This Thing Is Gluten Free: Does that mean it’s good for me?

Medical Center

Gluten, from the Latin word for glue, is a mixture of proteins found in cereal grains, and is responsible for the elastic texture of dough. The most commonly discussed proteins are gliadin and glutenin in wheat, but there are similar proteins in rye, barley and oats.

Many people report that their intake of grain products appears to have noticeable physical effects on their health, and while gluten has a well-understood role in celiac disease, its role in the nonspecific set of intestinal and non-intestinal symptoms known as “non-celiac gluten sensitivity” (NCGS) is poorly understood and quite controversial.

FODMAPs and other components of wheat

Wheat consists of proteins, carbohydrates, small amounts of fat and trace amounts of other substances. Although gluten is the main storage protein of wheat, there are also non-gluten proteins, including alpha-amylase/trypsin inhibitors. The carbohydrates within wheat consist of both digestible long-chain types and indigestible types, known as fodmaps.

Fhqwhgads? No, FODMAPs. Fermentable, Oligosaccharides, Disaccharides, Monosaccharides And Polyols, which are short-chain carbohydrates and related alcohols that are poorly absorbed in the small intestine and can act as a substrate for bacterial metabolism and growth, leading to fermentation and the release of gases.

This can lead to luminal distension, which can stimulate the gut and explain several functional GI complaints. Proper exploration of the other substances in wheat is warranted before settling on the claim that gluten is responsible for everyone’s symptoms.

Irritable bowel syndrome

Across the world, irritable bowel syndrome (IBS) is thought to affect roughly 10 percent of the population. It is characterized by abdominal pain, bloating, flatulence, distension and altered bowel habits in the absence of other specific pathology.

No single biological abnormality can explain these symptoms, and some patients have diarrhea-predominant IBS, while others have constipation-predominant IBS. Overall, it is thought to be an inappropriate response to sensory input to the intestine.

Since luminal distension is a major stimulus to the gut, via stretch receptors, the ingestion of fodmaps will aggravate symptoms, and in several studies, diets low in fodmaps have been shown to provide relief of functional gut symptoms in patients with IBS. Reducing fodmap intake has become an increasingly common approach to management of IBS in many countries.

Celiac disease

Celiac disease is an autoimmune disorder, primarily of the small intestine, caused by a reaction to gliadin. The enzyme tissue transglutaminase modifies this protein, and the immune system cross-reacts with the small bowel tissue, causing an inflammatory reaction, leading to flattening of the intestinal villi (elongated projections that increase the intestines’ absorptive surface).

This may manifest as abdominal pain or discomfort, malabsorption of nutrients or vitamins, diarrhea or constipation, any of several somatic complaints, and eventually even osteoporosis or certain types of lymphoma.

Diagnosis is performed using a combination of serum markers and small bowel biopsy, and current prevalence estimates are between 1:70 and 1:300. If you have been diagnosed with celiac disease, yes: gluten is bad for you. Don’t eat it. But you knew that already. Let’s move on.

Non-celiac gluten sensitivity (NCGS)

Patients are considered to have NCGS if celiac disease has been excluded and their intestinal IBS-like symptoms markedly improve on a gluten-free diet (GFD).

In some experimental models yet to be confirmed in human tissue, gluten has been suggested to cause low-grade intestinal inflammation, increased epithelial permeability and altered protein expression in cells that resemble human gut epithelium.

Certain animal models of NCGS have demonstrated some changes in gut neuromotor function and microbiota, independent of intestinal inflammation.

There is an abundance of at times contradictory data attempting to characterize genotypic and immune markers of patients with NCGS, looking at cell surface antigens or markers of innate immunity.

There are also cohorts with diarrhea-predominant IBS patients whose symptoms have been followed on gluten-free diets. The aggregate of these data has been largely inconclusive, either due to conflicting results, methodological weaknesses or the inclusion of some patients who would no longer meet the criteria for NCGS.

One of the major flaws of the above-mentioned studies was the failure to isolate gluten challenges from other components of wheat, most notably fodmaps. A group in Australia has recently conducted a randomized, double-blind, placebo-controlled trial of a single dose of fodmap-free gluten over six weeks, while otherwise continuing a GFD.

The gluten group had greater gastrointestinal (GI) symptoms and tiredness within the first week. There were no other marked lab abnormalities, and this was considered the first specific evidence indicating the existence of NCGS.

The same group conducted a follow-up study. Following a two-week run-in period on a low fodmap diet, 37 patients with NCGS and IBS who were symptomatically controlled on a gluten-free diet underwent a double-blind, placebo-controlled, randomized trial of three diets: placebo, low-gluten (2g/day) and high-gluten (16g/day). Participants would try one diet for one week, followed by a two-week washout period, and then switch to the next diet. Symptoms consistently and significantly improved on restriction of fodmap intake, but worsened during each dietary treatment period, irrespective of the amount of gluten in the diet.

A double-blind, placebo-controlled, randomized re-challenge was then done in 22 of these patients, and they were randomized to receive gluten, whey or a placebo for three days each. The reproducibility of symptom induction was not found to relate to which protein they got.

In fact, only two participants had symptoms induced in the gluten arm, and they were not the same two who had a positive response to the high-dose gluten in the seven-day trial. A very high nocebo effect was found in both trials (where an inert substance causes worsening of symptoms).

It is possible that fodmaps are responsible for the typical symptoms of NCGS, or it may be that gluten becomes a trigger only in the presence of dietary fodmaps.

Current reviews on NCGS suggest that the significant nocebo effect recognized in patients who have already been on a gluten-free diet make this population an unreliable group to evaluate.

Instead, IBS patients who are previously naïve to a GFD may be a more informative study population. Because the evidence does not even truly single out gluten as a causative agent, some suggest the disorder be renamed “non-celiac wheat sensitivity.”

In summary, we really do not have hard evidence that gluten is responsible for the complaints people often associate with it. This does not, however, mean it is all made up. Remember, it was once thought that peptic ulcer disease was primarily psychogenic, and we now know it to be related to the bacteria H. pylori.

As clinicians, it would be premature to suggest to our patients that we know gluten to be a trigger for the laundry list of problems with which it has been linked in the lay press, such as intestinal symptoms, skin problems, fatigue, headaches, weight gain and autism, but it may be reasonable to try a low fodmap diet (which will overlap greatly with a low-gluten diet) for those with diarrhea-predominant IBS.

Finally, if you do not have celiac disease, IBS or NCGS, gluten is probably fine for you, and bread is delicious.