Why Does Wheat Contribute to Inflammation and Arthritis?

Why Does Wheat Contribute to Inflammation and Arthritis?

  Aadam Quraishi M.D

Recently European scientists have discovered a new family of proteins called Amylase-trypsin inhibitors that are suspected in the development of inflammation beyond the gut and worsen immune-related chronic conditions such as Rheumatoid Arthritis.  This inflammation may occur in patients with celiac disease, as might be expected, but also in those who do not have celiac disease.  This increased occurrence highlights the need to ask the question of why gluten and non-gluten proteins can cause chronic inflammation.

The function of the gastrointestinal tract has historically been thought of as providing digestion, extraction, and absorption of macromolecules as well as nutrients from food. In order to maintain the body’s homeostasis the GI tract has a barrier mechanism at the cellular level. The intestinal entry of macromolecules is regulated between the intestinal cells through our guts’ endocrine and lymphoid systems, within tight intercellular junctions acting like doors to selectively allow entry of physiologically appropriate substances.  Intracellular tight junctions can be considered as doors that are regulated by a signaling mechanism as to when to open and close, thus protecting the body against foreign and pathogenic microorganisms. However, despite this, some micro-organisms have developed a system to override the signaling mechanism and compromise the barrier function. Zonulin is an enterotoxin released by the bacteria Vibrio cholera that allows for interruptions of the signaling that keeps the barriers closed.


Red blood cells contain the hemoglobin-iron complex. This complex can be released into the bloodstream, if hemoglobin becomes senescent or is needed as a response to injury.  This free hemoglobin iron complex can become oxidized and act as an inflammatory stimulus. To counter this, humans have evolved a system located on Chromosome 16 to produce Haptoglobin which can bind proteins; this system has an evolutionary basis.


Monocytes and macrophages help mediate the delivery and binding of haptoglobin to the oxidized form of hemoglobin, in order to turn it off thus promoting its clearance. The Haptoglobin gene has three forms; Hp 1-1, Hp 1-2, Hp 2-2. Individuals with Hp 2-2 produce the Haptoglobin variety that does not clear oxidized hemoglobin.  In fact, Haptoglobin 2-2 genotype individuals have a significantly increased amount of vascular disease and stroke, accumulation of iron in atherosclerotic plaque, and even have an increased risk of acute kidney damage after elective heart surgery. What is essential in all the above is that Zonulin is stimulated by gluten. 


Zonulin also is the precursor molecule for Haptoglobin 2-2 and as such decreases our ability to clear free oxidized Hemoglobin-iron complex and deregulates the GI tracts signaling ability to ward off the absorption of oxidized hemoglobin-iron and other inflammatory substances. The now open tight junctions that acted as a barrier will result in the creation of what is commonly called a “leaking gut”. The open doors will also allow large macromolecules and partially digested food molecules, as well as various other proteins, to enter.  These unwanted proteins and gut microorganisms get in between the cells and our body may recognize them as foreign, thus producing an inflammatory response.  


The anatomy of grain is composed of the outer part, which is called the brain, the next layer that grows into the new plant is the germ, and the center is the endosperm which is the food for the plant. With the refining of grains, we remove the brain and the germ layer where incidentally all the nutrition is located. Refined grains include white bread, white rice and a variety of cakes. Gluten are proteins found in wheat, rye but also in cakes, cereal and pasta. Its name is derived from the glue-like property that gives the dough its texture, allows it to rise when baked and feel chewy.

The modern wheat, however, changed about 50 years ago. Gliadin and glutenin, the primary protein of wheat has undergone genetic modification for the purpose of increasing the yield per acre for farmers.  This new wheat is suspected behind the sharp rise in Celiac Disease and gluten sensitivity. It seems to be not only an appetite stimulant but also have an addictive quality. Wheat, along with high fructose corn syrup increases blood sugar levels. Glycation is the process of modification of proteins in the body when the sugar level rises. When proteins, lipids, and DNA encounter high levels of glucose, they undergo a transformation which includes the generation of free radicals including the oxidation and reduction of molecules. For hemoglobin, the oxidation of iron has an inflammatory effect.  We can measure this because sugar also attaches to the hemoglobin and when performing an Hb-A1C test, those with persistent high sugar levels will reflect this with a higher number on the test. After the attachment of sugars to proteins, other changes will occur, such as the development of Advanced Glycation End products (AGE) and these mainly accumulate in cartilage, particularly in the articular cartilage of the joints. It causes the cartilage to become malformed and lose its ability to produce collagen and proteoglycans. This damaged cartilage no longer functions appropriately leading to arthritis.  However, it must be recognized the HbA1C of only a marker of sugar exposure and will not pick up the late effects of glycation or its inflammatory consequences.  These glycation end products can also enter through our food from protein sources that are fed wheat or other cultivated cereal crops. What accelerates this process is if these protein sources are further cooked.  The (AGE) products directly correlate with increased markers of inflammation including C-reactive protein. Researchers have noted that the older you are, the more difficult it is to remove AGE from your body.

Inflammation is a driver leading us to most chronic degenerative diseases. When faced with the task of fighting obesity, heart disease may lead to arthritis and diabetes. Awareness is the starting point for action. The first approach is to avoid refined grains and choose the whole wheat variety. Next choose alternatives to grains, if possible, such as Barley, Brown rice-gluten free, Buckwheat gluten-free, Quinoa-gluten free and whole rye.  We must be keen to embrace new insights, and this awareness may lead us to an earnest discussion of the widespread consequences of inflammation, however reducing gluten from our diet is just the starting point.