Seeking a diagnosis for gluten intolerance can be confusing in part because people often mistake gluten intolerance for celiac disease and vice versa. Both conditions are caused by an adverse reaction to gluten (a protein found in cereal grains like wheat, rye, and barley), causing symptoms like diarrhea, fatigue, nausea, stomach pain, and gas.

But, CD differs from gluten intolerance in that it is an autoimmune disorder in which the presence of gluten causes the body’s immune system to attack the lining of the intestines. By contrast, the cause of gluten intolerance remains poorly understood but does not involve any of the autoimmune proteins, called autoantibodies, associated with CD.

If you have symptoms of gluten intolerance, your healthcare provider will typically test you for CD first since there are tests available. If CD is not the cause, all other causes would need to be ruled out because there are no tests for gluten intolerance; the diagnosis involves a process of elimination.

This article explains what gluten intolerance is and the process by which it is diagnosed. It also describes the tests used to diagnose celiac disease and when screening is recommended.

What Is Gluten Intolerance?

Gluten intolerance is a range of adverse symptoms that can occur after eating gluten but that does not involve celiac disease. This is why the condition is more accurately referred to as non-celiac gluten sensitivity (NCGS).

Causes of Gluten Intolerance

The causes of gluten intolerance are unknown, but there are different hypotheses. Some research suggests that it may be due to other components found in gluten-containing cereal grains.

This includes a collection of short-chain carbohydrates (sugars) called FODMAPs, which stands for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. These sugars, found in all gluten-containing grains, are not well absorbed in the intestines. Because of this, they can start to ferment and cause gas, bloating, diarrhea, and abdominal pain.

Other research suggests that proteins called amylase/trypsin inhibitors (ATIs) found in all gluten-containing grains might cause an allergic reaction and trigger symptoms of gluten intolerance.

Even so, the findings from research studies are not consistent, and it could be that “gluten intolerance” is a broad range of related and unrelated reactions to one or several components in gluten-containing grains.

Symptoms of Gluten Intolerance

The symptoms of gluten intolerance can vary from one person to the next, both in the severity and type of symptoms they might experience. They not only involve gastrointestinal symptoms but also non-gastrointestinal symptoms.

Symptoms of gluten intolerance may include:

Abdominal pain Gas Bloating Diarrhea Constipation Concentration problems (“brain fog”) Headache Fatigue Anxiety Depression Joint pain Skin rash

Diagnosing Gluten Intolerance

There is no test for gluten intolerance. If you or your healthcare provider suspects that you are sensitive to gluten, the diagnosis will start with a review of your medical history and a physical exam, in part to identify possible explanations for your symptoms.

The diagnosis of gluten intolerance typically involves the following steps:

Test for celiac disease: Because the symptoms of CD and NCGS overlap, CD is the first place a gastroenterologist will typically look. Because tests are available to diagnose CD, it can quickly exclude CD as a cause if the results are negative. Exclude other possible causes: Diagnosing NCGS is a process of elimination. This might involve testing for wheat allergy, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and other possible causes based on your medical history and symptoms. Start a gluten-free diet: If no explanation can be found, your gastroenterologist will place you on a gluten-free diet for at least six weeks during which time you would keep a record of any symptoms you experience. If symptoms improve, gluten intolerance is likely the cause.

Excluding Other Conditions

The exclusion of possible causes is part of a process known as the differential diagnosis. As per its name, a differential diagnosis differentiates a suspected cause from all other possible explanations.

A differential diagnosis is important when test results are uncertain and even more important when no tests are available, such as with NCGS.

Among the possible causes a gastroenterologist will want to exclude if gluten intolerance is suspected are:

Celiac disease: CD tends to be more aggressive than NCGS and causes progressive damage to the intestines. CD can be differentiated from NCGC with CD-specific lab tests. Wheat allergy: A wheat allergy involves an immune response triggered by an antibody called immunoglobulin E (IgE). A wheat allergy can be differentiated with an IgE blood test. A wheat allergy might also involve sneezing and other respiratory symptoms. Irritable bowel syndrome (IBS): IBS mainly affects the lower part of the intestine, called the colon, causing mucus in stools and a feeling that your bowels are never fully empty. While there are no tests for IBS, it can be differentiated from NGCS by the lack of a specific reaction to gluten. Inflammatory bowel disease (IBD): IBD can cause severe damage to the intestines whereas NCGS generally does not. Rectal bleeding is also common with IBD. IBD can be differentiated from NGCS by examining the colon with a flexible scope called an endoscope.

Gluten Challenge

A gluten challenge is not the same thing as a gluten-free diet. It is a test used to see if the cause of your symptoms is really gluten or something else. It may be an option if there is any uncertainty about the diagnosis.

A gluten challenge takes place after you have undergone a gluten-free diet for at least six weeks. Your healthcare provider will then perform a “blinded” test in which you are either fed a gluten-containing food (called the control) or a non-gluten equivalent of that food (called the placebo). You will not know which is which.

The gluten challenge is conducted in steps over the course of three weeks:

You are given a daily serving of either the control or placebo food for one week (such as a muffin). You will eat it at the same time every day. The rest of the food you eat would be gluten-free. You then record any symptoms you experience, including the time. You are given a one-week break but will still continue eating a gluten-free diet. For the final week, you would repeat Step 1 but be given the opposite food.

At the end of the challenge, you and your healthcare provider will compare the results.

If your symptoms are at least 30% changed between the control and placebo week, it could indicate gluten sensitivity. If not, you may need to explore other causes of your symptoms.

Tests for Celiac Disease

Although there are a variety of tests available to diagnose celiac disease, the procedure is not always straightforward.

The diagnosis typically starts with blood tests to see if you have specific substances (called markers) for the disease. This is followed by procedures that directly or indirectly view the intestines and obtain tissue samples for evaluation in the lab.

Blood Tests

There are several blood tests that can detect markers for CD, including autoantibodies and genetic mutations linked to the disease. These include:

Anti-endomysial antibody (EMA) test: This detects a type of autoantibody found in 90% of people with CD. These immune proteins attack connective tissues in the lining of the intestines called the endomysium. Tissue transglutaminase IgA (TG-IgA) test: This detects another type of autoantibody involved with CD. These attack a part of the intestine called the lamina propria. Total serum IgA test: This tells how much TG-IgA is in a sample of blood. It helps qualify whether your symptoms correspond to elevations in TG-IgA levels. Deamidated gliadin peptide (DGP) test: This detects a less common autoantibody associated with CD. It is used when TG-IgA and EMA tests are negative. HLA-DQ2 and HLA-DQ8 tests: These detect specific gene mutations, called HLA-DQ2 and HLA-DQ8, that occur in 95% and 5% of people with CD, respectively.

Endoscopy

If the results of the blood tests indicate celiac disease, the next step would involve one of two procedures that view the intestine from the inside.

The aim of the procedures is to check for villous atrophy, a condition in which the finger-like projections in the lining of the intestines (called villi) are flattened and destroyed.

There are two viewing methods your gastroenterologist might use:

Endoscopy: This involves the insertion of a long tube with a tiny camera into your mouth and down the throat to view your small intestine. It is generally done under monitored anesthesia care (MAC) in a procedure room. Capsule endoscopy: This involves swallowing a capsule with a miniaturized capsule that takes pictures as it passes through the entire digestive tract. It does not involve anesthesia and eventually exits the body in a bowel movement.

Biopsy

Although villous atrophy is a central feature of celiac disease, it can occur with other diseases. It is for this reason that biopsy (the removal of a tissue sample) is needed to make a definitive diagnosis. It can be done during a regular endoscopy procedure.

The biopsy is examined by a lab specialist, called a pathologist, to determine whether it meets the criteria and characteristics or CD outlined in the Modified Marsh Classification system.

With that said, the increasing accuracy of blood tests has led some experts to suggest that strongly positive antibody tests accompanied by less-invasive capsule endoscopy are all that is needed to make a definitive diagnosis.

Other authorities contend that positive results for both HLA-DQ2 and HLA-DQ8 accompanied by CD symptoms are all that is needed to confirm the diagnosis.

Home Testing

There are several at-home kits you can purchase that are said to test for various food sensitivities, including gluten sensitivity. These require either a small sample of stool (poop) or a finger-prick blood sample. Brands include EverlyWell and EnteroLab.

To date, the accuracy of these tests (as measured by their specificity and sensitivity) is either extremely low or unproven. Because of this, the cost of these kits (which range from $100 to $400) is rarely ever covered by health insurance.

Summary

Gluten intolerance, also known as non-celiac gluten sensitivity, shares many of the same symptoms as celiac disease but is not the same thing. There are no tests available to diagnose gluten intolerance. The diagnosis is made by eliminating all other possible causes and seeing how your body responds to a gluten-free diet.

Children older than 3 and adults experiencing symptoms of CD Parents, siblings, or children of someone diagnosed with CD Anyone with an associated autoimmune disease or genetic disorder, especially type 1 diabetes, autoimmune thyroid disease, autoimmune liver disease, Down syndrome, Turner syndrome, Williams syndrome, and selective immunoglobulin A (IgA) deficiency.

Celiac disease is an autoimmune disease that can be diagnosed with a combination of antibody blood tests, genetic blood tests, endoscopy, and an intestinal biopsy.

A Word From Verywell

Diagnosing gluten intolerance is a process that takes time and requires patience. It can be frustrating because the results are not always conclusive. Even so, it is in your best interest to work with your gastroenterologist and undergo the necessary tests to confirm the diagnosis.

Skipping the diagnosis and jumping on the gluten-free bandwagon may seem like a reasonable option. But doing so may leave the true cause of your symptoms diagnosed. At the same time, there are nutritional considerations you need to address before starting a gluten-free diet, especially if you have diabetes.

Exclude all other possible causes, including celiac disease, wheat allergy, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD)Embark on a strict gluten-free diet for at least six weeks to see if your symptoms improve