Gluten Free Research in the News

Reviews on this page:

• November 2009: Interesting New Study on the effects of an enzyme on Celiac Disease
  
• A Celiac Molecule?
  
• Gene Testing for Gluten Sensitivity –are you positive or negative or not sure?
  
• Leading a great gluten free life…including some common symptoms

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November 2009: Interesting New Study on the effects of an enzyme on Celiac Disease

An interesting clinical trial with a double blind study of celiac disease sufferers has taken place in the Netherlands. The new clinical study to find out the effect of the Aspergillus Niger Prolyl Endoprotease (AN-PEP) Enzyme on the Effects of Gluten Ingestion in patients with celiac disease offers to provide further insight into this condition.

Many studies are now being conducted in different parts of the world since awareness has increased. Celiac Disease and an intolerance for gluten is more prevalent among all ethnic groups than ever before. As gluten intolerance, the major factor in Celiac Disease seems to be a contributing factor for many others, this bears a great deal of study.

The Netherland study which took place from May 2008 until May 2009 was sponsored by the VU University Medical Center –in Amsterdam under the guidance of C.J. Mulder with collaborators being the Leiden University Medical Center –in the Netherlands and a large ingredient supplier to the food industry, DSM Food Specialties in the USA. The ClinicalTrials.gov Identifier is  NCT00810654 and as of  November 05, 2009 the review of the study is still pending.

The trial consisted of fourteen patients with celiac disease from 18 to 70 years old in which for the first part of the study, participants ate a food with gluten in it once daily while also consuming the AN-PEP enzyme. In the second part of the study, patients were split up into two groups in a blind study. One group was given a placebo while the other group was given the AN-PEP enzyme. Both groups continued to eat gluten containing foods once per day.

Those in the study were monitored before the start of the trial and during the trial period. Blood samples were taken at periods throughout the study along with several, ‘spike-biopsies’ from the duodenum by oesophago-gastro-duodenoscopy for study after the trial period. Extensive written feedback of symptoms and feelings of patients during the study were given.

The study hopes to find out definitively if supplementation with enzymes can cut gluten reaction and/or damage in the treatment of celiac disease. The enzyme, prolyl endoprotease is derived from a food grade organism called Aspergillis niger (AN-PEP) and it is hoped that the addition of this can detoxify 8 grams of gluten in a commercial food product.

The review of the study is still going on. It is hoped that this interventional study will offer some new hope for celiac. People who are Celiac (Coeliac) or Gluten Intolerant are anxiously awaiting the results of the study to be published. As a gluten free diet is currently the only treatment. 
Read more about this study.

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A Celiac Molecule?

Scientists led by Alessio Fasano, M.D.,  at the University of Maryland School of Medicine have identified ‘zonulin’ as a molecule in the human body called a Haptoglobin 2 precursor and linked to inflammatory disorders and autoimmune disorders.  Dr. Fasano, who is a professor of pediatrics, medicine and physiology and director of the Mucosal Biology Research Center and the Center for Celiac Research at the University of Maryland School of Medicine, published an article on September 8th in the Proceedings of the National Academy of Sciences online version.

Dr. Fasano’s study indicates that zonulin the precursor to Haptoglobin 2, which is a gene permutation found only in humans, opens a gateway in the gut, or intestines, to let gluten damage the body. Ongoing studies are being conducted to further find how this knowledge can help in the treatment of celiac disease.

It has been discovered that an incredible 80% of people have the haptoglobin molecule. Scientists believe it evolved 800 million years ago and objectified itself in the population in India some two millions of years ago.

“This molecule could be a critical missing piece of the puzzle to lead to a treatment for celiac disease, other autoimmune disorders and allergies and even cancer, all of which are related to an exaggerated production of zonulin/pre-haptoglobin 2 and to the loss of the protective barrier of cells lining the gut and other areas of the body, like the blood brain barrier,” says Dr. Fasano. 

Gluten intolerance manifests itself in several types of illness from celiac disease, crohns, wheat allergies, etc. and is an autoimmune disorder. In brief, the consumption of gluten containing foods is a trigger for the gradual breakdown of the villi, which are hair-like protrusions emanating from the wall of the intestines. Their purpose is to allow food particles to be captured in among these finger-like villi so that the blood inside the villi will be able to absorb the nutrients in the food. Gluten or the protein gliadin not only gets trapped in the villi it eventually flattens the villi altogether making nutrient absorption difficult if not impossible.

After a period of the body not receiving the nutrients needed to sustain itself a breakdown in different aspects of health are noticed. As there are varying symptoms, about 300 different ones, many people go for long periods of time unaware of what is causing their discomfort and symptoms. Sometimes an obese looking person, someone who is always hungry, is actually starving due to the mal-absorption of nutrients, the body is desperately trying to find nourishment. Others appear extremely thin as the starvation is more apparent.

Either blood tests or a biopsy are used to determine gluten intolerance however: for some people, even testing is not the eventual decider that they should go on a gluten restricted diet, as many have had negative test results only  to try a gluten free diet out of desperation to try anything to feel better. After about 2 to 3 weeks on the diet, they start to feel better.

The problem here is that people who have either tested positive for a gluten intolerance or have found they feel better and have less troublesome symptoms; have to find a whole different way of eating and  that is not always easy. It takes the body a further 6 months or more to heal the villi sufficiently to begin again absorbing nutrients as they should. Unfortunately, just sneaking a little gluten here and there can be more damaging than one thinks.

For those who have immediate reactions as do celiacs, the diet becomes a way of life. For others who may not have as reactionary symptoms, find that temporarily, the choice between a delicious slice of pizza and taking care not too ingest gluten, is almost too hard to handle.

There are also three stages in the Gluten Free healing diet which are not always explained. Stage one, is eating very simple whole foods to heal, eliminating other possible allergens as well including milk. Stage two is adding small amounts milk or other possible allergens to see if there is any adverse reaction. Stage Three is when you are sufficiently healed that you can tolerate most foods as long as they are gluten free. It is only with the promise of the third stage, when eating is no longer a depriving experience that people find a joy in their diets again.

After all, a deprivation diet, is always short lived whereas an enjoyable diet can be maintained.

For an explanation of the Three Stages to Healing on a Gluten Free Diet, please refer to Health & Nutrition: by Trina Astor-Stewart

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Gene Testing for Gluten Sensitivity –are you positive or negative or not sure?

Blood testing for gluten sensitivity as well as biopsy testing has been the most common method of testing for Celiac or gluten intolerance. Now gene testing, through simply swabbing for saliva is becoming one of the best indicators. However, some tests can be misleading if they do not include a particular portion of the genetic make-up that can predispose gluten sensitivity. 

Here are a few things you should know about gene testing, where to go and what to ask for. Genetic testing can be done at any age and is not affected by the ingestion of gluten containing foods. 

The most commonly recognized HLA genetic patterns DQ2 or DQ8 associated with Celiac although you may not be experiencing any symptoms and are not expected generally to be at risk for the full autoimmune disease. This is good news, but you can still be intolerant to gluten.

Increased denominators suggesting an increased risk of Celiac disease are HLA DQ2 and DQ8, complex white blood cell patterns.  or types that are known to be associated with an increase risk of Celiac disease. The HLA term stands for human leukocyte antigen. Leukocytes are white blood cells, while antigens are the proteins that serve to elicit an immune response by the body. The HLA system is a complex set of proteins on the surface of the white blood cells.

Sometimes lab testing reports the single presence or absence of a copy of either DQ2 or DQ8, inherited from parents, which can be associated with an increase risk of developing Celiac disease. You need to request information about whether you inherited a single copy or two copies as this can further determine your risk factor.

“It also provides information about your parents and your childrens' risk of inheriting an at risk gene. If you have DQ2 and DQ8 we know your complete DQ pattern. We also known one of your parents had at least DQ2 and the other DQ8. All of your children will either get a DQ2 or a DQ8. So, both your parents and all of your children are at risk for Celiac in that situation. If you have only copy of DQ2 or DQ8 then we only know that at least one of your parents had one copy of the risk gene and each of your children will have a 50-50 chance of inheriting such a risk gene from you,” says Dr. Scot Michael Lewey. 

There is still research going on to really find out what is involved, there seem to be also other non-HLA genetic factors that can be involved, only time and research can tell the whole story. Some labs however are still not as up on the latest research as so do not include a full spectrum of the at risk components for even these patterns.

This could account for the number of very ill people who have gone for testing, come back with a negative result only to get much worse until out of desperation they stop eating gluten and gradually get better.

According to Dr. Scot Michael Lewey, the DQ2 and DQ8 are summary blood type designations or serotypes for the presence of several protein subunits, which contain alpha and beta subunits to these protein patterns. The beta subunit is the most influential and important component; therefore most laboratories only test for and report the beta subunit, while the alpha subunit also carries a risk on its own. 

It is important that your doctor be aware of these subtle differences in order to request both the beta and the alpha subunits testing from labs that are experienced in the full spectrum test needed.

Here is a list of labs in the USA that do this kind of testing.

Approximate cost of testing is between $350. and $400.
Kimball Genetics
LabCorp
Quest
Prometheus
Enterolab

If you are interested in reading more about this subject see,

“Celiac Genetics” by: Ludvig Sollid and Benedicte Lie of Oslo, Norway
“Current Concepts and Practical Applications" Clinical Gastroenterology and Hepatology 2005 and Bourgey's 2007 review.

Unfortunately the absence of a high-risk genes does not mean there will be no adverse reactions to gluten with symptoms such as leaky gut, skin rashes, digestive problems or what is commonly referred to as ‘brain fog’.

Researchers are learning more all the time, and what was once considered specifically Celiac disease is now considered that more people actually experience “gluten syndrome” which can be less severe in intensity, but nevertheless those individuals need to monitor their reactions to gluten ingestion.

Too many people I have talked to are searching for answers for minor symptoms that have not immediate  explanation but on being aware of what they are eating find that they began feeling overly sleepy after eating wheat for instance, or have catches of phlegm in the throat, or some other seemingly minor symptom. Only you can know how you feel, but if you are experiencing symptoms that are unexplained you may want to just eliminate gluten temporarily to see how you feel.

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Leading a great gluten free life…

You should be encouraged if you find that gluten is the culprit, it means you can change what you eat and lead a great life. Now there is hope, for many adhering to a Gluten Free Diet, it just takes a little education, time, and dedication.

It is worth the time you spend evaluating your foods and nutrition. You may have to learn to cook more. Hey, that is healthier right there as most nutritionists advise everyone to eat more whole foods keeping processed foods to a minimum.

Make sure you are getting the vitamins and minerals your body needs to function properly, now that you are not ingesting gluten, your villi will be able to assimilate nutrients better. Eat foods rich in calcium to help with bone density. People on a gluten free diet should monitor folic acid levels, vitamin B12, fat-soluble vitamins, iron and other trace minerals. Make sure you get a full range of vitamins and minerals including lots of Vitamin D through sunshine or supplementation. Remember vitamins and minerals are normally found in the foods we eat, so take any supplementations with food to help you obtain the maximum benefit.
 
A healthy diet full of vegetables, fruits, unprocessed meat, fish and poultry is best, with the addition of gluten free whole grains, rice and potatoes etc. People on a gluten free diet often find it difficult to obtain the nutrients needed on a strictly vegetarian diet. Especially children only need a few bites of meat to do what would take a lot of bites on a vegetarian diet.

There are many whole grains that are gluten free. If your system has not been damaged too much, you will find these a wonderful augmentation to your diet. Maybe a bit of an aquired taste for some, but wholesome. Always make sure these come from gluten free sources, for instance, oats are gluten free but normally ground in wheat mills making them unsafe from those sources.

Buckwheat adds fiber and nutrition as do Teff, Quinoa, Sorghum, etc. Try the easier to digest, rice, tapioca and corn first.

What symptoms could mean that you need a gluten free diet?
There are actually around 300 symptoms of gluten syndrome, as well as people who are  asymptomatic or asymptomatic until more damage occurs.

Here are a few of the most common symptoms.

Abdominal pain, diarrhea, unexplained fatigue, extreme weight loss, puffiness, obesity, abdominal distention, flatulence, osteoporosis, liver disjunction, nausea, iron deficiency, 'brain fog', constipation, skin rashes,  pain and swelling in joints, depression, unexplained sleepiness, constantly recurring colds and flu due to the weakened immune system, and many others. Gluten intolerance can also mimic other illnesses, some people have been diagnosed with very serious illnesses only to find out later it was a gluten intolerance.

Although the connection to eating wheat and gluten to Celiac disease and Gluten Intolerance as a cause for some ailments was only discovered in 1950 does not mean people didn’t have that. Unfortunately some people suffered life long illnesses while still eating the so called ‘staff of life’ wheat bread. It is not our desire to frighten or make anyone stop eating their usual diet of wheat pizzas, cakes and breads, but if you have any of these symptoms, why suffer or damage your system further. Find out if gluten is the culprit, breath a sigh of relief, change your diet and get your health back.

I have talked to people who now know what the cause of their symptoms is, and now understand what was wrong with an ill parent for instance. In some cases the only relief for a past generation was to turn to alcohol or prescription drugs in order to still the pain.  They did not know what it was that was causing their ills.

Even now there is a lack of information on the subject even among health professionals and food service professionals, although that is changing rapidly because of the internet as a source of information. 

So take heart, now there are answers,
Now there are good gluten free foods,
Now there is hope,
Now you can live your life filled with joy!
 

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References:
Bourgey, M et al. HLA related genetic risk for Coeliac disease. Gut 2007; 56:1054-1059.
Johnson, TC et al. Relationship of HLA-DQ8 and severity of Celiac disease: Comparison of New York and Parisian cohorts. Clin Gastroenterol Hep 2004; 2:888-894.
Kaukinen K. et al. HLA-DQ typing in the diagnosis of Celiac disease. Am J Gastroenterol 2002; 97(3): 695-699.
Lundin, KE. HLA-DQ8 as an Ir gene in Coeliac disease. Gut 2003; 52:7-8
Mazzarella G. et al. An immunodominant DQ8 restricted gliadin peptide activates small intestine immune response in in vitro cultured mucosa from HLA-DQ8 positive but not HLA-DQ8 negative Coeliac patients. Gut 2003; 52:57-62.
Sollid, LM and Lie, BA. Celiac disease genetics: Current concepts and practical applications. Clin Gastro Hep 2005; 3:843-851.
Wolters,VM and Wijenga C. Genetic background of celiac disease and its clinical applications. Am J Gastroenterol 2008; 103:190-195.
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