Non-Celiac Gluten Sensitivity: What We Know

Some people react badly to gluten but don’t have celiac disease. They test negative for celiac, but they feel better without gluten. What’s going on?

This is non-celiac gluten sensitivity (NCGS), and it’s one of the more controversial areas in gastroenterology.

What Is NCGS?

Non-celiac gluten sensitivity is defined as:

• Symptoms that respond to gluten elimination
• In people who have tested negative for celiac disease and wheat allergy
• Where symptoms return when gluten is reintroduced

It’s a diagnosis of exclusion, you rule out celiac and wheat allergy first, and if symptoms still respond to gluten, it might be NCGS.

The Controversy

NCGS is controversial for several reasons:

No Biomarkers

Celiac disease has measurable markers: antibodies (tTG-IgA, etc.), genetic markers (HLA-DQ2/8), and intestinal damage visible on biopsy.

NCGS has none of these. There’s no blood test or biopsy to confirm it. The only evidence is symptom improvement on a GF diet.

Placebo Effect

Studies using double-blind challenges (where neither patient nor researcher knows if the food contains gluten) have mixed results. Some show real reactions to gluten; others show equal reactions to placebo.

When people know they’re eating gluten, they report symptoms. When they don’t know, the results are less clear.

This doesn’t mean NCGS isn’t real, but it makes it hard to study and diagnose.

What’s Actually Causing Symptoms?

It might not be gluten itself. Possibilities:

FODMAPs: Wheat contains fructans, a type of FODMAP that can cause GI symptoms. Some “gluten sensitivity” might actually be fructan sensitivity.

Other wheat proteins: Wheat contains proteins besides gluten that could trigger reactions.

Amylase trypsin inhibitors (ATIs): Non-gluten proteins in wheat that can trigger immune responses.

Nocebo effect: The belief that gluten will cause symptoms becomes self-fulfilling.

Actual celiac disease: Some people with NCGS may actually have celiac that wasn’t caught by testing (particularly if they were already eating low-gluten).

The Current Science

Research is evolving. What we know:

Some NCGS Appears Real

Well-designed studies do find a subset of people who react to gluten in blinded conditions. The effect is smaller than in unblinded studies, but it exists.

It’s Probably a Spectrum

NCGS likely includes multiple conditions with different mechanisms. Some people may be reacting to gluten, others to FODMAPs, others to ATIs.

Intestinal Changes Exist

Some studies show subtle intestinal changes in NCGS, not the villous atrophy of celiac, but mild inflammation and permeability changes.

Symptoms Are Real

Whatever the mechanism, people with NCGS do experience real symptoms that improve on a GF diet. The cause may be debated; the symptoms aren’t imaginary.

How NCGS Differs from Celiac

Factor	Celiac Disease	NCGS
Autoimmune	Yes	No
Intestinal damage	Yes (villous atrophy)	None or mild
Blood markers	Yes (tTG-IgA, etc.)	No
Genetic markers	HLA-DQ2/8 required	Variable
Long-term complications	Yes (if untreated)	Unknown
Required GF strictness	Very strict	May tolerate small amounts

If You Think You Have NCGS

Rule Out Celiac First

Before assuming NCGS:

1. Get celiac testing (while eating gluten)
2. If testing is inconclusive, consider genetic testing
3. Discuss with a gastroenterologist

Starting a GF diet before testing can make celiac diagnosis impossible without returning to gluten.

Consider Other Explanations

Work with a dietitian to explore:

• FODMAP sensitivity (try low-FODMAP diet)
• Other food intolerances
• IBS (irritable bowel syndrome)

Trial Elimination

If celiac is ruled out, a supervised elimination trial makes sense:

1. Strict GF diet for 4-6 weeks
2. Document symptoms
3. Reintroduce gluten in controlled way
4. Document response

Ideally, this includes some blinding (someone else prepares food and you don’t know which has gluten).

Living with NCGS

If you have NCGS:

Strictness May Vary

Unlike celiac, you may tolerate small amounts of gluten. Your body might handle occasional exposure without damage. Work with your healthcare provider to determine your threshold.

Re-evaluate Periodically

NCGS diagnosis should be reconsidered periodically:

• Are symptoms still responding to diet?
• Has anything changed?
• Should celiac be retested?

Take It Seriously

Even without the autoimmune damage of celiac, if gluten makes you feel bad, avoiding it is reasonable. You don’t need to prove to anyone that your symptoms are “real enough.”

For People with Celiac

You may encounter people with NCGS who say things like:

• “I have what you have” (they don’t, it’s different)
• “I cheat sometimes and I’m fine” (implying you should be able to)
• “It’s not that serious” (for them, maybe not; for you, it is)

Be patient. Their condition is different. Their statements about their experience don’t apply to yours.

Also: NCGS has helped expand GF food options and restaurant awareness. More demand for GF products benefits everyone.

The Bottom Line

Non-celiac gluten sensitivity is real for some people, though the mechanisms aren’t fully understood and the diagnosis is challenging.

It’s different from celiac disease:

• Not autoimmune
• No proven long-term damage
• May not require the same strictness

If you suspect NCGS, get proper testing for celiac first. Then work with healthcare providers to understand your specific situation.

And regardless of the label, if avoiding gluten makes you feel better, that’s valid.