**Gluten-Free Diet in Children: An Approach to a Nutritionally Adequate and Balanced Diet**

**Francesca Penagini \*, Dario Dilillo, Fabio Meneghin, Chiara Mameli, Valentina Fabiano and Gian Vincenzo Zuccotti** 

Department of Pediatrics, University of Milan, Luigi Sacco Hospital, Milan 20157, Italy; E-Mails: dilillo.dario@hsacco.it (D.D.); meneghin.fabio@hsacco.it (F.M.); mameli.chiara@hsacco.it (C.M.); fabiano.valentina@hsacco.it (V.F.); gianvincenzo.zuccotti@unimi.it (G.V.Z.)

**\*** Author to whom correspondence should be addressed; E-Mail: frapenagini@tiscali.it; Tel.: +0039-0239-042-268; Fax: +0039-0239-042-254.

*Received: 25 October 2013; in revised form: 4 November 2013 / Accepted: 7 November 2013 / Published: 18 November 2013* 

**Abstract:** Gluten-free diet (GFD) is the cornerstone treatment for celiac disease (CD). GFD implies a strict and lifelong elimination from the diet of gluten, the storage protein found in wheat, barley, rye and hybrids of these grains, such as kamut and triticale. The absence of gluten in natural and processed foods, despite being the key aspect of GFD, may lead to nutritional consequences, such as deficits and imbalances. The nutritional adequacy of GFD is particularly important in children, this the age being of maximal energy and nutrient requirements for growth, development and activity. In recent years, attention has focused on the nutritional quality of gluten-free products (GFPs) available in the market. It is well recognized that GFPs are considered of lower quality and poorer nutritional value compared to the gluten-containing counterparts. The present review focuses on the nutritional adequacy of GFD at the pediatric age, with the aim being to increase awareness of the potential complications associated with this diet, to identify strategies in order to avoid them and to promote a healthier diet and lifestyle in children with CD.

**Keywords:** celiac disease; gluten-free diet; children; nutritional complications; balanced diet

#### **1. Introduction**

Celiac disease (CD) is a chronic systemic autoimmune disorder caused by a permanent intolerance to gluten proteins in genetically susceptible individuals. Gluten is a general term used to describe a mixture of storage proteins, including prolamins, hordeins and secalins found in wheat, barley and rye, respectively. These proteins may exert a toxic effect on intestinal mucosa in genetically susceptible individuals by triggering an immune-mediated response, responsible for the typical villous atrophy and lymphocyte infiltrate in small intestine mucosa seen in CD. In fact, these proteins contain epitopes that undergo deamidation, an important process for the binding of the CD associated human leukocyte antigen (HLA) DQ2/DQ8 haplotypes with T-lymphocytes, activating an autoimmune response [1–3].

A lifelong strict gluten-free diet (GFD) is the only available treatment for CD. Adherence to GFD leads to regression of symptoms, normalization of histological and laboratory findings and reduces the risk of CD associated complications [4]. Within the range of gluten-free foods, a distinction must be made between those that are naturally gluten-free and those that are made gluten-free through a process of purification. There are several foods that are naturally gluten-free, such as rice, corn, potatoes and a number of different grains, seeds and legumes. Historically, rice, corn and potatoes have been the first natural substitutes for gluten-containing grains. Today, a number of different grains, including pseudo-cereals, offer increased variety, improved palatability to GFD and are a good source of carbohydrates, protein, dietary fiber, vitamins and polyunsaturated fatty acids [5,6]. The commercially available gluten-free (GF) products are processed foods purified of gluten. The elimination of this storage protein inevitably alters the macro- and micro-nutrient composition, thus the nutritional value. First, wheat is not only a major source of protein, but also of iron, folates and B vitamins (thiamin, riboflavin and niacin); in fact, GF products are often low in these nutrients, as opposed to their gluten containing equivalents [7–9]. The various gluten-free and gluten containing foods are listed in Table 1.


**Table 1.** Gluten-free and gluten containing cereals and other foods.


**Table 1.** *Cont.*

\* Controversial; see paragraph on oats.

#### *1.1. Macronutrients*

Studies show that gluten-free products (GFPs) often have a greater carbohydrate and lipid content than their gluten containing equivalents [10–13]. Segura *et al.* analyzed the nutritional composition of a range of GF breads and found that these are starchy-based foods with a high glycemic index (estimated between 83.3 and 96.1 *vs.* 71 for white wheat flour bread), with low protein and high fat content [9]. With regards to lipid content and composition, Caponio *et al.* showed that commercially available GF biscuits are richer in saturated fatty acids compared to the gluten containing equivalents [13]. All these characteristics have a negative effect on health, and this should be seriously taken into account, because the limited choice of food products in the diet of children with CD induces a high consumption of packaged GFPs, such as snacks and biscuits.

#### *1.2. Micronutrients and Minerals*

It has been shown that some commercially available GFPs have a lower content of folates, iron and B vitamins or are not consistently enriched/fortified compared to their gluten containing counterparts [7–9]. Thompson [7,8] conducted two studies on US commercially available GFPs. The author analyzed the folate, iron and B vitamins (thiamin, riboflavin and niacin) composition of these products and compared them with the composition of their gluten containing counterparts, finding that GFPs were significantly lower in folates, iron and B vitamins.

#### *1.3. Dietary Fiber*

Some studies have reported that GFD is associated with a lower intake of dietary fiber than a standard gluten containing diet [14,15]. A study conducted in the USA on adults showed that the diet of CD patients on GFD was low in fiber intake [15]. This phenomenon is likely to be related to the composition of many GF foods made with starches and/or refined flours with low content in fiber. In fact, during the refining process, the outer layer of grain containing most of the fiber is removed, leaving only the starchy inner layer.

#### **2. Nutritional Imbalances in Children with Celiac Disease Following a GFD**

Studies conducted in adults and children show that approximately 20%–38% of patients with CD have nutritional complications, such as calorie/protein imbalance, dietary fiber, mineral and vitamin deficiencies [16–19]. These complications may be encountered both at diagnosis and during follow-up, whilst on GFD [9,18]. At diagnosis, the deficiencies are often secondary to nutrient malabsorption due to mucosal damage. Studies show that the more pronounced the villous atrophy, the greater the nutritional deficiencies, with lower levels of iron, copper, folate, vitamin B-12 and zinc [19]. For CD patients on GFD, the nutritional complications are likely to be caused by the poor nutritional quality of the GFPs mentioned above and by the incorrect alimentary choices of CD patients. The most common nutritional deficiencies encountered in adults with CD, at diagnosis and during GFD, are described in Table 2.


**Table 2.** Common nutrient deficiencies in adults with celiac disease (CD) at diagnosis and after Gluten-free diet (GFD). *Modified from Cynthia Kupper* [20].

Numerous studies focus their attention specifically on the nutrient intakes of CD children and adolescents on GFD. Mariani *et al.* [21] studied the nutritional habits of 47 adolescents (aged 10–20 years) affected by CD, by means of a three-day alimentary diary. A comparison with the Italian and American recommended daily allowance (RDAs) was done for the intakes of macronutrients, fiber, iron and calcium. The results showed that CD subjects followed a high-protein and high-lipid diet with low intakes of carbohydrates, iron, calcium and fiber compared to the recommended daily intakes. Furthermore, Hopman *et al.* [22] studied the nutrient intake of 37 adolescents with CD (aged 13–16 years) following a strict GFD and compared the intakes with a control group in the same age category. In the CD group, the intake of saturated fat was significantly higher than recommended by both the American and Dutch RDAs; the intake of fiber and iron was significantly lower than recommended. Furthermore, the comparison between the two groups showed that the intake of fiber and iron was lower in the CD group compared to controls (*p <* 0.05). Öhlund *et al.* [23] conducted a study in 2010 on 30 children aged 4–17 years with CD and on GFD, using a five-day food record. High intakes of saturated fat and sucrose and low intakes of dietary fiber, vitamin D and magnesium compared to recommendations (New Nordic Nutrition Recommendations, 2004) was observed.

An elegantly conducted study by Zuccotti *et al.* compared the dietary intake of CD children on GFD to a group of healthy children (healthy controls, HC) and evaluated the contribution of commercially available GFPs on the observed nutritional intake [24]. The study showed that the daily intake of vitamin D was significantly lower in the CD compared to the HC group (vitamin D 

½¾*vs.* 3.1 μg + 2.8, *p <* 0.01). With regards to macronutrients, the intake of simple sugars, fats and protein exceeded the national recommendations for health in both the CD and HC groups. The total daily energy intake was significantly higher in the CD group compared to HCs (8961.8 KJ day- *vs.* 5761.0 KJ day-1; *p <* 0.001). In the CD group, the carbohydrate-derived energy was higher, while the lipid-derived energy was lower, compared to the HC group. Protein-derived energy did not differ between the two groups. In the CD group, the contribution of commercially available GFPs on daily energy intake was studied. The main finding was that these products provided 36.3% of the total daily energy intake (3253.1 KJ day out of 8961.8 KJ day-) in these patients. Analyzing the contribution of the macronutrients derived from GFPs on the total daily energy intake, it was observed that protein derived from GFPs accounted for 7.3% of the total energy derived from protein, representing 18% of total daily energy intake. With regards to lipids, GFPs contributed a median of 12.9 g day of the median total daily fat intake of 73.0 g, which is equivalent to 17.7% of energy from fat. Furthermore, Mariani *et al.* [21] conducted a nutritional analysis of children with CD. The author found that children complying with a strict GFD had significantly greater nutritional imbalance in their diet than did children cheating on their GFD. More troubling, the incidence of children who were overweight or obese was more frequent (72%) in the strict GFD group compared with the children not following a strict GFD (51%) and healthy age-matched controls (47%). A study conducted by Ferrara *et al.* [25] compared the caloric intake and fat consumption of 50 children with CD following a GFD with 50 healthy children. A significant increase in fat consumption was observed in children with CD compared to healthy children (72.5 + 37.2 g *vs.* 52.9 + 35.4 g per 100 g of food, *p <* 0.008). Furthermore, a significant difference in fat intake was observed between the two groups (10.21 + 3.15 g per 100 g of food in CD group *vs.* 7.46 + 2.91 g/100 g in control group, *p =* 0.004).

#### **3. Effects of Gluten-Free Diet on Anthropometric Parameters**

The scientific literature on anthropometric parameters in children with CD on GFD provide contrasting data. On the one hand, there is evidence that good compliance with GFD is associated with a positive effect on anthropometric parameters, including: the reduction of fat and the recovery of lean body mass [26], normalization of body mass index (BMI) in both previously underweight and overweight subjects [27] and acceleration of linear growth [28]. A study conducted in children with CD and obesity at diagnosis showed a significant reduction in BMI after 12 months of GFD [29]. Another study conducted by Brambilla *et al.* found a lower frequency of being overweight and of obesity in children with CD, both at diagnosis and during GFD, compared to healthy controls [30]. Even though the frequency of being overweight and of obesity in the CD group increased on GFD, it remained lower than observed in the general population.

On the other hand, there are also studies that suggest that GFD may have a negative effect on body composition and anthropometric parameters in subjects with CD [31]. Mariani *et al.* [21] first reported the high prevalence of being overweight and of obesity in CD adolescents on GFD; the authors found that more than 50% of CD adolescents were overweight during GFD. However, in the latter paper, the authors used a relative body weight >110%, rather than BMI, to define being overweight, probably leading to an overestimation of being overweight. Furthermore, a study conducted by Valletta *et al.* showed that the frequency of being overweight in children with CD was nearly doubled after one year of GFD [32]. Potential explanations for the undesirable weight gain and obesity observed in these studies are possible overfeeding as the intestinal mucosa heals, consumption of less complex carbohydrates and fiber and more sugars, proteins and saturated fats in GFD. The conflicting data may in part be caused by differences in the timing of anthropometric assessment. Many children with CD, after introduction of GFD, may initially gain excessive weight and only thereafter start to show catch-up growth and normalization of weight. Even though the effect of GFD on body weight and BMI remains a controversial issue, it remains fundamental for pediatricians to be aware of the possible nutritional consequences of GFD for which early recognition can be crucial in the prevention of obesity-related complications.
