom onset, was assessed in IBD patients within one month from diagnosis; HCs underwent the same dietary assessment with regards to everyday nutritional intake. Data on dietary consumption was collected by a skilled dietician, through a 7-day dietary recall and by means of a computer programme, Software MètaDieta (Me.Te. Da. S.r.l San Benedetto del Tronto, Italy), which permitted an interactive dietary recall with images representative of food portions for every meal. The same Software also elaborated the data collected analyzing the macro- and micronutrient composition of the diet. The average macro and micronutrient intakes were compared between IBD and HCs groups, as a percentage of the current Italian recommended dietary intakes (RDI- Livelli di Assunzione di Riferimento di Nutrienti ed Energia per la Popolazione Italiana- LARN 2012) [8]. In IBD group comparison of dietary intakes was done between CD and UC subjects. Statistical analysis was carried out with Excel programme SPSS version 21. Values of p <0.05 were considered statistically significant. The study was approved by our Institution’s ethics committee.

RESULTS AND DISCUSSIONDemographic characteristics and anthropometric parameters

of IBD and HC subjects are illustrated in Table 1. Analysis of dietary intakes showed a higher daily energy intake (% of estimated energy requirements (EER)) in IBD vs HC group (p =0,017). With regards to macronutrient intakes, protein intake (g/kg/day % of population reference intake, PRI) was significantly higher in IBD vs HC group (p=0, 0001), lipid intake (kcal % of reference intake range for macronutrients, RI) was significantly higher in HC vs IBD group (p= 0, 0417), no between group difference was observed for carbohydrate intakes. Also fibre intake was similar in both IBD and HC groups. Animal/Vegetable protein ratio and Omega 6 /Omega 3 lipid ratio were significantly higher in IBD vs HC group (p=0, 0225 and p=0, 0523 respectively). For micronutrient analysis, no between group differences were observed in terms of vitamin and mineral intakes except for iron and vitamin E. Iron intake (mg/day % PRI) was significantly higher in IBD vs HC group (p=0, 0286). Intake of vitamin E (mg/day % of adequate intake, AI) was lower in IBD vs HC group, with values close to statistical significance (p=0, 0752). Results of macro- and micronutrient intakes are illustrated in Table 1 and in Figures 1 and 2. No significant differences were found for macro- and micronutrient intakes between CD and UC groups.

Our results show that also in paediatric IBD some nutrients are likely implicated in pathogenesis of disease. We have found that a high intake of animal protein and PUFA Omega 6 lipids are likely risk factors and PUFA Omega 3 lipids protective factors for development of IBD, confirming adult data [3-5]. Recently, de Silva et al. have demonstrated a positive association between arachidonic acid (AA) intake and the development of UC in adults with large effect sizes in a dose dependent manner [9]. Furthermore, the same study showed that oleic acid (OA)

Figure 1 Macro and micronutrient intakes in IBD and HC groups. EER: Estimated Energy Requirements; PRI: population reference intake; RI: Reference Intake range for macronutrients; AI: Adequate intake; CHO: carbohydrates; Ca: Calcium; Fe: Iron. * p=0.017, **p=0,0001, ***p=0,0286, δ p=0,0417, δδ p=0,0752.

Figure 2 Animal protein/Vegetable protein ratio and Omega 6/Omega 3 ratio intakes in IBD and HC groups. * p= 0,0225, ** p=0,0523.

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IBD, n=25mean + SD

HC, n=25mean + SD

Pvalue

Energykcal/day% EER

2702,32 + 1113,83113,02 + 36,96

2119,96 + 631,3083,82 + 23,63

0,0275*

0,0170*

Proteing/kg/dayg/kg/day - % PRIanimal/vegetable

2,45 + 0,87257,80 + 91,112,42 + 0,91

1,55 + 0,66164,54 + 66,231,86 + 0,74

0,0001*

0,0001*

0,0225*

Lipidsg/daykcal % RISaturated % tot kcal Monounsaturated % tot kcalPolyunsaturated % tot kcal Omega 6/Omega 3Cholesterol mg/day

92,87 + 38,88111,73 + 19,4711,73 + 2,6711,12 + 4,184,20 + 1,636,12 + 1,63293,61 + 131,78

81,34 + 28,34121,87 + 14,4512,15 + 2,6516,72 + 7,765,14 + 7,105,15 + 1,81240,70 + 122,99

0,2366 0,0417*

0,57350,0026*

0,5214 0,0523*

0,1488Carbohydrates g/day% RISoluble glucides g/day% to kcal Glycaemic index

341,51 + 150,1594,74 + 12,57

114,36 + 52,7217,95 + 3,9355,12 + 7,70

268,14 + 86,6190,76 + 8,93

94,13 + 33,7018,35 + 5,8758,35 + 5,07

0,0395*

0,2024

0,11250,77780,0862

Fibreg/day Soluble g/dayInsoluble g/day

25,39 + 13,323,46 + 2,089,33 + 7,43

19,92 + 7,113,12 + 1,498,61 + 4,76

0,07640,50550,6868

MineralsCalciummg/day% PRIIron mg/day% PRIMagnesiummg/day% PRIZincmg/day% PRI

867,40 + 375,1168,74 + 28,73

12,54 + 5,3787,79 + 43,26 227,25 + 209,9195,43 + 86,95

11,63 + 4,79125,57 + 45,46

779,51 + 285,3259,96 + 21,95

9,36 + 3,6964,68 + 27,41152,75 + 51,8163,97 + 35,69

10,14 + 3,51113,71 + 42,57

0,35580,2310

0,0181*

0,0286*

0,09130,1007

0,18330,3456

VitaminsVitamin D μg/day % PRIVitamin Emg/day% AIVitamin B6mg/day% PRIVitamin B12μg/day % PRIFolic acidμg/day % PRI

2,07 + 1,2013,82 + 8,00

8,95 + 3,29 87,94 + 37,19 2,00 + 0,85175,27 +78,83

4,34 + 2,33234,12 + 141,44319,82 + 168,5594,75 + 47,78

2,16 + 2,1314,37 + 14,22

10,69 + 2,77 108,64 + 43,081,93 + 0,88 176,88 + 94,10

4,24 + 1,74209,83 + 87,85297,26 + 154,0189,88 + 45,69

0,80030,8659

0,0488*

0,0752*

0,76050,9480

0,86170,46880,62350,7137

Table 1: Daily average macro- and micronutrient intakes in IBD and HCs. Statistically significant values are marked with*. EER: estimated energy requirements, PRI: Population Reference Intake according to LARN 2012 (Livelli di assunzione di riferimento per energia e nutrient per la popolazione taliana) [8]; RI: Reference Intake range for macronutrients according to LARN 2012; AI: Adequate Intake according to LARN 2012.

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IBD, n=25mean + SD

HC, n=25mean + SD

PValue

Energykcal/day% EER

2702,32 + 1113,83113,02 + 36,96

2119,96 + 631,3083,82 + 23,63

0,0275*

0,0170*

Proteing/kg/dayg/kg/day - % PRIanimal/vegetable

2,45 + 0,87257,80 + 91,112,42 + 0,91

1,55 + 0,66164,54 + 66,231,86 + 0,74

0,0001*

0,0001*

0,0225*

Lipidsg/daykcal % RISaturated % tot kcal Monounsaturated % tot kcalPolynunsaturated % tot kcal Omega 6/Omega 3Cholesterol mg/day

92,87 + 38,88111,73 + 19,4711,73 + 2,6711,12 + 4,184,20 + 1,636,12 + 1,63293,61 + 131,78

81,34 + 28,34121,87 + 14,4512,15 + 2,6516,72 + 7,765,14 + 7,105,15 + 1,81240,70 + 122,99

0,23660,0417*

0,57350,0026*

0,52140,0523*

0,1488Carbohydrates g/day% RISoluble glucides g/day% to kcal Glycaemic index

341,51 + 150,1594,74 + 12,57

114,36 + 52,7217,95 + 3,9355,12 + 7,70

268,14 + 86,6190,76 + 8,93

94,13 + 33,7018,35 + 5,8758,35 + 5,07

0,0395*

0,2024

0,11250,77780,0862

Fibreg/day Soluble g/dayInsoluble g/day

25,39 + 13,323,46 + 2,089,33 + 7,43

19,92 + 7,113,12 + 1,498,61 + 4,76

0,07640,50550,6868

Table 2: Daily average energy, macronutrient and fibre intakes in IBD and HCs. Statistically significant values are marked with *

Abbreviations: EER: Estimated Energy Requirementsl; PRI: Population Reference Intake According to LARN 2012 (Livelli Di Assunzione Di Riferimento Per Energia E Nutrient Per La Popolazione Taliana [8]; RI: Reference Intake range for macronutrients according to LARN 2012; AI: Adequate Intake according to LARN 2012.

Micronutrients IBD, n=25 mean + SD HC, n=25 mean + SD P valueMineralsCalciummg/day% PRIIron mg/day% PRIMagnesiummg/day% PRIZincmg/day% PRI

867,40 + 375,1168,74 + 28,73

12,54 + 5,3787,79 + 43,26 227,25 + 209,9195,43 + 86,95

11,63 + 4,79125,57 + 45,46

779,51 + 285,3259,96 + 21,95

9,36 + 3,6964,68 + 27,41152,75 + 51,8163,97 + 35,69

10,14 + 3,51113,71 + 42,57

0,35580,2310

0,0181*

0,0286*

0,09130,1007

0,18330,3456

VitaminsVitamin D μg/day % PRIVitamin Emg/day% AIVitamin B6mg/day% PRIVitamin B12μg/day % PRIFolic acidμg/day % PRI

2,07 + 1,2013,82 + 8,00

8,95 + 3,29 87,94 + 37,19 2,00 + 0,85175,27 +78,83

4,34 + 2,33234,12 + 141,44319,82 + 168,5594,75 + 47,78

2,16 + 2,1314,37 + 14,22

10,69 + 2,77 108,64 + 43,081,93 + 0,88 176,88 + 94,10

4,24 + 1,74209,83 + 87,85297,26 + 154,0189,88 + 45,69

0,80030,8659

0,0488*

0,0752*

0,76050,9480

0,86170,46880,62350,7137

Table 3: Daily average micronutrient intakes in IBD and HCs. Statistically significant values are marked with *.

Abbreviations: PRI: Population Reference Intake according to LARN 2012 (Livelli di assunzione di riferimento per energia e nutrient per la popolazione taliana) [8]; AI: Adequate Intake according to LARN 2012.

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was inversely associated with development of UC. A possible physiopathologic explanation for the role of these fatty acids in etiology of UC could be ascribed to the fact that AA, an n-6 PUFA, is a precursor of the pro inflammatory cytokines prostaglandin E2 and leukotriene B4 and its metabolism is competitively inhibited by OA. Furthermore, eicosanoids, a family of PUFA derived lipids mediators have been found to be significantly elevated in inflamed colonic mucosa biopsies in mild to moderate colitis [10]. In children, a very interesting observation has recently been described by Costea et al. These Authors have identified variants of genes that control PUFA metabolism (CYP4F3, FADS1 and FADS2) which seem to confer increased susceptibility to CD in children with increased dietary ratio of Omega6/Omega3 lipids [11].

Besides results on lipid intake, we have also found new and promising results regarding specific micronutrients: iron and vitamin E. In first instance, we observed significantly higher iron intakes in IBD compared to HCs, suggesting a potential role as risk factor for developing gastrointestinal disease. A possible biologic explanation could be ascribed to iron’s capacity of inducing free-radical mediated peroxidative reactions that produce reactive oxygen species (ROS) that can significantly damage cell lipid proteins and nucleic acids. Studies in animal models with experimentally induced colitis have shown higher scores of colonic inflammation in mice supplemented with oral iron compared to those not supplemented [12,13]. Reifen et al. conducted a study in a rat model with iodoacetamide induced colitis. Microscopic changes and significantly more severe colitis were seen in colonic biopsies in rats who received iron supplementation compared to those who didn’t. The study concluded that iron could amplify the inflammatory response and enhance the mucosal damage in a rat model of colitis [12]. Similarly, Carrier et al. demonstrated that oral iron supplementation enhanced the activity in dextran sulphate sodium-induced (DSS) colitis as demonstrated by higher histological scores, heavier rectal bleeding and further shortening of the colon. These parameters were associated with increased oxidative stress as demonstrated by increased lipid peroxidation and decreased antioxidant vitamins [13]. With regards to vitamin E results, the between group comparison showed a higher intake for HCs compared to IBD subjects. This data suggests a potential protective role of this vitamin for development of IBD in our population. A possible biologic explanation could be attributable to vitamin E’s antioxidant properties and its capacity of protecting cells from free radical damage. There is evidence in literature from studies conducted in mice with experimentally induced colitis showing that vitamin E supplementation ameliorates colonic inflammation [14,15]. A valuable study conducted by Hiratsuka et al. experimented high dose subcutaneous bolus injections of vitamin E in a model of DSS induced acute severe ulcerative colitis in mice. Disease activity index score, histological score and pro-inflammatory serum interleukin (IL)-6 were lower in the mice who received vitamin E compared to those who didn’t, suggesting a therapeutic role of this vitamin for acute severe UC [15].

CONCLUSIONOur results confirm data described for adult IBD on

the association between PUFAs Omega 6 and Omega 3 and

development of IBD. Our data on micronutrients, particularly on iron and vitamin E are new and promising and open new perspectives in the field of prevention and treatment of paediatric IBD. High intake of iron seems to play a role as risk factor whilst vitamin E intake may play a role as protective factor for development of IBD in children. In addition, ours is the first study to assess the role of diet in etiology of IBD in both CD and UC paediatric patients. Further clinical studies, possibly also interventional trials, are needed to confirm these data. Identification of dietetic interventions which could be protective or curative for intestinal inflammation is a valuable finding particularly in paediatric age, where steroid sparing agents are crucial to promote regular growth and puberty.

REFERENCES 1. Cashman KD, Shanahan F. Is nutrition an aetiological factor for

inflammatory bowel disease? Eur J Gastroenterol Hepatol. 2003; 15: 607-613.

2. K Amre D, G Seidman E. Etiopathogenesis of pediatric Crohn’s disease. Biologic pathways based on interactions between genetic and environmental factors. Med Hypotheses. 2003; 60: 344-350.

3. Shoda R, Matsueda K, Yamato S, Umeda N. Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am J Clin Nutr. 1996; 63: 741-745.

4. IBD in EPIC Study Investigators, Tjonneland A, Overvad K, Bergmann MM, Nagel G, Linseisen J, Hallmans G, et al. Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case–control study within a European prospective cohort study. Gut. 2009; 58: 1606–1611.

5. John S, Luben R, Shrestha SS, Welch A, Khaw KT, Hart AR. Dietary n-3 polyunsaturated fatty acids and the aetiology of ulcerative colitis: a UK prospective cohort study. Eur J Gastroenterol Hepatol. 2010; 22: 602-606.

6. Amre DK, D’Souza S, Morgan K, Seidman G, Lambrette P, Grimard G, et al. Imbalances in dietary consumption of fatty acids, vegetables, and fruits are associated with risk for Crohn’s disease in children. Am J Gastroenterol. 2007; 102: 2016-2025.

7. D’Souza S, Levy E, Mack D, Israel D, Lambrette P, Ghadirian P, et al. Dietary patterns and risk for Crohn’s disease in children. Inflamm Bowel Dis. 2008; 14: 367-373.

8. LARN. Livelli di Assunzione di Riferimento di nutrienti ed energia per la popolazione italiana. Documento di sintesi per il XXXV Congresso Nazionale SINU, Bologna 2012.

9. de Silva PS, Luben R, Shrestha SS, Khaw KT, Hart AR. Dietary arachidonic and oleic acid intake in ulcerative colitis etiology: a prospective cohort study using 7-day food diaries. Eur J Gastroenterol Hepatol. 2014; 26: 11-18.

10. Masoodi M, Pearl DS, Eiden M, Shute JK, Brown JF, Calder PC, et al. Altered colonic mucosal Polyunsaturated Fatty Acid (PUFA) derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology. PLoS One. 2013; 8: 76532.

11. Costea I, Mack DR, Lemaitre RN, Israel D, Marcil V, Ahmad A, et al. Interactions between the dietary polyunsaturated fatty acid ratio and genetic factors determine susceptibility to pediatric Crohn’s disease. Gastroenterology. 2014; 146: 929-931.

12. Reifen R, Matas Z, Zeidel L, Berkovitch Z, Bujanover Y. Iron supplementation may aggravate inflammatory status of colitis in a rat model. Dig Dis Sci. 2000; 45: 394-397.

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Penagini F, Dilillo D, Zuin G, Brunetti D, Zuccotti GV (2015) Dietary Intakes in Children and Adolescents with Inflammatory Bowel Disease: A Case-Control Study. J Hum Nutr Food Sci 3(2): 1061.

Cite this article

13. Carrier J, Aghdassi E, Platt I, Cullen J, Allard JP. Effect of oral iron supplementation on oxidative stress and colonic inflammation in rats with induced colitis. Aliment Pharmacol Ther. 2001; 15: 1989-1999.

14. Carrier J, Aghdassi E, Cullen J, Allard JP. Iron supplementation increases disease activity and vitamin E ameliorates the effect in rats with dextran sulfate sodium-induced colitis. J Nutr. 2002; 132: 3146-3150.

15. Hiratsuka T, Inomata M, Hagiwara S, Kono Y, Shiraishi N, Noguchi T, et al. Bolus injection of newly synthesized vitamin E derivative ETS-GS for the treatment of acute severe ulcerative colitis in a mouse model. New vitamin E derivative for acute severe UC. Int J Colorectal Dis. 2013; 28: 305-311.