Chapter 1

Gluten, celiac disease and non-celiac gluten sensitivity: What are they?

You are likely reading this book because you or your patients, friends or loved ones have mental health or neurological symptoms. You are not alone but may be like millions of others worldwide who have such concerns. Perhaps you are exploring the relationship between your/their symptoms and wheat and gluten? While sensitivity to gluten is not always related to neurological and mental health issues, in some people it may be an important contributing factor. We hope to shed light on these associations and on when it may be a good idea to consider further testing. We will start by explaining what gluten is, why it is related to brain health and what the evidence shows. Many people are looking for a cure. A gluten-free diet may not be the whole answer for you but we are writing this book to help you or your patients understand whether or not it may make a difference. The relationship between gluten and brain health remains under-recognized. After reading the chapters relevant to your situation, we hope you will be better equipped to consider this relationship, and whom it may affect, including yourself, your family or your patients.

In this book, we will discuss both celiac disease (CD) and non-celiac gluten sensitivity (NCGS), and the scientific evidence linking these conditions to brain-related disorders, including both neurological and psychiatric symptoms and diagnoses. Note that 'celiac' is often spelled coeliac in many areas of the world outside of the United States (US).

Both CD and NCGS are related to gluten consumption but there are several differences between the two. This chapter will provide you with an overview of both, and the next chapters will go into greater depth to give you more understanding of these conditions. However, before you learn more about CD and NCGS, it is helpful to start with an introduction to what gluten is and how it ends up in our food.

Gluten

What is gluten?

Gluten is a Latin word meaning 'glue' and this refers to the stickiness in wheat-based dough used to make bread and pasta.1 Gluten is a mix of several proteins found in certain grains, such as wheat, barley and rye. There are many varieties and crossbreeds of wheat, known by different names, that also contain gluten. These include triticale (a cross between wheat and rye), durum, spelt (see below), farro and semolina, amongst others, and they developed partly due to wheat's ability to self-pollinate.

Oats are naturally gluten free, but cross-contamination with gluten-containing grains during processing can occur and trigger a gluten reaction in those with CD and NCGS.2

Grains were first cultivated in Asia around 10,000 years ago. The use of an early form of wheat called spelt is documented in history books as far back as 5000 BCE.2 Gluten was first discovered in 1728 by Jacopo Bartolomeo Beccari, a physician and chemist in Bologna, Italy.3 However, wheat cultivation and milling by grinding or crushing in mass quantities did not occur until the 1800s. As this occurred, gluten consumption began to rise and has steadily increased worldwide ever since.4 While awareness of gluten has become more common over the last two decades, it has actually existed for thousands of years.

In the US, several time periods marked surges in wheat consumption. During World War II, when dairy products and meat were rationed, less expensive food options, such as pasta and bread, were promoted. 'Whole-wheat' products, referring to foods made from the entire wheat kernel, were introduced later in the US in the 1960s, and advertised as health foods.

In the 1990s, the 'Food Pyramid' developed by the US Department of Agriculture (USDA), placed wheat and grain products at the base of the pyramid, encouraging Americans to make these foods the largest portion of their dietary intake. In addition, since that time, take-away fast foods like hamburgers and sandwiches (made with buns, rolls, wraps and bread), donuts and pizza, which all contain wheat, have become part of a dietary norm, in the US and for much of the developed world. Wheat flour is also hidden in many soups, stews, sauces, and even processed meats, bought in stores or restaurants. In many places, potato fries are dipped in wheat flour before being cooked, in order to make them crispier. Therefore, it is no surprise that increased gluten consumption has not only been a global trend but also a result of the fast-food industry's growth.4

Wheat is now the most widely cultivated crop in the world, and it supplies 20% of all food calories and protein consumed by the global population.5 Americans on average eat around 10-20 grams of gluten daily. In West and Central Asia and North Africa, a staggering 30% or more of daily calories come from wheat products.5 After rice, wheat is the crop grown most abundantly in China, and some of the highest gluten consumption in the world now occurs there.6, 7 Perhaps it is not surprising that an increase in CD cases has been documented there as well. In the last decade, China has produced more research on CD than many other countries in Asia, and this has also led to increased medical testing for gluten-related disorders there.7

Components of gluten

The two main proteins in wheat are gliadin and glutenin. When gliadin and glutenin combine, they form gluten, and more will be detailed about this process below.8 Gliadin is known as a 'prolamin', a term created by the father of plant protein chemistry, T.B. Osborne. Using different solvents (fluids used to test and dissolve substances), Osborne developed a process of protein extraction from plants that was given the name 'Osborne fractionation'. By this means, Osborne was able to determine that gluten was comprised of many proteins, mainly gliadin and glutenin but also albumin and globulin. Prolamins, including gliadin, are storage proteins that dissolve in 60-70% alcohol, whereas glutenin was found to be dissolvable in alkaline solvents.8

Why is the distinction between these two types of protein important? Great question! While both gliadin and glutenin join to make gluten, gliadin is the culprit protein that induces adverse immune responses in the body, more so in genetically or otherwise predisposed individuals. Knowing this helps us understand some of the testing for gluten-related disorders.9

Other grains contain prolamin-type proteins which may trigger immune responses in a similar way to how gliadin does so when wheat is ingested. These include secalins (found in rye) and hordeins (found in barley). These are the proteins in non-wheat grains that trigger the immune response seen in gluten-related disorders. Avenins are found in low quantity in the endosperm (see Figure 1.1) of oats; they are not highly immunogenic and typically are tolerated by those with CD. The caveat to this is that oats can trigger an immune and/or inflammatory response if the oats were exposed to gluten (cross-contaminated) in the processing or handling of the product, as mentioned above.6

Wheat, however, is the gluten-containing grain that causes the most pronounced adverse immune response, especially in genetically predisposed individuals. The more removed, or different, a grain's prolamin protein is from wheat, the lower the severity of a potential immune response. Barley typically will produce an adverse immune response less severe than that of wheat but is more immunogenic than rye.10

Some people believe that one reason why wheat often causes a more severe immune response in many individuals relates to a six-fold increase in the gliadin content of wheat over time. This may be due to the use of high-nitrogen fertilizers and partly to how wheat is processed in the US.11

Components of grain

Let's take a closer look at what makes up a grain. Using wheat as our grain example, you will see in Figure 1.1 that the proteins that make up gluten are in the endosperm of a wheat kernel. The endosperm is part of the kernel and is the future nutrient store for the plant embryo contained within the grain; it usually contains starch, protein and other nutrients. Gliadin and glutenin constitute approximately 85-90% of the proteins found in wheat endosperm.6 Other proteins in the endosperm include albumin and globulin, as mentioned, but these typically represent less than 15% of the proteins in the core of the wheat kernel and do not contribute to the gluten response seen in CD and NCGS.12

The wheat kernel is found at the top of the plant stalk and is surrounded by an inedible husk, or 'hull'. The husk can vary from being thick and difficult to remove, to being paper-thin. Wheat kernels with practically no husk are known as 'naked grains'. While idioms and sayings from decades ago are not as recognized now, perhaps you may still remember the expression 'separating the...