ZONULINS: HOW WHEAT INVITES ITSELF INTO THE BLOODSTREAM
The gliadin protein of wheat, present in all forms of wheat from spongy Wonder Bread to the coarsest organic multi-grain loaf, has the unique ability to make your intestine permeable.
Intestines are not meant to be freely permeable. You already know that the human intestinal tract is home to all manner of odd things, many of which you observe during your morning ritual on the toilet. The wondrous transformation of baked salmon or three-egg omelet into the components of your body, the remainder discarded, is truly fascinating. But the process needs to be tightly regulated, allowing entry of only selected components of ingested foods and liquids into the bloodstream.
So what happens if various obnoxious compounds mistakenly gain entry into the bloodstream? One of the undesirable effects is autoimmunity—i.e., the body’s immune response is “tricked” into activation and attacks normal organs such as the thyroid gland or joint tissue. This can lead to autoimmune conditions such as Hashimoto’s thyroiditis and rheumatoid arthritis.
Regulating intestinal permeability is therefore a fundamental function of the cells lining the fragile intestinal wall. Recent research has fingered wheat gliadin as a trigger of intestinal release of a protein called zonulin, a regulator of intestinal permeability.24 Zonulins have the peculiar effect of disassembling tight junctions, the normally secure barrier between intestinal cells. When gliadin triggers zonulin release, intestinal tight junctions are disrupted, and unwanted proteins such as gliadin and other wheat protein fractions gain entry to the bloodstream. Immune-activating lymphocytes, such as T-cells, are then triggered to begin an inflammatory process against various “self” proteins, thus initiating conditions such as celiac disease, thyroid disease, joint diseases, and asthma. Gliadin wheat proteins are akin to being able to pick the lock on any door, allowing unwanted intruders to gain entry into places they don’t belong.
Outside of gliadin, few things share such a lock-picking, intestinal-disrupting talent. Other factors that trigger zonulin and disrupt intestinal permeability include the infectious agents that cause cholera and dysentery.25 The difference, of course, is that you contract cholera or amoebic dysentery by ingesting feces-contaminated food or water; you contract diseases of wheat by eating some nicely packaged pretzels or devil’s food cupcakes.
MAYBE YOU’LL WISH FOR DIARRHEA
After you read about some of the potential long-term effects of celiac disease, you just might find yourself wishing for diarrhea.
Traditional notions of celiac disease revolve around the presence of diarrhea: No diarrhea, no celiac. Not true. Celiac disease is more than an intestinal condition with diarrhea. It can extend beyond the intestinal tract and show itself in many other varied ways.
The range of diseases associated with celiac is truly astonishing, from childhood (type 1) diabetes to dementia to scleroderma. These conditions, like celiac disease, test positive for the various celiac antibody markers and involve the immune and inflammatory phenomena set in motion by genetic pre-disposition (presence of the HLA DQ2 and HLA DQ8 markers) and exposure to gliadin.
One of the most bothersome aspects of the conditions associated with celiac disease is that intestinal symptoms of celiac may not be expressed. In other words, the celiac sufferer might have neurological impairment, such as loss of balance and dementia, yet be spared the characteristic cramping, diarrhea, and weight loss. Lack of telltale intestinal symptoms also means that the correct diagnosis is rarely made.
Rather than calling it celiac disease without intestinal damage, it would be more accurate to speak about immune-mediated gluten intolerance that can have nothing to do with celiac disease. But because these conditions were first identified because they share the same HLA and immune markers with celiac disease, doctors speak about “latent” celiac disease or celiac disease without intestinal involvement. I predict that, as the medical world begins to better recognize that immune-mediated gluten intolerance is much more than celiac disease, we will be calling it something like immune-mediated gluten intolerance, of which celiac disease will be a subtype.
Immune-mediated gluten intolerance includes the following:
Dermatitis herpetiformis—This characteristic rash is among the more common manifestations of immune-mediated gluten intolerance. Dermatitis herpetiformis is an itchy, bumpy rash that usually occurs over the elbows, knees, or back. The rash disappears upon gluten removal.26
Liver disease—Liver diseases associated with celiac can assume many forms, from mild abnormalities on liver tests to chronic active hepatitis to primary biliary cirrhosis to biliary cancer.27 Like other forms of immune-mediated gluten intolerance, intestinal involvement and symptoms such as diarrhea are often not present, despite the fact that the liver is part of the gastrointestinal system.
Autoimmune diseases—Diseases associated with immune attacks against various organs are more common. People with celiac disease are more likely to develop rheumatoid arthritis, Hashimoto’s thyroiditis, lupus, inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease, as well as other inflammatory and immune disorders. Rheumatoid arthritis, a painful, disfiguring joint arthritis treated with anti-inflammatory agents, has been shown to improve, and occasionally remit entirely, with gluten removal.28 The risk for autoimmune inflammatory bowel disease, ulcerative colitis, and Crohn’s disease is especially high; incidence is as much as sixty-eight-fold higher compared to non-celiacs.29
Insulin-dependent diabetes—Children with insulin-dependent type 1 diabetes have a twenty-fold greater risk for developing celiac disease.30 Conversely, children with celiac disease have a greater likelihood of developing type 1 diabetes, though risk is markedly reduced with gluten elimination.31 Overlapping susceptibility to the two conditions appears to be driven by the presence of the HLA DQ2 and HLA DQ8 genes.
Neurological impairment—There are neurological conditions associated with gluten exposure that we will consider in greater detail later in the book. There is a curiously high incidence (50 percent) of celiac markers among people who develop otherwise unexplained loss of balance and coordination (cerebellar ataxia) or loss of feeling and muscle control in the legs (peripheral neuropathy).32 There is even a frightening condition called gluten encephalopathy, characterized by headaches, ataxia, and dementia, that eventually proves fatal, typically within two years after onset of symptoms; abnormalities are seen in the white matter of the brain by MRI, as well as by autopsy (not generally a good way to make a diagnosis).33
Nutritional deficiencies—Iron-deficiency anemia is unusually common among celiac sufferers, affecting up to 69 percent. Deficiencies of vitamin B12, folic acid, zinc, and fat-soluble vitamins A, D, E, and K are also common.34
BEYOND THOSE LISTED above, there are literally hundreds of conditions that have been associated with celiac disease and/or immune-mediated gluten intolerance, though less commonly. Gluten-mediated reactions have been documented to affect every organ in the human body, sparing none. Eyes, brain, sinuses, lungs, bones…you name it, gluten antibodies have been there.
In short, the consequences of gluten consumption are mind-bogglingly wide. It can affect any organ at any age, showing itself in more ways than Tiger Woods had mistresses. Thinking of celiac disease as just diarrhea, as is often the case in many doctors’ offices, is an enormous, and potentially fatal, oversimplification.
CELIAC DISEASE OR NOT? A TRUE STORY
Let me tell you about Wendy.
For more than ten years, Wendy struggled unsuccessfully with ulcerative colitis. A thirty-six-year-old grade school teacher and mother of three, she lived with constant cramping, diarrhea, and frequent intestinal bleeding necessitating blood transfusions. She endured several colonoscopies and required the use of three prescription medications, including the highly toxic methotrexate, a drug used in cancer treatment and medical abortions.
I met Wendy for an
unrelated minor complaint of heart palpitations that proved to be benign, requiring no specific treatment. However, she told me that, because her ulcerative colitis was failing to respond to medication, her gastroenterologist advised colon removal with creation of an ileostomy. This is an artificial orifice for the small intestine (ileum) at the abdominal surface, the sort to which you affix a bag to catch the continually emptying stool.
After hearing Wendy’s medical history, I urged her to try wheat elimination. “I really don’t know if it’s going to work,” I told her, “but since you’re facing colon removal and ileostomy, you’ve got nothing to lose by trying.”
“But why?” she asked. “I’ve already been tested for celiac disease and my doctor said I don’t have it. I’ve had two biopsies that were negative and the blood tests were normal.”
“Yes, I know. But you’ve got nothing to lose. Try it for four weeks. You’ll know if you’re responding.”
Wendy was skeptical but agreed to try.
She returned to my office three months later, no ileostomy bag in sight. “What happened?” I asked.
“Well, first I lost thirty-eight pounds.” She ran her hand over her abdomen to show me. (I hadn’t even told her that she would lose weight.) “And my ulcerative colitis is nearly gone. No more cramps or diarrhea. I’m off everything except my Asacol.” (Asacol is a derivative of aspirin often used to treat ulcerative colitis.) “I really feel great.”
In the year that followed, Wendy meticulously avoided wheat and gluten and eliminated the Asacol, with no return of symptoms. Cured. Yes, cured. No diarrhea, no cramps, no bleeding, no anemia, no more transfusions, no more drugs, no ileostomy, colon still happily in place.
So if Wendy’s colitis tested negative for celiac antibodies, but responded to—indeed, was cured by—wheat gluten elimination, what should we label it? Should we call it antibody-negative celiac disease? Antibody-negative wheat or gluten intolerance?
There is great hazard in trying to pigeonhole conditions such as Wendy’s into something like celiac disease. It nearly caused her to lose her colon and suffer the considerable lifelong health difficulties associated with colon removal, not to mention the embarrassment and inconvenience of wearing an ileostomy bag.
There is not yet any neat name to fit conditions such as Wendy’s, despite its extraordinary response to the elimination of wheat and related grains. Wendy’s experience highlights the many unknowns in this world of wheat sensitivities, many of which are as devastating as the cure is simple. Her experience also leads to the issues that we will discuss for much of the remainder of the book: You do not have to have celiac disease to suffer major health problems, even life-threatening effects, from the breading on shrimp or a dinner roll.
WHEAT AND BUNGEE JUMPING
Eating wheat, like ice climbing, mountain boarding, and bungee jumping, is an extreme sport. It is the only common food that carries its own long-term mortality rate.
Some foods, such as shellfish and peanuts, have the potential to provoke acute allergic reactions (e.g., hives or anaphylaxis) that can be dangerous in the susceptible, even fatal in rare instances. But wheat is the only common food that has its own measurable mortality rate when observed over years of consumption. In one large analysis over 8.8 years, there was up to 29.1 percent increased likelihood of death in people with celiac disease or who were antibody-positive without celiac disease, compared to the broad population.35 The greatest mortality from wheat gluten exposure was observed in the twenty-and-younger age group, followed by the twenty-to-thirty-nine age group. Mortality also increased across all age groups since 2000; mortality in people with positive antibodies to wheat gluten but without celiac has more than doubled compared to mortality prior to 2000.
Green peppers don’t result in long-term mortality, nor do pumpkin, blueberries, or cheese. Only wheat. And you don’t have to have celiac disease for this to happen.
Yet wheat is the food our own USDA encourages us to eat, including requiring all schoolchildren to consume it without benefit of screening for celiac or other markers. I personally don’t believe that it would be a stretch for the FDA (which now regulates tobacco) to require a warning on wheat-containing products, much as they require for cigarettes.
Imagine:
SURGEON GENERAL’S WARNING: Wheat consumption in all forms poses potentially serious threats to health.
In June 2010, the FDA passed a regulation requiring tobacco manufacturers to remove the deceptive “light,” “mild,” and “low” descriptors from cigarette packages, since they are all every bit as bad as any other cigarette. Wouldn’t it be interesting to see similar regulation highlighting that wheat is wheat, regardless of “organic,” “whole grain,” “multi-grain,” or “high-fiber”?
Our friends across the Atlantic published an extraordinary analysis of eight million residents of the United Kingdom, identifying more than 4,700 people with celiac disease, and comparing them to five control subjects for every celiac participant. All participants were then observed for three and a half years for the appearance of various cancers. Over the observation period, participants with celiac disease showed 30 percent greater likelihood of developing some form of cancer, with an incredible one of every thirty-three celiac participants developing cancer despite the relatively short period of observation. Most of the cancers were gastrointestinal malignancies.36
Observation of more than 12,000 Swedish celiac sufferers showed a similar 30 percent increased risk for gastrointestinal cancers. The large number of participants revealed the broad variety of gastrointestinal cancers that can develop, including malignant small intestinal lymphomas and cancers of the throat, esophagus, large intestine, hepatobiliary system (liver and bile ducts), and pancreas.37 Over a period of up to thirty years, the investigators tabulated a doubling of mortality compared to Swedes without celiac disease.38
You’ll recall that “latent” celiac disease means having one or more positive antibody tests for the disease but without evidence of intestinal inflammation observed via endoscopy and biopsy—what I call immune-mediated gluten intolerance. Observation of 29,000 people with celiac disease over approximately eight years showed that, of those with “latent” celiac disease, there was 30 to 49 percent increased risk for fatal cancers, cardiovascular disease, and respiratory diseases.39 It may be latent, but it ain’t dead. It’s very much alive.
If celiac disease or immune-mediated gluten intolerance goes undiagnosed, non-Hodgkin’s lymphoma of the small intestine can result, a difficult-to-treat and often fatal condition. Celiac sufferers are exposed to as much as forty-fold increased risk for this cancer compared to non-celiacs. Risk reverts to normal after five years of gluten removal. Celiac sufferers who fail to avoid gluten can experience as much as seventy-seven-fold increased risk for lymphoma and twenty-two-fold greater risk for cancers of the mouth, throat, and esophagus.40
Let’s think about this: Wheat causes celiac disease and/or immune-mediated gluten intolerance, which is underdiagnosed by an incredibly large margin, since only 10 percent of celiac sufferers know they have the disease. That leaves the remaining 90 percent ignorant. Cancer is a not-uncommon result. Yes, indeed, wheat causes cancer. And it often causes cancer in the unsuspecting.
At least when you bungee jump off a bridge and hang at the end of a 200-foot cord, you know that you’re doing something stupid. But eating “healthy whole grains”…who would guess that it makes bungee jumping look like hopscotch?
DON’T EAT COMMUNION WAFERS WITH LIPSTICK ON
Even knowing the painful and potentially severe consequences of eating gluten foods, celiac sufferers struggle to avoid wheat products, although it seems like an easy thing to do. Wheat has become ubiquitous, often added to processed foods, prescription drugs, even cosmetics. Wheat has become the rule, not the exception.
Try to eat breakfast and you discover that breakfast foods are a lan
d mine of wheat exposure. Pancakes, waffles, French toast, cereal, English muffins, bagels, toast…what’s left? Look for a snack, you’ll be hard-pressed to find anything without wheat—certainly not pretzels, crackers, or cookies. Take a new drug and you may experience diarrhea and cramping from the tiny quantity of wheat in one small pill. Unwrap a stick of chewing gum and the flour used to keep the gum from sticking may trigger a reaction. Brush your teeth and you may discover there is flour in the toothpaste. Apply lipstick and you can inadvertently ingest hydrolyzed wheat protein by licking your lips, followed by throat irritation or abdominal pain. At church, taking the sacrament means a wafer of…wheat!
For some people, the teensy-weensy quantity of wheat gluten contained in a few bread crumbs or the gluten-containing hand cream collected under your fingernails is enough to trigger diarrhea and cramps. Being sloppy about gluten avoidance can have dire long-term consequences, such as small intestinal lymphoma.
So the celiac sufferer or gluten-sensitive individual ends up making a nuisance of herself at restaurants, grocery stores, and pharmacies, having to inquire constantly if products are gluten-free. Too often, the minimum-wage salesclerk or overworked pharmacist has no idea. The nineteen-year-old waitress serving your breaded eggplant usually doesn’t know or care what gluten-free is. Friends, neighbors, and family will see you as a fanatic.
These people therefore have to navigate the world constantly on the lookout for anything containing wheat or other gluten sources such as rye and barley. To the dismay of the celiac community, the number of foods and products containing wheat has increased over the past several years, reflective of the lack of appreciation of the severity and frequency of this condition and the growing popularity of “healthy whole grains.”
Wheat Belly (Revised and Expanded Edition) Page 11