Review

A Review on the Gluten-Free Diet: Technological and

Nutritional Challenges
Dalia El Khoury 1,*, Skye Balfour-Ducharme 1 and Iris J. Joye 2
1 Department of Family Relations & Applied Nutrition, University of Guelph, 50 Stone Road East, Guelph, ON
N1G 2W1, Canada; balfourd@uoguelph.ca
2 Department of Food Science, University of Guelph, 50 Stone Road East, Guelph, ON N1G 2W1, Canada;

ijoye@uoguelph.ca
* Correspondence: delkhour@uoguelph.ca

Received: 9 August 2018; Accepted: 25 September 2018; Published: 2 October 2018

Abstract: Consumers, food manufacturers and health professionals are uniquely influenced by the
growing popularity of the gluten-free diet. Consumer expectations have urged the food industry to
continuously adjust and improve the formulations and processing techniques used in gluten-free product
manufacturing. Health experts have been interested in the nutritional adequacy of the diet, as well as its
effectiveness in managing gluten-related disorders and other conditions. In this review, we aim to provide
a clear picture of the current motivations behind the use of gluten-free diets, as well as the technological
and nutritional challenges of the diet as a whole. Alternative starches and flours, hydrocolloids, and fiber
sources were found to play a complex role in mimicking the functional and sensory effects of gluten in
gluten-free products. However, the quality of gluten-free alternatives is often still inferior to the gluten-
containing products. Furthermore, the gluten-free diet has demonstrated benefits in managing some
gluten-related disorders, though nutritional imbalances have been reported. As there is limited evidence
supporting the use of the gluten-free diet beyond its role in managing gluten-related disorders, consumers
are urged to be mindful of the sensorial limitations and nutritional inadequacies of the diet despite
ongoing strategies to improve them.

Keywords: celiac disease; gluten; wheat; auto-immune disease; non-celiac gluten sensitivity; gluten-free;
gluten-related disorders; weight management; nutritional adequacy; product development

1. Introduction
In cereal processing, gluten refers to the combined gliadin (prolamin) and glutenin (glutelin) fraction
of wheat [1]. The gluten protein fraction displays unique structure building properties that are used in food
processing. These structure building properties are also reflected in the terminology, as gluten is essentially
the Latin translation of “glue” [2]. Gluten in wheat flour forms a three-dimensional protein network upon
proper hydration and mixing. These network-forming properties are utilized in baking applications to
create viscoelastic dough matrices. Besides network formation, gluten functionality in food includes water
binding and viscosity yielding, which make gluten a widely used food additive [3].
Gluten is also a nutritional term used to refer to certain cereal prolamins, i.e., the ethanol-soluble
proteins of wheat, rye, barley, their cross bred grains, and possibly oats [1,4]. These prolamins are very
important in the context of coeliac disease (CD), non-coeliac gluten sensitivity (NCGS), gluten ataxia (GA)
and dermatitis herpetiformis (DH). For people suffering from CD, NCGS, GA, and DH, the only effective

Nutrients 2018, 10, 1410; doi:10.3390/nu10101410 www.mdpi.com/journal/nutrients

Nutrients 2018, 10, 1410 2 of 27

“treatment” to date consists of eliminating gluten completely and life-long out of their diet. In what follows,
general information on gluten-free products and the diet is provided. Challenges when formulating gluten-
free products, consumers’ motivations, knowledge and attitudes, as well as the nutritional and therapeutic
implications of the gluten-free diet, are also further elaborated on.

2. Gluten-Free Products
Global market data indicate that gluten-free product sales are forecasted to increase by a compound
annual growth rate of 10.4% between 2015 to 2020 [5]. As the clinical application and popularity of the
gluten-free diet escalate, consumer demands righteously continue to influence the food market and
labelling standards of gluten-free products. In 2013, the European Union Regulation 609/2013 set out rules
on compositional and labelling requirements for gluten-free products [6]. These guidelines ensure that
people who are intolerant to gluten are adequately informed of the difference between foods that are
naturally free of gluten and foods that are produced, prepared and/or processed in order to reduce their
gluten content [6]. In the same year, the Food and Drug Administration ruled that products labelled
“gluten-free” cannot surpass a threshold of 20 parts per million, although the official compliance date was
set for 2014 [7]. This guideline helps gluten-wary customers to navigate the current market and protect
themselves from consuming products that may exacerbate their symptoms and/or activate immune-
mediated mucosal damage even in the absence of symptoms. The gluten-free diet encompasses food
groups that are naturally devoid of gluten, such as fresh fruit, vegetables, seafood, meat, poultry, legumes,
nuts, and most dairy products [8]. However, some of these products may also contain “hidden” gluten.
Hence, product labels and ingredient lists need to be carefully reviewed. For the traditional gluten-
containing foods, such as bakery products, there is currently a wide variety of gluten-free options available
that use gluten-free cereals and pseudocereals, such as rice, corn, quinoa, millet, and amaranth as their base
ingredients [9].

2.1. Gluten Functionality

The unique properties of wheat flour can primarily be ascribed to its gluten fraction. Gluten has
unequalled network forming properties, which are important for products that are made with hard wheat
varieties, and typically involve an intermediate cohesive dough stage during their production process [10].
Examples of such products are bread, pasta, and pretzels. Gliadin is the 70% ethanol-soluble protein
fraction of wheat flour and is essentially present in wheat grain extracts as monomeric proteins [1].
Glutenin, on the other hand, is the protein fraction that cannot be extracted with water, diluted salt
solutions, and 70% ethanol, and is often referred to as the polymeric gluten [1]. Both gliadin and glutenin
are important for network formation and the quality of the final food product. Although the exact structure
and interactions of this protein network are still under debate, it is widely accepted that gliadin has a
viscosity-increasing effect, whilst the elastic properties of the network and wheat flour dough
predominantly stem from the glutenin fraction [1,10]. For soft wheat products such as cakes and cookies,
the gluten network-forming properties are not as crucial, but gluten is believed to nevertheless contribute
to final product structure and texture [11,12]. In what follows, focus will be laid on gluten-free bread
products as bread is an important staple food and its quality heavily relies on gluten properties and
functionality. Hence, bread is one of the more challenging food products when making gluten-free
alternatives.

2.2. Gluten Replacement Strategies

Bread baking without gluten essentially removes the most crucial ingredient for product structure and
quality. This presents a major challenge to bakers and cereal researchers. In addition, gluten-free products
Nutrients 2018, 10, 1410 3 of 27

are often consumed by people who have had the opportunity to try and enjoy gluten-containing foods.
These consumers, therefore, already have product expectations in terms of texture, structure, flavor and
overall quality imprinted. Besides designing gluten-free bread products in such way that they closely
mimic the texture of gluten-containing bread products, they also need to have the same sensory profile and
shelf life [13]. One possible strategy that has been identified for matching the volatile flavor of wheat-
containing products is combining proline and glucose in the gluten-free product recipe, as these are
precursors of the volatile components found in wheat-based bread products [14]. In what follows, different
ingredient and processing strategies will be reviewed, with a focus on texture, structure, and volume of
gluten-free bread products. Most of the research done on gluten-free bread formulations focused on the
effect of an extra ingredient or a (partial) replacement of one of the base ingredients with a promising other
compound. The product against which these new formulations have been tested in terms of quality is
almost always the gluten-free product, which does not contain the extra ingredient or the replacement
compound. However, as stated above, the real goal of formulating high quality gluten-free products is to
achieve the same product characteristics and quality of a regular gluten-containing bread. Therefore, it
would be more useful to compare the obtained gluten-free “dough” and bread characteristics with those
of an actual similar gluten-containing system.

2.2.1. Ingredients
Imitating the cohesiveness and elasticity of a gluten-containing dough was attempted using a wide
range of alternative raw ingredients and/or additives. Gluten-replacing ingredients include starches,
gluten-free flours of cereals/pseudocereals, hydrocolloids, and proteins. Minor ingredients that are added
to help build and strengthen gluten-free dough and bread structure are enzymes and emulsifiers.
Combinations of these are often used to improve the gluten-free product’s rheological characteristics. Some
researchers have also invested time and effort in breeding low-gliadin wheat varieties. In general, the recipe
alterations for gluten-free bread unfortunately often also lead to an increased product price [15].
Starch naturally occurs in wheat-based products, as 80% of wheat flour consists of starch. Although
starch predominantly acts as a quasi-inert filler material during the initial phases of breadmaking, (part of
the) starch gelatinizes upon baking. As a result, starch plays a key role in the structure setting of bread.
Hence, the elimination of wheat flour also removes starch from the product recipe. Starches of alternative
(gluten-free) sources, such as cassava, tapioca, corn, potato, bean, and rice, have been added to gluten-free
recipes [16–19]. In recent years, a gluten-free wheat starch was also developed, and has been tested in
combination with rice flour and corn starch for the production of gluten-free products [20,21]. In these
studies, it was postulated that wheat starch breads were generally better accepted and had an improved
loaf volume compared to the corn starch alternative. However, the gluten-freeness of wheat starch
preparations is a controversial theme. Starch naturally displays wide variability in terms of morphology,
gelatinization behavior, and viscosity yielding. The importance of starch granule morphology was studied
using rice starches. In this study, it was found that round starch granules were preferred over polygonal
starch structures for product quality [22]. The underlying reasons for this could, however, expand beyond
morphology, and be governed by a rapid gelatinization and good viscosity retention after gelatinization.
High viscosity of the batter is essential to build structure in gluten-free food products [22]. In some cases,
the natural variability of starch is not sufficient, and starches are then modified to display a specific
characteristic. The use of modified starches has also been investigated in the framework of gluten-free
products. Acetylated distarch adipate and hydroxypropyl distarch phosphate were found to increase bread
loaf volume, produce a more elastic bread crumb, and result in a slight decrease in hardness and chewiness
of the bread crumb [23].
In addition to starch, gluten-free flours have also been used as base ingredients (Table 1). Examples
are flours of pseudocereals, such as amaranth, buckwheat, chia and quinoa, but also cereal flours that do
Nutrients 2018, 10, 1410 4 of 27

not contain gluten, such as sorghum, rice, corn, teff, and millet. The use of oat flour is controversial, but
previous studies have shown that a moderate consumption of oats does not trigger any adverse health
effects in most CD patients [24]. However, the oats that are used need to be certified gluten-free. Oats often
become contaminated with gluten-containing cereals during harvest, and the separation of these gluten-
containing grains and oats is not that straightforward. Besides cereal and pseudocereal flours, legume
(chickpea, pea, carob germ, carob, marama bean, and soy) and chestnut flours have also been successfully
used in gluten-free bread applications [25–30]. The properties of the used gluten-free flours, such as particle
size, starch damage, and fiber content, significantly impact the resulting bread characteristics [31]. This
complicates the comparison of the outcomes of different studies on the performance of different ingredients
in gluten-free products.
One of the additives often used as a processing aid and/or quality-improving minor ingredient, is
dietary fiber (Table 2). The addition of dietary fiber does not only compensate for the nutritional loss of
dietary fiber when excluding wheat flour or whole meal from the product recipe, but it also introduces an
ingredient with excellent water-binding, viscosity-increasing, and even gel-forming capacities. As a result,
product thickening and texturizing characteristics are re-introduced in the gluten-free process. Examples
of dietary fiber that were used in gluten-free products are β-glucan, inulin, oligofructose, linseed mucilage,
apple pomace, carob fiber, bamboo fiber, polydextrose, and resistant starch [32–37]. Fiber structure and
molecular weight play a crucial role in gluten-free bread quality [38]. An alternative way of introducing
fiber in the (sourdough) bread recipe was explored by Wolter and colleagues [39]: exopolysaccharide
(essentially a dextran) production by bacteria, such as Weissella cibaria, was found to increase dough
strength [39].
Hydrocolloids (Table 3) are essentially polymers that display thickening properties through the
binding of water. As a result, the viscosity of the gluten-free “dough/batter” is enhanced and gas is better
retained in the “dough” matrix, which increases bread loaf volume and improves loaf crumb structure. The
most popular hydrocolloids are xanthan gum and hydroxypropyl methyl cellulose (HPMC) [40–44]. Other
gums that have been studied are pectin, guar gum, locust bean gum, agarose, tragacanth gum, cress seed
gum, and carboxymethyl cellulose [26,40,45–49].
Gluten is essentially a protein, and it is logical to explore alternative proteins to make up for the loss
of gluten functionality in gluten-free products. In the absence of other structure-forming molecules (such
as gums), the structure-forming capacity of proteins was explored. Non-gluten proteins have largely
varying effects on dough rheology, as well as final bread characteristics and appearance. In the study by
Ziobro and colleagues [50], the most promising protein in terms of volume increase was albumin, whilst
pea and lupine proteins were preferred over soy protein, sensory-wise. Examples of proteins used are
legume, egg, dairy, and non-gluten cereal proteins [13,43,51–54]. These alternative proteins/protein sources
often also display a better amino acid profile than gluten, which is deficient in essential amino acids such
as lysine, and hence, cannot be considered as a “balanced” protein. As a result, these alternative proteins
are preferred over gluten, from a nutritional perspective. These proteins also lead to a well-appreciated
sensory pallet, as they are involved in Maillard browning reactions, which do not only improve product
color but also flavor (compared to, e.g., hydrocolloid-based gluten-free products). However, the increased
darkness of the bread may not always be perceived as exceptionally desirable.
Enzymes, as processing aids, are often chosen based on their potential to induce the formation of
crosslinks in between the polymers present in the product recipe, thus triggering the formation of a
network, similar to what would be the case if gluten was present in the recipe. Examples of studied
enzymes are transglutaminase, glucose oxidase, tyrosinase, and laccase [55–57]. In addition, proteolysis,
through the addition of peptidases, has also been explored. These enzymes, similar to what glutathione
addition would trigger in bread recipes, lead to depolymerization [58]. In rice flour, for example, it has
been shown that the degradation of the high molecular weight protein fraction of rice is needed to allow
Nutrients 2018, 10, 1410 5 of 27

small protein aggregates to crosslink through disulfide bonds. This process helps to ensure better
rheological properties, improved gas retention during baking, and increased overall product quality
[59,60]. Starch hydrolyzing enzymes such as alfa-amylase and amyloglycosidase, were added in some
product recipes as well [45]. One of the reasons for alfa-amylase addition is the in situ production of sugars
to sustain yeast activity [61].
In gluten-free bread products, emulsifiers such as diacetyl tartaric esters of monoglycerides [40],
mono- and diacylglycerol [41], lecithin [62] and sodium stearoyl-2-lactylate [63] are used to establish better
interactions between the different ingredients. Emulsifiers may also play a role in stabilization of interfaces
such as water/air or water/lipid interfaces. The former interfaces are especially important to the fine crumb
structure of gluten-free bread loaves. Some proteins are known to display good interface stabilizing
properties as well.
Nutrients 2018, 10, 1410 6 of 27

Table 1. Alternative flours used in gluten-free product formulations with the main quality effects.

Formulation Main Conclusions References

Replacement of emulsifier and shortening by the chickpea protein and tiger nut lipids:
Base of corn starch with chickpea and tiger nut flour the combination of both maintains baking characteristics of bread loaves with [15]
eliminated shortening and emulsifier.
Base of rice flour, potato, tapioca and cassava starch and xanthan gum with Amaranth and quinoa flour do not affect texture and volume, and final bread loaves
[64,65]
amaranth and quinoa flour are considered ‘moderately acceptable’ in sensory trials.
Replacement of potato starch with buckwheat and quinoa flour increases bread
Base of rice flour and xanthan gum with amaranth, quinoa and buckwheat
volume and softens crumb. Amaranth flour only decreases the crumb firmness. None [66]
flour
of the three pseudocereal flours adversely affects the sensory properties.
Base of corn starch with vinal seed and corn flour Acceptable bread loaves are made with regard to volume and crumb structure. [67]
Base of rice flour, maize starch and HPMC with teff flour and dried rice- and Bread aroma is enhanced and visual appearance is good. Buckwheat-based sourdough
[68]
buckwheat based sourdough has a bitter taste.
Soy flour-barnyard millet blends Soy flour alters the textural properties and color of the bread. [69]
Base of rice flour, shortening, gum blend (xanthan, guar and locust bean Partial replacement of rice flour with chestnut flour results in lower hardness,
gum) and DATEM with partial replacement of the rice flour with chestnut increased specific volume, and better color and sensory properties. High chestnut flour [40]
flour recipes had low quality.
Base of rice and corn flour, corn starch, HPMC with gradual replacement Quinoa flour increases loaf volume and yields a more homogeneous crumb structure,
[61]
of rice/corn flour by quinoa flour whilst not affecting product taste.
Only oats bread is somewhat comparable to wheat bread. All other loaves are of
Base of oats, rice, buckwheat, maize, quinoa, sorghum and teff flour inferior quality in terms of loaf volume, physical crumb texture, shelf life and aroma [24]
profile.
Base of commercial gluten-free mixtures including corn starch, psyllium Dehulled buckwheat flour improved the baking performance of commercial mixtures,
fiber, guar gum or corn starch, tapioca starch, potato starch and rice flour, whilst puffed buckwheat flour had a clear effect on water availability and the [70]
HPMC with partial replacement of the flours by buckwheat flour interaction between the matrix biopolymers.
Base of corn starch and xanthan gum with soy and chickpea flour, pea isolate Carob germ flour loaves have the lowest volume, whilst chickpea flour yields the
[25]
and carob germ flour highest volume and the softest crumb.
Marama bean and cassava starch produce strong dough, similar to wheat flour dough
Base of marama bean flour with cassava starch [27]
that can hold gas in its structure.
Base of potato starch and rice flour with whole chia flour Chia flour does not adversely affect loaf volume and crumb firmness. [71]
Base of rice flour, gluten-free wheat starch, albumin, HPMC with green Green plantain flour produces good volume bread loaves, and soft crumb firmness
[21]
plantain flour breads having a regular porosity.
Sensory and nutritional properties are improved with acorn supplementation, whilst
Base of rice flour and corn starch with acorn meal [72]
the specific volume is decreased, and the crumb hardness is increased.
Carob germ flour is a good alternative to wheat flour to produce viscoelastic dough
Base of corn starch, HPMC with carob germ flour [73]
and high quality gluten-free bread.
DATEM, Diacetyl Tartaric Esters of Monoglycerides; HPMC, hydroxy propyl methyl cellulose
Nutrients 2018, 10, 1410 7 of 27

Table 2. Hydrocolloids used in gluten-free product formulations with the main quality effects.

Formulation Main Conclusions References

Hydrocolloid and β-glucan improve bread volume and aid zein to more closely resemble gluten in terms
Zein-starch base with HPMC and high β-glucan oat bran [74]
of structural and rheological properties.
Base of soybean flour and corn starch with HPMC, xanthan HPMC increases volume and softness more than xanthan gum, but xanthan gum gives a better crumb
[41]
gum and emulsifiers structure.
Xanthan gum increases the crumb hardness of teff and buckwheat breads, whilst corn breads become
Base of teff, buckwheat, corn or rice flour with HPMC and
softer. HPMC increases loaf volume of teff and corn breads, while xanthan adversely affects the loaf [42]
xanthan gum (combinations)
volumes in all different recipes.
Base of rice flour, corn starch and sodium caseinate with
pectin, carboxymethyl cellulose, agarose, xanthan gum and oats Except for xanthan, all gums result in a loaf volume increase. [46]
β-glucan
Base of potato flour with HPMC, carboxymethyl cellulose,
Gums yield loaves with higher specific volume and reduced hardness. [47]
xanthan gum and apple pectin
Base of rice flour, corn starch, soy flour with guar gum and Guar gum increases the specific volume and decreases crumb hardness, while transglutaminase
[56]
transglutaminase increases crumb hardness but yields a good texture.
Base of chestnut and chia flour with guar gum, HPMC and
All hydrocolloids increase “dough” elasticity. [26]
tragacanth gum
Base of rice flour, corn starch and sodium caseinate with
Carboxymethyl cellulose increases bread volume and sensorial properties. [48]
carboxymethyl cellulose
Base of broken rice berry flour with guar, locust bean or
Hydrocolloids increase loaf volume, texture, microstructure and sensory properties. [75]
xanthan gum
Base of tapioca starch, precooked corn flour with guar gum
Guar gum and HPMC reduce dough stickiness and soften the crumb. [76]
and HPMC
Base of rice and corn flour and corn starch with cress seed and Both gums improve crumb color and porosity, cress seed gum triggers the formation of more regular
[51]
xanthan gum and solid pores.
HPMC, hydroxy propyl methyl cellulose
Nutrients 2018, 10, 1410 8 of 27

Table 3. Fiber (sources) used in gluten-free product formulations with the main quality effects.

Formulation Main Conclusions References

Base of corn flour, corn starch, dried eggs and Addition of dietary fiber alters dough cohesion and starch pasting properties. (Glucose oxidase increased the [77]
carrageenan with psyllium and pea fiber and oat bran specific loaf volume).
and glucose oxidase
Base of corn starch, rice flour, starch and protein, Both psyllium and sugar beet fiber improve dough workability. Psyllium fiber is superior in its film forming ability [45]
HPMC, locust bean gum, guar gum and alfa- and has an antistaling effect due to higher water binding capacity.
amylase with psyllium and sugar beet fiber
Base of rice and corn flour, corn starch, HPMC Quinoa bran increases carbon dioxide production, while the gas retention is reduced. Bread volume can be [78]
with quinoa bran or quinoa wholemeal addition increased without adversely affecting the taste.
Base of corn and potato starch, pectin, guar gum Replacement of pectin or guar gum with linseed mucilage improves the sensory acceptance and does not affect [32]
with replacement of pectin and guar gum with texture and bread staling.
linseed mucilage (predominantly arabino-xylan)
Base of rice flour, corn starch and HPMC with Soluble fiber decreases dough consistency, increases bread volume and decreases crumb hardness. The fine [33]
insoluble fiber (oat and bamboo, pea and potato fiber) insoluble fibers also increase bread volume and decrease the crumb hardness, the coarse insoluble fibers decrease
and soluble fiber (barley and polydextrose) bread volume and increase hardness. In general, soluble fiber increases the structural stability, while insoluble
fiber disrupts the structure.
Base of rice flour, HPMC with β-glucan derived from Low molecular weight β-glucan develops a gel network structure, whilst high molecular weight β-glucan [79]
barley (low molecular weight) and oats (high molecular predominantly increases viscosity.
weight)
Base of white rice, corn and buckwheat flour with Carob fiber improves volume, color and crumb texture whilst increasing the antioxidant activity of the breads. [36]
carob fiber
Base of rice flour, cassava starch, full-fat active soy Insoluble fiber increases dough firmness and decreases loaf volume, whilst soluble fiber decreases dough [37]
flour with inulin (soluble fiber) and resistant starch firmness.
and oat bran (insoluble fiber)
Base of corn and potato starch, guar gum and Inulin addition leads to an increased loaf volume and reduces crumb hardness, whilst the internal structure is [80]
pectin with inulin more polydisperse.
HPMC, hydroxy propyl methyl cellulose
Nutrients 2018, 10, 1410 9 of 27

2.2.2. Processing
In addition to rational ingredient and/or additive choice, different processing paths have also been
explored to alter the gluten content of gluten-containing flours and improve rheological properties of
gluten-free products, particularly gluten-free dough.
Gluten-containing flours have been used in combination with protein hydrolysis strategies or
sourdough fermentation to produce gluten-free or so-called ‘gluten-reduced’ bread products. Both the
aforementioned technologies are believed to eliminate, or at least significantly reduce, gluten levels in
dough. Detoxification of gluten through proteolysis targeting proline and glutamine peptide bonds has
been explored recently [81]. These proteolytic enzymes essentially cleave those peptide bonds that human
peptidases cannot affect. The hydrolysis products should be broken down to less than nine amino acids in
order not to trigger any reaction in the gastrointestinal tract of people suffering from CD. Similarly, using
sprouted grain to formulate products safe for coeliac patients is based on extensive protein hydrolysis,
reducing the immune response to the hydrolyzed gluten in the product. However, in the latter case,
sprouting conditions need to be tightly controlled and monitored, not only to ensure proper gluten
hydrolysis, but also to retain some wheat flour functionality for baking applications. Sourdough
fermentation is another strategy which is believed to reduce the level of immunoresponse-triggering
gluten. In this framework, the right selection of lactic acid bacteria that display peptidase activity
hydrolyzing the appropriate peptide bonds is crucial [82].
In addition to modifying wheat flour, the gluten-free flours can also be processed in a particular way
to change their rheological behavior in dough-like systems. A myriad of different strategies has been
explored:
- Corn flour has been milled in various instruments. Different corn varieties were selected to explore
the varietal effect and the flour’s physical properties’ impact on its potential to produce high
quality gluten-free products [83].
- Germination of brown rice was studied as a pre-treatment to alter the functionality of brown rice
flour in gluten-free bread baking applications [84]. Rice germination did indeed alter the hydration
and pasting properties of the flour. This resulted in increased crumb softness. However, the
germination process had to be closely monitored to control the activity of α-amylase.
- Similar to wheat flour-based systems, sourdough fermentation of teff flour products has also been
explored [68,85]. The fermentation was shown to have a major impact on the physicochemical
properties of teff starch and a more limited effect on the protein fraction. Bread loaves made with
this fermented teff flour yielded better gluten-free breads than those produced with unfermented
teff flour [85].
- Phosphorylation of rice flour is another strategy that was studied. The resulting gluten-free breads
had a lower hardness and an improved bread volume, crumb appearance, and color [86].
- Pre-gelatinization of the starch used as a base ingredient has also been attempted and led to a
decreased dough elasticity, but a higher resistance to deformation, assuring a better retention of
gas in the dough structure. As such, hardness of the product was decreased [57].
- Heat treatment has been explored to unlock a specific functionality. Buckwheat grains e.g., have
been puffed prior to milling and use in gluten-free bread recipes [70]. Steaming or roasting of
soybeans was found to reduce the beany flour of whole soy bread [87].
- Extrusion of rice flour increased the dough consistency and hydration of rice flour gluten-free
bread, while increasing the crumb hardness and lowering the specific volume. However, these
bread quality effects can be counteracted by working with flours with coarser particle sizes [88].
- Particles of whey protein were shown to display elastic and strain hardening characteristics when
mixed with starch. Whey protein has been converted to whey protein particles using a cold gelation
Nutrients 2018, 10, 1410 10 of 27

method prior to being used to produce gluten-free bread [89]. Van Riemsdijk and colleagues [90]
found that the effect of whey protein particles on bread quality was heavily governed by the
amount of disulfide bonds present in the dough (and the particles).

3. Gluten-Free Diet
The origin of the gluten-free diet dates back to 1941, when it made its debut in a report on the dietary
treatment of CD by paediatrician and scientist Willem Karl Dicke [90]. Today, the diet continues to be
applied and investigated for a variety of additional health purposes, including the management of NCGS,
irritable bowel syndrome (IBS), diabetes, DH, inflammation and obesity.
Research interest in the gluten-free movement, in addition to the clinical and practical uses of the diet,
has been growing for many years. In what follows, the current trends, attitudes, and knowledge
surrounding the gluten-free diet, as well as its nutritional adequacy, will be covered. Furthermore, the
implications of the gluten-free diet on gluten-related conditions, diabetes and other autoimmune diseases,
as well as weight management, will be explored.

3.1. Consumers’ Motivations, Knowledge and Attitudes

3.1.1. Consumers’ Motivations

Over the past decade, surveys have been conducted to better understand the underlying reasons
behind rising trends in gluten-free living [91–94]. While the clinical diagnosis of CD influences adherence
to the gluten-free diet, data indicate that this disease affects less than 1% of the general population [95].
Studies show that adverse symptoms, as well as individual efforts to manage them without a clinical
diagnosis, impact gluten-avoidance behavior [92,93]. Symptomatic self-management strategies involving a
gluten-free diet have been supported by ethnographic research findings as well [96]. In their field-based
study, Copelton and Valle [96] learned that a self-imposed gluten-free diet was common among individuals
presenting with unexplained symptoms for extended periods of time. The anticipated length of time,
invasiveness, and frustrations associated with diagnostic tests persuade many of these people to eliminate
gluten from their diet on their own [96].
Expected health benefits of the gluten-free diet also influence dietary decisions. Although beneficial
effects of the diet have yet to be demonstrated in healthy individuals [97,98], consumer market survey data
demonstrate that 33% and 26% of Canadians and Americans, respectively, believe gluten-free products are
healthier [99,100]. These trends are consistent with the findings of another study investigating health beliefs
surrounding the gluten-free diet [101]. In Dunn et al.’s [101] study, 31% of participants believed that gluten
avoidance would promote general health, whilst 37% felt that gluten-free products were healthier than
their conventional equivalents. Weight loss was reported as another common motivator for adopting the
gluten-free diet, especially among younger adult populations [94]. However, evidence supporting the
effectiveness of a gluten-free diet in weight management is limited, as discussed later.

3.1.2. Consumers’ Knowledge

Mixed rationales for following the gluten-free diet may be reflective of society’s limited understanding
of gluten and gluten-free food formulation. In the United States, survey findings from 1012 respondents
suggested that, although gluten-awareness is high, a substantial proportion of citizens can neither describe
what it is, nor determine product sources of it [94]. These conclusions have been consistent among smaller
studies indicating confusion around gluten-free terms [102], and issues identifying the gluten content of
foods [103]. Dietitians also express concern for clients with CD who struggle to identify safe options due to
their limited knowledge about gluten-free foods [104].
Nutrients 2018, 10, 1410 11 of 27

According to Halmos et al.’s [105] findings, the greatest challenge may lie in identifying gluten-free
ingredients rather than gluten-containing ones. This supports the results of an earlier study by Zarkadas et
al. [106], in which 85% of respondents with CD struggled to determine whether or not certain foods were
gluten-free (n = 2681). Lack of knowledge surrounding the diet has implications for both CD patients and
the general public. Leffler et al. [107] reported that individuals commonly overestimate their adherence to
the diet. Recent literature points to the fact that an inadequate understanding of the diet may not only lead
to an unintentional ingestion of gluten, but also to an over-restriction of certain foods and poor adherence
to the diet overall [103,105,108].
Research has also explored the most common sources of information on gluten and gluten-free diets.
Questionnaire-derived data indicate that popular sources of gluten-free information include the internet,
print media sources, cookbooks, coeliac support groups, and other coeliac patients or individuals on the
diet [92,103,190,110]. Compared to dietitians, family physicians were found to be less likely referred to for
gluten-free information [103], and were rated low or lowest with respect to usefulness [109,110].

3.1.3. Consumers’ Attitudes

Individuals follow the gluten-free diet to varying degrees [101,103]. This may be influenced by the
attitudes that people share toward the diet. For example, purchasing gluten-free products may have some
negative economic consequences, especially for low-income families [104,109,111]. In contrast to their
gluten-containing counterparts, gluten-free products are considerably more expensive. In fact, gluten-free
items were reported to be approximately 200–500% more expensive than the equivalent standard products,
depending on the product and shopping location [112–115]. Thus, the affordability and long-term
sustainability of the diet continues to spark evaluation.
The inadequate availability of high quality gluten-free items is another burden. Many people report
challenges locating such products in local grocery stores [106,111], where their availability varies across
shopping venues [113,115]. Individuals with lower socioeconomic status, with limited resources available,
or those living in remote cities are certainly at a disadvantage.
Other opinions about the diet focus on the sensory aspects of gluten-free products, as well as the
impact it has on many personal and social domains. While consumers may be relatively satisfied with the
taste and texture of gluten-free products, continued efforts to improve the palatability of these items are
still being urged [111]. Furthermore, individuals avoiding gluten express a lack of confidence when eating
outside of the home [106,116], while many find the length of time involved in the at-home preparation of
gluten-free options a nuisance [110].

3.2. Nutritional Implications

The nutritional adequacy of the gluten-free diet and associated products has always been a concern
for consumers, health care professionals, and the industry. While the gluten-free diet is known to alleviate
symptoms and promote gastrointestinal healing in patients with gluten-related disorders, long-term
adherence to the diet may have concurrent nutritional limitations.
The nutritional profiles of gluten-free products, as well as the dietary intake patterns of individuals
on the diet, were assessed in several studies. According to Do Nascimento et al. [117], gluten-free products
share a common composition of raw ingredients, including corn, rice, soy, cassava, and potato. These
ingredients replace gluten-containing grains like wheat, rye, and barley in regular products. Overall,
gluten-free items are higher in fat, sugar, and sodium compared to regular products, though compositional
trends may vary by product type [118]. Studies have shown that the total fat content of gluten-free breads
is at least twice the amount found in their gluten-containing counterparts, contributing to the improved
mouthfeel of these products [119,120]. Conversely, many gluten-free pasta products appear to have
significantly higher carbohydrate [120] and sodium contents [121]. Gluten-free products are generally
Nutrients 2018, 10, 1410 12 of 27

inferior sources of protein and dietary fiber as well [118,119]. The glycemic index (GI) of gluten-free
products varies based on the type and quality of ingredients used, as well as the food-processing
procedures performed to manufacture them [121]. Since gluten-free items are not typically fortified or
enriched in the way that many regular products are, they are also generally lower in folate, iron, niacin,
thiamin and riboflavin [122,123]. Efforts have been made to improve the formulation of these products
without compromising their sensory appeal [64].
Studies evaluating the dietary intakes of CD patients on a gluten-free diet have reached similar
conclusions. According to Barone et al. [124], CD patients, compared to healthy adults, consume
significantly higher quantities of fat and sugar, and lower amounts of fiber on the gluten-free diet. Similar
findings were reported by other researchers reporting food-record and questionnaire-based data from
adults and children [125–128]. However, it is being questioned whether this trend is reflective of overall
dietary habits rather than the gluten-free diet alone [125,129]. For example, while CD patients have been
shown to share similar intake patterns of cereal-based products in general with the total population,
biscuits and crackers are consumed more frequently among individuals with CD [129]. According to
Valitutti et al. [129], the popularity of these high GI products may also reflect consumer dissatisfaction with
the palatability and availability of other gluten-free carbohydrate options, such as bread. Finally,
inadequate intakes of iron, folate, calcium, selenium, magnesium, zinc, niacin, thiamine and riboflavin, as
well as vitamins A and D were reported in CD patients following a gluten-free diet [125–127,130–132].
While it could be argued that nutrient deficiencies in CD patients can be largely explained by impaired
nutrient absorption resulting from CD-associated intestinal damage, Hallert et al. [131] argue that this may
not entirely be the case. Despite 10 years on the diet and evidence of mucosal recovery, the total plasma
homocysteine levels of CD patients were still higher than average, reflecting ongoing deficiencies in folate,
vitamin B6, and vitamin B12 [131].
Dietary evaluations performed on CD patients following a gluten-free diet have largely been based on
self or proxy-reported data. As always, it is important to acknowledge the potential for participant bias in
these types of studies. Nutritional inadequacies associated with gluten-free diets have been shown to vary
by gender and dietary experience [132]. It is therefore, reasonable to assume that gluten-free diet education,
health awareness, and other lifestyle factors may influence food choices, and consequently impact study
results. Researchers agree that proper follow-up, dietitian collaboration, and nutrition education are
important to ensure that those following the diet are not at any additional health risks [120,130,131].
Furthermore, a closer look into fortifying or improving the quality of ingredients in gluten-free products
continues to be recommended [121,130].
Media and celebrity endorsements of the gluten-free diet for weight loss have stimulated public
interest and driven gluten-free market sales [133]. Empirical evidence confirming the diet’s effects on
weight, however, is still unclear. Not only is there limited literature available on the weight-related
implications of the diet for the general public, but inconsistent study findings involving CD patient requires
further research in this area. To date, the influence of the gluten-free diet on body mass index (BMI), waist
circumference, and lipid profiles has been investigated.
It is possible that gluten avoidance might support weight management in healthy individuals,
although the evidence is minimal and largely derived from self-reported data [134]. It has been speculated
that losses in weight associated with the gluten-free diet may, instead, be a reflection of health-conscious
behaviors [134], exaggerated reductions in carbohydrates, and low availability of gluten-free food products
[133]. Therefore, contrary to popular belief, there are currently insufficient grounds to verify that gluten
elimination results in weight loss for the general public.
Conversely, studies indicate that strong adherence to the gluten-free diet may actually result in weight
gain in many CD patients [124,135–139]. For those who are underweight at diagnosis, weight gain on the
diet is generally more pronounced and favorable [136–139]. That said, some evidence suggests that, without
adequate dietary counselling, initially overweight and obese CD patients may be at increased long-term
Nutrients 2018, 10, 1410 13 of 27

health risks on the gluten-free diet [135,136,140]. CD patients may also be more susceptible to developing
metabolic syndrome in as early as 1 year on the diet [140]. Nutritional imbalances and shortcomings of
gluten-free products, as described in an earlier section, may contribute to some of these changes. On the
other hand, a few studies have revealed that a gluten-free diet may help some overweight and obese CD
patients lose weight [137–139]. Earlier diagnosis, perceived mastery of the diet [139] and counselling by a
dietitian [138] were shown to influence positive weight outcomes on the diet.
Variations between studies may reflect regional or cultural differences in the type and quality of foods
consumed on the gluten-free diet, as well as individual exercise practices [136,138]. To gain a better
understanding of the actual effects of gluten-free diet on weight and weight management, consistent efforts
should be made across studies to monitor the dietary and physical activity habits of participants, as well as
their compliance to the gluten-free diet. Additional research is recommended to ensure that healthy and
CD individuals are appropriately informed and advised.

4. Gluten-Related Disorders
As previously stated, the gluten-free diet is to date, the only effective treatment to a number of gluten-
related disorders, including CD, NCGS, GA, and DH. The role of this diet in alleviating the symptoms of
these disorders, in part through the modulation of gut microflora, is discussed in the following sections
and summarized in Figure 1.

4.1. CD, NCGS, GA, and DH

The introduction of wheat to the human diet prompted a myriad of health conditions derived from
the body’s immune response to gluten [141]. While there is an overlap in their symptomatic presentation,
experts have agreed on several distinctions between these gluten-related disorders [141,142]. Wheat can
trigger immunologic reactions depending on its route of exposure, by ingestion, inhalation, or skin contact
[141]. When consumed, wheat can act as a food allergen, initiating immunoglobulin E (IgE) or non-IgE
mediated reactions [143,144].
CD, DH, and GA are gluten-related autoimmune conditions [141]. CD is a chronic enteropathy
involving a gliadin-specific T-cell response, causing inflammation, villous atrophy, and malabsorption in
the small bowel of genetically vulnerable individuals [141,145]. In fact, an association between CD and
other gastrointestinal and extraintestinal disorders was reported. DH is a common comorbidity of CD and
is often called “coeliac disease of the skin” [141,145,146]. It presents as an itchy, blistering rash and is
detected by the existence of IgA epidermal transglutaminase antibody complexes in the papillary dermis
[147]. Finally, GA is a condition in which cerebellar damage results from the production of antibodies,
following gluten ingestion by susceptible patients [141]. NCGS, on the other hand, is diagnosed by
exclusion criteria; when a reaction to gluten is evident after both a wheat allergy and CD have been ruled
out [142,143]. A significant proportion of patients with IBS have a sensitivity to gluten [148]. Literature
indicates that similarities in the clinical presentation of NCGS and IBS generate confusion when evaluating
the causes and management options for the manifested symptoms [142,149,150].

4.1.1. Management of Symptoms

One way the gluten-free diet can be beneficial to gluten-related disorders is through the management
of related symptoms. Researchers agree that strict adherence to the gluten-free diet offers the greatest relief
of symptoms for most patients with CD [151–155]. However, symptom recovery rates differ across age and
gender [151–154]. It is also worth noting that diagnostic delays over 5 years may worsen recovery rates on
a gluten-free diet [151].
Changes in CD-related serum antibody concentrations and mucosal recovery rates, following the
gluten-free diet, have also been investigated. Studies provide clear evidence of a decline in tissue-
Nutrients 2018, 10, 1410 14 of 27

transglutaminase antibodies in CD patients on the diet [154,156], even as early as 3 months following a
diagnosis [157]. Rates of histological normalization on the gluten-free diet are less consistent across studies
[158–162]. Longer duration on the diet, however, appears to improve villous recovery [160]. Adherence to
the gluten-free diet, education level, and gluten-free knowledge, as well as age at CD diagnosis, were all
shown to influence mucosal recovery [158,160,161,163].
Although results may take months to years, patients with DH have shown significant improvements
and better long-term management of symptoms on a strict gluten-free diet. The diet may also provide a
protective effect against the development of lymphoma, which is a potential risk for patients with DH and
CD [164]. According to the literature, the diet can not only help clear skin lesions, but may also heal the
small bowel mucosa, decrease IgA and epidermal transglutaminase deposits in the skin, and reduce the
need for oral medications in these patients [165–168].
Case reports [169,170] and other studies [171,172] indicate that patients with GA may show clinical
improvements on a gluten-free diet as well. Neurological benefits, including improved cerebellar function
and stabilization of the condition, are influenced by patient adherence to the gluten-free diet [172]. At least
one year on the diet may be required for clear signs of improvement to be detected in GA patients [173].
The gluten-free diet’s effectiveness in managing NCGS and IBS symptoms is a popular area of debate.
For individuals with NCGS, whose symptoms are provoked by gluten, the gluten-free diet is shown to
keep the number and severity of their symptoms at bay [148,173–175]. However, randomized, double-blind
placebo-controlled challenge studies revealed that the true proportion of gluten-sensitive individuals may
be overestimated [174,176,177]. Furthermore, although the gluten-free diet was found to provide some
relief for patients with diarrhea-dominant IBS [178,179], the roles of α-amylase/trypsin inhibitors and
fermented oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) in triggering IBS-
type symptoms cannot be ignored [180–182].
Nutrients 2018, 10, 1410 15 of 27

The gluten-free diet is currently the

only effective treatment for CD. Early
Coeliac Disease detection and strict adherence to the
(CD) diet helps improve mucosal recovery
and reduce tissue-transglutaminase
antibodies in CD patients.

Longer duration on the diet can help

Dermatitis heal skin lesions, reduce epidermal
Herpetiformis transglutaminase and IgA deposits in
Autoimmune
the skin, and lessen medication
(DH) requirements for many patients with
DH.

Neurological improvements have

Gluten Ataxia been observed in GA patients
(GA) following a strict gluten-free diet for
at least one year.
Gluten (Ingestion)
Related Disorders Complete avoidance of wheat-based
& Wheat (Food)
Allergy products is the current dietary
Allergy
Gluten-Free Diet treatment for this food allergy.
Outcomes
Patients who are truly sensitive to
Neither Non-Coeliac gluten show symptomatic
Autoimmune Nor Gluten Sensitivity improvement on the gluten-free diet,
Allergy (NCGS) though the prevalence of NCGS is
overestimated.
Figure 1. Summary of the effects of the gluten-free diet on the outcomes of gluten-related disorders.
Nutrients 2018, 10, 1410 16 of 27

4.1.2. Management of Gut Microflora

Another way the gluten-free diet may benefit some gluten-related disorders is through
modulation of gut microflora. The gluten-free diet has been shown to beneficially alter the gut
bacterial composition and function in individuals with CD [183,184]. The low polysaccharide content
of the gluten-free diet could help explain some of the changes observed in the microbiota [185].
Intestinal healing on the diet may also help support the growth of different bacterial species [183].
However, findings are still inconsistent. In adults with CD, Nistal et al. [183] found that adult patients
on the diet began to show some changes similar to the microbial community patterns of healthy
adults, but that differences in the richness and presence of unknown bacterial communities still
existed. In child CD patients, more than 1 year on the diet seems to be needed to restore normal
functions of the gut microflora [184]. Differences in the reported benefits also exist between the gut
microbial composition of symptomatic and asymptomatic CD patients on a gluten-free diet [186].
Additional studies are still needed for a consensus to be reached. Research of this kind is limited
and mostly restricted to small sample sizes. There is also inconsistency in the target age groups across
studies, as well as the duration and adequacy of gluten-free dietary adherence. The effects of
confounding genetic and other environmental factors on the gut microbiome must also be considered.

4.2. Other Disorders Closely Linked to CD

An association was described between type 1 diabetes (T1D) and CD, with a 1–16% prevalence
of CD found in T1D cases [187]. In addition to T1D, patients with CD are more susceptible to
developing autoimmune diseases including autoimmune thyroiditis, psoriasis, rheumatoid arthritis,
Sjögren’s syndrome, DH, and Addison’s disease [188,189].

4.2.1. T1D
Both genetic and environmental elements are known to influence the development of T1D, and
researchers suspect that dietary gluten may be one contributing factor [190]. Human studies have
produced less conclusive results than pre-clinical studies and additional research is still needed.
Variations in the clinical backgrounds, age groups, and dietary compliance of subjects, as well as the
lack of controls and small sample sizes across studies might explain the inconsistencies. Owing to the
association between T1D and CD, researchers have also investigated the gluten-free diet’s impact on
glycemic control in patients with both autoimmune diseases. The gluten-free diet reduced severe
hypoglycemia in children with T1D and CD, over the short term [191]. Although the level of clinical
significance varies between studies, HbA1c levels were also found to improve in children with T1D
and CD following a gluten-free diet intervention [192,193]. However, other studies found no
significant improvement in metabolic control in T1D patients with CD following a gluten-free diet
[194–196]. Furthermore, the high GI of many gluten-free products could put ill-informed T1D patients
at risk of a loss of glycemic control [197].

4.2.2. Other Autoimmune Diseases

The role of the gluten-free diet in reducing the risk of comorbidities of autoimmune diseases in
CD patients remains unclear. In 1999, Ventura et al. proposed that the incidence of other autoimmune
diseases in patients with CD may be linked to prolonged exposure to gluten. Since then, other studies
have been conducted to further explore the association between gluten exposure in CD patients and
the development of these disorders [188,198–200]. Three of the studies revealed that the risk for
developing other autoimmune diseases does not appear to be significantly impacted by the duration
of gluten exposure in CD patients [188,198,199]. Cosnes et al. [200], on the other hand, reported a
possible protective effect of the gluten-free diet. As many of these studies are based on retrospective
data [198–200], prospective research in this area is advised.
Nutrients 2018, 10, 1410 17 of 27

5. Conclusions
The replacement of gluten as a vital ingredient in numerous food products is not
straightforward. Different ingredients and processing techniques have been investigated to date.
However, the quality of gluten-free products is often not comparable to gluten-containing products.
More effort should be devoted to a more rational approach which uses the gluten-containing product
as the golden standard.
The motivation to adopt a gluten-free lifestyle goes beyond its original application for CD
management. Perceived health benefits and relief of adverse symptoms on the diet influence
individual decisions to abstain from gluten. Even so, confusion surrounding gluten and gluten-free
options, as well as the high cost and low availability of gluten-free products, can be burdensome for
many people. For others, drawbacks of the gluten-free diet may be small in comparison to the clinical
improvements made on the diet. Despite media claims, there is also limited evidence confirming the
diet’s effectiveness in weight loss for the general public. Furthermore, the reported weight gain in
CD patients on the diet may not always be favorable, particularly among previously overweight and
obese individuals. However, to date, no beneficial effects from a gluten-free diet have been shown in
healthy individuals. Most importantly, individuals choosing to follow a gluten-free diet should take
caution of the macronutrient and micronutrient inadequacies of the diet. Overall, it is generally
recommended that dietary education and counselling be offered to support gluten-free dieters.
Author Contributions: Writing-Original Draft Preparation, D.E.K., S.B., I.J.J.; Writing-Review & Editing, D.E.K.,
S.B., I.J.J.; and Supervision, D.E.K., I.J.J.

Funding: This research received no external funding.

Conflicts of Interest：The authors declare no conflict of interest.

References
1. Wrigley, C.; Bekes, F.; Bushuk, W. Gliadin and Glutenin: The Unique Balance of Wheat Quality; AACC
International, Inc.: St. Paul, MN, USA, 2006.
2. El-Chammas, K.; Danner, E. Gluten-free diet in nonceliac disease. Nutr. Clin. Pract. 2011, 26, 294–299.
3. Wieser, H. Chemistry of gluten proteins. Food Microbiol. 2007, 24, 115–119, doi:10.1016/j.fm.2006.07.004.
4. Capriles, V.D.; Arêas, J.A.G. Novel approaches in gluten-free breadmaking: Interface between food science,
nutrition, and health. Compr. Rev. Food Sci. Food Saf. 2014, 13, 871–890, doi:10.1111/1541-4337.12091.
5. Market and Markets Gluten-Free Products Market by Type (Bakery Products, Pizzas & Pastas, Cereals &
Snacks, Savories, and Others), Source (Oilseeds & Pulses, Rice & Corn, Dairy & Meat Products, and Other
Crops), & by Region—Global Trends & Forecast to 2020. Available online:
https://www.marketsandmarkets.com/Market-Reports/gluten-free-products-market-738.html (accessed
on 31 July 2018).
6. European Parliament Regulation (EU) No 609/2013 of the European Parliament and of the Council on food
intended for infants and young children, food for special medical purposes, and total diet replacement for
weight control. Off. J. Eur. Union 2013, 2012, 35–56.
7. U.S Food and Drug Administration Guidance for Industry: Gluten-Free Labeling of Foods; Small Entity
Compliance Guide. Available online:
https://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ucm402549.
htm (accessed on 31 July 2018).
8. Theethira, T.G.; Dennis, M. Celiac disease and the gluten-free diet: Consequences and recommendations
for improvement. Dig. Dis. 2015, 33, 175–182, doi:10.1159/000369504.
9. Bascuñán, K.A.; Vespa, M.C.; Araya, M. Celiac disease: Understanding the gluten-free diet. Eur. J. Nutr.
2017, 56, 449–459.
10. Delcour, J.A.; Joye, I.J.; Pareyt, B.; Wilderjans, E.; Brijs, K.; Lagrain, B. Wheat gluten functionality as quality
determinant in cereal-based food products. Annu. Rev. Food Sci. Technol. 2012, 3, doi:10.1146/annurev-food-
022811-101303.
11. Wilderjans, E.; Pareyt, B.; Goesaert, H.; Brijs, K.; Delcour, J.A. the role of gluten in a pound cake system: A
model approach based on gluten-starch blends. Food Chem. 2008, 110, 909–915.
Nutrients 2018, 10, 1410 18 of 27

12. Pareyt, B.; Wilderjans, E.; Goesaert, H.; Brijs, K.; Delcour, J.A. The role of gluten in a sugar-snap cookie
system: A model approach based on gluten-starch blends. J. Cereal Sci. 2008, 48, 8630869.
13. Toufeili, I.; Shawky, D.; Sossy, S.; Abir, N.; Sarakbi, M.; Farran, M.T. Formulation of Gluten-Free Pocket-
Type Flat Breads : Optimization of Methylcellulose , Gum Arabic , and Egg Albumen Levels by Response
Surface Methodology. Am. Assoc. Cereal Chem. 1994, 71, 594–601.
14. Pacyński, M.; Wojtasiak, R.Z.; Mildner-Szkudlarz, S. Improving the aroma of gluten-free bread. LWT—Food
Sci. Technol. 2015, doi:10.1016/j.lwt.2015.03.032.
15. Aguilar, N.; Albanell, E.; Miñarro, B.; Capellas, M. Chickpea and tiger nut flours as alternatives to
emulsifier and shortening in gluten-free bread. LWT—Food Sci. Technol. 2015, doi:10.1016/j.lwt.2014.12.045.
16. Kim, M.; Yun, Y.; Jeong, Y. Effects of corn, potato, and tapioca starches on the quality of gluten-free rice
bread. Food Sci. Biotechnol. 2015, doi:10.1007/s10068-015-0118-8.
17. Krupa, U.; Rosell, C.M.; Sadowska, J.; Soral-ŚMietana, M. Bean starch as ingredient for gluten-free bread.
J. Food Process. Preserv. 2010, doi:10.1111/j.1745-4549.2009.00366.x.
18. Milde, L.B.; Ramallo, L.A.; Puppo, M.C. Gluten-free Bread Based on Tapioca Starch: Texture and Sensory
Studies. Food Bioprocess Technol. 2012, doi:10.1007/s11947-010-0381-x.
19. Onyango, C.; Mutungi, C.; Unbehend, G.; Lindhauer, M.G. Modification of gluten-free sorghum batter and
bread using maize, potato, cassava or rice starch. LWT—Food Sci. Technol. 2011,
doi:10.1016/j.lwt.2010.09.006.
20. Mancebo, C.M.; Merino, C.; Martínez, M.M.; Gómez, M. Mixture design of rice flour, maize starch and
wheat starch for optimization of gluten free bread quality. J. Food Sci. Technol. 2015, doi:10.1007/s13197-015-
1769-4.
21. Sarawong, C.; Gutiérrez, Z.R.; Berghofer, E.; Schoenlechner, R. Effect of green plantain flour addition to
gluten-free bread on functional bread properties and resistant starch content. Int. J. Food Sci. Technol. 2014,
doi:10.1111/ijfs.12491.
22. Kang, T.Y.; Sohn, K.H.; Yoon, M.R.; Lee, J.S.; Ko, S. Effect of the shape of rice starch granules on flour
characteristics and gluten-free bread quality. Int. J. Food Sci. Technol. 2015, doi:10.1111/ijfs.12835.
23. Ziobro, R.; Korus, J.; Witczak, M.; Juszczak, L. Influence of modified starches on properties of gluten-free
dough and bread. Part II: Quality and staling of gluten-free bread. Food Hydrocoll. 2012,
doi:10.1016/j.foodhyd.2012.02.009.
24. Hager, A.S.; Wolter, A.; Czerny, M.; Bez, J.; Zannini, E.; Arendt, E.K.; Czerny, M. Investigation of product
quality, sensory profile and ultrastructure of breads made from a range of commercial gluten-free flours
compared to their wheat counterparts. Eur. Food Res. Technol. 2012, doi:10.1007/s00217-012-1763-2.
25. Miñarro, B.; Albanell, E.; Aguilar, N.; Guamis, B.; Capellas, M. Effect of legume flours on baking
characteristics of gluten-free bread. J. Cereal Sci. 2012, doi:10.1016/j.jcs.2012.04.012.
26. Moreira, R.; Chenlo, F.; Torres, M.D. Effect of chia (Sativa hispanica L.) and hydrocolloids on the rheology
of gluten-free doughs based on chestnut flour. LWT—Food Sci. Technol. 2013, doi:10.1016/j.lwt.2012.06.008.
27. Nyembwe, P.M.; de Kock, H.L.; Taylor, J.R.N. Potential of defatted marama flour-cassava starch
composites to produce functional gluten-free bread-type dough. LWT—Food Sci. Technol. 2018,
doi:10.1016/j.lwt.2018.02.062.
28. Paciulli, M.; Rinaldi, M.; Cirlini, M.; Scazzina, F.; Chiavaro, E. Chestnut flour addition in commercial
gluten-free bread: A shelf-life study. LWT—Food Sci. Technol. 2016, doi:10.1016/j.lwt.2016.02.034.
29. Rostamian, M.; Milani, J.M.; Maleki, G. Physical properties of gluten-free bread made of corn and chickpea
flour. Int. J. Food Eng. 2014, doi:10.1515/ijfe-2013-0004.
30. Tsatsaragkou, K.; Gounaropoulos, G.; Mandala, I. Development of gluten free bread containing carob flour
and resistant starch. LWT—Food Sci. Technol. 2014, doi:10.1016/j.lwt.2014.02.043.
31. Trappey, E.F.; Khouryieh, H.; Aramouni, F.; Herald, T. Effect of sorghum flour composition and particle
size on quality properties of gluten-free bread. Food Sci. Technol. Int. 2015, doi:10.1177/1082013214523632.
32. Korus, J.; Witczak, T.; Ziobro, R.; Juszczak, L. Linseed (Linum usitatissimum L.) mucilage as a novel structure
forming agent in gluten-free bread. LWT—Food Sci. Technol. 2015, doi:10.1016/j.lwt.2015.01.040.
33. Martínez, M.M.; Díaz, Á.; Gómez, M. Effect of different microstructural features of soluble and insoluble
fibres on gluten-free dough rheology and bread-making. J. Food Eng. 2014,
doi:10.1016/j.jfoodeng.2014.06.020.
Nutrients 2018, 10, 1410 19 of 27

34. Pastuszka, D.; Gambuś, H.; Ziobro, R.; Buksa, K.; Sabat, R.; Augustyn, G. Impact of oats β-glucans on
properties of gluten-free bread. J. Microbiol. Biotechnol. 2012, 1, 972–979.
35. Rocha Parra, A.F.; Ribotta, P.D.; Ferrero, C. Apple pomace in gluten-free formulations: Effect on rheology
and product quality. Int. J. Food Sci. Technol. 2015, doi:10.1111/ijfs.12662.
36. Rózyło, R.; Dziki, D.; Gawlik-Dziki, U.; Biernacka, B.; Wójcik, M.; Ziemichód, A. Physical and antioxidant
properties of gluten-free bread enriched with carob fibre. Int. Agrophys. 2017, doi:10.1515/intag-2016-0060.
37. Sciarini, L.S.; Bustos, M.C.; Vignola, M.B.; Paesani, C.; Salinas, C.N.; Pérez, G.T. A study on fibre addition
to gluten free bread: Its effects on bread quality and in vitro digestibility. J. Food Sci. Technol. 2017,
doi:10.1007/s13197-016-2456-9.
38. Pérez-Quirce, S.; Lazaridou, A.; Biliaderis, C.G.; Ronda, F. Effect of β-glucan molecular weight on rice flour
dough rheology, quality parameters of breads and in vitro starch digestibility. LWT—Food Sci. Technol.
2017, doi:10.1016/j.lwt.2017.04.065.
39. Wolter, A.; Hager, A.S.; Zannini, E.; Czerny, M.; Arendt, E.K. Influence of dextran-producing Weissella
cibaria on baking properties and sensory profile of gluten-free and wheat breads. Int. J. Food Microbiol. 2014,
doi:10.1016/j.ijfoodmicro.2013.11.015.
40. Demirkesen, I.; Mert, B.; Sumnu, G.; Sahin, S. Utilization of chestnut flour in gluten-free bread formulations.
J. Food Eng. 2010, doi:10.1016/j.jfoodeng.2010.07.017.
41. Dizlek, H.; Ozer, M.S. The Impacts of Various Ratios of Different Hydrocolloids and Surfactants on Quality
Characteristics of Corn Starch Based Gluten-free Bread. Cereal Res. Commun. 2016,
doi:10.1556/0806.43.2015.049.
42. Hager, A.S.; Arendt, E.K. Influence of hydroxypropylmethylcellulose (HPMC), xanthan gum and their
combination on loaf specific volume, crumb hardness and crumb grain characteristics of gluten-free breads
based on rice, maize, teff and buckwheat. Food Hydrocoll. 2013, doi:10.1016/j.foodhyd.2012.12.021.
43. Mezaize, S.; Chevallier, S.; Le Bail, A.; De Lamballerie, M. Optimization of gluten-free formulations for
French-style breads. J. Food Sci. 2009, doi:10.1111/j.1750-3841.2009.01096.x.
44. Morreale, F.; Garzón, R.; Rosell, C.M. Understanding the role of hydrocolloids viscosity and hydration in
developing gluten-free bread. A study with hydroxypropylmethylcellulose. Food Hydrocoll. 2018,
doi:10.1016/j.foodhyd.2017.11.004.
45. Cappa, C.; Lucisano, M.; Mariotti, M. Influence of Psyllium, sugar beet fibre and water on gluten-free
dough properties and bread quality. Carbohydr. Polym. 2013, doi:10.1016/j.carbpol.2013.08.007.
46. Lazaridou, A.; Duta, D.; Papageorgiou, M.; Belc, N.; Biliaderis, C.G. Effects of hydrocolloids on dough
rheology and bread quality parameters in gluten-free formulations. J. Food Eng. 2007,
doi:10.1016/j.jfoodeng.2006.03.032.
47. Liu, X.; Mu, T.; Sun, H.; Zhang, M.; Chen, J.; Fauconnier, M.L. Influence of different hydrocolloids on dough
thermo-mechanical properties and in vitro starch digestibility of gluten-free steamed bread based on potato
flour. Food Chem. 2018, doi:10.1016/j.foodchem.2017.07.047.
48. Nicolae, A.; Radu, G.L.; Belc, N. Effect of sodium carboxymethyl cellulose on gluten-free dough rheology.
J. Food Eng. 2016, doi:10.1016/j.jfoodeng.2015.07.006.
49. Naji-Tabasi, S.; Mohebbi, M. Evaluation of cress seed gum and xanthan gum effect on macrostructure
properties of gluten-free bread by image processing. J. Food Meas. Charact. 2014, doi:10.1007/s11694-014-
9216-1.
50. Ziobro, R.; Juszczak, L.; Witczak, M.; Korus, J. Non-gluten proteins as structure forming agents in gluten
free bread. J. Food Sci. Technol. 2016, doi:10.1007/s13197-015-2043-5.
51. Crockett, R.; Ie, P.; Vodovotz, Y. Effects of soy protein isolate and egg white solids on the physicochemical
properties of gluten-free bread. Food Chem. 2011, doi:10.1016/j.foodchem.2011.04.030.
52. Espinosa-Ramírez, J.; Garzon, R.; Serna-Saldivar, S.O.; Rosell, C.M. Mimicking gluten functionality with β-
conglycinin concentrate: Evaluation in gluten free yeast-leavened breads. Food Res. Int. 2018,
doi:10.1016/j.foodres.2017.12.055.
53. Rodriguez Furlán, L.T.; Pérez Padilla, A.; Campderrós, M.E. Improvement of gluten-free bread properties
by the incorporation of bovine plasma proteins and different saccharides into the matrix. Food Chem. 2015,
doi:10.1016/j.foodchem.2014.08.033.
54. Phongthai, S.; D’Amico, S.; Schoenlechner, R.; Rawdkuen, S. Comparative study of rice bran protein
concentrate and egg albumin on gluten-free bread properties. J. Cereal Sci. 2016,
doi:10.1016/j.jcs.2016.09.015.
Nutrients 2018, 10, 1410 20 of 27

55. Marco, C.; Rosell, C.M. Breadmaking performance of protein enriched, gluten-free breads. Eur. Food Res.
Technol. 2008, doi:10.1007/s00217-008-0838-6.
56. Mohammadi, M.; Azizi, M.H.; Neyestani, T.R.; Hosseini, H.; Mortazavian, A.M. Development of gluten-
free bread using guar gum and transglutaminase. J. Ind. Eng. Chem. 2015, doi:10.1016/j.jiec.2014.06.013.
57. Pongjaruvat, W.; Methacanon, P.; Seetapan, N.; Fuongfuchat, A.; Gamonpilas, C. Influence of
pregelatinised tapioca starch and transglutaminase on dough rheology and quality of gluten-free jasmine
rice breads. Food Hydrocoll. 2014, doi:10.1016/j.foodhyd.2013.09.004.
58. Yano, H. Improvements in the bread-making quality of gluten-free rice batter by glutathione. J. Agric. Food
Chem. 2010, doi:10.1021/jf1003946.
59. Hamada, S.; Suzuki, K.; Aoki, N.; Suzuki, Y. Improvements in the qualities of gluten-free bread after using
a protease obtained from Aspergillus oryzae. J. Cereal Sci. 2013, doi:10.1016/j.jcs.2012.10.008.
60. Hatta, E.; Matsumoto, K.; Honda, Y. Bacillolysin, papain, and subtilisin improve the quality of gluten-free
rice bread. J. Cereal Sci. 2015, doi:10.1016/j.jcs.2014.10.004.
61. Elgeti, D.; Nordlohne, S.D.; Föste, M.; Besl, M.; Linden, M.H.; Heinz, V.; Jekle, M.; Becker, T. Volume and
texture improvement of gluten-free bread using quinoa white flour. J. Cereal Sci. 2014,
doi:10.1016/j.jcs.2013.10.010.
62. Nunes, M.H.B.; Moore, M.M.; Ryan, L.A.M.; Arendt, E.K. Impact of emulsifiers on the quality and
rheological properties of gluten-free breads and batters. Eur. Food Res. Technol. 2009, doi:10.1007/s00217-
008-0972-1.
63. López-Tenorio, J.A.; Rodríguez-Sandoval, E.; Sepúlveda-Valencia, J.U. The influence of different
emulsifiers on the physical and textural characteristics of gluten-free cheese bread. J. Texture Stud. 2015,
doi:10.1111/jtxs.12121.
64. Alencar, N.M.M.; de Morais, E.C.; Steel, C.J.; Bolini, H.M.A. Sensory characterisation of gluten-free bread
with addition of quinoa, amaranth flour and sweeteners as an alternative for coeliac patients. Int. J. Food
Sci. Technol. 2017, 52, 872–879, doi:10.1111/ijfs.13349.
65. Machado Alencar, N.M.; Steel, C.J.; Alvim, I.D.; de Morais, E.C.; Andre Bolini, H.M. Addition of quinoa
and amaranth flour in gluten-free breads: Temporal profile and instrumental analysis. LWT—Food Sci.
Technol. 2015, doi:10.1016/j.lwt.2015.02.029.
66. Alvarez-Jubete, L.; Auty, M.; Arendt, E.K.; Gallagher, E. Baking properties and microstructure of
pseudocereal flours in gluten-free bread formulations. Eur. Food Res. Technol. 2009, doi:10.1007/s00217-009-
1184-z.
67. Bernardi, C.; Sánchez, H.; Freyre, M.; Osella, C. Gluten-free bread formulated with Prosopis ruscifolia
(vinal) seed and corn flours. Int. J. Food Sci. Nutr. 2010, doi:10.3109/09637480903373336.
68. Campo, E.; del Arco, L.; Urtasun, L.; Oria, R.; Ferrer-Mairal, A. Impact of sourdough on sensory properties
and consumers’ preference of gluten-free breads enriched with teff flour. J. Cereal Sci. 2016,
doi:10.1016/j.jcs.2015.09.010.
69. Chakraborty, S.K.; Gupta, S.; Kotwaliwale, N. Quality characteristics of gluten free bread from barnyard
millet–soy flour blends. J. Food Sci. Technol. 2016, doi:10.1007/s13197-016-2429-z.
70. Mariotti, M.; Pagani, M.A.; Lucisano, M. The role of buckwheat and HPMC on the breadmaking properties
of some commercial gluten-free bread mixtures. Food Hydrocoll. 2013, doi:10.1016/j.foodhyd.2012.07.005.
71. Sandri, L.T.B.; Santos, F.G.; Fratelli, C.; Capriles, V.D. Development of gluten-free bread formulations
containing whole chia flour with acceptable sensory properties. Food Sci. Nutr. 2017, doi:10.1002/fsn3.495.
72. Skendi, A.; Mouselemidou, P.; Papageorgiou, M.; Papastergiadis, E. Effect of acorn meal-water
combinations on technological properties and fine structure of gluten-free bread. Food Chem. 2018,
doi:10.1016/j.foodchem.2018.01.144.
73. Smith, B.M.; Bean, S.R.; Herald, T.J.; Aramouni, F.M. Effect of HPMC on the Quality of Wheat-Free Bread
Made from Carob Germ Flour-Starch Mixtures. J. Food Sci. 2012, doi:10.1111/j.1750-3841.2012.02739.x.
74. Andersson, H.; Öhgren, C.; Johansson, D.; Kniola, M.; Stading, M. Extensional flow, viscoelasticity and
baking performance of gluten-free zein-starch doughs supplemented with hydrocolloids. Food Hydrocoll.
2011, doi:10.1016/j.foodhyd.2010.11.028.
75. Numfon, R. Effect of different hydrocolloids on properties of gluten-free bread based on small broken
broken rice berry flour. Food Sci. Technol. Int. 2017, 23, 310–317.
Nutrients 2018, 10, 1410 21 of 27

76. Rodriguez-Sandoval, E.; Cortes-Rodriguez, M.; Manjarres-Pinzon, K. Effect of hydrocolloids on the pasting
profiles of tapioca starch mixtures and the baking properties of gluten-free cheese bread. J. Food Process.
Preserv. 2015, doi:10.1111/jfpp.12398.
77. Aprodu, I.; Banu, I. Influence of dietary fiber, water, and glucose oxidase on rheological and baking
properties of maize based gluten-free bread. Food Sci. Biotechnol. 2015, doi:10.1007/s10068-015-0167-z.
78. Föste, M.; Nordlohne, S.D.; Elgeti, D.; Linden, M.H.; Heinz, V.; Jekle, M.; Becker, T. Impact of quinoa bran
on gluten-free dough and bread characteristics. Eur. Food Res. Technol. 2014, doi:10.1007/s00217-014-2269-x.
79. Ronda, F.; Perez-Quirce, S.; Lazaridou, A.; Biliaderis, C.G. Effect of barley and oat β-glucan concentrates
on gluten-free rice-based doughs and bread characteristics. Food Hydrocoll. 2015,
doi:10.1016/j.foodhyd.2015.02.031.
80. Ziobro, R.; Korus, J.; Juszczak, L.; Witczak, T. Influence of inulin on physical characteristics and staling rate
of gluten-free bread. J. Food Eng. 2013, doi:10.1016/j.jfoodeng.2012.10.049.
81. Caputo, I.; Lepretti, M.; Martucciello, S.; Esposito, C. Enzymatic strategies to detoxify gluten: Implications
for celiac disease. Enzyme Res. 2010, doi:10.4061/2010/174354.
82. Diowksz, A.; Leszczyńska, J. Hypoallergenic wheat bread: Response to an emerging issue. Food Agric.
Immunol. 2014, doi:10.1080/09540105.2013.848184.
83. Brites, C.; Trigo, M.J.; Santos, C.; Collar, C.; Rosell, C.M. Maize-based gluten-free bread: Influence of
processing parameters on sensory and instrumental quality. Food Bioprocess Technol. 2010,
doi:10.1007/s11947-008-0108-4.
84. Cornejo, F.; Rosell, C.M. Influence of germination time of brown rice in relation to flour and gluten free
bread quality. J. Food Sci. Technol. 2015, doi:10.1007/s13197-015-1720-8.
85. Marti, A.; Marengo, M.; Bonomi, F.; Casiraghi, M.C.; Franzetti, L.; Pagani, M.A.; Iametti, S. Molecular
features of fermented teff flour relate to its suitability for the production of enriched gluten-free bread.
LWT—Food Sci. Technol. 2017, doi:10.1016/j.lwt.2016.12.042.
86. Kringel, D.H.; da Silva Filipini, G.; de Las Mercedes Salas-Mellado, M. Influence of phosphorylated rice
flour on the quality of gluten-free bread. Int. J. Food Sci. Technol. 2017, 52, 1291–1298.
87. Shin, D.J.; Kim, W.; Kim, Y. Physicochemical and sensory properties of soy bread made with germinated,
steamed, and roasted soy flour. Food Chem. 2013, doi:10.1016/j.foodchem.2013.03.005.
88. Martínez, M.M.; Oliete, B.; Román, L.; Gómez, M. Influence of the addition of extruded flours on rice bread
quality. J. Food Qual. 2014, doi:10.1111/jfq.12071.
89. Van Riemsdijk, L.E.; van der Goot, A.J.; Hamer, R.J. The use of whey protein particles in gluten-free bread
production, the effect of particle stability. Food Hydrocoll. 2011, doi:10.1016/j.foodhyd.2011.03.017.
90. Van Berge-Henegouwen, G.P.; Mulder, C.J.J. Pioneer in the Gluten Free Diet: Willem-Karel Dicke 1905–
1962, over 50 Years of Gluten Free Diet. Gut 1993, 34, 1473–1475.
91. Choung, R.S.; Unalp-Arida, A.; Ruhl, C.E.; Brantner, T.L.; Everhart, J.E.; Murray, J.A. Less hidden celiac
disease but increased gluten avoidance without a diagnosis in the United States. Mayo Clin. Proc. 2017, 92,
30–38, doi:10.1016/j.mayocp.2016.10.012.
92. Golley, S.; Corsini, N.; Topping, D.; Morell, M.; Mohr, P. Motivations for avoiding wheat consumption in
Australia: Results from a population survey. Public Health Nutr. 2015, 18, 490–499,
doi:10.1017/S1368980014000652.
93. Stevenson, J.C.; Rankin-Sunter, K.; Maki, C.; Bruna, S.; Mosher, M.J.; Barrett, C.E. Community based pilot
study of diagnostic paths to the gluten free diet. Int. J. Celiac Dis. 2015, 3, 14–24, doi:10.12691/ijcd-3-1-7.
94. NSF International NSF International Survey Finds U.S. Consumers Struggle to Define and Identify Gluten.
Available online: http://www.nsf.org/newsroom/nsf-survey-finds-us-consumers-struggle-to-define-
identify-gluten (accessed on 1 August 2018).
95. Singh, P.; Arora, A.; Strand, T.A.; Leffler, D.A.; Catassi, C.; Green, P.H.; Kelly, C.P.; Ahuja, V.; Makharia,
G.K. Global Prevalence of Celiac Disease: Systematic Review and Meta-analysis. Clin. Gastroenterol. Hepatol.
2018, 16, 823–836, doi:10.1016/j.cgh.2017.06.037.
96. Copelton, D.A.; Valle, G. “You don’t need a prescription to go gluten-free”: The scientific self-diagnosis of
celiac disease. Soc. Sci. Med. 2009, 69, 623–631, doi:10.1016/j.socscimed.2009.05.012.
97. Gaesser, G.A.; Angadi, S.S. Gluten-free diet: Imprudent dietary advice for the general population? J. Acad.
Nutr. Diet. 2012, 112, 1330–1333, doi:10.1016/j.jand.2012.06.009.
98. Lebwohl, B.; Cao, Y.; Zong, G.; Hu, F.B.; Green, P.H.R.; Neugut, A.I.; Rimm, E.B.; Sampson, L.; Dougherty,
L.W.; Giovannucci, E.; Willett, W.C.; Sun, Q.; Chan, A.T. Long term gluten consumption in adults without
Nutrients 2018, 10, 1410 22 of 27

celiac disease and risk of coronary heart disease: Prospective cohort study. BMJ 2017, 357, j1892,
doi:10.1136/bmj.j1892.
99. Hartman Group Gluten Free Trend. Available online: https://www.hartman-group.com/hartbeat-
acumen/120/gluten-free-trend (accessed on 2 August 2018).
100. Gluten-Free Foods in Canada; Packaged Facts: Rockville, MD, USA, 2013.
101. Dunn, C.; House, L.; Shelnutt, K.P. Consumer Perceptions of Gluten-Free Products and the Healthfulness
of Gluten-Free Diets. J. Nutr. Educ. Behav. 2014, 46, S184–S185, doi:10.1016/j.jneb.2014.04.280.
102. Haroldson, A.; Yen, C.-L. (Alan) Consumer Understanding of Nutrition Marketing Terms: A Pilot Study.
J. Fam. Consum. Sci. 2016, 108, 24–31, doi:10.14307/JFCS108.3.24.
103. Silvester, J.A.; Weiten, D.; Graff, L.A.; Walker, J.R.; Duerksen, D.R. Is it gluten-free? Relationship between
self-reported gluten-free diet adherence and knowledge of gluten content of foods. Nutrition 2016, 32, 777–
783, doi:10.1016/j.nut.2016.01.021.
104. O’Donnell, B.; Edelstein, S. Dietitians’ perceptions of adherence to a gluten-free diet among low-income
individuals with celiac disease. Top. Clin. Nutr. 2009, 24, 82–89, doi:10.1097/TIN.0b013e3181989c27.
105. Halmos, E.P.; Deng, M.; Knowles, S.R.; Sainsbury, K.; Mullan, B.; Tye-Din, J.A. Food knowledge and
psychological state predict adherence to a gluten-free diet in a survey of 5310 Australians and New
Zealanders with coeliac disease. Aliment. Pharmacol. Ther. 2018, 48, 78–86.
106. Zarkadas, M.; Cranney, A.; Case, S.; Molloy, M.; Switzer, C.; Graham, I.D.; Butzner, J.D.; Rashid, M.;
Warren, R.E.; Burrows, V. The impact of a gluten-free diet on adults with coeliac disease: Results of a
national survey. J. Hum. Nutr. Diet. 2006, 19, 41–49, doi:10.1111/j.1365-277X.2006.00659.x.
107. Leffler, D.A.; Edwards-George, J.; Dennis, M.; Schuppan, D.; Cook, F.; Franko, D.L.; Blom-Hoffman, J.;
Kelly, C.P. Factors that influence adherence to a gluten-free diet in adults with celiac disease. Dig. Dis. Sci.
2008, 53, 1573–1581, doi:10.1007/s10620-007-0055-3.
108. Villafuerte-Galvez, J.; Vanga, R.R.; Dennis, M.; Hansen, J.; Leffler, D.A.; Kelly, C.P.; Mukherjee, R. Factors
governing long-term adherence to a gluten-free diet in adult patients with coeliac disease. Aliment.
Pharmacol. Ther. 2015, 42, 753–760, doi:10.1111/apt.13319.
109. Zarkadas, M.; Dubois, S.; Macisaac, K.; Cantin, I.; Rashid, M.; Roberts, K.C.; La Vieille, S.; Godefroy, S.;
Pulido, O.M. Living with coeliac disease and a gluten-free diet: A Canadian perspective. J. Hum. Nutr. Diet.
2013, 26, 10–23, doi:10.1111/j.1365-277X.2012.01288.x.
110. Silvester, J.A.; Weiten, D.; Graff, L.A.; Walker, J.R.; Duerksen, D.R. Living gluten-free: Adherence,
knowledge, lifestyle adaptations and feelings towards a gluten-free diet. J. Hum. Nutr. Diet. 2016, 29, 374–
382, doi:10.1111/jhn.12316.
111. Do Nascimento, A.B.; Fiates, G.M.R.; Dos Anjos, A.; Teixeira, E. Gluten-free is not enough-perception and
suggestions of celiac consumers. Int. J. Food Sci. Nutr. 2014, 65, 394–398.
112. Stevens, L.; Rashid, M. Gluten-free and regular foods: A cost comparison. Can. J. Diet. Pract. Res. 2008, 69,
147–150, doi:10.3148/69.3.2008.147.
113. Singh, J.; Whelan, K. Limited availability and higher cost of gluten-free foods. J. Hum. Nutr. Diet. 2011, 24,
479–486, doi:10.1111/j.1365-277X.2011.01160.x.
114. Lambert, K.; Ficken, C. Cost and affordability of a nutritionally balanced gluten-free diet: Is following a
gluten-free diet affordable? Nutr. Diet 2016, 73, 36–42, doi:10.1111/1747-0080.12171.
115. Lee, A.R.; Ng, D.L.; Zivin, J.; Green, P.H.R. Economic burden of a gluten-free diet. J. Hum. Nutr. Diet. 2007,
423–430, doi:10.1111/j.1365-277X.2007.00763.x.
116. Lee, A.; Newman, J.M. Celiac diet: Its impact on quality of life. J. Am. Diet. Assoc. 2003, 103, 1533–1535,
doi:10.1016/j.jada.2003.08.027.
117. Do Nascimento, A.B.; Fiates, G.M.R.; Dos Anjos, A.; Teixeira, E. Analysis of ingredient lists of commercially
available gluten-free and gluten-containing food products using the text mining technique. Int. J. Food Sci.
Nutr. 2013, 64, 217–222, doi:10.3109/09637486.2012.718744.
118. Fry, L.; Madden, A.M.; Fallaize, R. An investigation into the nutritional composition and cost of gluten-free
versus regular food products in the UK. J. Hum. Nutr. Diet. 2018, 31, 108–120, doi:10.1111/jhn.12502.
119. Miranda, J.; Lasa, A.; Bustamante, M.A.; Churruca, I.; Simon, E. Nutritional Differences Between a Gluten-
free Diet and a Diet Containing Equivalent Products with Gluten. Plant Foods Hum. Nutr. 2014, 69, 182–187,
doi:10.1007/s11130-014-0410-4.
120. Kulai, T.; Rashid, M. Assessment of nutritional adequacy of packaged gluten-free food products. Can. J.
Diet. Pract. Res. 2014, 75, 186–190, doi:10.3148/cjdpr-2014-022.
Nutrients 2018, 10, 1410 23 of 27

121. Berti, C.; Riso, P.; Monti, L.D.; Porrini, M. In vitro starch digestibility and in vivo glucose response of gluten-
free foods and their gluten counterparts. Eur. J. Nutr. 2004, 43, 198–204, doi:10.1007/s00394-004-0459-1.
122. Thompson, T. Thiamin, riboflavin, and niacin contents of the gluten-free diet: Is there cause for concern? J.
Am. Diet. Assoc. 1999, 99, 858–862, doi:10.1016/S0002-8223(99)00205-9.
123. Thompson, T. Folate, iron, and dietary fiber contents of the gluten-free diet. J. Am. Diet. Assoc. 2000, 100,
1389–1396, doi:10.1016/S0002-8223(00)00386-2.
124. Barone, M.; Della Valle, N.; Rosania, R.; Facciorusso, A.; Trotta, A.; Cantatore, F.P.; Falco, S.; Pignatiello, S.;
Viggiani, M.T.; Amoruso, A.; et al. A comparison of the nutritional status between adult celiac patients on
a long-term, strictly gluten-free diet and healthy subjects. Eur. J. Clin. Nutr. 2016, 70, 23–27,
doi:10.1038/ejcn.2015.114.
125. Wild, D.; Robins, G.G.; Burley, V.J.; Howdle, P.D. Evidence of high sugar intake, and low fibre and mineral
intake, in the gluten-free diet. Aliment. Pharmacol. Ther. 2010, 32, 573–581, doi:10.1111/j.1365-
2036.2010.04386.x.
126. Babio, N.; Alcázar, M.; Castillejo, G.; Recasens, M.; Martínez-Cerezo, F.; Gutiérrez-Pensado, V.; Masip, G.;
Vaqué, C.; Vila-Martí, A.; Torres-Moreno, M.; et al. Patients with celiac disease reported higher
consumption of added sugar and total fat than healthy individuals. J. Pediatr. Gastroenterol. Nutr. 2017, 64,
63–69, doi:10.1097/MPG.0000000000001251.
127. Öhlund, K.; Olsson, C.; Hernell, O.; Öhlund, I. Dietary shortcomings in children on a gluten-free diet. J.
Hum. Nutr. Diet 2010, 23, 294–300, doi:10.1111/j.1365-277X.2010.01060.x.
128. Ferrara, P.; Cicala, M.; Tiberi, E.; Spadaccio, C.; Marcella, L.; Gatto, A.; Calzolari, P.; Castellucci, G. High fat
consumption in children with celiac disease. Acta Gastroenterol. Belg. 2009, 72, 296–300.
129. Valitutti, F.; Iorfida, D.; Anania, C.; Trovato, C.M.; Montuori, M.; Cucchiara, S.; Catassi, C. Cereal
Consumption among Subjects with Celiac Disease: A Snapshot for Nutritional Considerations. Nutrients
2017, 9, doi:10.3390/nu9040396.
130. Shepherd, S.J.; Gibson, P.R. Nutritional inadequacies of the gluten-free diet in both recently-diagnosed and
long-term patients with coeliac disease. J. Hum. Nutr. Diet. 2013, 26, 349–358, doi:10.1111/jhn.12018.
131. Hallert, C.; Grant, C.; Grehn, S.; Grännö, C.; Hultén, S.; Midhagen, G.; Ström, M.; Svensson, H.;
Valdimarsson, T. Evidence of poor vitamin status in coeliac patients on a gluten-free diet for 10 years.
Aliment. Pharmacol. Ther. 2002, 16, 1333–1339, doi:10.1046/j.1365-2036.2002.01283.x.
132. Thompson, T.; Dennis, M.; Higgins, L.A.; Lee, A.R.; Sharrett, M.K. Gluten-free diet survey: Are Americans
with coeliac disease consuming recommended amounts of fibre, iron, calcium and grain foods? J. Hum.
Nutr. Diet. 2005, 18, 163–169, doi:10.1111/j.1365-277X.2005.00607.x.
133. Marcason, W. Is there evidence to support the claim that a gluten-free diet should be used for weight loss?
J. Am. Diet Assoc. 2011, 111, 1786, doi:10.1016/j.jada.2011.09.030.
134. Kim, H.; Demyen, M.F.; Mathew, J.; Kothari, N.; Feurdean, M.; Ahlawat, S.K. Obesity, Metabolic Syndrome,
and Cardiovascular Risk in Gluten-Free Followers Without Celiac Disease in the United States: Results
from the National Health and Nutrition Examination Survey 2009–2014. Dig. Dis. Sci. 2017, 62, 2440–2448,
doi:10.1007/s10620-017-4583-1.
135. Dickey, W.; Kearney, N. Overweight in celiac disease: Prevalence, clinical characteristics, and effect of a
gluten-free diet. Am. J. Gastroenterol. 2006, 101, 2356–2359, doi:AJG750 [pii].
136. Kabbani, T.A.; Goldberg, A.; Kelly, C.P.; Pallav, K.; Tariq, S.; Peer, A.; Hansen, J.; Dennis, M.; Leffler, D. a
Body mass index and the risk of obesity in coeliac disease treated with the gluten-free diet. Aliment.
Pharmacol. Ther. 2012, 35, 723–729, doi:10.1111/j.1365-2036.2012.05001.x.
137. Siddh, L.; Sengar, G.; Nagraj, N.; Shyam, R.; Garg, P. Body mass index in celiac disease and effect of a
gluten-free diet on body mass index. Int. J. Adv. Med. 2016, 3, 813–815, doi:10.18203/2349-3933.ijam20162611.
138. Cheng, J.; Brar, P.S.; Lee, A.R.; Green, P.H.R. Body mass index in celiac disease: Beneficial effect of a gluten-
free diet. J. Clin. Gastroenterol. 2010, 44, 267–271, doi:10.1097/MCG.0b013e3181b7ed58.
139. Ukkola, A.; Mäki, M.; Kurppa, K.; Collin, P.; Huhtala, H.; Kekkonen, L.; Kaukinen, K. Changes in body
mass index on a gluten-free diet in coeliac disease: A nationwide study. Eur. J. Intern. Med. 2012, 23, 384–
388, doi:10.1016/j.ejim.2011.12.012.
140. Tortora, R.; Capone, P.; De Stefano, G.; Imperatore, N.; Gerbino, N.; Donetto, S.; Monaco, V.; Caporaso, N.;
Rispo, A. Metabolic syndrome in patients with coeliac disease on a gluten-free diet. Aliment. Pharmacol.
Ther. 2015, 41, 352–359, doi:10.1111/apt.13062.
Nutrients 2018, 10, 1410 24 of 27

141. Sapone, A.; Bai, J.C.; Ciacci, C.; Dolinsek, J.; Green, P.H.R.; Hadjivassiliou, M.; Kaukinen, K.; Rostami, K.;
Sanders, D.S.; Schumann, M.; et al. Spectrum of gluten-related disorders: Consensus on new nomenclature
and classification. BMC Med. 2012, 10, doi:10.1186/1741-7015-10-13.
142. Elli, L.; Villalta, D.; Roncoroni, L.; Barisani, D.; Ferrero, S.; Pellegrini, N.; Bardella, M.T.; Valiante, F.; Tomba,
C.; Carroccio, A.; et al. Nomenclature and diagnosis of gluten-related disorders: A position statement by
the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO). Dig. Liver Dis. 2017, 49,
138–146.
143. Cianferoni, A. Wheat allergy: Diagnosis and management. J. Asthma Allergy 2016, 9, 13–25,
doi:10.2147/JAA.S81550.
144. Catassi, C.; Bai, J.C.; Bonaz, B.; Bouma, G.; Calabrò, A.; Carroccio, A.; Castillejo, G.; Ciacci, C.; Cristofori, F.;
Dolinsek, J.; et al. Non-celiac gluten sensitivity: The new frontier of gluten related disorders. Nutrients 2013,
5, 3839–3853.
145. Monsuur, A.J.; Wijmenga, C. Understanding the molecular basis of celiac disease: What genetic studies
reveal. Ann. Med. 2006, 38, 578–591, doi:10.1080/07853890600989054.
146. Fasano, A.; Catassi, C. Celiac Disease. N. Engl. J. Med. 2012, 25367, 2419–2426, doi:10.1056/NEJMcp1113994.
147. Reunala, T.; Salmi, T.T.; Hervonen, K. Dermatitis herpetiformis: Pathognomonic transglutaminase IgA
deposits in the skin and excellent prognosis on a gluten-free diet. Acta. Derm. Venereol. 2015, 95, 917–922.
148. Shahbazkhani, B.; Sadeghi, A.; Malekzadeh, R.; Khatavi, F.; Etemadi, M.; Kalantri, E.; Rostami-Nejad, M.;
Rostami, K. Non-celiac gluten sensitivity has narrowed the spectrum of irritable bowel syndrome: A
double-blind randomized placebo-controlled trial. Nutrients 2015, 7, 4542–4554, doi:10.3390/nu7064542.
149. Makharia, A.; Catassi, C.; Makharia, G.K. The overlap between irritable bowel syndrome and non-celiac
gluten sensitivity: A clinical dilemma. Nutrients 2015, 7, 10417–10426, doi:10.3390/nu7125541.
150. Niland, B.; Cash, B.D. Health benefits and adverse effects of a gluten-free diet in non-celiac disease patients.
Gastroenterol. Hepatol. 2018, 14, 82–91.
151. Sansotta, N.; Amirikian, K.; Guandalini, S.; Jericho, H. Celiac disease symptom resolution: Effectiveness of
the gluten-free diet. J. Pediatr. Gastroenterol. Nutr. 2018, 66, 48–52, doi:10.1097/MPG.0000000000001634.
152. Jericho, H.; Sansotta, N.; Guandalini, S. Extraintestinal manifestations of celiac disease: Effectiveness of the
gluten-free diet. J. Pediatr. Gastroenterol. Nutr. 2017, 65, 75–79, doi:10.1097/MPG.0000000000001420.
153. Pulido, O.; Zarkadas, M.; Dubois, S.; Macisaac, K.; Cantin, I.; La Vieille, S.; Godefroy, S.; Rashid, M. Clinical
features and symptom recovery on a gluten-free diet in Canadian adults with celiac disease. Can. J.
Gastroenterol. 2012, 27, 449–453.
154. Casella, S.; Zanini, B.; Lanzarotto, F.; Villanacci, V.; Ricci, C.; Lanzini, A. Celiac disease in elderly adults:
Clinical, serological, and histological characteristics and the effect of a gluten-free diet. J. Am. Geriatr. Soc.
2012, 60, 1064–1069, doi:10.1111/j.1532-5415.2012.03997.x.
155. Murray, J.A.; Watson, T.; Clearman, B.; Mitros, F. Effect of a gluten-free diet on gastrointestinal symptoms
in celiac disease. Am. J. Clin. Nutr. 2004, 79, 669–673, doi:10.1093/ajcn/79.4.669.
156. Bazzigaluppi, E.; Roggero, P.; Parma, B.; Brambillasca, M.F.; Meroni, F.; Mora, S.; Bosi, E.; Barera, G.
Antibodies to recombinant human tissue-transglutaminase in coeliac disease: Diagnostic effectiveness and
decline pattern after gluten-free diet. Dig. Liver Dis. 2006, 38, 98–102, doi:10.1016/j.dld.2005.10.020.
157. Sugai, E.; Nachman, F.; Váquez, H.; González, A.; Andrenacci, P.; Czech, A.; Niveloni, S.; Mazure, R.;
Smecuol, E.; Cabanne, A.; et al. Dynamics of celiac disease-specific serology after initiation of a gluten-free
diet and use in the assessment of compliance with treatment. Dig. Liver Dis. 2010, 42, 352–358,
doi:10.1016/j.dld.2009.07.011.
158. Galli, G.; Esposito, G.; Lahner, E.; Pilozzi, E.; Corleto, V.D.; Di Giulio, E.; Aloe Spiriti, M.A.; Annibale, B.
Histological recovery and gluten-free diet adherence: A prospective 1-year follow-up study of adult
patients with coeliac disease. Aliment. Pharmacol. Ther. 2014, 40, 639–647, doi:10.1111/apt.12893.
159. Lanzini, A.; Lanzarotto, F.; Villanacci, V.; Mora, A.; Bertolazzi, S.; Turini, D.; Carella, G.; Malagoli, A.;
Ferrante, G.; Cesana, B.M.; Ricci, C. Complete recovery of intestinal mucosa occurs very rarely in adult
coeliac patients despite adherence to gluten-free diet. Aliment. Pharmacol. Ther. 2009, 29, 1299–1308,
doi:10.1111/j.1365-2036.2009.03992.x.
160. Rubio-Tapia, A.; Rahim, M.W.; See, J.A.; Lahr, B.D.; Wu, T.T.; Murray, J.A. Mucosal recovery and mortality
in adults with celiac disease after treatment with a gluten-free diet. Am. J. Gastroenterol. 2010, 105, 1412–
1420, doi:10.1038/ajg.2010.10.
Nutrients 2018, 10, 1410 25 of 27

161. Bardella, M.T.; Velio, P.; Cesana, B.M.; Prampolini, L.; Casella, G.; Di Bella, C.; Lanzini, A.; Gambarotti, M.;
Bassotti, G.; Villanacci, V. Coeliac disease: A histological follow-up study. Histopathology 2007, 50, 465–471,
doi:10.1111/j.1365-2559.2007.02621.x.
162. Lee, S.; Lo, W.; Memeo, L.; Rotterdam, H.; Green, P. Duodenal histology in patients with celiac disease after
treatment with a gluten-free diet. Gastrointest. Endosc. 2003, 57, 187–191.
163. Lebwohl, B.; Murray, J.A.; Rubio-Tapia, A.; Green, P.H.R.; Ludvigsson, J.F. Predictors of persistent villous
atrophy in coeliac disease: A population-based study. Aliment. Pharmacol. Ther. 2014, 39, 488–495,
doi:10.1111/apt.12621.
164. Lewis, H.M.; Renaula, T.L.; Garioch, J.J.; Leonard, J.N.; Fry, J.S.; Collin, P.; Evans, D.; Fry, L. Protective effect
of gluten-free diet against development of lymphoma in dermatitis herpetiformis. Br. J. Dermatol. 1996, 135,
363–367.
165. Hietikko, M.; Hervonen, K.; Salmi, T.; Ilus, T.; Zone, J.J.; Kaukinen, K.; Reunala, T.; Lindfors, K.
Disappearance of epidermal transglutaminase and IgA deposits from the papillary dermis of patients with
dermatitis herpetiformis after a long-term gluten-free diet. Br. J. Dermatol. 2018, 178, e198–e201,
doi:10.1111/bjd.15995.
166. Reunala, T.; Blomqvist, K.; Tarpila, S.; Halme, H.; Kangas, K. Gluten-free diet in dermatitis herpetiformis.
Br. J. Dermatol. 1977, 97, 473–480, doi:10.1111/j.1365-2133.1977.tb14122.x.
167. Garioch, J.J.; Lewis, H.M.; Sargent, S.A.; Leonard, J.N.; Fry, L. 25 Years’ Experience of a Gluten-Free Diet in
the Treatment of Dermatitis Herpetiformis. Br. J. Dermatol. 1994, 131, 541–545, doi:10.1111/j.1365-
2133.1994.tb08557.x.
168. Fry, L.; Riches, D.J.; Seah, P.P.; Hoffbrand, A.V. Clearance of skin lesions in dermatitis herpetiformis after
gluten withdrawal. Lancet 1973, 301, 288–291, doi:10.1016/S0140-6736(73)91539-0.
169. Pellecchia, M.T.; Scala, R.; Perretti, A.; De Michele, G.; Santoro, L.; Filla, A.; Ciacci, C.; Barone, P. Cerebellar
ataxia associated with subclinical celiac disease responding to gluten-free diet. Neurology 1999, 53, 1606–
1606, doi:10.1212/WNL.53.7.1606-a.
170. Helsing, P.; Frøen, H. Dermatitis herpetiformis presenting as ataxia in a child. Acta Derm. Venereol. 2007, 87,
163–165, doi:10.2340/00015555-0220.
171. Hadjivassiliou, M.; Davies-Jones, G.A.B.; Sanders, D.S.; Grünewald, R.A. Dietary treatment of gluten ataxia.
J. Neurol. Neurosurg. Psychiatry 2003, 74, 1221–1224, doi:10.1136/JNNP.74.9.1221.
172. Hadjivassiliou, M.; Grünewald, R.A.; Sanders, D.S.; Shanmugarajah, P.; Hoggard, N. Effect of gluten-free
diet on cerebellar MR spectroscopy in gluten ataxia. Neurology 2017, 89, 705–709,
doi:10.1212/WNL.0000000000004237.
173. Tovoli, F.; Masi, C.; Guidetti, E.; Negrini, G.; Paterini, P.; Bolondi, L. Clinical and diagnostic aspects of
gluten related disorders. World J. Clin. Cases 2015, 3, 275–284, doi:10.12998/wjcc.v3.i3.275.
174. Elli, L.; Tomba, C.; Branchi, F.; Roncoroni, L.; Lombardo, V.; Bardella, M.T.; Ferretti, F.; Conte, D.; Valiante,
F.; Fini, L.; et al. Evidence for the presence of non-celiac gluten sensitivity in patients with functional
gastrointestinal symptoms: Results from a multicenter randomized double-blind placebo-controlled gluten
challenge. Nutrients 2016, 8, doi:10.3390/nu8020084.
175. Di Sabatino, A.; Volta, U.; Salvatore, C.; Biancheri, P.; Caio, G.; De Giorgio, R.; Di Stefano, M.; Corazza, G.R.
Small amounts of gluten in subjects with suspected nonceliac gluten sensitivity: a randomized, double-
blind, placebo-controlled, cross-over trial. Clin. Gastroenterol. Hepatol. 2015, 13, 1604–1612,
doi:10.1016/j.cgh.2015.01.029.
176. Dale, H.F.; Hatlebakk, J.G.; Hovdenak, N.; Ystad, S.O.; Lied, G.A. The effect of a controlled gluten challenge
in a group of patients with suspected non-coeliac gluten sensitivity: A randomized, double-blind placebo-
controlled challenge. Neurogastroenterol. Motil. 2018, e13332, doi:10.1111/nmo.13332.
177. Molina-Infante, J.; Carroccio, A. Suspected Nonceliac Gluten Sensitivity Confirmed in Few Patients After
Gluten Challenge in Double-Blind, Placebo-Controlled Trials. Clin. Gastroenterol. Hepatol. 2017, 15, 339–348,
doi:10.1016/j.cgh.2016.08.007.
178. Aziz, I.; Trott, N.; Briggs, R.; North, J.R.; Hadjivassiliou, M.; Sanders, D.S. Efficacy of a gluten-free diet in
subjects with irritable bowel syndrome-diarrhea unaware of their HLA-DQ2/8 genotype. Clin.
Gastroenterol. Hepatol. 2016, 14, 696–703.e1, doi:10.1016/j.cgh.2015.12.031.
179. Vazquez-Roque, M.I.; Camilleri, M.; Smyrk, T.; Murray, J.A.; Marietta, E.; O’Neill, J.; Carlson, P.; Lamsam,
J.; Janzow, D.; Eckert, D.; et al. A controlled trial of gluten-free diet in patients with irritable bowel
Nutrients 2018, 10, 1410 26 of 27

syndrome-diarrhea: Effects on bowel frequency and intestinal function. Gastroenterology 2013, 144, 903–911,
doi:10.1053/j.gastro.2013.01.049.
180. Junker, Y.; Zeissig, S.; Kim, S.-J.; Barisani, D.; Wieser, H.; Leffler, D.A.; Zevallos, V.; Libermann, T.A.; Dillon,
S.; Freitag, T.L.; et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-
like receptor 4. J. Exp. Med. 2012, 209, 2395–2408, doi:10.1084/jem.20102660.
181. McIntosh, K.; Reed, D.E.; Schneider, T.; Dang, F.; Keshteli, A.H.; De Palma, G.; Madsen, K.; Bercik, P.;
Vanner, S. FODMAPs alter symptoms and the metabolome of patients with IBS: A randomised controlled
trial. Gut 2017, 66, 1241–1251, doi:10.1136/gutjnl-2015-311339.
182. Gibson, P.R.; Muir, J.G. Not all effects of a gluten-free diet are due to removal of gluten. Gastroenterology
2013, 145, 693.
183. Nistal, E.; Caminero, A.; Herrán, A.R.; Arias, L.; Vivas, S.; Ruiz De Morales, J.M.; Calleja, S.; Sáenz De Miera,
L.E.; Arroyo, P.; Casqueiro, J. Differences of small intestinal bacteria populations in adults and children
with/without celiac disease: Effect of age, gluten diet, and disease. Inflamm. Bowel Dis. 2012, 18, 649–656,
doi:10.1002/ibd.21830.
184. Tjellström, B.; Högberg, L.; Stenhammar, L.; Fälth-Magnusson, K.; Magnusson, K.-E.; Norin, E.; Sundqvist,
T.; Midtvedt, T. Faecal short-chain fatty acid pattern in childhood coeliac disease is normalised after more
than one year’s gluten-free diet. Microb. Ecol. Heal. Dis. 2013, 24, doi:10.3402/mehd.v24i0.20905.
185. De Palma, G.; Nadal, I.; Collado, M.C.; Sanz, Y. Effects of a gluten-free diet on gut microbiota and immune
function in healthy adult human subjects. Br. J. Nutr. 2009, 102, 1154–1160, doi:10.1017/S0007114509371767.
186. Wacklin, P.; Laurikka, P.; Lindfors, K.; Collin, P.; Salmi, T.; Lähdeaho, M.L.; Saavalainen, P.; Mäki, M.;
Mättö, J.; Kurppa, K.; et al. Altered Duodenal Microbiota Composition in Celiac Disease Patients Suffering
From Persistent Symptoms on a Long-Term Gluten-Free Diet. Am. J. Gastroenterol. 2014, 109, 1933–1941,
doi:10.1038/ajg.2014.355.
187. Rewers, M.; Liu, E.; Simmons, J.; Redondo, M.J.; Hoffenberg, E.J. Celiac disease associated with type 1
diabetes mellitus. Endocrinol. Metab. Clin. North Am. 2004, 33, 197–214.
188. Viljamaa, M.; Kaukinen, K.; Huhtala, H.; Kyrönpalo, S.; Rasmussen, M.; Collin, P. Coeliac disease,
autoimmune diseases and gluten exposure. Scand. J. Gastroenterol. 2005, 40, 437–443,
doi:10.1080/00365520510012181.
189. Ventura, A.; Magazzù, G.; Greco, L. Duration of exposure to gluten and risk for autoimmune disorders in
patients with celiac disease. Gastroenterology 1999, 117, 297–303.
190. Antvorskov, J.C.; Josefsen, K.; Engkilde, K.; Funda, D.P.; Buschard, K. Dietary gluten and the development
of type 1 diabetes. Diabetologia 2014, 57, 1770–1780.
191. Abid, N.; McGlone, O.; Cardwell, C.; McCallion, W.; Carson, D. Clinical and metabolic effects of gluten free
diet in children with type 1 diabetes and coeliac disease. Pediatr. Diabetes 2011, 12, 322–325,
doi:10.1111/j.1399-5448.2010.00700.x.
192. Sanchez-Albisua, I.; Wolf, J.; Neu, A.; Geiger, H.; Wäscher, I.; Stern, M. Coeliac disease in children with
Type 1 diabetes mellitus: The effect of the gluten-free diet. Diabet. Med. 2005, 22, 1079–1082,
doi:10.1111/j.1464-5491.2005.01609.x.
193. Amin, R.; Murphy, N.; Edge, J.; Ahmed, M.L.; Acerini, C.L.; Dunger, D.B. A longitudinal study of the effects
of a gluten-free diet on glycemic control and weight gain in subjects with type 1 diabetes and celiac disease.
Diabetes Care 2002, 25, 1117–1122, doi:10.2337/diacare.25.7.1117.
194. Kaukinen, K.; Salmi, J.; Lahtela, J.; Siljamaki-Ojansuu, U.; Koivisto, A.-M.; Oksa, H.; Collin, P. No effect of
gluten-free diet on the metabolic control of type 1 diabetes in patients with diabetes and celiac disease.
Diabetes Care 1999, 22, 1747–1748.
195. Taler, I.; Phillip, M.; Lebenthal, Y.; de Vries, L.; Shamir, R.; Shalitin, S. Growth and metabolic control in
patients with type 1 diabetes and celiac disease: A longitudinal observational case-control study. Pediatr.
Diabetes 2012, 13, 597–606, doi:10.1111/j.1399-5448.2012.00878.x.
196. Acerini, C.L.; Ahmed, M.L.; Ross, K.M.; Sullivan, P.B.; Bird, G.; Dunger, D.B. Coeliac disease in children
and adolescents with IDDM: Clinical characteristics and response to gluten-free diet. Diabet. Med. 1998, 15,
38–44, doi:10.1002/(SICI)1096-9136(199801)15:1<38::AID-DIA520>3.0.CO;2-L.
197. Scaramuzza, A.E.; Mantegazza, C.; Bosetti, A.; Zuccotti, G.V. Type 1 diabetes and celiac disease: The effects
of gluten free diet on metabolic control. World J. Diabetes 2013, 4, 130–134, doi:10.4239/wjd.v4.i4.130.
Nutrients 2018, 10, 1410 27 of 27

198. Sategna Guidetti, C.; Solerio, E.; Scaglione, N.; Aimo, G.; Mengozzi, G. Duration of gluten exposure in adult
coeliac disease does not correlate with the risk for autoimmune disorders. Gut 2001, 49, 502–505,
doi:10.1136/gut.49.4.502.
199. Ouaka-Kchaou, A.; Ennaifer, R.; Elloumi, H.; Gargouri, D.; Hefaiedh, R.; Kochlef, A.; Romani, M.; Kilani,
A.; Kharrat, J.; Ghorbel, A. Autoimmune diseases in coeliac disease: Effect of gluten exposure. Therap. Adv.
Gastroenterol. 2008, 1, 169–172, doi:10.1177/1756283X08096612.
200. Cosnes, J.; Cellier, C.; Viola, S.; Colombel, J.F.; Michaud, L.; Sarles, J.; Hugot, J.P.; Ginies, J.L.; Dabadie, A.;
Mouterde, O.; et al. Incidence of Autoimmune diseases in celiac disease: protective effect of the gluten-free
diet. Clin. Gastroenterol. Hepatol. 2008, 6, 753–758, doi:10.1016/j.cgh.2007.12.022.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).