Gluten sensitivity is the most common gluten-related ailment, affecting up to 13% of the general population. Symptoms of gluten sensitivity are very similar to irritable bowel syndrome, celiac disease, and wheat allergy; however, it is its own distinct medical diagnosis. The lack of conventional diagnostic markers makes diagnosis difficult, leaving many without a diagnosis or solution to their symptoms. (2)

This article will discuss gluten sensitivity, a functional medicine approach to evaluation and diagnosis, and commonly implemented, evidence-based natural modalities that can be used for its treatment.

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What is Gluten?

Gluten proteins are stored in the endosperm of wheat and related grains. The three main naturally gluten-containing grains are wheat, barley, and rye. Other gluten-containing wheat derivates include wheatberries, spelt, and farro. 

Wheat gluten is composed of gliadin and glutenin. Gliadin is the protein fraction responsible for most adverse health effects associated with gluten. 

Although some grains do not contain gluten, they have proteins that appear and act very similarly to gluten in the body (referred to as "cross-reactivity"). The avenin protein found in oats is the most notorious of these; it is the reason some people with gluten-related disorders cannot tolerate oats in their diet.

What is Gluten Sensitivity?

Gluten sensitivity, non-celiac gluten sensitivity (NCGS), and gluten intolerance all refer to the same digestive disorder. Gluten sensitivity is the presence of intestinal and/or extraintestinal symptoms after consuming gluten. These individuals do not have celiac disease or wheat allergy but experience symptomatic improvement when gluten is eliminated from their diet. (1, 2)

NCGS is recognized as less severe than celiac disease because it does not induce the same extent of small intestinal erosion and inflammation, leading to malabsorption and malnutrition, as celiac disease. However, there is research to support that gluten exposure does cause small intestinal morphological changes, immune activation, and increased intestinal permeability in patients with NCGS (5, 6).

Gluten sensitivity is a clinically distinct medical diagnosis from celiac disease and wheat allergy. For NCGS to be diagnosed, celiac disease and wheat allergy must be ruled out. Celiac disease is an autoimmune disease that results in inflammation and damage to the small intestine after consuming gluten. Celiac disease is diagnosed by key cellular morphological changes on small intestinal biopsy, and serological testing usually confirms the presence of celiac-associated autoantibodies. Wheat allergy is an immune-mediated allergic response by which the consumption of wheat results in allergic symptoms, including hives, rash, swelling of the skin, shortness of breath, wheezing, and swelling of the airways. Wheat allergy is confirmed by measuring IgE antibodies specific to wheat by skin prick or blood testing. (3, 4)

Gluten Sensitivity Symptoms

Gluten sensitivity most commonly triggers gastrointestinal (GI) symptoms after consuming gluten-containing foods. Symptoms related to gluten sensitivity can occur hours to days after consumption of the trigger food. Bloating, abdominal pain, diarrhea, nausea, and reflux are reported to be the most common GI symptoms. (7)

Gluten sensitivity can cause non-digestive symptoms, as well. Extraintestinal symptoms can vary widely, including headache, fatigue, brain fog, muscle and joint pain, skin rash, and depression. (7)

Top 5 Functional Medicine Tests for Gluten Sensitivity

While there are a multitude of tests available, here are the top 5 tests that functional medicine providers order for gluten sensitivity:

Celiac Disease

Celiac disease must be ruled out before making a diagnosis of gluten sensitivity. The gold standard for celiac disease diagnosis is a small intestinal biopsy for visual confirmation of small intestinal damage and inflammation. Histological villous atrophy is the characteristic diagnostic feature of celiac disease. (8)

Given this procedure's invasiveness, serological testing while the patient is consuming a gluten-containing diet is often recommended. The American College of Gastroenterology recommends using immunoglobulin A (IgA) anti-tissue transglutaminase (TTG) antibody as first-line screening (8). Functional medicine doctors often order a more comprehensive antibody panel, which includes IgA and immunoglobulin G (IgG) antibodies to TTG, endomysium, and deamidated gliadin peptide.

Wheat Allergy

A blood test negative for wheat IgE antibodies can rule out wheat allergy before diagnosing gluten sensitivity (4). 

Gluten Sensitivity

There are no conventional biomarkers for NCGS, allowing many cases to go undiagnosed in the allopathic setting (2). Specialty blood panels measuring antibodies and the immune response to various wheat- and gluten-related proteins help to measure the exact level of gluten reactivity and allow for better recognition of gluten sensitivity.

Gluten Cross-Reactivity

The Cyrex Array 4 panel identifies food sensitivities to foods that frequently cross-react with gluten-containing foods. This panel can be helpful for patients beginning to implement dietary modifications or who continue to experience NCGS-like symptoms despite eating a gluten-free diet.

Comprehensive Stool Testing

NCGS has been documented to trigger dysbiosis within the gut microbiome. Dysbiosis can further exacerbate intestinal inflammation and GI symptoms, increasing the severity of NCGS. A comprehensive stool test assesses the gut microbiome, along with measuring other markers of digestion and inflammation, for an extensive gut-health evaluation.

Other Lab Tests to Check 

Due to a phenomenon called molecular mimicry, gluten sensitivity and autoimmune thyroid disease are highly correlated. A comprehensive thyroid panel, measuring multiple markers of thyroid function and autoimmunity, can screen for thyroid autoimmunity and hypothyroidism caused by gluten sensitivity.

Integrative Medicine Treatment for Gluten Sensitivity

Functional medicine practitioners utilize the information they gain from the lab tests and create thorough treatment plans that may consist of the following:

Nutrition for Gluten Sensitivity

First-line therapy with patients with gluten sensitivity is to remove food sensitivities: gluten-containing foods and any identified cross-reactive foods. Strict adherence to a gluten-free diet (GFD) is recommended for at least one year for patients with gluten sensitivity. It is debated whether patients with NCGS require a life-long GFD. While some continue to have wheat triggers after up to eight years of dietary restrictions, evidence suggests many patients have gluten-tolerance thresholds and can reintroduce gluten into the diet in small amounts. (1, 7) 

Additionally, some patients with gluten sensitivity may benefit from reducing the consumption of high-FODMAP foods. A low FODMAP diet aims to reduce certain types of carbohydrates (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) from the diet. Research suggests a low FODMAP diet can further reduce GI symptoms in patients with NCGS and wheat-sensitive irritable bowel syndrome.

Supplements & Herbs for Gluten Sensitivity 

Endopeptidases, digestive enzymes specific to breaking down gluten proteins, effectively support the digestion of gluten and reduce its immunotoxic effects in sensitive patients. These digestive enzymes are effective at digesting small amounts of gluten in cases of accidental exposure but should not replace a GFD. (9)

Supporting a healthy gut microbiome and correcting dysbiosis is essential in treating NCGS and maintaining overall gut health. The gut microbiota can contribute to NCGS by controlling the digestion of gluten proteins, modulating intestinal permeability, and regulating pro-inflammatory immune responses. Probiotics containing Lactobacillus spp., Bifidobacterium spp., and Saccharomyces boulardii have been shown to reduce intestinal inflammation and promote the digestion of gluten in gluten-sensitive patients. (9)

Utilizing nutritional supplements and herbs to repair the small intestinal barrier once gluten has been eliminated from the diet can speed up the healing of a leaky gut caused by gluten exposure. L-glutamine, zinc carnosine, and demulcent herbs (e.g., aloe, deglycyrrhizinated licorice, and marshmallow) are routinely recommended by functional providers for gut-healing protocols.

Summary

Gluten sensitivity is a type of adverse food reaction to gluten-containing foods, distinct from celiac disease and wheat allergy. Because conventional biomarkers are unavailable to diagnose gluten sensitivity, it often goes undiagnosed, causing many debilitating digestive and extraintestinal symptoms similar to celiac disease. Functional lab panels can assist in the diagnosis of gluten sensitivity and the identification of cross-reactive foods causing symptoms. A gluten-free diet and nutritional supplements to improve gluten tolerance and heal leaky gut are often recommended by functional medicine doctors to treat gluten sensitivity.