Celiac.com 10/15/2022 - I’m constantly amazed at how many parents call me to say their gluten-free children are unable to eat the usual gluten-free flours such as rice, beans, or soy. That’s when I suggest sorghum flour––a flour I’ve used for over six years now, but that many people still don’t know about or are afraid to try.

Old Grain, New Uses

I’ve known about sorghum since my childhood on a Nebraska farm where we called it milo. Back then, it was grown for livestock feed and if someone had told me that humans would eventually eat it, I would have been dumbfounded. Back then, I didn’t know that sorghum has been consumed for centuries by people all over the world.

Today, growers in the U.S. produce a special grade called sweet white sorghum which is designed for human consumption and extremely tasty. In fact, the U.S. exports it to countries seeking alternatives to wheat. Lucky for us, because it gives all of us yet another choice when the usual flours are off-limits due to allergies or intolerances.

Advantages of Sorghum Flour

There are several reasons that sorghum flour fits nicely into our gluten-free diet, including:

• Sorghum flour has a neutral color—beige to light tan— which increases its versatility for all kinds of baked goods. Use it for even the most light-colored dishes or in the children’s cookie recipe below.
• Its flavor—which some people think is fairly close to wheat—is still decidedly neutral and unlikely to alter the flavor of delicate baked goods the way stronger-flavored flours can do. Children in particular like this neutral flavor.
• Nutritionally, sorghum flour has a fairly good protein content (11 grams per cup) which makes it good for gluten-free baking, especially since this protein is “watered down” when mixed with the lighter, low-protein flours such as potato starch or tapioca flour. It also has a good B-vitamin and fiber content.
• Sorghum flour produces baked goods with superior texture, without the grittiness common in rice flours.

Sorghum Flour Cookies Delight the Kids

I know you’ll like this sorghum-based recipe for children’s cookies, adapted from Savory Palate’s newest publication, Gluten-Free Friends: An Activity Book for Kids, by Nancy Patin Falini, MA, RD, LDN.

Since there are no other flours in the recipe, it will work great for kids who can’t eat rice, bean, or soy flour. These cookies make a great after-school snack or can be tucked into your child’s lunch box. In fact, the rest of the family will love them, too, so you might want to make an extra batch!

My favorite version is to use the dried cranberries and pecans, but I also like using chopped almonds for the nuts and dried apricots for the fruit. Get creative…use whatever you have on hand. Store them in a tightly covered container to keep them soft and chewy.

Carol Fenster’s Raisin Kiss Treats

Adapted from Gluten-Free Friends: An Activity Book for Kids by Nancy Patin Falini, MA, RD, LDN with permission from Carol Fenster, Ph.D.’s Savory Palate Press (1889374091)

Ingredients:

• 2 egg whites
• 3⁄4 cup brown sugar
• 1⁄4 cup sorghum flour
• 1⁄4 teaspoon ground cinnamon
• 1⁄4 teaspoon xanthan gum
• 1⁄4 teaspoon salt
• 1 cup raisins or dried cranberries 
• 1 cup chopped walnuts or pecans

Directions:
Preheat oven to 300F. Beat egg whites until stiff. Thoroughly mix brown sugar, flour, cinnamon, xanthan gum, and salt together and stir into egg whites with spatula. Stir in raisins and nuts. Drop from a tablespoon or shape into 1-inch balls and place on baking sheet that is well greased or lined with parchment paper. Bake 25-30 minutes or until bottoms of cookies are lightly browned. Cool thoroughly. Makes approximately two (2) dozen. Store in tightly closed container to keep cookies soft and chewy.

Celiac.com 10/08/2022 - Celiac disease is now recognized as a spectrum of gluten-sensitive illness in which the gut is no longer seen as the sole target. For example, dermatitis herpetiformis is a skin manifestation of gluten sensitivity. Celiac disease is no longer considered just in individuals with classic intestinal damage but in individuals with other signs of immune activation and/or degrees of gut involvement, triggered by the ingestion of gluten. Substantial evidence demonstrates that the nervous system also can be a target organ with or without the presence of gut involvement(1).

Neurological Complications in Celiac Disease

Approximately ten percent of celiac disease patients develop neurological complications(2) . Based on case studies, the most common neurological disorders associated with celiac disease are cerebellar dysfunction, epilepsy and peripheral neuropathy. From 1964 to 2000, data compiled from case reports of 83 celiac patients with neurological complications revealed that 70% of them were diagnosed with either ataxia or peripheral neuropathy(3) . A retrospective data survey of 620 patients attending the Derby Coeliac Clinic found the following neurological and psychiatric complications: Depression (12%), epilepsy (4%), migraine (3%), carpal tunnel syndrome (2%), stroke (2%), anxiety (2%), self poisoning (2%), myopathy (1%), learning difficulty (1%), sciatica (1%), meningitis (1%), Parkinson’s disease (1%), tension headache (1%), multiple sclerosis (1%) and peripheral neuropathy (1%)2 . However, further study needs to clarify the relationship between celiac disease and these complications.

A recent study found 13 (8%) among 160 celiac patients had neurological disorders(4) . Ten of the thirteen patients had central nervous system disorders such as epilepsy, attention/memory impairment, and cerebellar ataxia. The remaining patients had peripheral nervous system disorders. In eleven out of thirteen cases, the celiac disease diagnosis came after the onset of the neurological disorder. Seven celiac patients were diagnosed and treated within six months of the neurological onset. All seven had either substantial or complete resolution of their neurological symptoms. In contrast, four out of five patients who were diagnosed with celiac disease from 10 to 264 months after the appearance of their neurological disorder showed no improvement in their neurological symptoms on the gluten-free diet. This study demonstrated that the crucial timing of treatment with a gluten-free diet in celiac patients who have neurological disorders might affect whether the neurological symptoms are reversible.

While the incidence of neurological complications in celiac disease is estimated to be ten percent, the incidence of celiac disease in neurological patients is still unknown. Celiac disease can escape detection in blood antibody screenings(5). Not all gluten-sensitive individuals demonstrate classic biopsy evidence of celiac disease, but exhibit milder intestinal features. Also, not all celiac patients present with gastrointestinal symptoms. Therefore, neurological patients with gluten-sensitivity may be missed if they are evaluated for neurological symptoms alone.

To identify gluten-sensitivity in neurological patients, antigliadin antibodies were determined in two groups of neurological patients. In a group with idiopathic neurological illness versus another group with identifiable neurological illness, a marked difference of 57% versus 5%, respectively, were antigliadin antibody positive(2) . Twenty-six (86%) of those in the idiopathic group consented to small bowel biopsy and nine (34%) of them had intestinal features characteristic of celiac disease. However, 12% of the healthy blood donors were also antigliadin antibody positive and no explanation was given. Therefore, it was unclear whether the rate of gluten-sensitive neurological illness could be overstated by 12 percent or that 12 percent of the normal population could have gluten-sensitivity.

Gluten Ataxia

Gluten ataxia is the most common form of neurological dysfunction to be attributed to gluten sensitivity1 . Up to 41% of sporadic idiopathic ataxia is caused by gluten ataxia, as evidenced by the presence of antigliadin antibodies. Patients with gluten ataxia have difficulty controlling their upper and/or lower limb movements. Hadjivassiliou et al found 79% (54 of 68) of gluten ataxia patients had damage to the part of the brain called the cerebellum which is involved in coordination and steadiness.

Not all gluten-sensitive, neurological patients will also have classic intestinal biopsy evidence of celiac disease. Of 51 gluten ataxia patients who underwent duodenal biopsy, 24% of them had biopsy proof of celiac disease and only 13% had gastrointestinal symptoms1 . Yet, treatment with a gluten-free diet can be helpful, irrespective of gut involvement. For example, 26 patients with gluten ataxia were offered a gluten-free diet and were confirmed to be adhering to the gluten-free diet by evidence of negative serology within six months to one year of treatment(6). When compared to the control group of patients with gluten ataxia who did not receive treatment of a gluten-free diet, all 26 patients in the treatment group improved significantly in their ataxia based on a battery of tests. The response observed in the treatment group was irrespective of gut involvement or the duration of the ataxia (mean duration of nine years). These results contrasted with the expectation that the ataxia would remain despite evidence of the loss of cerebellar Purkinje cells which are the target cells in gluten ataxia(3, 6).

Malabsorption or Autoimmunity? Two potential mechanisms to explain the neurological dysfunctions of celiac disease are nutrient deficiencies due to malabsorption, and autoimmune disease. Currently, it is unknown which of these, or both, is the underlying cause of neurological disorder in celiac disease. A reference to these potential mechanisms came in 1966 when Cooke and Smith reported a landmark study of 16 adult celiac patients with neurological complications3 . For most of them, symptoms of classic celiac disease pre-existed their neurological symptoms. All 16 were found with extreme weight loss and vitamin deficiencies along with anemia due to severe malabsorption. Subsequently, over half of them died, despite gluten restriction, due to the progression of their neurological complications involving sensory ataxia and/or other features. Post-mortem findings in four patients revealed cerebellar Purkinje cell loss and T-cells (type of white blood cell) infiltrating parts of the brain, brainstem, and spinal cord(7).

Deficiencies of folic acid, vitamin B-12, and vitamin E have been implicated as a potential cause of neurological complications(4). However, vitamin deficiencies alone do not explain the absence of neurological deficits in some patients(2). In addition, vitamin deficiencies are rarely found or can be attributed to neurological dysfunction in association with gluten ataxia patients of which the majority don’t have histological evidence of celiac disease(3). Furthermore, in a current study of 13 neurological celiac patients, only 2 had been diagnosed with malabsorption(4).

In support of the hypothesis of an autoimmune mechanism of celiac disease neurological complications, Hadjivassiliou et al found that gluten ataxia patients with inflammation located in the white matter of the cerebellum part of the brain was marked by the loss of Purkinje cells. The inflammation in celiac disease, which is thought to be mediated by T-cells, is not confined to the small bowel as gliadin-specific T cells and antigliadin antibodies are found in the blood(8). Antigliadin antibodies also have been found in the cerebrospinal fluid(3) . In gluten ataxia patients, antigliadin antibodies were found to bind to Purkinje cells in the cerebellum that might result in damage to this part of the brain(9). This finding suggests that common binding sites are shared between cerebellar Purkinje cells and gliadin proteins. Patients with gluten ataxia also have anti-Purkinje cell antibodies. How antigliadin antibodies gain access to the cerebellum might be due to possible alterations of the blood-brain barrier.

In further support of an autoimmune basis of celiac disease neurological complications, 8 of 13 celiac patients with neurological dysfunction had anti-neuronal antibodies to the central nervous system(4). This was significantly higher when compared with only 1 in 20 celiac patients who had anti-neuronal antibodies but no neurological involvement. Furthermore, 30 non-celiac control patients, who had other autoimmune gastrointestinal diseases or had donated blood, had no detectable anti-neuronal antibodies. After one year of treatment on a gluten-free diet, anti-neuronal antibodies disappeared in 6 of the 8 celiac patients with neurological dysfunction. In 5 of these 6 patients, the neurological symptoms partially or completely resolved. However, anti-neuronal antibodies are not specific for neurological disorders associated with celiac disease since they are also found in other patients with nervous system disorders.

Identification of neurological patients with gluten-sensitivity with or without histological evidence of celiac disease is necessary in order to provide them the opportunity for treatment with a gluten-free diet. Identification should be further aided when the exact mechanisms of neurological complications in gluten-sensitive patients are understood. Finally, immediate treatment with a gluten-free diet early in the progression of the disease may be crucial in the prognosis of whether the neurological disorder is reversible.

Glossary of Terms:

• ataxia: impaired muscle coordination
• Central Nervous System (CNS): the portion of the nervous system involving the brain and spinal cord
• cerebellum: portion of the brain involved in equilibrium and coordination; cerebellar (adj.)
• dementia: impaired intellectual function
• epilepsy: neurologic disease resulting in convulsions or loss of consciousness
• idiopathic: the disease has an unknown cause
• neurological: having to do with the nervous system
• neuron: nerve cell
• neuropathy: any disease of the nervous system
• paroxysm: convulsion
• Peripheral Nervous System (PNS): the portion of the nervous system outside of the brain and spinal cord; peripheral (adj.)
• Purkinje cell: a type of neuron that is highly branched, mostly found in the cerebellum

References:

1. Hadjivassiliou M et al 2003. Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Brain 126: 685-91.
2. Tengah D et al 2002. Neurological complications of coeliac disease. Postgrad Med J 78: 393-98.
3. Hadjivassiliou, et al. 2002. Gluten sensitivity as a neurological illness. J Neurol Neurosurg Psychiatry 72: 560-3
4. Volta U, et al. 2002. Clinical findings and anti-neuronal antibodies in coeliac disease with neurological disorders. Scand J Gastroenterol 37: 1276-81.
5. Tursi A et al 2001. Low prevalence of antigliadin and anti-endomysium antibodies in subclinical/silent celiac disease. Am J Gastroenterol 96: 1507-1510.
6. Hadjivassiliou M, et al. 2003. Dietary treatment of gluten ataxia. J Neurol Neurosurg Psychiatry 74: 1221-24.
7. Will AJ. 2000. The neurology and neuropathy of coeliac disease. Neuropathy and Applied Neurobio 226: 493-96.
8. Cross A, and Golumbek, P. 2003. Neurologic manifestations of celiac disease. Neurology 60: 1566-1568.
9. Hadjivassiliou M, et al.  2002. The humoral response in the pathogenesis of gluten ataxia. Neurology 58: 1221-26.

Celiac.com 09/24/2022 - When an individual is diagnosed with celiac disease, every family member is affected. Suddenly, the diagnosing physician or the helpful support group informs the new celiac that first and second degree relatives must be regularly tested for celiac disease. They learn that it is necessary because celiac disease is a genetic condition and could appear at any time in other family members.

Antibody vs. Genetic Testing

The blood tests that celiacs are more familiar with are the antibody tests. These tests, such as the tissue transglutaminase test, or the antiendomysial antibody test, measure the immune response to gluten that occurs at a point in time (think of it as a photograph). These are important tests because they characterize the extent to which the immune system is responding to a specific antibody created in response to gluten.

More celiacs and their families are learning about genetic testing, which is also a blood test. Unlike antibody testing, the HLA gene testing for celiac disease measures the presence or absence of genetic material that is found on the surface of cells. Celiac disease is associated with the presence of HLA DQ2 and HLA DQ8.

Genetics of Celiac Disease

When the genetic predisposition for celiac disease was detected (on Chromosome 6) researchers noted that the genes were a necessary but not sufficient condition for the disease to develop. In fact, up to one third of the U.S. population has the genes for celiac disease, but it is thought that only 1-4% will actually develop the disease at some point during their lifetimes.

This means that people with DQ2 or DQ8 can develop celiac disease, but aren’t destined to develop it. This is most evident in the case of identical twins, where only one of the twins is affected by celiac disease. Despite the fact that the twins have identical genes, the unaffected twin only has a 70% chance of developing the condition. How can this happen?

Researchers and medical professionals use the term “environment” to refer to lifestyle factors, diet, or medical history that affect an individual’s chances of developing a disease. It is thought that environmental factors such as the duration of breast feeding and the presence of other autoimmune disorders can impact the development of celiac disease. Environmental factors can have a protective effect or a promotional effect with regard to the development of a genetic disease.

Medical Knowledge and Celiac Genetics

At the International Celiac Conference in Paris last summer, numerous presentations were made by researchers looking at the role that of other genes that could modify, protect, or directly lead to the development of celiac disease. Most of them, however, failed to establish a direct connection between a gene and the disease process.

Since the Paris conference, however, researchers have published work that looks at subsets of HLA DQ2 and HLA DQ8 and have determined that some combinations of these subsets lead to a greater or lesser risk of developing celiac disease (called gene dosing). In addition, it is thought that a certain genetic typing (within DQ2 and DQ8) can identify people who will develop celiac disease later in life.

Gene Testing Considerations

The gene test for celiac disease is a blood test that looks to measure HLA DQ2 and HLA DQ8 positivity on the surface of cells. It does not diagnose celiac disease. It places an individual into an “at-risk” group for celiac disease, which indicates the individual should be closely monitored with antibody testing in the future.

Celiac centers across the United States have different approaches towards the use of genetic testing with patients and families concerned about celiac disease. Be sure to talk to your doctor about his/her perspective on genetic testing for celiac disease.

Rule Out Celiac Disease

Given that two-thirds of the U.S. population does not have DQ2 or DQ8, which are necessary for celiac disease to occur, the gene test can “rule out” with a very high degree of certainty that person’s potential for becoming celiac (95% of celiacs are DQ2 positive, 5% are DQ8 positive). In families where the potential celiacs are children, many parents feel that genetic testing offers them additional information—the ability to know which of their children to monitor more closely.

On the Diet before Diagnosis

In individuals with symptoms who have been on the gluten-free diet for a significant period of time, the gene test is often the only way to determine if symptoms could possibly be related to celiac disease. For a person who faces this situation, a negative gene test would indicate that symptoms are not likely to be celiac disease. A positive gene test, however, does not diagnose the disease but increases the likelihood that it is present.

The Blame Game

Genetic testing provides very useful information for clinicians and families facing celiac disease. However, family members may joke about or comment that testing will determine whose side of the family is at fault for the presence of celiac disease. Genetic testing of any kind affects everyone in the family (close and distant relatives). Interpersonal relationships and potential problems should at least be considered before testing.

In considering the genetic test, families have to realistically assess what they will do with the information if and when members test positive. If the family is planning to have a gluten-free household anyway, genetic testing will not offer information that will change the health outcome of each family member. In this circumstance, the family is probably not a good candidate for genetic testing.

The Cost of Genetic Testing

Genetic testing can be very expensive, and this can vary by geography and the type of medical center where the testing is done. Costs include the cost of the actual test, the hospital laboratory fees, equipment/supplies, and processing. Ask your doctor’s office about the cost of the test before you have it done. In addition, you should take steps to insure that your insurance company will cover the test before the blood is drawn, unless you plan to pay for the test yourself.

Celiac.com 11/22/2021 - The year 2003 was one filled with considerable accomplishments for the Celiac Sprue Research Foundation. In January the Foundation opened its research laboratory in Sunnyvale, California with the primary goal of developing a pill that may make it safe for celiacs to eat gluten. Under the scientific direction of Gary Gray, M.D., researchers Qing Li, Ph.D., Thomas Marti, Ph.D. and Gail Pyle, M.D. have begun evaluating whether certain enzymes called prolyl endopeptidases (PEPs) can counter the toxic effects of gluten. This is a highly complex undertaking involving a combination of scientific creativity, hard work, careful planning and collaboration.

As a result of the extraordinary efforts of these scientists, the Foundation is currently engaged in a pivotal clinical trial in adult celiac volunteers to test whether a PEP can detoxify gluten in foods eaten by celiacs. If the trial is successful, further studies into the safety and efficacy of a PEP pill can be expected in 2004 and beyond. Regardless of the outcome this work, the Foundation expresses its heartfelt thanks to the many members of celiac support groups who have aided this work. Special thanks are given to the volunteers who have participated directly in clinical studies sponsored by the Foundation.

In addition to an enzyme pill, the Foundation has taken steps to initiate two other drug development projects aimed at suppressing the tendency of the immune system in a celiac patient’s gut to respond adversely to gluten. These include inhibition of tissue transglutaminase, a key enzyme involved in celiac sprue pathogenesis; and inhibition of HLA-DQ2 mediated presentation of antigenic gluten peptides to disease-specific T cells. On the latter, Dr. Marti has received an exploratory grant from the NIH that will, we hope, allow him to identify a suitable drug candidate in collaboration with researchers at the University of Oslo and at Stanford University.

Over the past year the Foundation has spent nearly $700,000 for research, enzyme production and clinical trials. The Foundation’s projected R&D budget for 2004 is more than twice this amount. Although some of these costs are expected be defrayed through grants and contracts from the U.S. government, the pharmaceutical industry and other non-profit organizations, the Foundation’s dependence on donations from the celiac community, family and friends continues to be crucial if it is to meet its goals for the next year. The Foundation hopes you will look favorably on its accomplishments in 2003 and consider investing in its work at year’s end to assure that progress continues to be made in this vital endeavor.

The Foundation thanks you for your support and look forward to continued advancement toward our shared goal of developing a safe and convenient therapy that will allow those with Celiac Sprue to take in a regular diet.

The Celiac Sprue Research Foundation is a public charity that relies upon donations from individuals to support its activities. As an Internal Revenue Code Section 501(c)(3) non-profit organization, your donations are tax deductible to the extent permitted by law.

Celiac.com 09/25/2014 - Every year, life seems to get more hectic.  There is never enough time to get the things done on the ever-growing “to-do” list, let alone find time to relax.  Then you are diagnosed with celiac disease and suddenly realize you can no longer stop at Subway for a hoagie sandwich on your way home.  You get a sinking feeling in the pit of your stomach as you acknowledge that you will have to actually cook most of your own meals at home!  

There is no need to panic.  There are many shortcuts that can help you get in and out of the kitchen faster.  Here are just a few:

• Make a list of all the items you buy at the grocery store.  Make your list very specific, organized by aisles at the store.  Print off multiple copies.  As you run out of things during the week, put a check mark next to the item on your list.  When it is time to go shopping, most of your list will already be done.
• Keep a “basic pantry.”  These are items you should always have on hand.  Not only does this include spices, household cleaners, paper products, and canned goods, but a back-up pantry meal is always good to stock as well.  This can be anything from cans of beans for a bean salad, gluten-free pork and beans or a can of tuna fish, to gluten-free spaghetti and gluten-free spaghetti sauce.
• Make extras.  If you are making soup, chili, spaghetti sauce, marinated chicken breasts, cookie dough, etc., make two or three times the quantity you need; freeze the extra portions so you have meals that just need to be popped into the microwave on the days you don’t have time to cook.
• Use disposable foil cookware for those really messy recipes.  Also, dish out dinners in the kitchen, from pot to plate; that way, you won’t have serving dishes to wash.
• Soak whole potatoes in hot water before baking them—they will cook much faster.  When potatoes need peeling, peel them after they are cooked when they are cool enough to handle and the skins will slip right off.
• Use leftovers to make a different meal.  Open a bag of ready-to-use lettuce and top it with last night’s leftover corn, taco filling, diced tomatoes, and sprinkle with gluten-free cheddar cheese.  Or top the salad with thin slices of the leftover roast beef, diced leftover asparagus spears…you get the idea.  You can also chop leftovers into bite-sized pieces and place them in a resealable freezer bag, and the next time you have leftovers toss them in.  When the bag is full, open a large can of gluten-free chicken or beef broth, add the contents of the bag, and voila—you have Recycled Soup!
• Save the crusts.  If you can’t get the kids to eat their crusts, trim them from their bread and store them in a resealable freezer bag (gluten-free bread is too expensive to buy and too time-consuming to make to throw out the crusts!).  When the bag is full, let the crusts dry out for 24 hours, then run them through a food processor or blender, adding spices like dried parsley, garlic powder, paprika, and/or Italian seasoning, and make breadcrumbs.
• Use a crock pot.  There are many meals that can be made in crock-pots, such as the recipe that follows.  Cut up your leftover veggies and meat from the night before.  You can also cut up potatoes ahead of time and soak them in cold water in the refrigerator.  In the morning, layer everything in the crock pot, add some liquid (gluten-free barbecue sauce, gluten-free spaghetti sauce, tomato sauce, gluten-free broth, or salsa), turn the temperature to low or slow cook, and eight hours later your meal is ready.

With a little practice and planning, you can enjoy healthy, quick, gluten-free meals.  Planning ahead is the key to saving time.  Plan your meals for the week, including how you are going to use up the leftovers.  There definitely is time for “life after cooking” on a gluten-free diet.  You can find more quick meal ideas in my book, Wheat-free Gluten-free Cookbook for Kids and Busy Adults.

Connie Sarros’ Crock Pot Pork Chops

This recipe takes only 4 minutes to assemble!

Ingredients:

• 2 pounds pork chops
• 1⁄2 teaspoon garlic powder
• 3 tablespoons gluten-free soy

Sauce:

• 1⁄2 cup gluten-free Italian dressing
• 1 small bottle gluten-free barbecue sauce

Directions:
The night before, wash chops then pat them dry with paper towels. Sprinkle garlic powder on both sides of the chops, and then place them in a resealable plastic bag. 

Pour in soy sauce and Italian dressing; seal bag and refrigerate overnight. In the morning place chops and marinade in a crock-pot, add the barbecue sauce by lifting the chops with a fork to distribute it evenly. Cover and cook on low for 8 hours.

This recipe serves 4-6 people.

This article originally appeared in the Winter 2004 edition of Celiac.com's Journal of Gluten-Sensitivity.

Celiac.com 09/19/2014 - Experts have decreed that pure oats are safe for people with celiac disease(1,2,3).  The definition of this disease is based on a very specific type of injury to the intestinal wall that heals following the removal of gluten from the diet.  This intestinal damage, called villous atrophy, is caused by the interaction between the immune system and certain proteins found in wheat, rye, and barley.  Identical proteins are not found in oats (although there is also some variation between the protein groups found in wheat, rye, and barley).  Further, many newly diagnosed celiac patients have been shown to recover from their celiac symptoms while eating significant quantities of oats and their intestinal biopsies do not show signs of villous atrophy1 (Admittedly, the quantity of oats consumed by these study subjects does not rival the grain protein consumption in a regular, gluten-laden diet, but the quantity is significant).  Therefore, this food is considered safe for celiac consumption.

Given these facts, it is not surprising that many gastroenterologists are now recommending that their patients eat oats.  Some claim that patients are more likely to follow a gluten-free diet if that diet allows oats.  Others point to the definition of celiac disease, which clearly requires gluten-induced villous atrophy.  Still others insist that since we now know which proteins cause the villous atrophy, oats must be safe for celiac patients to consume.

There are several problems with these perspectives, beginning with the assumption that patients will be more compliant with the diet if it includes oats.  I have explored the medical literature and have been unable to find a single study that investigates dietary compliance as a function of including oats in the gluten-free diet.  I’d be happy to hear about such a study.  But until the question is investigated, the assumption is just one more opinion afloat in a sea of unfounded beliefs about grains and diet.

Many celiac patients experience an addictive element in gluten.  I have long suspected that is the result of morphine-like, opioid peptides found in the digests of gluten(4-8).  Are some peptides from oats capable of producing these opioids?  Has anyone investigated that issue?  Again, I can find no evidence that this issue has been studied.

Reliance on the biopsy to reveal problems with oat consumption is another relevant problem.  As many of us can attest, and the medical literature reports, gluten challenges that intentionally involve ingestion of relatively large quantities of gluten often fail to reveal villous atrophy for weeks, months, and sometimes, years(9).  Many celiac patients will also agree that despite our best efforts at compliance, gluten sometimes manages to sneak into our diets, particularly in the early months of following the diet.  Yet a second biopsy usually shows dramatic healing of the intestinal wall, despite these dietary errors.  Clearly, the intestinal biopsy is a fairly crude tool for measuring intestinal health.  Its use in exonerating oats thus becomes suspect.  An even more troubling element of this issue is that there are gastroenterologists who are recommending that their patients consume breakfast cereals that contain malt flavoring, because patients consuming such small quantities of malt do not show villous atrophy(10).

Also troubling is the fact that many of the studies that support the safety of oats have not employed the Marsh system for identifying intestinal injury, a refinement that significantly increases the sensitivity of the intestinal biopsy.

The greatest weakness of the pro-oats position is the underlying assumption that we fully understand celiac disease and gluten sensitivity.  This is simply not the case.  The research shows that some celiacs do develop symptoms when consuming oats.  While most newly diagnosed celiacs experience reduced symptoms and improved health, this may simply be the result of consuming less grain-derived protein.  Researchers have long known that even partial compliance with the gluten-free diet produces health improvements in celiac patients(11).

The definition of celiac disease that requires villous atrophy followed the discovery of the beneficial impact of the gluten-free diet by more than 20 years (If in doubt about this point, please refer to the English translation of Dr. Dicke’s Ph.D. thesis at Open Original Shared Link).  Our current understanding of the disease began with the observed benefits of the gluten-free diet.  Intestinal biopsies were a much later development.

A similar debate arose regarding the inclusion of wheat starch.  It was long held to be a safe nutrient in the gluten-free diet in many European countries.  In fact, the studies that showed a reduced risk of cancer and a variety of celiac-associated conditions were often conducted among patient groups living where wheat starch was deemed acceptable(12, 13).  Yet when wheat starch consumption was studied in Canada, against a back-drop of zero tolerance, most of the subjects developed signs and symptoms of celiac disease(14).

Many celiacs and gluten-sensitive individuals know that their symptoms do not fit with the conventional view of celiac disease.  Some of us believe that there is a continuum of severity.  Others believe that there are many sub-types of celiac disease.  Still others believe, me included, that it really doesn’t matter whether a person has intestinal damage.  The important, defining characteristic should be whether a person is mounting an immune response against the proteins in the most common substance in our food supply.  

Whatever our beliefs we turn to the experts when faced with health concerns and crises.  However, those answers often rely on the medical definition of celiac disease, where villous atrophy heals in response to a gluten-free diet.  In cases where the biopsy was improperly taken, or too few samples were taken, or patchy intestinal lesions were missed, or other forms of gluten-induced ailments are causing symptoms, we may not get answers that aid our health.  Many individuals who are gluten sensitive will be, under such circumstances, dismissed with a diagnosis of IBS.

Given the facts, we have several hurdles to overcome before we can, in my opinion, render an informed judgment about the safety of oats.  We need a much better understanding of gluten-induced disease in all of its manifestations.  We also need a definition of celiac disease that is more useful to the patient who is experiencing symptoms of gluten sensitivity/celiac disease.  As part of this, we also need a test that is more accurate, and can identify celiac disease after beginning the diet––a challenge that many of us face.  Until we have overcome these hurdles, any pronouncement regarding the safety of oats is premature.

Further research is, in my opinion, the greatest need of the celiac community.  We need to know more, not just about celiac disease, but about the whole range of nutritional and pathological impacts of eating grains. In my own quest, I have learned from the experiences of other celiac patients.  Each new facet of my own experience has been illuminated by someone else’s story.  I have come to understand ADHD as a frequent companion of celiac disease.  Learning disabilities are also common among celiacs.  Behavioral disturbances are the norm, and speech problems are common.  My understanding continues to grow as I hear from others who struggle with gluten sensitivity.

Despite its usefulness, this patient-to-patient network of information sharing is not enough.  We need well designed, well executed research.  We need a better understanding of our disease and how to protect future generations from the current, inaccurate assumptions about grains.  The oats question is only one facet of a much larger need for more information and better testing methods.

Sources:

1. Storsrud S, Olsson M, Arvidsson Lenner R, Nilsson LA, Nilsson O, Kilander A.    Adult coeliac patients do tolerate large amounts of oats. Eur J Clin Nutr. 2003 Jan;57(1):163-9.
2. Kilmartin C, Lynch S, Abuzakouk M, Wieser H, Feighery C.  Avenin fails to induce a Th1 response in coeliac tissue following in vitro culture. Gut. 2003 Jan;52(1):47-52.
3. Janatuinen EK, Kemppainen TA, Julkunen RJ, Kosma VM, Maki M, Heikkinen M, Uusitupa MI.  No harm from five year ingestion of oats in coeliac disease. Gut. 2002 Mar;50(3):332-5.
4. Teschemacher H.  Opioid receptor ligands derived from food proteins. Curr Pharm Des. 2003;9(16):1331-44. Review.
5. Yoshikawa M, Takahashi M, Yang S. Delta opioid peptides derived from plant proteins. Curr Pharm Des. 2003;9(16):1325-30. Review.
6. Horvath K, Graf L, Walcz E, Bodanszky H, Schuler D. Naloxone antagonises effect of alpha-gliadin on leucocyte migration in patients with coeliac disease. Lancet. 1985 Jul 27;2(8448):184-5.
7. Zioudrou C, Streaty RA, Klee WA. Opioid peptides derived from food proteins. The exorphins. J Biol Chem. 1979 Apr 10;254(7):2446-9.
8. Hoggan R.  Considering wheat, rye, and barley proteins as aids to carcinogens. Med Hypotheses. 1997 Sep;49(3):285-8.
9. Fukudome S, Yoshikawa M.   Opioid peptides derived from wheat gluten: their isolation and characterization. FEBS Lett. 1992 Jan 13;296(1):107-11.
10. Kuitunen P, Savilahti E, Verkasalo M.  Late mucosal relapse in a boy with coeliac disease and cow's milk allergy. Acta Paediatr Scand. 1986 Mar;75(2):340-2.
11. Holmes, et. al. "Malignancy in coeliac disease - effect of a gluten free diet" Gut 1989; 30: 333-338
12. Holmes GK.  Coeliac disease and malignancy.Dig Liver Dis. 2002 Mar;34(3):229-37
13. Collin P, Pukkala E, Reunala T.  Malignancy and survival in dermatitis herpetiformis: a comparison with coeliac disease. Gut. 1996 Apr;38(4):528-30.
14. Chartrand LJ, Russo PA, Duhaime AG, Seidman EG.  Wheat starch intolerance in patients with celiac disease. J Am Diet Assoc. 1997 Jun;97(6):612-8.

Celiac.com 10/04/2010 - When Tyler was diagnosed with celiac disease at the age of 18 months, I wanted desperately to talk to a kid––one who could talk––about what it’s like to have celiac disease.  Do you feel jipped?  Does it make you sad?  Do you feel “different” from the other kids?!?  I was heartbroken––grief-stricken––I had a long way to go before I would evolve into the cheerleader I hope I’ve become in helping people live––and love––the gluten-free lifestyle.

Oh, sure, friends and family told me “it would be okay,” the way friends and family do in tough situations.  But I felt they were just placating me––after all, what did they know?  They hadn’t even heard of celiac disease before I had explained the diagnosis.  And to be honest, I didn’t care much at that time about what adults thought of the situation––I wanted desperately to hear from a kid: “Look at me––I turned out just fine!”

That was nearly 13 years ago, and there weren’t any kids who had celiac disease––none that I knew of, anyway.  So we blazed our own trail, working hard to approach our unique challenges with optimism each and every step of the way.

Recently, I was reminded of the way I felt when Tyler was first diagnosed, when a woman with tears in her eyes approached me after one of my talks.  “I know you talk about how we can all learn to live and love this lifestyle, and I appreciate your suggestions for raising happy, healthy, gluten-free kids––but,” she seemed shy and embarrassed to continue, looking at the floor as she asked, “would you mind if I talked directly to Tyler?”

But of course!  How could I have forgotten?  That need to talk to a child who had been through it was so compelling at first––and now Tyler could talk!  Sure you can, was my automatic reply, knowing that my 14 (and-a-half) year-old-I-at-least-like-to-pretend-that-everything-you-do-annoys-me son would be less than thrilled to take the call. 

I would love for Tyler to write an article telling you how celiac disease is no big deal in his life.  He did so a few years ago for my first book, “Kids with Celiac Disease,” when he wrote Chapter One:  “What it’s like to be a kid with celiac disease,” but that was when he was only ten.  That was before he turned into a teenager and had to start pretending not to want to do the things we ask him to do.

The truth is that this has never been a big deal for Tyler.  We gave him control of his diet from day one, which I believe is crucial.  We have always maintained an optimistic, yet realistic approach, with Tyler and his non-celiac but oh-so-supportive sister Kelsie, her being our guiding light in terms of inspiration and positive attitude.

One day, a few months after he had been interviewed on a local TV station, Tyler was approached by a woman who attended one of our R.O.C.K. (Raising Our Celiac Kids) parties.  I watched with curiosity and felt somewhat protective and guarded as this woman I didn’t know quickly approached him and took one of his hands in both of hers in what seemed to be an affectionate gesture.  “Tyler, you have changed my life,” she said boldly.  Then 13 years old, he did what most 13-year-old boys might do, and said nothing––shooting an anxious glance my way, looking for guidance, but I was as bewildered as him.  She began to get tears in her eyes as she continued.  “I’m 65 years old.  Three months ago, I was as sick as I could be.  I had been to dozens of doctors, and had a list of symptoms a mile long.  Everyone thought I was crazy––I even had to quit my job, because I was so sick.  I truly wanted to die.  Then I saw you on TV talking about celiac disease.  I insisted on being tested, and was positive for celiac disease.  I’ve been gluten-free ever since, and feel absolutely wonderful.”  With that, she gave him a bear hug, and he shot me a glance that I couldn’t read. 

I’ve learned not to embarrass my kids (well, sometimes I do it intentionally, but that’s another story), so I said nothing, and Tyler went about his business.  Several minutes later, Tyler approached me with a beaming smile.  “Mom, now I know why you do this!  It feels really good to help other people!” 

He has since decided that he’s blessed to have celiac disease, because it has provided him with an opportunity to reach out and help others––an act that even at his young age he realizes is as satisfying for him as it is for those he helps.  Quite a perspective for a teenage boy, if I may brag about him a little!

So while I would love for Tyler to write an article about this, those of you who have teenagers understand that it would be easier to teach my dog quantum physics than to have him sit down and write an article––so you’ll have to take my word for it.  Thankfully, at this point, Tyler is a happy, healthy, gluten-free young man who thinks a lot more about baseball and his friends than he does about the restrictions of his diet.  Other kids, teens, and young men and women I’ve met over the years have been equally optimistic and inspiring.  So rest easy, parents––your kids will, in fact, be just fine…and I really do know this!

Celiac.com 03/04/2004 - Gluten sensitivity is the process by which the immune system reacts to gluten contained in wheat, barley, rye, and oats. The reaction begins in the intestine because that is where the inciting antigen, gluten, is present (from food). When this immunologic reaction damages the finger-like surface projections, the villi, in the small intestine (a process called villous atrophy), it is called celiac disease (or sometimes celiac sprue or gluten-sensitive enteropathy). The clinical focus of gluten-induced disease has always been on the intestine because that is the only way the syndrome was recognized before screening tests were developed. The intestinal syndrome consists mainly of diarrhea, gas, bloating, nausea, vomiting, fat in the stool, nutrient malabsorption, and even constipation. Although the small intestine is always the portal of the immune response to dietary gluten, it is not always affected in a way that results in villous atrophy. Even though recent research has shown that celiac disease is much more common than previously suspected, affecting 1 in 100-200 Americans and Europeans, past and emerging evidence indicates that it accounts for only a small portion of the broader gluten sensitive clinical spectrum (often referred to as the "Tip of the Gluten Sensitive Iceberg"). With better understanding of how gluten triggers immune and autoimmune reactions in the body under the control of various genes, and advancing techniques of detecting these reactions, it is becoming apparent that the majority of the gluten sensitive population (the submerged "mass of the iceberg") do not manifest villous atrophy in its classic, complete form and therefore do not have celiac disease. In these non-celiac, gluten sensitive individuals, the brunt of the immune reaction either affects the function of the intestine, causing symptoms without structural damage, affects other tissues of the body (and virtually all tissues have been affected in different individuals), or both. This is important because the commonly used diagnostic tests of clinically important gluten sensitivity (blood tests for certain antibodies and intestinal biopsies) are only positive when villous atrophy of the small intestine is present. But if only a small minority of gluten sensitive individuals actually develop celiac disease, the majority, who have not yet or may never develop villous atrophy, with or without symptoms, can remain undiagnosed and untreated for years. This can result in significant immune and nutritional consequences, many of which are irreversible even after treatment with a gluten-free diet. Some of these disorders include loss of hormone secretion by glands (hypothyroidism, diabetes, pancreatic insufficiency, etc), osteoporosis, short stature, cognitive impairment, and other inflammatory bowel, liver, and skin diseases, among others. Only with early diagnosis, can these problems be prevented or reversed.

I am here to report on a scientific paradigm shift regarding early diagnosis of gluten sensitivity based on about 30 years of medical research by myself and others. My message is that earlier and more inclusive diagnosis of gluten sensitivity than has been allowed by blood tests and intestinal biopsies must be developed to prevent the nutritional and immune consequences of long-standing gluten sensitivity. Imagine going to a cardiologist because your blood pressure is high or you're having chest pain, and the doctor says he is going to do a biopsy of your heart to see what is wrong. If it "looks" O.K., you are told you have no problem and no treatment is prescribed because you have not yet had a heart attack showing on the biopsy. You would not think very highly of the doctor utilizing this approach because, after all, isn't it damage to the heart that you would want to prevent? But for the intestine and gluten sensitivity, current practice embraces this fallacious idea that until an intestinal biopsy shows structural damage, no diagnosis or therapeutic intervention is offered. This has to change now because with newly developed diagnostic tests, we can diagnose the problem before the end stage tissue damage has occurred, that is "before the villi are gone," with the idea of preventing all the nutritional and immune consequences that go with it.

There are many misconceptions regarding the clinical presentation of gluten sensitivity or celiac disease: For example, that you cannot be gluten sensitive if you have not lost weight, are obese, have no intestinal symptoms, or are an adult or elderly. However, the most widely held and clinically troublesome misconception is that a negative screening blood test, or one only showing antigliadin antibodies (without the autoimmune antiendomysial or anti-tissue transglutaminase antibody) rules out any problem caused by gluten at that time or permanently. For some reason, the high "specificity" of these blood tests has been tightly embraced. Specificity means if the test is positive, you surely have the disease being tested for with little chance that the positive is a "false positive." But sadly, a negative test does not mean you do not have the problem. This is the biggest pitfall of all because the only thing a very specific test, like blood testing for celiac disease, can do is "rule in" the disease; it can not "rule it out." If you've got very far advanced and/or long-standing celiac disease, it is likely that the test will be positive. However, several studies have now revealed that it is only those with significant villous atrophy of the small intestine who regularly show a positive antiendomysial or anti-tissue transglutaminase antibody, the specific tests relied upon most heavily for diagnosis of gluten-induced disease. When there was only partial villous atrophy, only 30% had a positive test. More disturbing perhaps, were the results with respect to screening first degree relatives of celiacs with blood tests. Despite some biopsy-proven early inflammatory changes in the small intestine but without villi damage, all blood tests were negative.

For some reason, it's been perfectly acceptable to celiac diagnosticians that a patient must have far advanced intestinal gluten sensitivity, i.e., villous atrophy, to be diagnosed and a candidate for treatment with a gluten-free diet. That means from the specific testing standpoint, there's never (or rarely) a false positive. But what about the larger majority of gluten-affected people who do not presently have or may never get this end stage, villous atrophic presentation? They are out of luck as far as blood testing is concerned. So the fact is that we have erroneously relied on specificity (always picks up gluten sensitivity after it has caused villous atrophy, never having a false positive) instead of sensitivity (doesn't miss gluten sensitive people even though they might be picked up early, even before full-blown celiac disease develops). Would a test relying on specificity rather than sensitivity be good enough for you, or your children? Consider the risk of not getting an early diagnosis versus going on a gluten free diet a few months or years prematurely. While I do not recommend anyone to have a biopsy (especially children) for diagnosis because of the shortcomings and invasive nature of this technique, I particularly do not want someone to have a biopsy showing villous atrophy, since by that time, associated bone, brain, growth, and/or gland problems are all but guaranteed. And here is another related problem: You have a positive blood test, but, if a small bowel biopsy comes back normal or nearly normal, you are told that the blood test must have been a "false positive" and that gluten is not your problem. Would you believe that, especially in light of the fact that most such people would have gotten the blood test in the first place because of a specific symptom or problem? Let's hope not. All that means (positive blood test, negative biopsy) is that the gluten sensitivity (evidenced by antibodies to gliadin in the blood) has not yet damaged your intestines severely.

Evidence of this comes from a study that I performed. We tested 227 normal volunteers with blood tests for celiac disease. Twenty-five of these people (11%) had either antigliadin IgG or IgA in their blood versus only one (0.4%) that had antiendomysial, anti-tissue transglutaminase, and antigliadin IgA in the blood. So for every one person in a population that has the antibodies that have 100% specificity for celiac disease of the intestine (antiendomysial and anti-tissue transglutaminase), there are 24 that have antibodies to gliadin that may not have celiac disease. So what is going on with the 11% with antigliadin antibodies in blood? Are these false positives (rhetorically)? You're telling me that there is a disease called celiac disease and it is associated with antibodies to gliadin in the blood and sometimes it damages the intestine? But people with antigliadin antibody in their blood but no other antibodies do not have a clinically significant immunologic reaction to gluten? Do you see the problem? How can 11% be false positives? What about the 89% with none of these antibodies? You cannot equate having no antibodies at all (a negative test) with having antigliadin antibodies alone. If you have antibodies to gliadin, something is going on here. Where there's smoke there's fire. The purpose of this study was to test this hypothesis: That an antigliadin antibody alone does indicate the presence of an immune reaction to gluten that may be clinically important. Using tests for intestinal malabsorption and abnormal permeability (i.e., tests of small bowel function, unlike a biopsy which says nothing about function), we found that 45% of people with only an antigliadin IgG or IgA antibody in blood (without either antiendomysial or anti-tissue transglutaminase antibody) already had measurable intestinal dysfunction, compared to only 5% of people with no antibodies to gliadin in their blood. When we did biopsies of these people's intestines, none had villous atrophy with only a few showing some early inflammation. Thus, having an antigliadin antibody in your blood does mean something: That there is nearly a 1 in 2 chance that functional intestinal damage is already present even though it may not be visible structurally at the resolution attained by a light microscope assessment of a biopsy.

As mentioned at the outset, not all gluten sensitive individuals develop villous atrophy. Evidence for this has been around for a long time. In 1980, a medical publication titled "Gluten-Sensitive Diarrhea" reported that eight people with chronic diarrhea, sometimes for as long as 20 years, that resolved completely when treated with a gluten-free diet, had mild small bowel inflammation but no villous atrophy. In 1996 in a paper called "Gluten Sensitivity with Mild Enteropathy," ten patients, who were thought to have celiac disease because of a positive antiendomysial antibody blood test, had small bowel biopsies showing no villous atrophy. But amazingly, these biopsies were shown to react to gluten when put in a Petri dish, proving the tissue immunologically reacted to gluten (which was likely anyway from their positive blood tests). Two other reports from Europe published in 2001 showed gluten sensitivity without villous atrophy (and hence without celiac disease). In one of these studies, 30% of patients with abdominal symptoms suggestive of irritable bowel syndrome having the celiac-like HLA-DQ2 gene but no antibodies to gliadin in their blood, had these antibodies detected in intestinal fluid (obtained by placing a tube down into the small intestine). Thus, in these people with intestinal symptoms, but normal blood tests and biopsies, the antigliadin antibodies were only inside the intestine (where they belong if you consider that the immune stimulating gluten also is inside the intestine), not in the blood. This is the theme we have followed in my research, as we are about to see.

More proof that patients in these studies were gluten sensitive came from the fact that they all got better on a gluten-free diet, and developed recurrent symptoms when "challenged" with gluten. Although the gluten-sensitive patients in these studies did not have the villous atrophy that would yield a diagnosis of celiac disease, small bowel biopsies in many of them showed some, albeit minimal, inflammatory abnormalities. Yet, when a symptomatic patient in clinical practice is biopsied and found to have only minimal abnormalities on small bowel biopsy, clinicians do not put any stock in the possibility of their having gluten sensitivity. As much as I would like to take credit for the concept, you can see from these studies that I did not invent the idea that not all gluten sensitive patients have villous atrophy. It has been around for at least 23 years, and reported from different parts of the world.

For many years there has also been proof that the intestine is not the only tissue targeted by the immune reaction to gluten. The prime example of this a disease called dermatitis herpetiformis where the gluten sensitivity manifests primarily in skin, with only mild or no intestinal involvement. Now from more recent research it seems that the almost endless number of autoimmune diseases of various tissues of the body also may have the immune response to dietary gluten and its consequent autoimmune reaction to tissue transglutaminase as the main immunologic cause. A study from Italy showed that the longer gluten sensitive people eat gluten, the more likely they are to develop autoimmune diseases. They found that in childhood celiacs, the prevalence of autoimmune disease rose from a baseline of 5% at age two to almost 35% by age 20. This is a big deal if you think of how much more complicated one's life is when one is both gluten sensitive AND has an additional autoimmune disease.

So preventing autoimmune disease is one very important reason why early diagnosis and treatment of gluten sensitivity is important. Early diagnosis before celiac disease develops also holds the potential of preventing other clinical problems such as malnutrition, osteoporosis, infertility, neurologic and psychiatric disorders, neurotube defects (like spina bifida) in your children, and various forms of gastrointestinal cancer. Another reason for early diagnosis and treatment is very straightforward and that is because many gluten sensitive individuals, even if they have not yet developed celiac disease (villous atrophy), have symptoms that abate when gluten is removed from their diet. Furthermore, from a study done in Finland, a gluten sensitive individual who reports no symptoms at the time of diagnosis can improve both psychological and physical well-being after treatment for one year with a gluten-free diet.

Despite the common sense and research evidence that early diagnosis of gluten sensitivity offers many health advantages over a diagnostic scheme that can only detect the minority and end-stage patients, until now, the limitation was still in the tests being employed. As mentioned above, the main tests used for primary (before symptoms develop) and secondary (after symptoms develop) screening for celiac disease, blood tests for antigliadin and antiendomysial/anti-tissue transglutaminase antibodies, are only routinely positive after extensive damage to intestinal villi. As shown in a 1990 publication, this is because unless you have full blown, untreated celiac disease, the IgA antibodies to gliadin are only INSIDE the intestine not in the blood. Measuring antigliadin antibody in blood and intestinal fluid (obtained by the laborious technique of having research subjects swallow a long tube that migrates into the upper small intestine), researchers found that in untreated celiacs, antigliadin antibody was present in the blood and inside the intestine, whereas after villous atrophy healed following a year on a gluten-free diet, the antigliadin antibody was no longer in the blood but was still measurable inside the intestine in those with ongoing mild inflammation.

An important conclusion can be drawn from these results, as these researchers and myself have done: Gluten sensitive individuals who do not have villous atrophy (the mass of the iceberg), will only have evidence of their immunologic reaction to gluten by a test that assesses for antigliadin IgA antibodies where that foodstuff is located, inside the intestinal tract, not the blood. This makes sense anyway, because the immune system of the intestine, when fighting an antigen or infection inside the intestine, wages the fight right in that location in an attempt to neutralize the invading antigen, thereby preventing its penetration into the body. It does this with T cells on the surface of the epithelium, the intraepithelial lymphocytes, and with secretory IgA made with a special component called secretory piece that allows its secretion into the intestine.

The excellent English researchers that made the discovery that they could detect the immunologic reaction to gluten inside the intestine before it was evident on blood tests or biopsies knew it was a breakthrough, testing it many times over in different ways, and further extending the clinical spectrum of gluten-induced disease to include a phase before the villi are damaged, so-called "latent celiac sprue". Furthermore, they developed this technique of assessing the intestinal contents for antigliadin antibodies into what they viewed as a "noninvasive screening test for early or latent celiac sprue" (what others and I would simply call "gluten sensitivity"). However, this was not exactly noninvasive, nor was it simple. It still required the patient to swallow a tube, followed by a complete lavage of all their gastrointestinal contents with many gallons of nonabsorbable fluid that had to be passed by rectum and collected into a large vat to be analyzed for the presence of antigliadin antibodies.

While this was indeed a conceptual breakthrough, it practically went unnoticed by the medical community because the cumbersome procedure of washing out the intestine just could not be done in a normal clinical setting. To this day, I am not sure how many people even know that it was not me, but rather this well known celiac research group, led by the late Dr. Anne Ferguson, who pioneered the assessment of the intestinal contents as a viable and more sensitive source of testing material for the early reactions of the immune system to gluten. What we did in my research was to refine and simplify the method of collecting and measuring these intestinal IgA antigliadin antibodies before they can be detected in blood. That is, instead of washing out the antibodies from the intestine, we allow them to be excreted naturally in the stool (feces). And so with that idea, and our ability to measure these antibodies in stool, as others before us had done for fecal IgE antibodies directed to food antigens, our new gluten (and other food) sensitivity stool testing method was born.

It was actually my research of microscopic colitis that led me to discover that stool analysis was the best way of assessing for gluten sensitivity before celiac disease develops. Microscopic colitis is a very common chronic diarrheal syndrome, accounting for 10% of all causes of chronic diarrhea in all patients, and is the most common cause of ongoing chronic diarrhea in a treated celiac, affecting 4% of all celiac patients. However, from my published research, despite the presence of the celiac HLA-DQ2 gene in 64% of patients with microscopic colitis, very few get positive blood tests or biopsies consistent with celiac disease. Yet, small bowel biopsies revealed some degree of inflammation sometimes with mild villous blunting in 70% of cases. According to the facts and previously discussed shortcomings of celiac blood tests, antibodies to gliadin are unlikely to be detected in the blood in these patients because they lack villous atrophy. So negative blood tests for antigliadin antibodies per se did not, in my mind, rule out the possibility that these patients with microscopic colitis, a disease that under the microscope looks like celiac disease (but of the colon), and that affects many celiac patients, were not gluten sensitive themselves. But as Dr. Ferguson's research revealed, these antibodies might be detectable inside the intestine. And since we surely were not going to perform that cumbersome intestinal lavage test in my patients, we decided to see if we could find these antibodies in the stool as a reflection of what is coming through the intestine.

Here's the first set of data that we found showing the superior sensitivity of stool testing versus blood tests for antigliadin IgA antibodies. In untreated celiac disease patients, we found a 100% positivity in the stool versus only 76% in blood. In hundreds of microscopic colitis patients since tested, only 9% have antigliadin antibody in blood but 76% have it in stool. And the same is true of 79% of family members of patients with celiac disease; 77% of patients with any autoimmune disease; 57% of people with irritable bowel syndrome-like abdominal symptoms; and 50% of people with chronic diarrhea of unknown origin, all of whom have only about a 10-12% positivity rate for blood tests (like normal volunteers). Thus, when you go to the source of production of these antibodies for testing, the intestine, the percentage of any population at a higher than normal genetic and/or clinical risk of gluten sensitivity showing a positive antigliadin stool test is 5 to 7.5 times higher than would be detected using blood tests. In normal people without specific symptoms or syndromes, the stool test is just under 3 times more likely to be positive than blood (29% vs. 11%, respectively). That's a lot more people reacting to gluten than 1 in 150 who have celiac disease. 29% of the normal population of this country, almost all of whom eat gluten, showing an intestinal immunologic reaction to the most immune-stimulating of dietary proteins really is not so high or far fetched a percentage, especially in light of the fact that 11% of them display this reaction in blood, and 42% carry the HLA-DQ2 or DQ8 celiac genes.

Why is this so important? Because some people with microscopic colitis never get better when they're treated, and most autoimmune syndromes only progress with time, requiring harsh and sometimes dangerous immunosuppressive drugs just for disease control. If the immune reaction to gluten is in any way at the cause of these diseases as research suggests, and if we had at our disposal a sensitive test that can diagnose this gluten sensitivity without having to wait for the intestinal villi to be damaged, then treatment with a gluten free diet might allow the affected tissues to return to normal or at least prevent progression. We now have that test in fecal antigliadin antibody. Just a few weeks ago we completed the first follow-up phase of our study: What happens when a gluten sensitive person without villous atrophy goes on a gluten-free diet for one or two years. While I am still gathering and analyzing the data, most of the subjects reported a much improved clinical status (utilizing an objective measure of symptoms and well being). Not everybody gets well, because sadly not everyone stays on a gluten-free diet (as they sometimes admit on the surveys). Some people have the misconception that if they don't have celiac disease, but "I just have gluten sensitivity" then maybe they do not have to be strict with their gluten elimination diet. I do not think that is the case. Although a gluten free diet is like anything: Less gluten is not as damaging as more gluten, but certainly no gluten is optimal if a gluten sensitive person desires optimal health.

Of the first 25 people with refractory or relapsing microscopic colitis treated with a gluten-free diet, 19 resolved diarrhea completely, and another five were notably improved. Thus, a gluten-free diet helped these patients with a chronic immune disease of a tissue other than small bowel (in this case the colon), who have been shown to be gluten sensitive by a positive stool test in my lab. The same may be true of patients with chronic autoimmune diseases of any other tissue, but who do not have full-blown celiac disease. Gluten-free dietary treatment, sometimes combined with dairy-free diet as well, has been shown to help diabetes, psoriasis, inflammatory bowel disease, eczema, autism, and others.

Thus, my approach (and I believe the most sensitive and most complete approach) for screening for early diagnosis and preventive diagnosis for clinically important gluten sensitivity is a stool test for antigliadin and anti-tissue transglutaminase IgA antibodies (IgG is not detectable in the intestine) and a malabsorption test. The malabsorption test we developed is special, because you no longer have to collect your stool for three days; we can find the same information with just one stool specimen. Stool testing in combination with HLA gene testing, which we do with a cotton-tipped swab rubbed inside the mouth, is the best diagnostic approach available for gluten sensitivity.

Who should be screened for gluten sensitivity? Certainly family members of celiacs or gluten sensitive people being at the highest genetic risk. For the most part, all of the following patient groups have been shown to be at higher risk than normal for gluten sensitivity: Chronic diarrhea; microscopic colitis; dermatitis herpetiformis; diabetes mellitus; any autoimmune syndrome (of which there is an almost end-less number like rheumatoid arthritis, multiple sclerosis, lupus, dermatomyositis, psoriasis, thyroiditis, alopecia areata, hepatitis, etc.); Hepatitis C; asthma; chronic liver disease; osteoporosis; iron deficiency anemia; short stature in children; Down's syndrome; female infertility; peripheral neuropathy, seizures, and other neurologic syndromes; depression and other psychiatric syndromes; irritable bowel syndrome; Crohn's Disease; and people with severe gastroesophageal reflux (GERD). Autism and possibly the attention deficit disorders are emerging as syndromes that may improve with a gluten- free (and additionally casein-free) diet. A diagnosed celiac might be interested in our testing to know (after some treatment period no shorter than a year) that there is no on-going damage from malabsorption, for which we have a test. If a celiac is having ongoing symptoms or other problems, a follow-up test should be done just to be sure there's no hidden gluten in the diet, or something else that could be present, like pancreatic enzyme deficiency which often accompanies celiac disease, especially in its early stages of treatment.

Historically, with respect to diagnostic methods for celiac disease, from 100 A.D., when celiac disease was first described as an emaciating, incapacitating, intestinal symptom-causing syndrome, to 1950, we had just one diagnostic test: Clinical observation for development of the end stage of the disease. Then in 1940 to 1960, when the discovery of gluten as the cause of celiac disease occurred, the best diagnostic test was removing gluten from the diet and watching for clinical improvement. It was during this period that the 72-hour fecal fat and D-xylose absorption tests were developed as measures of gluten-induced intestinal dysfunction/damage. In the mid- to late1950's, various intestinal biopsy methods were pioneered and utilized, showing total villous atrophy as the diagnostic hallmark of celiac disease. You've heard the intestinal biopsy called the "gold standard"; well as you can see, it is a 50 year-old test, and thus, the "old" standard. It was not until the 1970's and 80's (and improved upon in the 1990's) that blood tests for antigliadin and antiendomysial/anti-tissue transglutaminase were developed, but again these tests like all methods before, can reliably reveal only the "heart attack" equivalent of the intestinal celiac syndrome: Significant villous atrophy or bad celiac disease.

We are in a new century, a new millennium, and I have built upon what my research predecessors have started; mostly on the work of researchers who laboriously put down tubes and sucked out intestinal fluid for testing for antigliadin antibody when it was not present in blood. We now know that a stool test for antigliadin antibody is just as good and much simpler. The wide-reaching ramifications of knowing that so many more people and patients are gluten sensitive than have ever been previously known has led me to assume a professional life of medical public service. To do so, I started a 501©3 not-for-profit institute called the Intestinal Health Institute, have brought these new diagnostic tests to the public on the internet (at http://www.enterolab.com), and volunteer my time helping people with health problems by email and by lecturing. With greater awareness and education of both the public and medical community that early diagnosis of gluten sensitivity can be achieved before the villi are gone, more of the gluten sensitive iceberg will be diagnosed and treated early, leading to far fewer gluten-related symptoms and diseases than has ever been experienced before.

Dr. Fine has been an intestinal researcher and an academic and clinical gastroenterologist for 15 years. He is the Director of The Intestinal Health Institute and The www.EnteroLab.com Clinical Laboratory in Dallas Texas.