
These days gluten has been getting a lot of press. While many people have heard of it, a lot of people do not know what gluten is.  Many people just think that a gluten-free diet is the latest fad that marketers are promoting to make money. Some people have heard of celiac disease, also called coeliac disease, but believe that if you do not have celiac disease then there is no reason to avoid gluten. Then there are the few people that have not tested positive for celiac disease, yet still have an adverse reaction to eating foods containing gluten. Patients that experience this are said to have non-celiac gluten sensitivity (NCGS) or non-celiac wheat sensitivity (NCWS) (From here on out both will be referred to as just NCWS). Additionally, it is very common for other people not to believe them or even make fun of them for choosing a gluten-free diet. They may even experience their own doctor not believing that NCWS is real. Nevertheless, recent scientific and medical studies have found that it is not all in their heads. Not only has NCWS been found to be an actual medical condition but researchers have also found that in both celiac disease and NCWS gluten not only affects the gastrointestinal tract but also affects psychological and neurological disorders. However, research has not pinpointed what the actual cause of NCWS is yet. Due to the recent evidence that NCGS is a real and separate condition from celiac disease and can be quite damaging, more research should be devoted towards uncovering the cause, damages, and cure.

First of all, in order to understand what NCWS is, it helps to understand what exactly is gluten? According to the Celiac Disease Foundation, they explain on their website that "gluten is a general name for the protein found in wheat… Rye, barley and triticale… gluten helps foods maintain their shape, acting as a glue that holds food together," (“What Is Gluten?”).  Basically, gluten is found in baked goods, cereal, noodles, and much of the processed food that is sold here in the United States of America. Sometimes, it can also be used as a filler, therefore, it can be found in almost any type of food product, even including powdered drink mix. 

Now, you also have to understand what exactly celiac disease is, what non-celiac gluten sensitivity is, and how they are different. On one hand, celiac disease is an autoimmune disorder, as reported by the Celiac Disease Foundation, that is estimated to affect one in 100 people (“What Is Celiac Disease?”). When a person with celiac disease ingests gluten, their immune system attacks the small intestine (“Celiac Disease Symptoms”; “What Is Celiac Disease?”). This disease is hereditary and the only known treatment at this time is to not eat any gluten (“Celiac Disease Symptoms”; “What Is Celiac Disease?”). Celiac disease can be divided into two different types: classical and non-classical (“Celiac Disease Symptoms”). In the first one, patients have symptoms of malabsorption such as unexplained weight loss or diarrhea (“Celiac Disease Symptoms”). In the second one, non-classical celiac disease, patients do not have clear signs of malabsorption or they have what one may think of as unrelated symptoms such as chronic fatigue, chronic migraine, bone fractures, unexplained infertility, depression, and anxiety (“Celiac Disease Symptoms”). Right now, there are over 200 known symptoms of celiac disease (“Celiac Disease Symptoms”). Due to this very wide array of possible symptoms plus a lack of medical training of healthcare professions, it is estimated that 80% of people with celiac disease in the United States of America are undiagnosed (“Celiac Disease Symptoms”).

On the other hand, non-celiac gluten sensitivity or non-celiac wheat sensitivity is described as when a person experiences symptoms in response to wheat and other grains that are known to have gluten (“Non-Celiac Wheat Sensitivity”; Uhde et al. 1930-1931). These symptoms are similar to celiac disease but the individual has tested negative for celiac disease (“Non-Celiac Wheat Sensitivity”; Uhde et al. 1930-1931). Studies have just found in the past couple of years that NCGS or NCWS are in fact an actual medical condition (Calabrese; Capili 666-667; Deans; Uhde et al. 1930). Due to the fact that there has been a lot of research on the celiac disease side of the coin but there is very little research that has been done so far on the NCWS side of the coin, we will be focusing mainly on NCWS from here on out.

Evidence that NCWS is a real medical condition separate from celiac disease can be seen in a study that was published in the gastroenterology and hepatology journal, Gut, in June 2016, titled, “Intestinal Cell Damage and Systemic Immune Activation in Individuals Reporting Sensitivity to Wheat in the Absence of Coeliac Disease,” (Uhde, et al). In this article Melanie Uhde, et al, who are research scientists and doctors from the Department of Medicine, Celiac Disease Center, and the Institute of Human Nutrition at Columbia University Medical Center, and the Departments of Medical and Surgical Sciences and Digestive System at the University of Bologna, studied what, if anything, affects the immune system or intestinal lining when people with NCWS eat wheat (1930). Uhde and her colleagues found that when patients with NCWS ingested wheat and related cereals they have a systemic immune activation along with compromised intestinal epithelium (the lining of the intestines) (1930, 1932-1936). That is to say, their immune system gets turned on against these grains as if they were an illness and the lining of their intestines doesn’t work fully.

Despite the fact that these diseases are commonly only associated with problems in the gastrointestinal tract, both celiac disease and NCWS have symptoms that fall under psychiatric or neurological disorders. As stated in the Celiac Disease and Gluten-Related Conditions Psychological Health Training Program Manual, the most common typical and atypical celiac disease symptoms include: depression, inability to concentrate, anxiety, obsessive-compulsive disorder, attention deficit hyperactivity disorder, seizures, migraines, and brain atrophy  and according to the article “Non-Celiac Wheat Sensitivity,” these are some of the same symptoms found in NCWS (The Celiac Disease Program at Children's National Health System, and The Celiac Disease Foundation; “Celiac Disease Symptoms”; “Non-Celiac Wheat Sensitivity”). In agreement with that, for NCWS as well, S. L. Peters, et al reported in, “Randomized Clinical Trial: Gluten May Cause Depression in Subjects with Non-Coeliac Gluten Sensitivity – An Exploratory Clinical Study,” that they had conducted a randomized, placebo-controlled, double-blind, crossover dietary rechallenge study to see if there was a link between gluten and depression in individuals with NCWS (1108). What they found is that short-term exposure to gluten appears to induce feelings of depression, in keeping with the State Trait Personality Inventory (Peters 1108). According to the author of the inventory, Charles D. Spielberge, the State Trait Personality Inventory can be used to measure anger, anxiety, curiosity, and depression (Spielberge). Nevertheless, not nearly enough research has been done on NCWS, yet. 

Just in case it is still not obvious how much eating gluten can affect a patient with NCWS, Martha R. Herbert and Julie A. Buckley explained how gluten affected one child with autism in their report, “Autism and Dietary Therapy: Case Report and Review of the Literature,” which was published in Journal of Child Neurology (975-979). The child that was studied was originally neurologically normal but then she developed autism and epilepsy (Herbert and Buckley 976-977). Starting a gluten-free, casein-free diet greatly reduced her autistic symptoms, however, when she started having seizures, Medicine wasn’t controlling them (Herbert and Buckley 975-978).  When her parents continued her gluten-free casein-free diet while starting ketogenisis in addition to her medication improved her seizures significantly (Herbert and Buckley 975-978). In addition to her seizures, after being placed on a gluten-free, casein-free diet, her IQ score increased by 70 points and, according to her Childhood Autism Rating Scale score she went from severe autism to non-autistic (Herbert and Buckley 975, 977). While this is just one clear example from among published research showing that ingesting gluten containing grains can cause damage, even severe damage, in individuals with NCWS, doctors have not been able to find why this happens.

Even though enough research has being done to conclude that NCWS is a medical condition, the means of how gluten containing grains cause these symptoms in patients is still not understood. However, there are some plausible causes that have been suggested by researchers. One hypothesis is that individuals with NCWS may actually have celiac disease but for some reason they are lacking or have an insufficient amount of the antibodies that are used to diagnose celiac disease (“Non-Celiac Wheat Sensitivity”). Another cause may be opioid peptides made from partly digested proteins that can cross the blood-brain barrier and mess things up through the opioid receptors (Peters et al. 1110). A third possibility may be that gluten changes to gut microbiota which can influence emotional behavior (Peters et al. 1110). The fourth possible reason may be that wheat reduces the concentration of tryptophan in the brain which is used to create serotonin and decreased the concentration of serotonin is a suggested cause of depression (Peters et al. 1110).

One thing that many research studies have found is that it may not be gluten, specifically, that is triggering these symptoms in those with NCWS. One thing that has shown up in multiple studies as a possible cause of NCWS is fermentable, poorly absorbed short-chain carbohydrates (FODMAPs) (Biesiekierski et al.; Capili et al; Deans; Peters et al). According to Jessica Biesiekierski, et al, in their paper, "No Effects of Gluten in Patients with Self-Reported Non-Celiac Gluten Sensitivity After Dietary Reduction of Fermentable, Poorly Absorbed, Short-Chain Carbohydrates," they found that patients with NCGS who ate a low FODMAP diet had their symptoms relieved (325). They believe that it may actually be FODMAPs instead of gluten causing symptoms or gluten may only cause symptoms in the presence of a certain amount of FODMAPs (Biesiekierski 327). Wheat and rye, two sources of gluten, are also high in FODMAPs (Capili 669). In addition to FODMAPs, it may also be possible that there are actually other proteins besides gluten that are partially, or completely, the cause of these symptoms, according to Bernadette Capili, et al, in the paper, "A Clinical Update: Nonceliac Gluten Sensitivity–Is It Really the Gluten?" (669).

Since so little is still unknown about NCWS, more research needs to be done. Especially, in consideration of the fact that this disease can cause many problems and wreak a lot of havoc in people's lives, particularly when it is undiagnosed. Researchers need to find out if it is the gluten, other proteins, FODMAPs, a combination of these, or even something else entirely that is causing these symptoms. Also, scientists need to find out the full extent of the symptoms and the damages that are caused by NCWS in order to better take care of patient’s health. This will also make it easier to identify NCWS by making a comprehensive diagnostic check sheet of symptoms available. Finally, research also needs to be done in order to find what can be done to alleviate the symptoms and also find if there is a cure. 

In conclusion, research is proving that NCWS is real but, it is still not understood how gluten causes these symptoms, or if it is actually something else altogether that is commonly found in gluten-containing grains, such as FODMAPs. In addition to our lack of knowledge, these findings to back up NCWS have only been found very recently. Outside of the additional psychological stress of patients with NCWS being told that they are faking it and being made fun of, there is even still a lot of doctors that are: not up-to-date on this research; do not know how to diagnose NCWS, or do not even think that it is real. Not only do we need to spend more resources on researching NCWS to understand exactly what the cause is and how it can be treated, but we also need to spend resources on mass education. First off, the misinformation and joking that goes on in popular culture need to be corrected. We would never tell a leg amputee that their inability to walk is all in their head nor would we tell a cancer patient that their illness is all in there had. In the same way, we should not be telling people who have NCWS that what is wrong with them is all in their head. Especially, since this medical condition can cause and worsen depression. Secondly, updated research on this topic needs to continue to be published and it needs to be distributed to healthcare providers. This is a legitimate medical condition, and while the exact cause is not completely known, that is no excuse for a medical doctor to believe that NCWS is not real. So, in a nutshell, we need to do more research into the cause and extent of NCWS; we need to educate the public, and we need to educate our healthcare professionals.
