Research estimates that 18 million Americans have gluten sensitivity, and only 2 million have Celiac Disease. Yet if a patient complains of gluten sensitivity symptoms, most doctors will only rule out celiac disease or wheat allergy. Based on the numbers above, that leaves over 16 million gluten-sensitive patients with no actual diagnosis.

The science of gluten sensitivity is evolving, and we're learning new information on this condition regularly. This article will discuss non-celiac gluten sensitivity and a functional medicine approach to treating this increasing problem.

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What is Gluten?

Gluten is a name for the proteins found in wheat, barley, and rye. Gluten helps these foods maintain their shape, acting as a glue that holds food together. Wheat is one of the most common sources of gluten, mainly consisting of the proteins glutenin and gliadin. Proteins similar in structure to gliadin have also been found to trigger gluten-related GI upset, including hordein in barley, secalin in rye, and avenin in oats.

What is Non-Celiac Gluten Sensitivity?

Non-celiac gluten sensitivity is characterized by intestinal and extra-intestinal symptoms triggered by the consumption of gluten-containing foods that is relieved by a gluten-free diet. These patients are not allergic to wheat or have Celiac Disease. When people say they are "gluten sensitive," this is the most likely condition they are referring to.

What are Non-Celiac Gluten Sensitivity (NCGS) Signs & Symptoms?

The most common signs and symptoms of NCGS include:

• Bloating
• Abdominal pain
• Diarrhea
• Nausea
• Reflux

Some people may also have:

• Fatigue
• Headaches
• Skin rashes
• Brain fog
• Joint pain
• Irritable bowel syndrome
• Other inflammatory symptoms

What is Celiac Disease?

Celiac disease, or "gluten enteropathy," is a more widely acknowledged condition that also requires sufferers to follow a strict gluten-free diet. Celiac disease is an autoimmune condition with a predisposing genetic factor, the (HLA)-DQ2/DQ8 haplotypes.

Celiac disease triggers an immune system attack that damages the lining of the intestines after consuming gluten-containing foods.

Diagnosis of celiac disease is by blood tests to identify the antibodies, followed by an upper endoscopy and tissue biopsy to confirm the villi and intestinal wall damage and lymphocyte infiltration (immune attack) that is characteristic of the condition.

What's the Difference Between Gluten Sensitivity and Celiac Disease?

There are several differences & similarities between celiac disease and non-celiac gluten sensitivity. Let's break them down.

Genetic Markers

Celiac Disease: has a specific HLA genotype,

Non-Celiac Gluten Sensitivity: there doesn't appear to be a genetic marker for NCGS.

Damage to Intestines

Celiac Disease: creates significant villous atrophy, often to the point that the patient cannot absorb sufficient nutrition from food and develops uncontrolled weight loss.

Non-Celiac Gluten Sensitivity: The effect on the villi is not as pronounced with NCGS. However, there is evidence of reduced villous height and increased intraepithelial lymphocytes (immune attack of gut lining).

Diagnosis

Celiac Disease: is a well-established and recognized disease entity.

Non-Celiac Gluten Sensitivity: Knowledge about the scientific validity of NCGS and available lab testing is not as widespread. Many practitioners do not believe NCGS is a valid diagnosis.

What's the Difference Between Gluten Sensitivity and Wheat Allergy?

Immunoglobulins

Wheat Allergy: IgE-mediated

Wheat allergy is another condition often conflated with NCGS but is a unique condition of its own. For patients with a wheat allergy, the body activates immunoglobulin E (IgE) and non-IgE immune responses. IgE-mediated reactions to wheat are well-known and can be either ingestion (food allergy) or inhalation (respiratory allergy).

A wheat allergy reaction can occur within hours of gluten ingestion but often is faster, and the onset of symptoms can happen within minutes. Symptoms are often swollen lips, tongue or throat, shortness of breath, and hives.

Non-Celiac Gluten Sensitivity: IgG-mediated

In contrast, the antibodies typically identified in lab work for non-celiac gluten sensitivity are Immunoglobulin G, a part of the immune system that normally is used to fight infections and activate the complement system to help antibodies and white blood cells attack.

IgG immune responses typically occur over days or even weeks following ingestion of gluten. This timing can make it challenging to diagnose by symptoms, making lab work preferable.

Functional Medicine Labs to Test for Root Cause of Non-Celiac Gluten Sensitivity

Gluten Sensitivity

Functional lab tests to evaluate for NCGS could start with Wheat Zoomer. This test panel evaluates the immune reaction (antibodies) to wheat, gluten, and the peptides that gluten protein breaks down into, such as gliadins and glutenins. It also includes testing for intestinal permeability, celiac disease, and gluten-related autoimmunity.

This test is critical to identifying gluten sensitivity because simply testing for immune reactions to gluten and not also testing for the peptides it breaks down into can miss positive cases.

Gluten-Associated Cross-Reactive Foods

Cyrex Array 4 (serum) Identifies reactivity to foods known to cross-react with gliadin and can be used to identify possible reactions to newly introduced foods on a gluten-free diet. This test helps identify foods a patient with Non-Celiac Gluten Sensitive (NCGS) or Celiac Disease (CD) may have difficulties with and explore cross-reactions with patients who are not improving on a gluten-free diet.

Comprehensive Thyroid Panel

If Wheat Zoomer results do show the presence of non-celiac gluten sensitivity, it's important to be aware that some of the antibodies to transglutaminase or gluten peptides can cross-react with the thyroid, and this is the basis for the association of Hashimoto thyroiditis (an autoimmune reaction to the thyroid) and gluten sensitivity. For this reason, a comprehensive thyroid panel can evaluate whether the gluten antibodies have impacted this vital gland.

Comprehensive Stool Test

Another area that is important to evaluate with NCGS is the gut microbiome. A comprehensive stool test provides a complete picture of the overall gut microbiome. The GI-Map detects a microbial imbalance and indicators of digestion, absorption, inflammation, and immune function- all important factors when working on healing the gut. It can also detect calprotectin, secretory IgA (SIgA), and anti-gliadin SIgA, which are helpful markers reflecting inflammation and immune response.

Micronutrient Testing

Evidence shows that non-celiac gluten sensitivity has many similar aspects to irritable bowel syndrome and has been shown to disrupt the digestion of food and directly interfere with micronutrient absorption. Therefore a nutrient panel can help guide practitioners on an individualized approach to proper nutrient supplementation.

Functional Medicine Treatment for Non-Celiac Gluten Sensitivity

Strict Gluten Removal

When considering how to treat and support the patient with gluten sensitivity, one of the first goals is to eliminate the offending agent, which means a strict gluten-free diet (GFD). This single step will require some learning and willpower on the part of the patient. It is important to note that complete gluten avoidance must be achieved for the body to stop making antibodies against gluten and have time to heal. "Cheating" or having occasional gluten-containing foods can trigger an IgG response, slowing or even completely halting the healing process.

The amount of time of elimination varies per individual, but research suggests that after six months of a strict gluten-free diet, the majority of non-celiac gluten sensitivity patients (93.2%) showed the disappearance of anti-gliadin antibodies of IgG.

It's essential to retest or re-introduce patients to gluten with proper symptom tracking once they show a significant clinical difference. If a patient shows a reaction to gluten via symptoms or positive IgG/IgA antibodies after reintroduction, they may require a gluten-free diet long term.

Nutrition Choices

A gluten-free diet can vary dramatically depending on the approach.

Many patients choose to stick to a similar diet the patient already was eating before nonceliac gluten sensitivity diagnoses. This diet will include many items such as gluten-free bread and other "substitution foods." While this way of eating can help control gluten reactions, it should be noted that it is not the preferred method for healing the gut. A diet high in processed foods tends to lack nutrients and can be inflammatory for the body. Gluten-free substitution foods are also significantly more expensive.

A second nutrition option for non-celiac gluten sensitivity and most likely to be prescribed by your practitioner would be a whole foods-based approach. An example of this would be a Paleo diet or modified paleo diet, which would allow the inclusion of some organic, gluten-free grains.

Polyphenols

Polyphenols are a category of plant compounds that offers various health benefits. They can act as antioxidants and are known to reduce inflammation.

There is evidence that Polyphenols mitigate the effects of gluten and help the gut heal. This is thought to happen partly by binding the gluten, making it less bioavailable for the immune system to react to. A commonly used polyphenol is curcumin, an ethanol extract of turmeric that is much more concentrated. If used prior to gluten exposure, curcumin has been shown to have protective value from the damage gliadins cause and can help cells to recover as well.

Stress Reduction

Autonomic control and the influence of stress have been shown to lead to leaky gut and bacterial toxin translocation, leading to immune reactions. For this reason, stress reduction and relaxation should be considered part of the healing process in NCGS. It can also be beneficial to test neurotransmitters, allowing an assessment of excitatory/inhibitory balance and stress-based neurotransmitters. This helps to plan interventions and a path forward to recovery.

Summary

Non-celiac gluten sensitivity is a condition that can cause a variety of symptoms that patients seek help for. Despite the progressive awareness of its existence, NCGS is still a condition with many unanswered questions. In contrast to celiac disease, the prevalence of NCGS is far from being established since few reliable epidemiologic studies have been so far published. Functional Medicine practitioners recognize the need for more testing and proper diagnoses based on the number of patients with non-celiac gluten sensitivity symptoms.