Is gluten intolerance real?

If you are around the alternative health blogs at all, or really many mainstream health sources these days, you might have seen mention that ‘perhaps a gluten free diet can help you too!’ But if you don’t have celiac disease, is going gluten free of any use? Are there gluten issues other than celiac disease and a true gluten allergy? Is gluten and wheat intolerance real? What I think this really gets to is, if we don’t medically understand something yet, is it real? I’ve heard many people argue that gluten intolerance simply isn’t real. Either you have celiac disease or you don’t. It’s not a stance I agreed with, especially after reading this article.

All I know is, some people do report that they feel better when they eat gluten free. While I call myself a celiac, I actually count myself as one of those who don’t really know. If you’ve been here long enough, you know I went gluten free long before I realized there was a test for this whole thing. But between a vast improvement on a gluten free diet and the fact that my father has in fact tested positive for celiac disease, I figure I have it too. And finally, some groups are putting some research time into this. This is the first major study that I’ve seen that actually attempts to do Good Science:

Biesiekierski J. R., E. D. Newnham, P. M. Irving, J. S. Barrett, M. Haines, J. D. Doecke, S. J. Shepherd, J. G. Muir, and P. R. Gibson. 2011. Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized Placebo-Controlled Trial. The American journal of gastroenterology. 1-7.

The authors had two main aims: do non-celiacs react to gluten and if so, what is/are the mechanism(s)? While there are some things that need to be worked out, we know quite a bit about celiac disease. There is modification of the gliadin portion of gluten by a molecule known as tissue transglutaminase causing them to be presented to immune cells, but only in patients who have at least one of two different genes (HLA-DQ2 or HLA-DQ8). 99.4% of patients express the gene products from one of these genes. This process results in the symptoms we see in celiac patients.

As with most good medical studies, the authors went about this by doing a double-blind, randomized, placebo-controlled trial. They took 34 people; 30 female, 4 male, ranging in age from 29-59. All reported problems that labeled them as having ‘IBS’. They responded well to a gluten free diet, but tested negative for celiac disease. 19 were placed into a gluten eating group and asked to follow their regular diet along with consuming two provided pieces of gluten containing bread and a gluten containing muffin. 15 were placed into a gluten free group and asked to follow their regular diet along with consuming two provided pieces of gluten free bread and a gluten free muffin. They were followed for 6 weeks. 56% of them had either one or both of the genes associated with celiac disease (HLA-DQ2 or HLA-DQ8).

Now, as with many medical studies, sometimes they seem to miss obvious things. The patients they recruited had to have been adhering to a gluten free diet for only 6 weeks. I don’t know about anyone else who is gluten free, but it took me much longer than 6 weeks to really get this diet. Hell, even at 8 years I still sometimes make mistakes. I think this is a major weakness of their study, despite the food diaries they asked patients to keep.

The set up was that in the 2 weeks prior to the study, patients kept a 7 day food diary. They were also asked to maintain their gluten free diet throughout the study, with 2 food diary checks in between, expect that they were to eat the two provided pieces of bread and the muffin every day for the entire 6 weeks of the study. If they were consuming the gluten containing products, this was 16g of gluten, well above the threshold for getting a response in celiac patients. Every week, and for 3 weeks after, patients symptoms were evaluated. At the beginning and end of the study serum, urine and stool were also collected for testing.

Here’s where I think things get pretty neat in a nonscience way. These researchers were crafty. To control for potential differences between gluten free and gluten containing products, they had their own muffins and breads made. The only difference between the two was that the gluten containing products had added wheat gluten. Why is this crafty? Some people have a reaction to FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), and wheat is a food that falls under this category. So by making sure these were not present in the bread products, they ensured that they really were testing the presence of the gluten, and not any of these other compounds that might also cause symptoms not related to the gluten. And according to them, 10 normal people couldn’t tell the difference based on taste or texture between the gluten free and the gluten containing products. Crafty mofos!

Also a problem with medical studies, you don’t often get as many people as you think you need. And then some drop out. The authors estimated that they needed 30 people in each group to get good reliable statistics. But out of the 300 who applied, and the 100 that they screened, only 39 met the criteria to be included. And then 5 dropped out. Such is science.

So that leaves us 19 in the gluten group and 15 in the gluten free group. Of the 19 in the gluten group, 6 withdrew after only a week because symptoms were intolerable. 3 in the gluten free group withdrew for the same reasons after 2 weeks. Of the 19 in the gluten group, 13 (68%) reported problems on the gluten diet, while 6 of the 15 in the gluten free group reported problems (40%). While these numbers seem pretty shitty, the authors state that for the gluten eating group, even after just a week, they reported worse overall symptoms, more pain, bloating and tiredness, along with problems with their stool consistency. However, importantly, the antibodies that signify active celiac disease were not induced in either group. They also found no significant difference between those that had the celiac associated genes and those who didn’t.

Their conclusion, and one I agree with based on the study design and their data, is that non-celiac gluten sensitivity does indeed exist. While this study isn’t perfect, they have the stats to back up that 68% feeling shitty on a gluten containing diet is enough to say that there is indeed a problem. They do note, the biggest difference between the two groups was that the gluten eating group reported feeling more tired (I wonder if you can have celiac disease AND whatever this issue is, as I remember feeling incredibly tired). While they also had more problems with bloating, pain and the stool form, it was really tiredness that explained the biggest difference between the two groups.

The bad news? They have no clues as to the mechanism of the problem. C-reactive proteins, a marker for systemic immune activation, were not elevated in either group. Fecal lactoferrin levels, an indication of intestinal inflammation, were also not different between the two groups. They also measured general intestinal permeability to see if it was an issue of intestinal injury, but that too was negative. They do go into some hypotheses at the end that could explain what is happening that they did not or were not able to test for, but I don’t understand them enough to summarize here. But suffice it to say, it looks like non-celiac gluten intolerance is gaining some traction as a real medical issue.

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