Gluten Intolerance or Celiac Disease: What's the Difference and What Can You Do?

Millions of Dutch people avoid gluten — but do they know why? There is an important distinction between celiac disease and gluten intolerance, also known as non-celiac gluten sensitivity (NCGS). Both conditions can cause similar symptoms, but their causes, severity, and approach differ significantly. Going on a gluten-free diet without a diagnosis risks drawing the wrong conclusions — or overlooking a more serious condition. In this article, we clearly explain the difference so you can make informed decisions about your health.

What is Celiac Disease?

Celiac disease is an autoimmune disease in which the ingestion of gluten — a protein found in wheat, rye, and barley — triggers an immune reaction that damages the lining of the small intestine. The disease is estimated to affect about 1% of the Dutch population, although a large portion remains undiagnosed. In celiac disease, the immune system attacks the villi (finger-like projections in the small intestine), severely impairing nutrient absorption.

The consequences are not limited to abdominal complaints. Long-term exposure to gluten in celiac patients can lead to anemia, bone demineralization, infertility, and — in rare cases — an increased risk of certain forms of lymphoma. It is therefore essential that celiac disease is diagnosed and treated promptly.

Diagnosis of celiac disease

Diagnosis involves two steps. First, a blood test is performed to check for antibodies, particularly anti-tissue transglutaminase IgA (tTG-IgA). If positive, a small intestinal biopsy is performed via gastroscopy, where tissue samples are assessed for typical damage (Marsh classification). Both steps are necessary for a reliable diagnosis. Celiac disease is also strongly genetically determined: more than 95% of patients carry the HLA-DQ2 or HLA-DQ8 genes. The only proven treatment is a strict, lifelong gluten-free diet.

What is Gluten Intolerance (NCGS)?

Gluten intolerance — or non-celiac gluten sensitivity (NCGS) — is a relatively new clinical entity. Individuals with NCGS experience symptoms after eating gluten-containing products, but do not have autoimmune damage to the intestinal lining and test negative for celiac-specific antibodies. The exact mechanisms are not yet fully understood; research suggests that in addition to gluten, amylase-trypsin inhibitors (ATIs) and certain carbohydrates (FODMAPs) may also play a role.

The prevalence of gluten intolerance varies widely in the literature — estimates range from 0.5% to 13% of the population — partly due to the lack of an objective diagnostic biomarker. Research by Catassi et al. (2015, Nutrients) established NCGS as a full clinical category, distinct from celiac disease and wheat allergy.

Symptoms of gluten intolerance

The symptoms largely overlap with those of irritable bowel syndrome (IBS) and celiac disease. Typical symptoms include:

• Bloating and flatulence
• Abdominal pain and cramps
• Diarrhea or constipation
• Fatigue and lack of energy
• Brain fog: concentration problems and mental sluggishness
• Headache
• Joint pain

Unlike celiac disease, these symptoms usually disappear quickly after eliminating gluten from the diet and return when gluten intake is resumed. However, intestinal damage is absent in NCGS.

Diagnosis of gluten intolerance

There is no specific blood test or biopsy for gluten intolerance. The diagnosis is made by exclusion: celiac disease and wheat allergy are first ruled out via blood tests and possibly biopsy. Then, a controlled elimination and challenge protocol is applied to confirm that symptoms are related to gluten intake. This should always be supervised by a doctor or dietitian.

How Do You Distinguish Them?

The table below provides an overview of the main differences between celiac disease and gluten intolerance:

The most important practical difference: those with celiac disease must follow a strict gluten-free diet to prevent serious health damage. For gluten intolerance, the diet is primarily aimed at symptom relief, and the degree of strictness can vary per individual.

Hidden Gluten: The Biggest Problem

Even the most dedicated follower of a gluten-free diet is exposed to so-called hidden gluten. Gluten appears in products where you wouldn't expect it: soy sauces, bouillon cubes, some medications and supplements, herbal teas, and foods produced in the same factory as gluten-containing products (cross-contamination). Cross-contamination is also difficult to avoid in restaurants, even when dishes are offered as "gluten-free."

Research published in Scientific Reports (Konig et al., 2017) shows that people on a non-strict gluten-free diet unknowingly ingest an average of approximately 150 mg of gluten daily through unintended exposure. Even with strict adherence, daily unconscious exposure can be up to 7 mg. Other research shows that an average of 244–363 mg of gluten per day is ingested by people who believe they are following a gluten-free diet. This has direct consequences: for celiac disease, even traces above 10 mg per day can damage the intestinal villi.

Sources of hidden gluten include:

• Sauces and spice mixes (soy, Worcestershire, teriyaki sauce)
• Processed meat and fish products (sausages, surimi)
• Certain medications and vitamin supplements (as a binder)
• Beer and malt beverages
• Fried foods prepared in shared fryer oil
• Oats (unless certified gluten-free)
• Products labeled "may contain traces of gluten"

The Role of Gluten-Degrading Enzymes

In recent years, there has been growing scientific attention to the use of enzymes as an additional strategy for accidental gluten intake. The most researched enzyme is prolyl endoprotease from Aspergillus niger (AN-PEP), a fungal species that naturally produces this protein-splitting enzyme.

How does AN-PEP work?

Gluten is a complex protein that is particularly rich in the amino acid proline. Precisely that makes gluten so difficult to break down by human digestive enzymes: prolyl bonds are resistant to most proteases in the human gastrointestinal tract. AN-PEP — a gluten enzyme — specifically cleaves after proline residues, thereby breaking down the immunogenic fragments (epitopes) of gluten into small, non-immunogenic peptides of eight amino acids or less.

AN-PEP is active at a pH of 2 to 8 and optimally effective at pH 4–5 — precisely the acidity found in the human stomach. The enzyme is also not broken down by pepsin and therefore remains fully functional during the normal gastric transit time of 2 to 3 hours.

Clinical evidence: König et al. (2017)

The most direct clinical evidence comes from a randomized, double-blind, placebo-controlled crossover study by König J. et al. (2017), published in Scientific Reports (Nature Publishing Group). The study design and results are as follows:

• Study Population: 18 participants with self-reported gluten sensitivity (non-celiac); 16 completed all three test days.
• Gluten Dose: 0.5 g gluten per test meal (two crumbled wheat cookies in oatmeal), representative of typical exposure to hidden gluten in a normal gluten-free diet.
• Enzyme Dosages: low dose 83,300 PPI AN-PEP (two tablets) or high dose 166,700 PPI AN-PEP (two tablets), versus placebo.
• Primary Outcome: at least 50% reduction of gluten concentration in the duodenum compared to placebo (calculated as AUC_{0–180 min}).

Results — stomach (AUC_{0–180 min}, μg × min/ml, median):

Results — duodenum (AUC_{0–180 min}, μg × min/ml, median):

The primary outcome — at least 50% gluten reduction in the duodenum compared to placebo — was achieved in 10 out of 13 available comparisons for the high dose (success rate at least 51% at 95% exact-binomial confidence interval). In the stomach, AN-PEP reduced gluten concentrations by 88% (high dose) and 86% (low dose) respectively — both with p = 0.001. Significance was determined using the non-parametric Wilcoxon signed-rank paired test with Bonferroni correction.

The authors concluded: "AN-PEP is effective in degrading small amounts of gluten as part of a complex meal in the stomach. Even though the use of AN-PEP is not intended to replace a gluten-free diet in gluten-related disorders, it appears to be effective as a digestive aid protecting against the unintentional intake of gluten."

Crucial detail: gluten was measured over a period of 180 minutes — corresponding to the normal gastric transit time of 2 to 3 hours — which demonstrates that AN-PEP is effective within the physiologically relevant time window of digestion.

Clinical evidence: Salden et al. (2015)

A second, independent randomized, double-blind, placebo-controlled crossover study by Salden BN et al. (2015), published in Alimentary Pharmacology & Therapeutics (42:273–285), studied AN-PEP in 12 healthy volunteers who ingested 4g of gluten in a low- or high-calorie liquid meal.

Key findings Salden et al. (2015):

• α-gliadin AUC₂₄₀ in the duodenum: 7 vs. 168 μg×min/mL (low-calorie meal, AN-PEP vs. placebo) — a reduction of >95%
• α-gliadin AUC₂₄₀ in the stomach: 35 vs. 389 μg×min/mL (low-calorie meal) and 53 vs. 386 μg×min/mL (high-calorie meal)
• The caloric density of the meal had no impact on the effectiveness of AN-PEP — the enzyme was equally effective with both light and heavy meals

The researchers concluded: "AN-PEP significantly enhanced gluten digestion in the stomach of healthy volunteers." The combination of König (2017) and Salden (2015) thus forms a robust clinical basis for the efficacy of AN-PEP in breaking down gluten before it reaches the small intestine.

AN-PEP versus competing gluten enzymes

Not all gluten enzyme supplements work in the same way. The table below shows the main differences between AN-PEP (active ingredient in Ineopep/Gluteostop) and common competing enzymes such as DPP-IV:

The crucial advantage of AN-PEP: gluten is broken down in the stomach, before it reaches the small intestine where immunological damage occurs in celiac patients. Competing enzymes that are only active in the small intestine therefore offer structurally less early protection against immunogenic gluten fragments.

EU Novel Food authorization

AN-PEP (Aspergillus niger-derived prolyl endopeptidase) received EU Novel Food authorization in 2017. DSM (now dsm-firmenich), the licensor of the enzyme, obtained this European approval for Tolerase G — the same AN-PEP active ingredient included in Ineopep/Gluteostop. This authorization confirms the food safety of the enzyme within the European Union.

Regulatory note: Ineopep/Gluteostop is a dietary supplement. There is no EFSA-approved health claim for AN-PEP specifically for celiac disease or gluten intolerance. The product is not intended as a substitute for a gluten-free diet and is not suitable as a treatment or prevention of celiac disease. Patients with celiac disease should follow a strict gluten-free diet under the guidance of a doctor or dietitian.

Ineopep® (also known as Gluteostop) from Walhalla Health contains this clinically studied AN-PEP enzyme and is the only supplement available in the Netherlands that contains the clinically validated AN-PEP formulation. It is specifically developed for people following a gluten-free diet who want extra protection against unintentional exposure to hidden gluten — for example, when eating out, traveling, or when labels are unclear. No other gluten enzyme supplement on the Dutch market has the same clinical validation behind the same AN-PEP active ingredient.

Are you considering a gluten intolerance supplement as an addition to your gluten-free diet? Consult your GP first to get a proper diagnosis.

Practical Advice: Living with Gluten (Intolerance)

Whether you have gluten intolerance or celiac disease — or suspect both — the following five practical guidelines will help you minimize daily gluten exposure.

1. Learn to read labels
   Gluten hides behind terms like "wheat starch," "malt extract," "modified starch," and "hydrolyzed vegetable protein." Always look for the certified gluten-free logo (the crossed-out wheat ear). Also, pay attention to "may contain traces of gluten": for celiac patients, this is a risk.
2. Communicate clearly in restaurants
   Don't just ask if a dish is "gluten-free," but also if it is prepared in the same water, on the same baking sheet, or with the same utensils as gluten-containing products. Cross-contamination in kitchens is the most common source of unintentional exposure.
3. Prevent cross-contamination at home
   Use separate cutting boards, toasters, and spread knives. Wash hands thoroughly after handling gluten-containing food. Store gluten-free products in a separate cupboard or in sealed containers.
4. Plan trips carefully
   In many countries, awareness of gluten-free eating is more limited than in the Netherlands. Bring safe snacks, learn the local language for "gluten-free," and research gluten-free restaurants in advance using apps like Find Me Gluten Free. For uncertain meals, consider an enzyme supplement as an extra buffer.
5. Work with a dietitian
   A specialized dietitian not only helps you identify hidden sources of gluten but also monitors the nutritional value of your diet — because without proper guidance, a gluten-free diet is susceptible to deficiencies in fiber, iron, folic acid, and B vitamins.

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