Cross-Reactive Foods: The Reason You're Not Healing Gluten-Free?

wheat and corn - cross-reactive foods?
Is corn cross-reactive with gluten grains?. Dalvir Ubhi/EyeEm/Getty Images

Ever hear of the concept "cross-reactivity"? Supposedly, cross-reactivity occurs when people with celiac disease or non-celiac gluten sensitivity consume certain foods (including grains, dairy, processed foods such as chocolate, and even coffee) that "mimic" gluten in your body.

According to this theory, these foods cause you to have symptoms of a glutening even when you haven't actually consumed any gluten.

Certain companies are heavily promoting tests that supposedly tell you whether your body is mistaking other substances (such as other grains, chocolate or coffee) for gluten, and reacting accordingly. In addition, some clinicians advocate eliminating all grains from your diet — not just gluten-containing grains — because of cross-reactivity.

The problem is, there's just no strong scientific or medical backing for the concept of "cross-reactivity" of many foods with gluten grains, other than for oats (which are a problem for some people with celiac and gluten sensitivity) and possibly corn. Here are the facts.

Cross Reactivity: Plausible-Sounding but Unproven

The idea that people with celiac disease and gluten sensitivity suffer from cross-reactivity sounds plausible when you consider that many react to foods even though they're supposed to be gluten-free. It's certainly reasonable to be frustrated when you're following the gluten-free diet carefully, but continue to have frequent reactions.

It's not unusual for people who are carefully eating gluten-free but still getting sick to create a long list of additional foods to which they believe they're reacting.

However, the research doesn't bear out this concept of cross-reactivity. Instead, medical studies show that at least some of those who fail to feel better and heal on a gluten-free diet are getting glutened by the tiny amounts of gluten in their "gluten-free" foods.

How Much Gluten Do You React To?

Many of the gluten-free-labeled foods we see on grocery store shelves contain a tiny bit of gluten. Just as something can be labeled "fat-free" if it contains less than half a gram of fat per serving (it's not truly fat-free, it simply meets the legal definition for "fat-free"), something can be labeled "gluten-free" even if it contains a small amount of gluten.

One landmark study showed that the majority of people with celiac disease did fine when they ate foods with less than 20 parts per million of gluten in them, and that's the standard required in most countries. Many manufacturers produce products that are well below 20 parts per million. However, some people still react to much less gluten than that.

Sadly, many grains and many other ingredients common in processed foods (such as chocolate) can be cross-contaminated with gluten, albeit at very low levels. Grain-based products are a particular problem, but there are other, surprising sources of trace gluten, too.

Therefore, celiac disease experts recommend that people who continue to have symptoms try a diet completely free of processed foods and almost all grains, as a way of reducing these sources of trace gluten.

Oats a Problem; Corn May Be Problematic

Oats are one exception to this "no-such-thing-as-gluten-cross-reactivity" rule: There's no doubt that some people who react to the three gluten grains (wheat, barley and rye) also react to oats — even oats that are grown and processed to prevent gluten cross-contamination (regular oats are heavily cross-contaminated with gluten, which is why you always should buy gluten-free oats).

Oats contain a protein that's similar to, but not the same as, gluten.

There's also some preliminary research indicating people who carry either of the two "celiac disease genes," HLA-DQ2 and HLA-DQ8, may have cross-reactivity issues with corn. 

That study, published in 2012 in the journal Plant Foods for Human Nutrition, looked at the amino acid sequences in corn and compared them to the sequences found in gluten molecule. The researchers found some similarities between the amino acid sequences in the two different grains.

Next, they performed a computer analysis to see if the corn amino acid sequences might bind to the antibodies produced by the body's immune system to fight gluten. They found evidence that those corn amino acid sequences did interact with the gluten-specific antibodies.

This finding "may be of paramount clinical relevance," the authors concluded. "The use of maize [corn] in the formulation and preparation of gluten-free foods must be re-evaluated in some cases of celiac disease."

The Bottom Line

So does this mean that people with celiac disease should avoid corn as well as gluten grains? That's far from clear — the study itself is extremely preliminary and hasn't yet been duplicated by other studies. But the research does appears to show that it's at least possible (as many people with celiac disease and gluten sensitivity have reported) to also react to corn.

As far as the other claims of cross-reactivity go, though, you should first closely examine your diet (and talk to your doctor and possibly a nutritionist) to see if your problem may in fact be trace amounts of gluten.


Cabrera-Chávez F et al. Maize prolamins resistant to peptic-tryptic digestion maintain immune-recognition by IgA from some celiac disease patients. Plant Foods for Human Nutrition. 2012 Mar;67(1):24, 30.

Hardy MY et al. Ingestion of oats and barley in patients with celiac disease mobilizes cross-reactive T cells activated by avenin peptides and immuno-dominant hordein peptides. Journal of Autoimmunity. 2015 Jan;56:56-65.

Hollon JR et al. Trace gluten contamination may play a role in mucosal and clinical recovery in a subgroup of diet-adherent non-responsive celiac disease patients. BMC Gastroenterology. 2013 Feb 28;13:40.

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