Celiac.com 02/11/2023 - The Celiac Sprue Research Foundation has opened its research laboratory in Sunnyvale, California at the dawn of the new year. Foundation Scientific Director, Gary M. Gray, M.D., is working closely with founder Chaitan Khosla, Ph.D., in establishing the Foundation’s drug development programs and priorities. Dr. Gray also supervises two Research Associates, Qing Li, Ph.D., and Thomas Marti, Ph.D., and Clinical Associate, Gail G. Pyle, M.D. Blair W. Stewart is Vice President and General Counsel of the Foundation.

Dr. Li received her Ph.D. in Biophysical Chemistry from Stanford University in 2002 after studying at Nanjing University and North Carolina State University. She has authored papers in protein chemistry and structural biology. Dr. Marti received his Ph.D. in Organic Chemistry from the Swiss Technical Institute (ETH) in Zurich, and performed postdoctoral research at Stanford University between 1998 and 2000. From 2000 through 2002 he worked as a management consultant at McKinsey & Co. in their Zurich offices. A Celiac herself, Dr. Pyle received her M.D. from Stanford School of Medicine. The mother of two young children, she is a Board Certified Internist, and practiced Primary Care Internal Medicine in the Stanford area for several years before joining the Foundation.

Promoting the development of a safe and effective therapeutic alternative to a lifelong gluten-free diet is the number one goal of the Celiac Sprue Research Foundation. Toward this end the Foundation’s current efforts are predominantly focused on laying the groundwork for a proof-of-principle clinical trial that will test whether dietary gluten can be detoxified via treatment with a prolyl endopeptidase enzyme. This work builds on recent studies by Drs. Gray, Khosla and their collaborators from Stanford University and the University of Oslo, published last year (Science, 297, 2275-2279, 2002).

A key prerequisite for this trial is the production of a recombinant enzyme, produced in bacteria. To do so Drs. Li, Marti, and Khosla recently installed two fermentors at the Foundation’s laboratory. These fermentors, on loan from Kosan Biosciences, Inc., a Hayward, California-based biotechnology company, will enable CSRF to produce intermediate amounts of the enzyme for research using advanced recombinant biotechnology methods. Later this year, production of the enzyme will be scaled up to the larger quantities needed for the proof-of-principle clinical trial.

The bacteria are grown in the fermentor in a water-based environment that requires careful control of such variables as temperature, oxygen level, and nutrients. Drs. Li, Marti, and Khosla worked long into the night setting up and calibrating pumps, instruments, air and water supplies and an automatic control system. Actual fermentation began in early March and samples of the active enzyme have been produced in the Foundation laboratory.

Dr. Marti has also installed a state-of-art High Performance Liquid Chromatography system, which is being used to develop a reproducible large-scale procedure for preparing enzyme-treated gluten for clinical trials. The scientific protocols for production and testing of the enzyme are being designed for reproducibility from batch to batch and to allow scaling up production to the larger batches of material needed for the clinical trial.

In parallel with these laboratory efforts, Drs. Gray and Pyle are developing the protocols and consent forms for the clinical trial, and making arrangements with a local clinic for performing this trial. Resources permitting, the trial will be completed by the end of the year. If successful, it will provide a firm basis for initiating further clinical studies on whether an orally administered enzyme pill can effectively counter the toxic effects of dietary gluten in a Celiac Sprue patient.

To ramp up its enzyme therapy project and also initiate a second drug development project, the Celiac Sprue Research Foundation is recruiting additional Ph.D. level scientists with strong backgrounds in the life sciences. Of particular interest are outstanding immunologists, cell biologists, molecular biologists and chemists, who are interested in a career opportunity at the interface between academia and industry that allows them to gain a unique perspective on preclinical and clinical To ramp up its enzyme therapy project and also initiate a second drug development project, the Celiac Sprue Research Foundation is recruiting additional Ph.D. level scientists with strong backgrounds in the life sciences. Of particular interest are outstanding immunologists, cell biologists, molecular biologists and chemists, who are interested in a career opportunity at the interface between academia and industry that allows them to gain a unique perspective on preclinical and clinical aspects of drug development.

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 02/04/2023 - Flax is widely grown across the Canadian prairies and northern USA, with Canada being the world’s top producer. It is harvested for a variety of purposes. The stems are used in the production of linen cloth and fine quality papers. Flaxseeds are sold whole or ground and incorporated into a number of food products or packaged for individual consumer use. Flax oil is an edible oil produced by cleaning, cracking and pressing flaxseeds under controlled temperatures and sold as a “cold-pressed oil” that is bottled in dark colored bottles and refrigerated. The seeds are also used for industrial purposes to make linseed oil, which is produced by using solvents to extract the oil from the seed during the crushing process. Sold in raw or boiled form, linseed oil is a main ingredient in paints, stains, coatings and linoleum floorings.

Flax has been consumed throughout history for its nutritional and health benefits. It is loaded with dietary fiber, vitamins, minerals, protein and other healthy substances.

“F” is for fiber

Flax contains two types of dietary fiber- soluble and insoluble. Soluble fiber can lower blood lipid levels and helps regulate blood sugar levels. Insoluble fiber acts as a bulking agent and promotes regularity and may also reduce the risk of colon cancer. Three tablespoons of ground flax contains 6 grams of total dietary fiber.

“L” is for lignans

Lignans are naturally occurring compounds found in a variety of plant foods. Flax is the richest source of lignans, containing 75 times more than any other plant food. Lignans are referred to as phytoestrogens and have weak estrogen-like properties. Recent research has revealed that lignans may protect against hormone-sensitive cancers such as breast cancer.

“A” is for Alpha-Linolenic Acid (ALA)

Flaxseed is rich in ALA, an omega-3 fatty acid. Omega-3 fatty acids play a role in reducing the risk of heart disease by lowering blood fat levels and making blood platelets less sticky, thereby reducing the risk of blood clots. They also have been cited as beneficial for people with immune system aliments.

“X” is for excellent

Flax is high in vitamins and minerals such as Vitamin B6, folic acid, potassium, iron, calcium, magnesium, phosphorus, and zinc. It is also a rich source of plant protein.

DIETARY FLAX

1. Whole Flaxseed

• The whole seed provides dietary fiber, which pass undigested through the body, and act as a laxative.
• They can be stored at room temperature for up to one year.
• Add them to a variety of recipes for a pleasant change in texture and flavor.

2. Ground Flax

• Flaxseeds can be ground in a coffee grinder or food processor. You can also purchase “milled/ground” flax available in vacuum-sealed packages from health food stores or grocery stores. When the seeds are ground you receive the maximum nutritional benefits from flax including dietary fiber, alpha-linolenic acid (ALA), lignans, protein and other nutrients.
• Use ground flax immediately or store in an opaque container in the fridge or freezer for up to 90 days. For optimum freshness it is best to grind flax as you need it.
• Ground flax has a light, nutty flavor and can be added to hot or cold cereals, muffins, cookies, breads, pancakes, waffles, meat loaf, burgers, casseroles, soups, salads, yogurt, frozen yogurt, ice cream, pudding or a fruit smoothie blender drink. Remember that baked goods with flax will brown more readily.
• As with any new high fiber food, start slowly, 1-2 teaspoons, and make sure you consume enough fluids. To get the health benefits from ground flax, use 1-4 tablespoons/day. • One tablespoon of ground flax contains 25 calories, 2.5 grams of fat, 2 grams of dietary fiber and 2 grams of ALA.

3. Flax Oil

• The oil is rich in alpha-linolenic acid, however it does not contain all the other nutritional components such as dietary fiber, protein, and lignans.
• Flax oil needs to be refrigerated at all times and once opened must be used within six to eight weeks, as it goes rancid after that time.

4. Omega-3 Enriched Eggs

Hens fed a specially formulated flaxseed diet produce an omega-3 rich egg. These eggs contain 8-10 times more alpha-linolenic acid (ALA) than a regular egg.

5. Flax in Gluten-Free Products

Several companies are adding flax to their products. Some examples are bars and bagels from Enjoy Life Foods, fortified rice pasta from Pastariso, fortified potato and rice pasta from Pastato, Omega Smart nutritional snack bars, sunflower flax rice bread and Kinni-Kwik sunflower flax bread and bun mix from Kinnikinnick Foods.

People with gluten intolerance need to keep nutrition a top priority, and flax can be a healthy addition to the gluten-free diet!

Celiac.com 01/28/2023 - Focaccia is the “in” bread these days! It is a cross between pizza and Italian flatbread and is served in many Italian restaurants, along with a plate of extra-virgin olive oil for dipping. Sometimes, the server adds a dash of balsamic vinegar and a sprinkle of dried Italian herbs for a real taste treat.

You can recreate this wonderful bread at home with this easy recipe, using my new versatile sorghum flour blend. Sorghum is a nutritious flour that works beautifully in our gluten-free foods. Focaccia is undoubtedly one of my most popular recipes and I know it will become a favorite at your house, too.

Carol Fenster’s Gluten-Free Sorghum Flour Blend

Use this versatile flour blend for the recipes in Gluten-Free 101: Easy, Basic Dishes without Wheat. You can make your own corn flour (not cornstarch) by grinding cornmeal in a small coffee grinder until it is the consistency of flour.

If you prefer almond flour, you’ll find it at Bob’s Red mill (www.bobsredmill.com) or grind blanched almond silvers in the coffee grinder until it reaches a flour-like texture. You can purchase bean flour (either plain garbanzo or a garbanzo/fava blend) at your local health food store.

Note: If you use almond flour, you must refrigerate the flour blend.

*Makes 4.5 cups

• 1 1⁄2 cups sorghum flour
• 1 1⁄2 cups potato starch or 
• cornstarch
• 1 cup tapioca flour
• 1⁄2 cup corn flour or almond 
• flour or bean flour or chestnut flour

Carol Fenster’s Focaccia Bread

Bread Ingredients:

• 1 1⁄2 tsp. dry yeast
• 1 1⁄2 cups Flour Blend (pg. 15)
• 1 1⁄2 tsp. xanthan gum
• 1 tsp. unflavored gelatin 
• 1 tsp. dried rosemary
• 1⁄2 tsp. onion powder
• 3⁄4 tsp. salt
• 3⁄4 cup warm water (110°)
• 1 tsp. sugar 
• 2 large eggs
• 2 Tbsp. olive oil
• 1⁄2 tsp. cider vinegar

Topping

• 1 Tbsp. olive oil
• 1 1⁄4 tsp. Italian seasoning
• 1⁄4 tsp. kosher or coarse sea salt

1) Combine all bread ingredients in mixing bowl. Beat dough with mixer (regular beaters, not dough hooks) for 2 minutes. Dough will be soft and sticky.

2) Transfer dough to greased 11 x 7-inch nonstick pan. Cover with aluminum foil tent and let rise in warm place (75-80º) for 30-40 minutes or until desired height.

3) Preheat oven to 400 º. Sprinkle dough with topping ingredients. Bake 15-20 minutes or until top is golden brown and crisp when tapped with your fingernail. (A sprinkle of Parmesan cheese is optional.) Serves 10.

Additional Focaccia Toppings

Try these variations for an even more flavorful Focaccia:

Herb Focaccia:

Combine 1⁄2 tsp. each dried rosemary, sage, and thyme, 1⁄4 tsp. black pepper, and 2 Tbsp. Parmesan cheese. Sprinkle over bread before baking.

Sun-Dried Tomato & Olive Focaccia:

Sauté 1⁄4 cup minced sun-dried tomatoes, 1⁄4 cup sliced black olives, and 1⁄4 cup chopped onion in 1 tsp. oil. Sprinkle over bread before baking.

Pesto Focaccia:

Purée in food processor just until smooth, leaving bit of texture: 1 cup fresh basil leaves, 1 garlic clove, 1⁄2 cup pine nuts. With motor running, slowly add 1⁄4 cup olive oil through feed tube. Add 1⁄4 cup Parmesan cheese and dash of black pepper. Spread over bread before baking.

Recipes Reprinted from the new Gluten-Free 101: Easy, Basic Dishes without Wheat, 2003 by Carol Fenster, Ph.D. with permission from Savory Palate Press.

Celiac.com 01/19/2023 - Is gluten sensitivity celiac disease? You might not believe that gluten sensitivity could be celiac disease if you still believe the world is flat. By definition, celiac disease is still clinically diagnosed in the presence of villous atrophy, whereby the absorptive villi, tiny-fingerlike projections of the intestinal surface lining, are blunted to varying degrees by the actions of lymphocytes (a type of white blood cell) responding to gluten(1) . In 1992, Marsh introduced the gluten sensitive spectrum to give wider recognition of the types of intestinal lesions seen in gluten sensitivity, in addition to the classic celiac lesion(2) . In the Marsh I lesions, lymphocytes are found in increased numbers in the villi. Marsh II lesions are comparable to Marsh I lesions with the addition of increased cellular growth in the crypts (the bottom of the valleys in the intestinal lining where new cells are produced). In the classic celiac lesion, villous atrophy is present and is graded as partial, subtotal, and total flattening of the villi (Marsh IIIa, IIIb, and IIIc lesions, respectively)(3). Normal villi architecture with no increased lymphocytic infiltration is sometimes referred to as Marsh 04 . Researchers studying milder Marsh lesions are providing corroboration to the gluten sensitivity of such patients and describing them as having borderline, silent, and subclinical celiac disease. Some gluten-sensitive patients with normal villi architecture are being described as having either latent or potential celiac disease.

Borderline Celiac Disease

Patients with borderline celiac disease have clinical symptoms of celiac disease with demonstrated intestinal abnormality but no villous atrophy(5) . To determine which patients have borderline celiac disease, a trial of a gluten-free diet can demonstrate if such patients respond favorably in symptomatic terms with biopsy improvement. Another approach is the use of a gluten challenge to aid in the diagnosis of patients with initially only mild intestinal damage. In a study by Wahab et al, 38 patients, who had Marsh I lesions along with signs and symptoms of malabsorption, were subjected to a gluten challenge for two months(4) . Five of the 38 patients worsened to Marsh II and seven worsened to Marsh III with villous atrophy. Of the 12 patients whose intestinal lesions had worsened, all had improved symptomatically and histologically (Marsh 0 in seven patients) after six to12 months on a gluten-free diet. In another study, 23 of 35 patients with gastrointestinal symptoms of unknown origin agreed to an eight to 12 month trial of a gluten-free diet(5) . Of seven who were initially found to have Marsh I lesions, six normalized (Marsh 0) and one still had a Marsh I lesion. Of 16 patients who initially had Marsh II lesions, seven normalized, six improved to Marsh I, and three still had Marsh II lesions. All of the patients on a gluten-free diet experienced substantial or complete resolution of clinical symptoms (i.e., diarrhea, weight loss, fatigue, slow gastric emptying, epilepsy, and abdominal pain). Conversely, seven of 12 patients (five lost to follow-up) who refused a gluten-free diet had persistent lesions and symptoms while one progressed from Marsh I to Marsh IIIa lesion and experienced a worsening of symptoms. The response to gluten was clear. Patients with gluten sensitivity who were given a gluten-free diet found relief in their symptoms and improvement or normalization in their biopsies, while those who were gluten challenged had to endure a further provocation of their symptoms and lesions.

Silent and Subclinical Celiac Disease

With the acceptance of the broader spectrum of celiac disease, some researchers are making the case for the diagnosis of celiac disease in the presence of mild intestinal lesions. In a recent study of 115 silent and subclinical celiac patients, 13% of each form were identified with the presence of mild intestinal damage (Marsh I or II lesions) due to gluten sensitivity(6) . Patients with subclinical celiac disease had extra-intestinal symptoms (i.e., iron deficiency anemia, dental enamel defects, epilepsy, and hair loss) but no gastrointestinal symptoms. Subclinical celiac patients without villous atrophy were detected by antibody testing only 33% of the time. Patients were classified as having silent celiac disease because they had no symptoms and were high-risk for celiac disease due to their status as first degree relatives of celiac patients or as having type I diabetes. Silent celiac patients without villous atrophy were not detected by antibody testing. In practice, the recognition of the silent and subclinical forms of celiac disease will be more accurately diagnosed through the alertness of gastroenterologists and other specialists.

Gluten Sensitivity in Patients with Normal Intestinal Villi

The expression of gluten-sensitive symptoms is exhibited in patients even with normal intestinal villi. Identifying patients with gluten sensitivity involves exclusion of all other possible causes and utilizing various ways of detection. Also, a finding of increased lymphocytes just as villous atrophy is not always a prerequisite for gluten sensitivity. In a study by Picarelli et al, ten patients with celiac-like symptoms and normal villi architecture at some stage during their illness were found to have positivity to anti-endomysial antibodies which disappeared on a gluten-free diet(7) . Only four of the ten patients had an increased lymphocyte infiltrative (Marsh I) lesion in addition to normal villi architecture. Also, six of these patients did not have the common HLA genes associated with celiac disease. Cells cultured from biopsies were challenged with gliadin peptides resulting in immune activation. Challenge with similar corn peptides did not have evidence of immune activation. Also, the patients themselves showed signs of immune activation on a normal diet which went away after the removal of gluten and came back in three patients on a four month gluten challenge. Similarly, latent celiac disease was found in another study of seven children with normal biopsies who were positive for anti-endomysial antibodies and were later found to develop villous atrophy by three years(8) . These studies highlight a need for better diagnosis of non-atrophic celiac disease patients.

Antibody Detection of Mild Intestinal Damage

Although blood antibody testing is useful in predicting the degree of villous atrophy, it can often fail to detect patients with milder intestinal lesions as well as partial villous atrophy (Marsh I-IIIa). A study confirmed that the largest percentage of patients with positive antibody results were found with the most severe intestinal damage(6) . 78% of patients with total villous atrophy were positive for anti-gliadin antibodies while 89% of patients with total villous atrophy were positive for anti-endomysium antibodies. None of the patients with Marsh I lesions or silent celiac disease patients with Marsh II lesions were positive for anti-gliadin or anti-endomysial antibodies. A study of 119 adult celiac patients found a poor correlation between slight intestinal damage and antitissue transglutaminase (anti-tTG) positivity(9) . Only one of 13 patients with Marsh I lesions and eight of 24 patients with Marsh II lesions were anti-tTG positive. Even in the presence of villous atrophy, only 56% of those patients with partial villous atrophy (Marsh IIIa) while 96% of those with total villous atrophy (Marsh IIIc) were positive for anti-tTG. As a method of detecting patients with the potential to develop villous atrophy ('potential' celiac disease), celiac disease patient biopsies were challenged in culture with gliadin peptides while the patients were on a gluten-free diet(8) . Such biopsies were found to produce anti-endomysial antibodies. Therefore, biopsy culture production of anti-endomysial antibodies may be more sensitive than blood anti-endomysial antibodies which fail to detect less severe intestinal damage.

Current research reviewed here demonstrates that patients with non-classical forms of celiac disease can go on to develop the classic diagnostic celiac lesion when they continue on a gluten-containing diet. Conversely, patients with these non-classical forms of celiac disease can heal when given the treatment of a gluten-free diet. Thus, these studies highlight the need for doctors and pathologists to be alert to celiac disease in all its forms in order to recognize it. “(J)ust as Christopher Columbus sailed past an apparently flat horizon to help prove the world is round, the time has come to broaden the horizons of the histologic diagnosis of celiac disease”(10).

References:

1. Kennedy NP. 2000. Clinical features of coeliac disease today. Biomed & Pharmacother 54:373-80.
2. Marsh MN, 1992. Gluten, major histocompatibility complex, and the small intestine: a molecular and immunobiologic approach to the spectrum of gluten sensitivity ('celiac sprue'). Gastroenterol 102:330-54.
3. Rostami K, et al. 1997. SAT and serology in adult coeliacs, seronegative coeliac disease seems a reality. Neth J Med 53:15-19.
4. Wahab P, et al. 2001. Gluten challenge in borderline gluten-sensitive enteropathy. Am JGastroenterol 96:1464 - 69.
5. Tursi A, and Brandimarte G. 2003. The symptomatic and histologic response to a gluten-free diet in patients with borderline enteropathy. J Clin Gastroenterol 36:13-17.
6. Tursi A, et al 2001. Low prevalence of antigliadin and anti-endomysium antibodies in subclinical/silent celiac disease. Am J Gastroenterol 96:1507-10.
7. Picarelli A, et al 1996. Gluten-sensitive disease with mild enteropathy. Gastroenterol 111:608-16.
8. Holmes G, 2001. Potential and latent coeliac disease. Eur J Gastroenterol Hepatol 13:1057-60.
9. Tursi A, et al. 2003. Prevalence of antitissue tranglutaminase antibodies in different degrees of intestinal damage in celiac disease. J Clin Gastroenterol 36:219-21.
10. Moskaluk C, 2001. The histologic diagnosis of celiac disease in "nonflat" intestinal mucosa. Am J Clin Pathol 116:7-9.

Celiac.com 01/07/2023 - First reported in 1925, the coexistence of diabetes mellitus and celiac disease is not a new phenomenon. However, as late as 1984, the connection was viewed with skepticism. Prior to the use of intestinal biopsies, some researchers reported an increase of diabetes mellitus among family members of celiac patients, while others reported contradictory findings.

After development of techniques for taking jejunal biopsies, modestly increased rates of diabetes were reported. These numbers were usually close to 1% of the celiac patients who were reported as having both diseases. When faced with these increased numbers of diabetes mellitus among celiac families and celiac patients, many asserted that certain genetically determined features of the immune system (HLA) were common among people with either condition. Such genetic factors, they argued, might predispose to autoimmune diseases in general, and would therefore be likely to increase the frequency of both conditions within the same families, and sometimes, within the same individual. The issue was further confounded by the overlap between classical symptoms of celiac disease and diabetes mellitus. Thus, a second diagnosis was often overlooked because all symptoms were considered to result from the first condition diagnosed. The reported rates of coexistence thus underrepresented the true overlap.

It was only through systematic research among large numbers of diabetic patients who were biopsied, along with the development and use of serological testing for celiac disease, that the increased coexistence of these diseases gained recognition during the mid to late 1980s. Still, the dominant view ascribed a common origin for both autoimmune conditions. Thus, when other autoimmune diseases were recognized as overly common among celiac patients, little thought was given to the notion that gluten might trigger more than celiac disease.

Several startling research findings threatened this perspective and offered a new window through which to view celiac disease and autoimmunity in general. Although this work was initially paid little attention, each of several distinct areas of research were building toward a critical mass.

Exploration of intestinal permeability, and its relationship to celiac disease, was investigated throughout the 1990s. This work not only provided convincing evidence for the use of sugar absorption tests to screen for celiac disease in developing nations, it also established that intestinal leakage of food proteins is a consistent feature of active celiac disease.

One spin-off result of this work was to increase the credibility of molecular mimicry as a dynamic that followed the leakage of food proteins into the bloodstream. These foreign proteins were shown to cause immune system reactions that damaged both the foreign proteins and self tissues with similar protein structures.

Meanwhile, another area of research was increasing the use of serum antibody testing, called celiac panels, which soon revealed that celiac disease was dramatically more common than previously believed. These tests also established that the coexistence of celiac disease and diabetes mellitus was also common. When diabetic patients were tested, about 5% were shown to have celiac disease. When celiac patients were tested, about 10% were found to have diabetes mellitus.

Developments in similar serum antibody testing, related other autoimmune diseases, also revealed that compliance with a gluten-free diet, following diagnosis of celiac disease, actually resulted in reductions of these other antibodies. These studies suggested that gluten might actually play a causal role, not only in diabetes, but in a wide range of autoimmune diseases that were previously considered to be coincidentally associated with celiac disease. Hope dawned for many who suffered from a wide range of autoimmune diseases . Simple dietary changes might aid new treatments and bring relief to these many sufferers of autoimmunity. Even in cases where gluten is not the underlying cause, we are gaining understanding of the dynamics by which autoimmunity develops.

The crowning moment, with respect to diabetes, came in January of this year when A.J. MacFarlane, et al. published their findings in the Journal of Biological Chemistry. Their work demonstrated that wheat proteins might be a major causal factor in at least some cases of diabetes mellitus. Rooted in prior animal research that was largely spearheaded by Fraser Scott, this most recent research identified immune reactions, in diabetic humans, against wheat proteins which were also closely linked with the attack on the islet cells of the pancreas. This is an exciting moment for those with type 1 diabetes. Many of them may be aided in the maintenance of islet cell transplants (another new development) through following a gluten-free diet.

This work also provides a potential turning point for everyone who suffers from autoimmunity. Thanks to the recent establishment of celiac disease as very common in North America, we now know that about 1 in 133 Americans have celiac disease. We also know that this common condition is triggered by gluten. This family of grain proteins also appears to cause some, perhaps many, cases of diabetes mellitus.

The evidence against gluten is also growing in the investigation of other autoimmune conditions. It appears that celiac disease will soon be the window through which we will gain a better understanding of autoimmunity, and the gluten-free diet may be the cornerstone of the treatment of many cases of autoimmune diseases.

Celiac.com 12/14/2011 - Finding a slice of pre-packaged gluten-free bread that is 100% enjoyable seems to be the bane of many celiacs.  So you finally decide to make your own.  You read up on baking breads; you spend money to buy the ingredients; you take the time to prepare the mixture, then you put your creation in the oven.  Oh, the wonderful aroma of bread begins to fill the air.  You wait in anticipation.  Finally, the oven timer goes off and you remove your creation, only to discover that something went terribly wrong!  Don’t despair.  Below are some of the more common problems and solutions. 

Bread machines have become very popular.  While they are tooted as being time-savers, baking bread in the oven actually takes very little extra time and effort, and usually yields better results.

The most common complaint in gluten-free bread-baking is that the top of the loaf is dark brown while the inside is still doughy.  If this is a problem for you, try lowering the oven temperature by 25 degrees the next time you bake, and set your oven rack higher.  After the loaf is partially baked, cover it with a piece of foil for the remainder of the baking time.  A sure-fire way to get the inside to bake thoroughly is to use two small loaf pans instead of one large one.  Something else that will cause your bread not to bake through is the density factor, which leads us to issue number two.

Number two in the complaint department is that gluten-free breads are too dense and heavy.  The alternative flours are heavier than wheat flour, so “tricks” must be played with the dough to obtain lighter, wheat-like results.   The use two smaller pans to bake the bread instead of a single large pan will also help avoid this problem by giving the bread more room to expand.  You can also use a bit more leavening and sugar (the sugar-to-yeast ratio must remain the same for the bread to rise properly).  Use only fresh yeast that is dissolved in warm—not hot—liquid; if the liquid is too hot, the yeast will not rise properly.

Another trick is to have all of the liquid ingredients at room temperature, and then whip the liquid ingredients together in a blender to incorporate more air before adding them to the flour mixture.  You can also use a little less xanthan gum, and be sure to blend the dough mixture thoroughly, and then knead it a little more.

The issue of how much liquid to use to make your bread lighter is much more confusing.  If you are using an egg replacer, you may need to add a little more liquid to replace the liquid in eggs.  If you use extra large eggs, and your bread is too dense, try using a smaller size egg.  For a lighter loaf of bread, use slightly less liquid in the recipe; this also applies if you live at a high altitude.  When baking at very low altitudes, slightly increase the amount of liquid.  If you are not confused yet, then continue reading!

Different gluten-free flours absorb different amounts of liquids.  Some alternative flours require that you add more liquid to your recipe to prevent the loaf from being too dry and crumbly, while others require that you reduce the amount of liquid used to enable the loaf to be lighter and less dense so that it will bake evenly all the way through.  Now “humidity” quietly enters into the picture.  If it is humid, reduce the amount of liquid.  Ultimately, only experimentation will determine exactly how much liquid will be needed for the flours you are using.

Have you ever taken a perfect loaf of bread out of the oven, only to watch it slowly collapse as it cools?  You are not alone.  This usually indicates that the bread is not completely cooked inside.  The simplest remedy is to use two smaller baking pans instead of one large one.  Increase your oven temperature slightly, and slightly decrease the amount of liquid used.

After experimenting and adjusting oven temperatures, amounts of liquids used, types of flours used, you finally remove the perfect of loaf bread from the oven.  You wait in anticipation for it to cool.  You get out the knife to cut your first slice—and it crumbles.  Oh, the disappointment!  The dough was too dry, resulting in a loaf that will not hold together.  First—do not throw out the crumbs!  Put them in a small freezer bag and freeze them for the day when you want to make bread dressing, croutons, a crumb topping for a casserole, or breadcrumbs to coat fish, chicken or pork chops, or for use in a meatloaf. 

To avoid the crumbling when you make bread in the future, reduce the amount of flour mixture slightly.  Add a little more binding by increasing the amount of xanthan gum or dough enhancer.  Use milk (cow, soy or rice) in place of the water called for in the recipe.  Once the bread is baked, cool the loaf completely before slicing it with a serrated knife that has been sprayed with a gluten-free nonstick spray.

There are many variables when baking with gluten-free flours and yeast.  The important thing to remember is that the “real” taste of bread is achievable.  All the time spent in trial and error will be worth it—enjoy!

No-Knead Toasting Bread

This bread slices without crumbling, is moist, and is perfect for toasting!

Ingredients:
3 eggs
1 ½ Tbsp. warm water
1 Tbsp. quick-rising gluten-free yeast
¾ tsp. sugar
¾ cup milk
2 cups gluten-free flour mixture
½ tsp. gluten-free baking powder
1 tsp. cinnamon
¼ tsp. salt
½ cup + 1 Tbsp. sugar
¼ tsp. cider vinegar
2 tsp. gluten-free mayonnaise
4 Tbsp. butter, melted
½ cup gluten-free flour mixture*
1 egg
1 Tbsp. sesame seeds

Directions:

1. Place 3 eggs in a bowl of warm water for 10 minutes.  In a small bowl, stir together the 1 ½ Tbsp. warm water, yeast, and ¾ tsp. sugar; set aside for 15 minutes.  Scald milk, then let it cool till lukewarm.  Sift together the 2 cups flour mixture, baking powder, cinnamon, salt, and sugar; set aside. 
2. In a mixer bowl, mix together vinegar, mayonnaise, eggs and melted butter.  Add the yeast and milk and beat until smooth.  Slowly add the flour mixture, beating at low speed until blended.  With a spoon, stir in the remaining ½ cup of flour mixture.  
3. Generously spray a loaf pan (9X5”) with gluten-free nonstick spray.  Spoon the batter into the pan.  Dip a spoon in a little gluten-free flour and use the back of the spoon to smooth the dough in the pan.  Whip the remaining egg with a few drops of warm water, then brush this egg mixture on top of the loaf.  Sprinkle loaf with sesame seeds.  Spray one side of a piece of waxed paper with gluten-free nonstick spray; cover loaf with paper, sprayed side down. 
4. Place a bowl of very hot water on the bottom shelf of the oven.  Place the loaf pan on the shelf above the water.  Close oven door and let the dough rise for 1 hour.  Remove water and loaf pan from oven.  Preheat oven to 350F for 10 minutes.  Remove waxed paper and place bread in oven to bake for 25 to 30 minutes. 
5. If the top of the bread is browning too quickly, cover pan with a sheet of foil until loaf is baked through.  Let baked bread sit in pan for 5 minutes, then remove bread and let it finish cooling on a wire rack.  If you are not going to be eating the bread the day you bake it, wrap it well and freeze it. 

Spray a serrated knife with gluten-free nonstick spray to cut the bread.

*Gluten-free Flour Mixture:
The flour mixture I use is a combination of rice, potato starch, tapioca and garbanzo bean flours, cornstarch and xanthan gum.  If you are allergic to any of these products, alternative flours may be substituted.

-Yes, there’s more to life than rice and corn!

Variety, it’s been said, is the spice of life.  So what’s a person to do when they’re told to eliminate wheat and/or gluten from their diet?  Most turn to rice, corn, and potatoes—an adequate set of starches, but ones that are sorely lacking in nutrients, flavor, and imagination.

The superheroes of gluten-free grains are often referred to as “ancient” or alternative grains, which are loaded with nutrients and unique, interesting flavors.  The following is a condensed excerpt from my newly published book, Wheat-Free, Worry-Free: The Art of Happy, Healthy, Gluten-Free Living.

“Alternative” Grains: The Superheroes of Gluten-Free Grains
If you’re an adventuresome eater, you’re in for a treat.  In searching for alternatives to wheat, rye, or barley, you’ll discover a variety of wheat-free/gluten-free grains that you may never have heard of before, many of them loaded with nutrients and robust flavors not found in typical grains like wheat and rice.  If you’re not the adventurous type and you just long for the ease of a few tried-and-true favorites, you’ll find them here as well.

Perhaps you fall into still another category—you’ve been eating a wheat or gluten-free diet for a while and you think you already know everything there is to know.  Okay, what’s quinoa, and how the heck is it pronounced?  Is teff wheat-free?  Do Job’s Tears have religious significance?  If you don’t know the answers to these questions, or if you think ragi is a spaghetti sauce and sorghum is what you get when you have your teeth cleaned, it’s time to move on to lesson one.

Alternative Grains and Non-Grains
Even if you can’t eat wheat, rye, barley, or oats, there are several other grains, fruits, and legumes that are not only acceptable alternatives to them, but they also happen to be loaded with flavor and nutrients.  Here are some of the many choices available to those on a wheat and gluten-free diet (WF/gluten-free):

• Amaranth (WF/gluten-free)
• Buckwheat/groats/kasha (WF/gluten-free)
• Cassava (arrowroot) (WF/gluten-free)
• Chickpea (garbanzo) (WF/gluten-free)
• Job’s Tears (WF/gluten-free)
• Millet (WF/gluten-free)
• Montina (WF/gluten-free)
• Oats (WF/gluten-free, but oats can be contaminated with wheat and other grains)
• Quinoa (WF/gluten-free)
• Ragi (WF/gluten-free)
• Rice (WF/gluten-free; only brown rice is whole grain)
• Sorghum (WF/gluten-free)
• Soy (WF/gluten-free)
• Tapioca (WF/gluten-free)
• Taro root (WF/gluten-free)
• Teff (WF/gluten-free)

Many of the proteins found in these alternatives are a great source of complex carbohydrates.  The fuel from these carbohydrates, found in plant kingdom starches, produces what nutritionists call a protein-sparing effect, which means the body can meet its energy requirements without dipping into its protein reserves.

Several of these alternative grains and non-grains are high in lysine, an amino acid that controls protein absorption in the body.  Because this amino acid is absent from most grains, the protein fraction of those grains is utilized only if eaten in conjunction with other foods that do contain lysine.  All high protein grains are better utilized by the body when they are eaten with high-lysine foods such as peas, beans, amaranth, or buckwheat.

Amaranth (WF/gluten-free): Loaded with fiber and more protein than any traditional grain, amaranth is nutritious and delicious, with a pleasant peppery flavor.  The name means “not withering,” or more literally, “immortal.”  While it may not make you immortal, it is extremely healthful, especially with its high lysine and iron content.

Buckwheat (groat; kasha) (WF/gluten-free): It sounds as though it would be closely related to wheat, but buckwheat is not related to wheat at all.  In fact, it’s not even a grain; it’s a fruit of the Fagopyrum genus, a distant cousin of garden-variety rhubarb, and its seed is the plant’s strong point.  The buckwheat seed has a three-cornered shell that contains a pale kernel known as a “groat.”  In one form or another, groats have been used as food by people since the 10th century b.c.

Nutritionally, buckwheat is a powerhouse.  It contains a high proportion of all eight essential amino acids, which the body doesn’t make itself but are still essential for keeping the body functioning.  In that way, buckwheat is closer to being a complete protein than any other plant source.

Whole white buckwheat is naturally dried and has a delicate flavor that makes it a good stand-in for rice or pasta.  Kasha is the name given to roasted hulled buckwheat kernels.  Kasha is toasted in an oven and tossed by hand until the kernels develop a deep tan color, nutlike flavor, and a slightly scorched smell.

Be aware, however, that buckwheat is sometimes combined with wheat.  Read labels carefully before purchasing buckwheat products.

Millet (WF/gluten-free): Millet is said by some to be more ancient than any grain that grows.  Where it was first cultivated is disputed, but native legends tell of a wild strain known as Job’s Tears that grows in the Philippines and sprouted “at the dawn of time.”

Millet is still well respected in Africa, India, and China, where it is considered a staple.  Here in the United States, it is raised almost exclusively for hay, fodder, and birdseed.  One might consider that to be a waste, especially when considering its high vitamin and mineral content.  Rich in phosphorus, iron, calcium, riboflavin, and niacin, a cup of cooked millet has nearly as much protein as wheat.  It is also high in lysine—higher than rice, corn, or oats.

Millet is officially a member of the Gramineae (grass) family and as such is related to montina.

Montina (Indian Rice Grass) (WF/gluten-free): Indian rice grass was a dietary staple of Native American cultures in the Southwest and north through Montana and into Canada more than 7,000 years ago, even before maize (corn) was cultivated.  Similar to maize, montina was a good substitute during years when maize crops failed or game was in short supply.  It has a hearty flavor, and is loaded with fiber and protein.

Quinoa (“KEEN-wah”) (WF/gluten-free): The National Academy of Science described quinoa as “the most nearly perfect source of protein from the vegetable kingdom.”  Although new to North Americans, it has been cultivated in the South American Andes since at least 3000 b.c.  Ancient Incas called this annual plant “the mother grain,” because it was self-perpetuating and ever-bearing.  They honored it as a sacred food product, since a steady diet appeared to ensure a full, long life; and the Inca ruler himself planted the first row of quinoa each season with a gold spade.

Like amaranth, quinoa is packed with lysine and other amino acids that make a protein complete.  Quinoa is also high in phosphorus, calcium, iron, vitamin E, and assorted B vitamins.  Technically a fruit of the Chenopodium herb family, quinoa is usually pale yellow in color, but also comes in pink, orange, red, purple, and black.

Quinoa’s only fault is a bitter coating of saponins its seeds.  The coating comes off with thorough rinsing prior to cooking, and some companies have developed ways to remove the coating prior to delivering quinoa to stores.

Sorghum (milo) (WF/gluten-free): Sorghum is another of the oldest known grains, and has been a major source of nutrition in Africa and India for years.  Now grown in the United States, sorghum is generating excitement as a gluten-free insoluble fiber.

Because sorghum’s protein and starch are more slowly digested than that of other cereals, it may be beneficial to diabetics and healthy for anyone.  Sorghum fans boast of its bland flavor and light color, which don’t alter the taste or look of foods when used in place of wheat flour.  Many cooks suggest combining sorghum with soybean flour.

Soy and Soybeans (WF/gluten-free): Like the ancient foods mentioned at the beginning of this section, soy has been around for centuries.  In China, soybeans have been grown since the 11th century b.c., and are still one of the country’s most important crops.  Soybeans weren’t cultivated in the United States until the early 1800s, yet today are one of this country’s highest yielding producers.

Soybeans are a legume, belonging to the pea family.  Comprised of nearly 50 percent protein, 25 percent oil, and 25 percent carbohydrate, they have earned a reputation as being extremely nutritious.  They are also an excellent source of essential fatty acids, which are not produced by the body, but are essential to its functioning nonetheless.

Teff (WF/gluten-free): Considered a basic part of the Ethiopian diet, teff is relatively new to Americans.    Five times richer in calcium, iron, and potassium than any other grain, teff also contains substantial amounts of protein and soluble and insoluble fiber. Considered a nutritional powerhouse, it has a sweet, nutty flavor. Teff grows in many different varieties and colors, but in the United States only the ivory, brown, and reddish-tan varieties can be found. The reddish teff is reserved for purveyors of Ethiopian restaurants, who are delighted to have an American source for their beloved grain.

A Word About Sprouted Grains
Some people believe that “sprouted grains,” even ones that contain gluten such as wheat, are gluten-free—not true!  The sprouting process sparks a chemical reaction that begins to break down gluten, so some people who are slightly sensitive to gluten may find that they can tolerate sprouted grains better, but too many of the peptides that are reactive for celiacs are still present, so sprouted grains are not safe for people with celiac disease or gluten intolerance.

What is refractory sprue?
This question has been the subject of great scientific inquiry, and there are differing opinions on the relationship between celiac disease and refractory sprue. However, there are several general characteristics of refractory sprue that researchers seem to agree on:

• Presence of persistently damaged villi in the small intestine that are not repaired after the gluten free diet has been successfully initiated and/or maintained
• An increased presence of intraepithelial lymphocytes (IEL) in the small bowel
• Severe malabsorption

Researchers think of celiac disease as the beginning of a spectrum of conditions that could, for a small percentage of patients, end up at the other end to be enteropathy associated T-Cell Lymphoma. Most people with celiac disease will respond to the gluten free diet and never move to the next stage in this spectrum. But for those that do, they will experience changes in their immune system and in the cells lining their intestine that could lead to cancer.

The spectrum would start with celiac disease, and the next step would be the non-responsiveness of the immune system to the gluten-free diet, in other words, refractory sprue. Then in some cases, a condition called ulcerative jejunitis develops, and finally, the damaged lining of the intestine produces cancer cells that mimic the mutations of the abnormal immune system cells.

How many people with celiac disease are affected by refractory sprue?
First, there are no reported cases in the medical literature of celiac sprue in people under 20 years of age. Second, the number of celiacs affected by refractory sprue, while not known, appears to be very small. We know this because the current estimates for small bowel cancers in people affected by celiac disease, as reported at the 10th International Conference on Celiac Disease is less than 2.5%. Refractory sprue can result in small bowel cancers, but not in all cases.

It is interesting to note that in a recent study of patients with "unresponsive" celiac disease, Dr. Joseph Murray and his colleagues found that of 49 patients evaluated, only nine actually had refractory sprue—25 were found to have gluten contamination in their diets. The most common symptoms presented by the patients who truly had refractory sprue were weight loss, steatorrhea and diarrhea, in that order.

What makes refractory sprue different than celiac sprue?
Again, there are several medical points of view on this, but all researchers would agree that one marker indicates the presence of refractory sprue, and it is not found in celiac disease.

Abnormal Intraepithelial Lymphocytes (Immune Cells)
The intraepithelial lymphocytes found in celiac disease have a normal-looking appearance under the microscope and they behave like normal celiac immune cells (they respond to gluten when they shouldnt). These lymphocytes have the ability to communicate with other cells using different types of messages on their cell surfaces. When diagnosing celiac disease, pathologists look for an increased number of IELs as an indication of celiac disease.

In refractory sprue, however, there is a different kind of IEL that is found in great numbers. This immune cell does not look normal, and it ignores the presence or absence of gluten. This type of cell does not have the ability to communicate normally with other cells as it would be expected to do. However, it does have the ability to communicate with cancer cells, contributing to their development. It is not clear what causes this type of IEL to develop or mutate, contributing to refractory sprue.

It is possible to have refractory sprue without having these abnormal lymphocytes; in this case, treatment with steroids often results in response to the gluten free diet and a reversal of the condition.

French researchers have developed a test to determine whether a biopsy specimen reflects a normal course of celiac disease with a slow response to the diet, or the need for further testing because refractory sprue may be present. In paraffin wax, a specimen can be stained to determine whether or not the immune cells express CD8, a protein often found on intraepithelial lymphocytes in celiac disease. If CD8 is positive, the individual has celiac and is responding very slowly to the diet. If the sample is CD8 negative, refractory sprue could be the reason.

How is refractory sprue diagnosed and treated?
It must be established through a thorough diet history and antibody testing that the individual is adhering to a strict gluten-free diet. Then, all other gastrointestinal diseases have to be ruled out before a diagnosis of refractory sprue is made. Conditions to be ruled out include pancreatic insufficiency, lactose malabsorption, parasite infestation, intolerance to other food proteins, coexisting inflammatory bowel disease, and autoimmune enteropathy, among others.

Diagnosis should include a test called an enteroscopy, which is a procedure that explores more of the small intestine, and often finds ulcerative jejunitis, a marker of damage in refractory sprue. In addition, because the abnormal IELs can proliferate throughout the gut, a colonoscopy is recommended to determine if lymphocytic colitis is present.

Treatment options include the elemental diet (also used in Crohns Disease), total parenteral nutrition (tube feedings), steroids, immunosuppressive therapies such as Cyclosporine, Infliximab, and in some cases, chemotherapy. Treatment options depend on the extent of refractory sprue found on biopsy and the nature of the clinical symptoms involved.

How can I reduce the chances of developing refractory sprue?
Researchers agree that most cases of refractory sprue develop in people who were diagnosed very late in life or who didnt follow the diet completely. Note that it doesn't matter how much gluten was consumed in these patients, they still developed refractory sprue. So the best protection against developing refractory sprue is to follow the diet. Be honest with yourself, especially if you cheat a little. What are you eating? Are you sure there isnt a great gluten-free alternative out there? Hey, there's even beer nowadays, so don't dismiss the suggestion of great gluten-free brownies, cakes, pies, pasta, crackers, cookies, or whatever else you are craving.

Deal with your feelings too. Its easy to get angry about how life is much harder for people with celiac disease—how everything related to food requires too much planning, preparation, and explanation. These feelings are perfectly justified, but they do not justify cheating on your diet. There are great "quick fix" cookbooks out there, even convenience meals that are gluten free. Do whatever it takes to stay healthy, and gluten-free for life.

Don't forget regular visits to your gastroenterologist or internist. Follow-up care for people with celiac disease is incredibly important, even if the medical community hasn't recognized it yet. Regular antibody testing to monitor compliance with the diet is an extra level of protection that every celiac needs. A simple anti-gliadin antibody test (IGG and IGA), six months post diagnosis, a year post-diagnosis and then every year after that for the first three years is key. In fact, the most serious celiac disease complications tend to occur in the first three years after diagnosis. Veteran celiacs should have their antibody levels checked every couple of years.

While refractory sprue remains a potential complication for any adult with celiac disease, a majority of adult celiacs in this country will not have to face this difficult condition. For those diagnosed, treatment options continue to improve and the disease is becoming easier to manage. Researchers continue to study refractory sprue in order to better understand how the condition behaves and to develop new treatments. For now, the best defense against refractory sprue is a good offense—living a completely gluten-free life.