Accurate Education - Food Intolerance & Sensitivity: Gluten

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Food Intolerance & Sensitivity: Gluten

Gluten is a protein found in wheat, rye, and barley. For those with sensitivity to gluten, ingestion of gluten may give rise to a wide range of systemic, behavioral and gastroinstestinal (GI) symptoms such as headaches, muscle cramps, bone and joint pain, rashes, fatigue, depression and brain fog as well as abdominal cramps, diarrhea, bloating and nausea.

Classically, gluten sensitivity has been the hallmark of Celiac disease, also known as sprue, an auto-immune condition affecting the small intestine. In recent years there has been growing evidence of other conditions associated with gluten sensitivity that are not based on an auto-immune mechanism and do not meed diagnostic criteria for Celiac disease. These conditions, referred to as non-celiac gluten sensitivity (NCGS), do not have specific or well-defined diagnostic criteria but appear to affect a significant portion of the population. Additionally, NCGS may overlap with other conditions including fibromyalgia and irritable bowel syndrome (IBS) sometimes creating a diagnostic blur.

Definitions:

Food Sensitivity:

A catch-all term for conditions which result in symptoms due to ingestion of a food or nutrient, regardless of the mechanism by which the symptoms occur.

Food Intolerance:

Symptoms resulting from the inability to digest/metabolize a food or nutrient – symptoms that are usually limited to the gastrointestinal (GI) tract.

Food Hypersensitivity:

An immune/allergic response to a food or nutrient that causes gastrointestinal (GI) symptoms and/or systemic symptoms.

See:

Food Intolerance & Sensitivity: An Overview

Elimination Diet – Gluten

Elimination Diet – FODMAPs

See also:

Diet & Diets

Diet & Pain – An Overview

Diet & Fibromyalgia

Irritable Bowel Syndrome (IBS)

Wellness/Anti-Inflammatory Diets (coming soon):

Mediterranean Diet

Paleo Diet

Okinowan Diet

Elimination Diets

Fasting

Diet Supplements:

Supplements – An Overview

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Minerals

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Food Intolerance and Sensitivity – Gluten

For those with gluten sensitivity, ingestion of gluten, a protein found in wheat, rye, and barley. may give rise to a wide range of systemic, behavioral and GI symptoms.

Symptoms associated with gluten sensitivity include:

Intestinal
Abdominal pain, cramps

Diarrhea

Nausea

Loss of appetite

Bloating & flatulence

Skin

Erythema (redness)

Eczema

Oral sores

General/Systemic

Headaches

Bone and joint pain

Muscle cramps and contractions

Numbness in hands and feet (small fiber neuropathy – SFN)

Chronic fatigue

Osteopenia or osteoporosis

Elevated liver enzyme tests (ALT, AST) which may resolve with a gluten-free diet (GFD).

Vitamin deficiencies (B12, B9-folate, carotene)

Mineral Deficiencies (calcium, iron)

Behavioral

Attention deficit (“Brain Fog”)

Depression

Irritability

Hyperactivity

Types of Gluten Sensitivity

Gluten sensitivity falls into two categories: Celiac disease (CeD), an autoimmune disorder; and non-celiac gluten sensitivity (NCGS), a poorly defined condition related to multiple, different underlying factors. Gluten sensitivity that does not fulfill the diagnostic criteria for Celiac disease (CD) is increasingly recognized as a frequent and treatable condition with a wide spectrum of manifestations that overlap with other conditions including fibromyalgia (FM), chronic musculoskeletal pain, chronic fatigue syndrome, and irritable bowel syndrome (IBS).

Celiac Disease (CeD)

Celiac disease (CeD) is an autoimmune disease. An autoimmune disease occurs when the body’s immune system, which usually fights infections to maintain health, inappropriately attacks organs or tissues. In the case of Celiac disease, the organ that is most commonly damaged is the small intestine but multiple organs may become involved. In CeD, this damage only occurs when gluten is eaten. In those affected, dietary exposure to gluten triggers the formation of antibodies by the immune system which subsequently attack and damage various organs.

Ingested food is normally broken down into small particles in the stomach and then digested and absorbed in the small intestine. In CeD, when gluten is ingested and crosses the lining of the small intestine it activates the immune system to form antibodies, which is termed a hypersensitivity response. The villi, which are finger-like projections on the surface of the intestinal lining, become damaged which impairs their ability to absorb nutrients, potentiallly leading to nutritional deficiencies, commonly including vitamins such as A, B9 (folate), B12, D, E and K and minerals such as calcium, magnesium, zinc and iron. Damage to the villi also leads to loss of lactase, the enzyme that digests lactose, leading to lactose intolerance associated with ingesting milk and dairy products.

In those affected, this formation of antibodies by the immune system can also result in damage to other organs and tissues including the liver and brain, skin and joints resulting in a wide range of symptoms both locak and systemic. This often leads to missed or inaccurate diagnoses, especially when CeD co-occurs with other conditions such as fibromyalgia.

With a prevalence of 1-2% of the population, Celiac disease (CeD) occurs most commonly in those of European descent but can affect anyone. CeD is an inherited disease. The risks are higher for those with an affected family member; 4% to 15% of first-degree relatives will also have CeD. CeD is substantially more common in patients with Type I DM.

Celiac disease may be first diagnosed at any age and, because it is an autoimmune disorder, it affects multiple organ systems. Childhood presentation is the most common, but some individuals remain without symptoms at all, even as adults. While there there are no typical celiac disease-specific symptoms, most people with the disease have gastrointestinal (GI) symptoms such as intermittent diarrhea, abdominal pain, and bloating. However, the signs and symptoms of CeD are quite variable and can overlap with irritable bowel syndrome (IBS), gastric ulcers, Crohns disease, parasite infections, anemia, skin disorders, or nervous conditions.

The diagnosis of CeD is based on positive autoantibody blood tests and characteristic intestinal biopsy results. Auto-antibody testing is the best option for screening for CeD and those patients testing as high risk should have intestinal biopsy performed. Those individuals testing as low risk should be evaluated for other diseases. The definitive diagnosis of CeD is ultimately confirmed when symptoms resolve after institution of a gluten-free diet (GFD).

Non-Celiac Gluten Sensitivity (NCGS)

Persons afflicted with gluten sensitivity that do not meet criteria for Celiac disease or wheat allergy generally fall into the nonspecific category of non-celiac gluten sensitivity (NCGS). NCGS is characterized by gastrointestinal or extraintestinal symptoms that respond to withdrawal of gluten from the diet. Many factors contribute to NCGS but no definitive biomarkers or specific diagnostic criteria have been established for the diagnosis of NCGS. As such, the diagnosis of NCGS is generally one of exclusion.

While the cause of CeD is due to an auto-immune basis, the causes of NCGS are not well understood and there are likely many contributing factors such as low-grade intestinal inflammation, intestinal barrier dysfunction (Leaky Gut) and changes in the intestinal microbiota (microbiome). Underlying immune mechanisms may also play a role. A possible explanation for the different immune activating mechanisms between CeD and NCGS is the fact that it is uncertain whether it is the gluten that triggers symptoms in NCGS patients or other components of grains that are responsible, possibly FODMAPs.

While in some cases FODMAPs may be the trigger for NCGS, it is unlikely that FODMAPs are the sole responsible for symptoms related to NCGS because FODMAPs are known to inhibit rather than cause inflammation by inducing beneficial changes in the intestinal microbiota and generation of short-chain fatty acids. FODMAPs may be additional elements of disturbance that exacerbate symptoms associated with the gut lumen which is already compromised due to other causes, particularly if individuals with NCGS also have at the same time a lack of one or more enzymes for the digestion of FODMAPs. Others have suggested that both conditions could coexist independently, without necessarily sharing a common pathophysiological basis.

Like Celiac disease, manifestations of NCGS include intestinal symptoms such as constipation and diarrhea, abdominal discomfort, cramps or pain, bloating, flatulence and/or extraintestinal symptoms of variable severity including fatigue, “brain fog,” headache, joint and muscle pain, and/or lethargy that occur within a few hours or days after ingestion of gluten and improve after gluten is removed from the diet. Symptoms of NCGS have significant overlap with irritable bowel syndrome (IBS) and fibromyalgia although NCGS may coexist with these conditions as well.

NCGS: An ATIs/low butyrate-producing Firmicutes/low Bifidobacteria-dysbiosis-induced disorder

A recent study published in November 2017 appears to confirms the presence of increased intestinal permeability (Leaky Gut) in individuals with NCGS, and provides evidence for a possible pathogenic role of the intestinal microbiota (microbiome). This study proposes that NCGS “may be considered a multi-factor-onset disorder, potentially transient and preventable,” without any known specific genetic cause. The authors theorize that an imbalance of the diet leads to changes in the microbiome (specifically low butyrate-producing Firmicutes/low Bifidobacteria bacteria) which lead to a reduction in butyrate, a small chain fatty acid (SCFA), in the lining of gut. Butyrate protects the integrity of the gut lining and a deficiency of butyrate contributes to a breakdown in the intestinal barrier allowing food-borne antigens to be absorbed into the blood, triggering an immune response which leads to the many associated symptoms. They propose also that it may not be glutens in the diet responsible for this chain of events but ATIs (amylase trypsin inhibitors) that are also found in grains, especially wheat.

If their hypotheses are confirmed, it suggests that the use of specific probiotics may offer an effective treatment that along with dietary changes may permit a reversal of the underlying problem and ultimately allow for the reintroduction of trigger foods without creating recurrence of symptoms.

As noted above, it is unclear whether it is the gluten in grains, especially wheat, that provokes symptoms in NCGS patients. Other constituents of grains may be responsible. One theory is based on the fact that grains were only introduced into the human diet 10,000 years (or some 300 generations) ago. From an evolutionary perspective, this is too short for humans to adapt to specific proteins in wheat, allowing for the possibility of increased immune sensitivity to these proteins. Recent wheat modifications in modern agriculture have potentially further increased immunogenicity. The protein contents of modern wheat varies between 7% and 22% and gluten proteins are the main proteins in wheat, classically divided into two groups, the monomeric gliadins and the polymeric glutenins.

Although risk factors for this disorder have not yet been identified, NCGS seems to be more common in females and in young/middle age adults. The overall prevalence of NCGS in adults is uncertain but possibly ranges from 0.6% to 6% and the prevalence in children is still unknown

Testing for Celiac Disease

Blood Tests

Patients with GI or systemic symptoms suspicious for gluten hypersensitivity, especially those patients with an immediately family member with CeD, should be screened for CeD with blood tests. Three types of blood tests are available:

Celiac-specific blood tests

TTG-IgA (tissue transglutaminase antibody)

This is the preferred single screening blood test for CeD, with a 95% sensitivity for untreated CeD (and the higher the titer of TTG-IgA, the greater the likelihood of a true positive result).

DPG-IgA (deamidated gluten peptide antibody-IgA)

DPG-IgG (deamidated gluten peptide antibody-IgG)

DPG-IgA is more specific but DPG-IgG should be considered if possible IgA deficiency coexists in a high-probability patient.

IgA deficiency is more common in CeD than in the general population. It affects less than 1% of the general population, but occurs in 3-5% of patients with CeD and 5% to 10% of patients with selective IgA deficiency have celiac disease.. In patients in whom there is a probability of CeD, the measurement of IgA levels should be considered, especially if IgA-TTG (or IgA-EMA) is negative. It has also been suggested that IgA deficiency should be considered if the TTG-IgA levels are undetectable.

One approach is to measure total IgA along with IgA-TTG as part of the initial screening to determine whether IgA levels are sufficient and, if not, add IgG-based testing. DGPs IgG and/or TTG IgG would then be the preferred test in this circumstance. EMA IgG is not widely available.

Anti-Endomysial Antibody (EMA) – IgA & IgG

EMA testing is expensive and EMA-IgG is not widely available; these tests are not generally used for diagnosing Celiac disease.

Non-celiac specific gluten sensitivity tests

Native Gliadin Antibody (AGA) – IgA & IgG

While these older tests may be helpful for establishing support for the diagnosis of NCGS, their diagnostic accuracy is inferior to IgA-TTG and IgA-DPG for diagnosing CeD.

Genetic Testing

Genetic testing for HLA-II genotypes, DQ2 and DQ8, can also be performed as these variants are highly associated with CeD. Nearly 100% of patients with celiac disease carry the HLA markers DQ2 or DQ8 (>90% are DQ2; <10% are DQ8).

Recommendations for genetic testing (HLA-DQ2/DQ8):

(1) HLA-DQ2/DQ8 testing should not be used routinely in the initial diagnosis of CeD.

(2) HLA-DQ2/DQ8 genotyping testing should be used to effectively exclude the disease in selected clinical situations such as:

(a) Equivocal small-bowel biopsy findings in patients with negative CeD-specific blood tests

(b) Evaluation of patients already on a gluten-free diet (GFD) in whom no testing  for CeD was done before establishing a GFD

Intestinal Biopsy

For those with severe symptoms and high suspicion for Celiac disease, it may be necessary to perform a duodenal (small intestine) mucosal biopsy to identify the diagnosis if blood tests are negative. Even with a positive celiac-specific blood test, a biopsy should be considered for confirmation and consultation with a gastroenterologist is strongly recommended. Positive CeD-specific blood testing (TTG, DGP, and EMA) in patients with villous atrophy found on intestinal biopsy is the gold standard confirmation of the diagnosis of CeD.

Elimination Diet

If the Celiac-specific blood tests are negative in symptomatic patients, a positive IgA-AGA (anti-gliadin antibody test) is suggestive but not diagnostic of NCGS and a trial of a gluten-free diet (GFD) is strongly advised. Since the diagnosis of NCGS is compromised by the lack of a reliable diagnostic test, in order to identify NCGS once the diagnosis of CeD is excluded, dietary elimination of gluten to observe for improvement of symptoms is advised. An improvement in symptoms while on a GFD would support the diagnosis of NCGS/wheat hypersensitivity.

See: Elimination Diet – Gluten

Treatment of Celiac Disease (CeD)

For those with CeD and severe gluten hypersensitivity, the only treatment is lifelong, complete avoidance of gluten; with CeD even small amounts of gluten can cause intestinal damage and significant symptoms. On a gluten-free diet, the intestinal damage will heal, the villi will regrow, and the symptoms will disappear. Some individuals with Celiac disease only realize that they had symptoms after they start to feel better on the gluten-free diet.

Adherence to a completely gluten-free diet (GFD) is difficult, especially since food processing can add gluten to foods that would otherwise be considered safe. For example, while potatoes are safe, depending on the processing used to prepare them, french fries may not be safe. More problematic for complete avoidance are the less well-known uses of gluten in some prescription or over-the-counter medicines and other common products, even stamp and envelope adhesive.

Treatment of NCGS

For those with NCGS and mild to moderate gluten hypersensitivity, small amounts of gluten exposure may be tolerated. Each individual needs to determine their own regimen of foods and quantities that are allowable. Since the causes of NCGS are not well understood, treatment of NCGS may respond differently with different people. Given that the microbiome may be a factor in NCGS, there may be a role for the use of pre- and probiotics in the management of NCGS symptoms. Also since a leaky gut may also play a role in NCGS, evaluation and management of leaky gut should be considered in treating NCGS.

That being said, the starting point of treatment for those with FM and NCGS should include a completely GFD. After a period of a few months when symptoms of NCGS have resolved by avoiding gluten ingestion, a retrial may be appropriate by re-introducing gluten back into the diet. With the potential return of a healthier gut, gluten may again be tolerated.

Who Should Do a Trial of a Gluten-Free Diet?

Celiac Disease

For those diagnosed with Celiac disease, the only successful treatment of gluten hypersensitivity is a gluten-free diet (GFD). It may takes weeks or even up to a year to experience the full benefit of the GFD in those with CeD. Blood tests can be performed to monitor antibody levels to track an individual’s response .

NCGS

For those symptomatic patients who test negative for CeD, there is no specific test that can be performed to determine if gluten sensitivity (NCGS) is contributing to or causing their symptoms. Furthermore, there is no diagnostic marker for NCGS and the diagnosis is confirmed only when symptoms improve with a gluten-free diet and symptoms reappear with addition of gluten back into the diet. At present, there are no defined predictors of response to a gluten-free diet in patients with symptoms suggestive of NCGS, including those with IBS or fibromyalgia. Therefore, anyone with symptoms consisten with NCGS, including those with IBS and/or fibromyalgia should consider a trial GFD as a diagnostic test.

Fibromyalgia (FM) & IBS

As noted above, it is advisable that anyone with FM symptoms significantly impacting their quality of life should consider a trial of a GFD for 3-4 weeks. However, due to the additional potential for other food intolerances in FM including FODMAPs and excitatory toxins such as MSG and aspartame, a more extensive elimination diet including these foods/agents is advised.

Additionally, IBS symptoms may be similar and difficult to distinguish from gluten sensitivity. In fact, these two conditions may coexist in the same person. Studies indicate that about 50% of those with IBS have improvement of symptoms with a gluten-free diet, compared with 75% who improve with a FODMAP-free diet. Therefore, for patients with symptoms consistent with IBS, a 3-4 week trial of dietary elimination of both gluten and FODMAPs to observe for improvement of symptoms is advised, once the diagnosis of CeD is excluded.

See: Elimination Diet – Fibromyalgia

Resources:

References:

Gluten: Celiac Disease

**Gluten: FM and Celiac Disease**

Clinical impact of a gluten-free diet on health-related quality of life in seven fibromyalgia syndrome patients with associated celiac disease

Gluten: Non-Celiac Gluten Sensitivity (NCGS)

Gluten: Gluten-Free Diet (GFD)

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Accurate Education – Food Intolerance & Sensitivity: Gluten