If you’ve been gluten-free for any amount of time at all, you’ve probably read over and over, and even recited this same mantra yourself: “Gluten is a protein found in wheat, barley and rye.” But that isn’t exactly correct!
The term gluten has often been used to describe, very generally, any non-starchy portion of any cereal grain, including rice and corn. But gluten has also often been defined as, very specifically, a protein composite in wheat, made up of gliadin and glutenin. So what is the true definition? The answer isn’t that simple!
See, gluten is just a name (ok, you can say, duh!). But really, it all boils down to nomenclature, classification, naming conventions. A way to describe things. While a system of nomenclature is very important – we all want to be sure that we are talking about the same thing – it is not an exact science. And the question is, are we all describing gluten the same way? Even cereal scientists themselves admit that the nomenclature of grain proteins is “confusing” and that “so far, it has not been possible to introduce a standard nomenclature for these groups.”
Whether talking botany, or medicine, names for things can and do evolve, especially as more discoveries come to light. It turns out that the term “gluten” is not applied to one specific protein or DNA marker or amino acid sequence. It’s a loosely applied term, whose definition, at least in terms of diagnosing disease and producing gluten-free foods, may need to be revisited.
So how did the term gluten and today’s gluten-free diet come about?
gluten (n.) 1630s, “any sticky substance,” from Middle French gluten (16c.) or directly from Latin gluten “glue” (see glue (n.)). Used 16c.-19c. for the part of animal tissue now called fibrin; used since 1803 of the nitrogenous part of the flour of wheat or other grain; hence glutamic acid (1871), a common amino acid, and its salt, glutamate.
Gluten was originally used to mean “any sticky substance,” even describing the “gluey nature of muscle, blood and egg white” of humans and animals.[3 In 1745, Italian scholar Beccari discovered that wheat contained some of this same “animal glue” substance, which he was able to separate from the starchy portion of wheat. He did this by first rinsing, then kneading wheat flour to form a substance similar to dough, but without yeast and other ingredients. Think… play-dough. Thus the term “gluten” as applied to wheat, was born. While not quite as “sticky” as wheat, the term gluten was also applied to rye and barley, when “subsequent work showed … similar alcohol-soluble proteins were present in rye and barley.” 
The first grain-free diet, that we know of, was prescribed by Dr. Willem Dicke, a Dutch pediatrician in 1934. “It was a young mother’s statement of her celiac child’s rash improving rapidly if she removed bread from the diet, that alerted his interest.” He was further convinced that eating less cereal was beneficial for his patients, when they were forced to go without their staple foods of wheat, rye and oatmeal during the ‘Winter of Starvation’ at the end of World War II. His patients all remarkably improved during this period, only to deteriorate again, once their staple grains were readily available and consumed regularly again at the end of the war.
Together with van de Kamer and Weyers, Dicke later isolated a component of the wheat flour by rinsing and kneading it, just as Beccari had done more than two hundred years earlier, leaving behind that same sticky mass of play-dough-like substance we now know of as gluten. This gluten was then fed to his patients, proving conclusively that it was the major cause of malabsorption and other symptoms in Celiac Disease (CD) patients. And the “gluten-free” diet was born. Oats were included in this list of “gluten grains”, because Dicke had observed reactions to oats by his patients, as well.
Dicke made huge strides in helping celiac disease patients, and he rightly deserves our gratitude for getting us this far on the study of gluten-related diseases. But since his landmark studies, we’ve neglected to look at least one key point.
First, what is that sticky, play-dough-like mass really comprised of? Is it just one protein?
Actually, it’s a composite of proteins, which Dicke et al. differentiated into two main components: one group of proteins called gliadin (which are alcohol-soluble) and another, called glutenin (which are insoluble except in acid or alkali). Gliadin is the prolamin of wheat, and other grains have similar prolamins, but with different names (e.g barley = hordein, rye = secalin, etc.). Both gliadin and glutenin can be further broken down into more groups, and some of the amino acid sequences in these groups have been given names, such as alpha-gliadin and beta-gliadin,  (see infographic). All of this makes gluten a very complex creature!
So why should any of this anatomy and nomenclature matter to you and me?
Well… how do you know if your food is being tested for the right fraction of gluten? And how do you know if your doctor looked for the right fraction of gluten antibodies when testing for celiac disease?
Back to Dicke, et al.’s 1953 study. When Dicke proved that gluten was the ingredient in wheat flour making his patients sick, he singled out gliadin as the class of proteins most responsible for the symptoms of celiac disease. And today, celiac disease is defined, primarily by an immune reaction to gliadin antibodies, and only the alpha-gliadin fraction, at that.
Keyword there: most.
So scientists have been hard at work whittling down THE ONE specific protein, component, isolate, whatever you want to name it, in the gliadin prolamin, that is responsible for celiac disease and gluten sensitivity “to separate the coeliac toxic factor.” But instead of trying to find that little, tiny molecule that (we hope) is the one and only cause of this epidemic of people who are forced to give up the “staff of life,” sad as it may be, we should be looking at the bigger gluten picture. We’re missing the forest for the trees!
Loren Cordain nicely sums up the weakness that lies in using alpha-gliadin in the primary diagnostic test for celiac disease:
Because gliadins are a complex mixture of proteins that contain at least 40 different components in a single variety of wheat, it is unlikely that a single gliadin protein causes celiac disease, but rather several prolamines that express similar or identical epitopic domains.
Not only that, while Dicke focused on gliadin, he did note that glutenin caused problems, too. Just not as severe. But he did note a reaction to glutenin in one out of his five subjects! Granted, it’s a statistically small sample size, but still, 1 out 5 is no small ratio to ignore. This is important! This may explain why you know that wheat is affecting you, but your doctor can’t give you a diagnosis of celiac disease.
In fact, as Braly and Hoggan point out, there are studies that suggest “glutenin may also be involved in the disease process” and that “other studies indicate that glutenin peptides are toxic to cells.”,  Furthermore, as far back as 1982, Kieffer, et al. found that the immune response to glutenin was just as high as it was to gliadin!
So a negative diagnosis of celiac disease, does not necessarily mean that gluten isn’t making you sick! Glutenin may be making you sick, but we just aren’t looking for reactions to it.
In the same way, when food manufacturers typically test their food for gluten, what do you think they test for? You guessed it! The gliadin fraction of gluten. So if a manufacturer tells you their food is gluten-free because it contains < 20ppm gluten, they really mean < 20 ppm of gliadin. They aren’t looking for glutenin or any other portion of wheat/gluten! Their food may be gliadin-free (or low gliadin, really), but how we can say for sure that its gluten-free?
This may explain why you might react to foods that are labeled gluten-free. It also reinforces my theory that < 20 ppm may not be a safe threshold for the gluten sensitive. In fact, food technologist Mermelstein says “Cereal chemists… can’t really tell how much gluten is in wheat flour because it is variable and there is no gold-standard way to measure it.” So how much do you trust a food product made with wheat or barley that has been “de-glutenized”? Can it be considered safe beyond a reasonable doubt? Personally, I won’t touch it. I’d rather play it safe, just in case.
In summary, gluten is not just a protein found in wheat, barley and rye. Nor is it easily isolated into components small enough for us to determine diagnostic tests for celiac disease. And finally, the “gluten” that we are looking for in food, may not be the complete picture of gluten.
Now that we know what gluten really is, I propose our own version of the definition of gluten. What do you think?
gluten (n.) 1. a complex compound found in wheat and other grains, made up of a couple types of protein groups, whose anatomical complexities can be even further differentiated. In wheat, these protein groups are called gliadin and glutenin. 2. the complex compound that is the major cause of autoimmune diseases including (but not limited to) Celiac Disease, as well as hundreds of other disorders that fall under the medical category of Gluten Sensitivity. gluten-free diet: a diet devoid of all parts of the complex compound, gluten.
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