Gluten Cross-Reactivity: How your body can still think you’re eating gluten even after giving it up.

October 4, 2012 in Categories: , , , , , by

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NOTE:  An updated version of this post can be found here.

For those 20% of us with celiac disease or gluten-intolerance/sensitivity (whether diagnosed or not), it is critical to understand the concept of gluten cross-reactivity.  Essentially, when your body creates antibodies against gluten, those same antibodies also recognize proteins in other foods.  When you eat those foods, even though they don’t contain gluten, your body reacts as though they do.  You can do a fantastic job of remaining completely gluten-free but still suffer all of the symptoms of gluten consumption—because your body still thinks you are eating gluten.  This is a very important piece of information that I was missing until recently.

Proteins are made of long chains of amino acids (small proteins may only be 50 amino acids long whereas large proteins may be 2000 amino acids long) and it is the specific sequence of these amino acids that determines what kind of protein is formed.  These amino acid chains are folded, kinked and buckled in extremely complex ways, which gives a protein its ‘structure’.  This folding/structure is integral to the function of the protein.

An antibody is a Y shaped protein produced by immune cells in your body.  Each tip of the Y contains the region of the antibody (called the paratope) that can bind to a specific sequence of amino acids (called the epitope) that are a part of the protein that the antibody recognizes/binds to (called the antigen).  The classic analogy is that the antibody is like a lock and a 15-20 amino acid section of a protein/antigen is the key. There are 5 classes (or isotypes) of antibodies, each with distinctive functions in the body.  The IgE class of antibodies are responsible for allergic reactions; for example, when someone goes into anaphylaxis after eating shellfish. The two classes IgG and IgA are critical for protecting us from invading pathogens but are also responsible for food sensitivities/intolerances.  Both IgA and IgG antibodies are secreted by immune cells into the circulation, lymph, various fluids of the body (like saliva!) and tissues themselves.  And both IgG and IgA antibodies are found in high concentrations in the tissues and fluids surrounding the gut (this is part of why the gut is considered our primary defense against infection).

The formation of antibodies against an antigen (whether this is an invading pathogen or a food) is an extremely complex process.  When antibodies are being formed against a protein, the antibodies recognize specific (and short) sequences of amino acids in that protein.  Depending on how the antigenic protein is folded, certain amino acid sequences in that protein are more likely to be the target of new antibody formation than others, simply because of the location of that sequence in the structure of the protein.  Certain sequences of amino acids are more antigenic than others as well (i.e., more likely to stimulate antibody formation).  This is also part of why certain foods have a higher potential to cause allergies and sensitivities.

Understanding that antibodies recognize short sequences of amino acids and not an entire protein is key to understanding the concept of cross-reactivity (and molecular mimicry, but that’s a topic for another post).  It also is the reason why many different antibodies can be formed against one protein (this redundancy is important for protecting us from pathogens).  Many different antibodies can also be formed against one pathogen or, more relevant to this discussion, one specific food.

So what happens in cross-reactivity?  In this case the amino acid sequence that an antibody recognizes is also present in another protein from another food (in the case of molecular mimicry, that sequence is also present is a protein in the human body).  There are only 20 different amino acids, so while there are millions of possible ways to link various amount of each amino acid together to form a protein, there are certain amino acid sequences that do tend to repeat in biology.

The take home message:  depending on exactly what antibody or antibodies your body forms against gluten, it/they may or may not cross-react with other foods.  So, not only are you sensitive to gluten, but your body now recognizes non-gluten containing foods as one and the same.  Who needs to worry about this?  Any of the estimated 20% of people who are gluten sensitive/intolerant or have celiac disease, i.e., have formed antibodies against gluten.

Cyrex Labs offers a simple blood test that tests for cross-reactivity to the most common culprits (Chris Kresser vouches for the high quality tests done by this company, which is good enough for me!).  Here is the full list (some of these are obviously not paleo, but you might consider them cheat foods, which is why I mention them):

  • Rye
  • Barley
  • Spelt
  • Polish Wheat
  • Oats
  • Buckwheat
  • Sorghum
  • Millet
  • Amaranth
  • Quinoa
  • Corn
  • Rice
  • Potato
  • Hemp
  • Teff
  • Soy
  • Milk (Alpha-Casein, Beta-Casein, Casomorphin, Butyrophilin, Whey Protein)
  • Chocolate
  • Yeast
  • Coffee
  • Sesame
  • Tapioca (a.k.a. cassava or yucca)
  • Egg

Just like trace amounts of gluten can cause a reaction in at least those with celiac disease (the threshold for a reaction has not been tested in non-celiac gluten sensitivity), even a small amount of these foods can perpetuate inflammation and immune responses.  This is important when you think of the small amounts of soy used in so many foods and even the trace milk proteins that can be found in ghee.

If you have autoimmune disease (which has a very high correlation with gluten-sensitivity), celiac disease, gluten-sensitivity, or are simply not seeing the improvements you were hoping for by following a standard paleo diet, one or all of these foods may be the culprit.  You have the choice of either cutting these foods out of your diet and seeing if you improve or get tested to see if your body produces antibodies against these foods.  For me, it’s a no brainer (because it just all makes so much sense now!): I have to stop eating chocolate (sniff), fermented foods like sauerkraut and kombucha (because of the yeast content), eggs, and tapioca.  I am very happy to report dramatic improvement in my lichen planus lesions in just four days! (and as much as I miss chocolate and kombucha, it’s worth it!)

A great overview of proteins and antibodies (and source of protein folding image): http://publications.nigms.nih.gov/structlife/chapter1.html

A fairly technical review of food IgG-mediated food sensitivities:  http://www.usbiotek.com/Downloads/information/criticalReview.pdf

Cyrex Labs Array 4:  http://www.cyrexlabs.com/CyrexTestsArrays/tabid/136/Default.aspx

Image of antibody binding taken from http://classes.midlandstech.edu/carterp/Courses/bio225/chap17/ss2.htm

Comments

Hi, I’d like to know about the symptoms. When I eat gluten accidentally I know by going to the the wc. Plus I might get a migrane. Are these the same symptoms I should feel when eating cross reactive foods? I have vitiligo and still don’t see changes. I’ve been on the diet since february, but making mistakes every 3 weeks or so.

Symptoms would typically be similar to what happens when you eat gluten, but not necessarily. They could include any kind of gastrointestinal symptom, any kind of skin change or symptom, headaches, fatigues, trouble sleeping, anxiety, or mood changes.

Help! I had my gall bladder removed back in February(laproscopic), the stone was so large they had to open the removal incision larger than normal to remove. I guess I may have been having symptom/trouble from my diet before but never noticed anything major. Now I do. I think I have a problem with gluten. I am not aware of when I eat gluten because I have never had to be. With my current diet, almost everyday I have feel nauseous, have sharp pains in my stomach, gas in my stomach, and 75% of the time loosey goosey. I have no idea how to start to change my diet as I have eating the same way for 30yrs. What do I do??? Thanks.

Well, definitely removing gluten is important (check out celiac.com for lists of which foods contain gluten). I also recommend digestive enzyme supplements with your meals, especially ox bile.

Hi PaleoMom, great blog, and I look forward to reading the book. So far the GAPS and SCD books have been very helpful, but I’m excited to see someone taking a broader look at autoimmunity issues and how diet can help manage/mitigate symptoms.

My question on this post is, what is your take on the possibility of other non-listed foods presenting a cross-reactivity issue, due to yeast content. For example, fruits, Vitamin C and also, although they’re listed, coffee and chocolate.

Many fruits contain natural yeast/mold spores on their skins, some of which can be washed off, but perhaps not entirely. The biggest examples I’ve come up with are grapes, possibly bananas and cantaloupe.

Also, it is my understanding that most commercially produced Vitamin C is created using a yeast fermentation process. For a while I was researching celiac, IBS and Crohn’s. For Crohn’s patients, saccharomyces cerevisiae (bakers yeast), is an issue, and my research on that yeast led to a lot of information about products that may contain it, including Vitamin C, as well as many commercial probiotics.

I think yeast could also be a tie-in for coffee and chocolate sensitivity, due to the fact that these two products are processed in ways which encourage fermentation (coffee bean pods are literally placed in heaps and encouraged to get hot), and while the pods are washed and processed, possibly they contain trace amounts of yeast antigens in the end product. I wonder if when sensitivity testing is done, it is possible that folks do *not* react to the native protein in the product, i.e. cocoa or coffee proteins, but they *do* react in the real world to tag-along yeast proteins. I tested negative for cocoa, but positive for yeast in IGG tests, and have always noticed flare-ups of symptoms after chocolate consumption, even non-dairy chocolate chips, darn it! Because of cyclical cravings, parsing out the science on this one has always been on my radar, to see if it would be possible to consume somehow without triggering reactions. Likely not, although I’d love if someone could come up with a yeast-free way of producing coffee and chocolate to give it a try :)

Thanks!

It’s certainly possible. Most of the natural yeasts are typically a different strain, but still saccharomyces genus. I would think that this would probably affect a very small percentage of people with gluten sensitivity (yeast is one of the weaker cross-reactors and then you would have to have antibodies that recognize several species of yeast).

Hi Kelly,

Another issue wrt cacao, chocolate and coffee is MOLD! The majority of products contain mold! Lindt chocolate does not. You might try that and see if it works for you. The very dark versions probably don’t have dairy. You can get mold-free coffee and cacao from Upgradedself.com

Curious to know if vinegars, ie balsamic, red wine…, are problematic and should be avoided on the AI protocol? Also, maybe more importantly, I have an issue with not producing adequate HCl. I am currently taking HCl with pepsin supplements and a digestive enzyme prior to meals. I have read conflicting information about these supplements, where some experts say they are necessary for a period of time, and others say they should be avoided. What are your thoughts in taking these in conjunction with the AI Protocol?

The only vinegar that should be avoided is malt vinegar due to gluten. I think that HCl supplements and/or other digestive support supplements can be very helpful for those on the auotimmune protocol. I always recommend checking with your doctor before taking HCl supplements because they are contraindicated in a variety of conditions (like eosinophilic esophagitis, history of ulcers, blood clotting disorders, etc.) in which case, digestive enzymes is a great alternative.

Is the soy in multivitamins (e.g. Pure Encapsulations Nutrient 950 w/ vit K2) a concern?

I do my best to stay away since it is a gluten cross reactive food that I am still trying to find out if I am sensitive to.
Just curious if it is not a problem when extracted from soy to make vit E in vitamins? I have not found any valid data for either side.

The only good quality multivitamin that I can find that is soy free, etc. with Vit K2 and Folate. Is Dr. Ron’s Ultra Pure: Doc’s Best the next generation. It is a bit expensive.

It depends a little on exactly what is being used (soy oil, soy lecithin, tocopherols from soy, etc.) and how sensitive you are. I’m very sensitive, so I work hard to avoid it, but most people are okay, especially with these very isolated compounds (the soy oil is high omega-6 so that’s probably the worst of the bunch in terms of frequency of reactions).

Thanks for the quick reply!
It is tocopherols from soy. Appreciate the clarification. My body works much better on a multi. I have border line thyroid issues and it keeps me in check.

I’ve been looking for this post for days as I read it recently and couldn’t find it again. I am wondering if you’ve rewritten and expanded it though B/C the post I read was much longer and went into more detail about the acutal cross-reactivity process of specific non-gluten containing foods.

Regarding the testing for the cross-reactivity: What kind of practitioner would order these cryex tests and how to find one?

Thanks in advance

I believe this is the post you are looking for: http://www.thepaleomom.com/2013/03/gluten-cross-reactivity-update-how-your-body-can-still-think-youre-eating-gluten-even-after-giving-it-up.html Sarah recommends both http://www.paleophysiciansnetwork.com and http://www.primaldocs.com as excellent directories for finding qualified health professionals in your area (and many of which can work with patients long distance). — Tamar, Sarah’s assistant

Julie, another source to help you locate a Certified Gluten Practitioner is http://www.thedr.com. This is the website of Dr. Tom O’Bryan, who is probably one of the most knowledgeable doctors regarding gluten related disorders you will ever run across. He even did a week-long webinar—called the Gluten Summit—in which he featured interviews with 28 of the world’s leading specialists on the subject. On his site, click the tab that says Certified Gluten Practitioners and you can enter your zip code to find one near you. These doctors should be very familiar with the Cyrex tests and utilize them in their practice.

Hi
Great blog. Is it ok to introduce in diet eggs, brown rice or groats after 2 month period of time on AIP? If it doesn’t call any sympthoms that means it’s ok to eat?

I just left some questions about edible foods on the post about the elimination diet. And now I am reading that you say no to sauerkraut? So all the eczema website say to eat this to restore good gut bacteria. I also started drinking apple cider vinegar?

So I’m thinking I should just eliminate everything? And start with the basics (your list that is)? This seems so hard to do without an idea of what to make…at least a guideline of ideas. So like I said earlier, if you know any please pass that along.

I feel that I should just start a juice fast…lol!

Thanks so much!

Sarah recommends starting with the autoimmune protocol (http://www.thepaleomom.com/autoimmunity/the-autoimmune-protocol) and then only making additional restrictions if the AIP does not seem to be working after 30-90 days. Not everyone is sensitive to gluten cross-reactive foods. You can find a more recent version of this post with an updated list here: http://www.thepaleomom.com/2013/03/gluten-cross-reactivity-update-how-your-body-can-still-think-youre-eating-gluten-even-after-giving-it-up.html — Christina, Sarah’s assistant

I’m pretty confused and find this a bit overwhelming in the UK we have stricter laws around food so I eat glutenfree oats with no problem at all would you advice cutting them out still? but our dr’s do not see leaky gut as a real thing so they will not do tests against it. I have bile reflux disease for no reason I do not eat gluten dairy or eggs so I was wondering what is there to eat for breakfast!?

Gluten-free oats, along with other grains and pseudograins, are not considered Paleo. Sarah recommends treating breakfast just like lunch or dinner. Soup, leftovers, and sausage patties are great breakfasts. – Christina, Sarah’s assistant

Hi,
I am investigating GAPS and auto immune protocol at the moment. I am pretty sure I have a fairly rampant case of SIBO and am being treated by my homeopath for Hypo thyroid. I am gluten, sugar, soy and grain free and am about to implement Auto immune protocol restrictions as of next weekly food shop.
I have a persistent case of Lichen Planus that my homeopath is having trouble getting rid of. It took years to diagnose and I was told by the skin specialist that there is a small risk of it turning cancerous if not treated (she wants me on steroids).
Do you know if any one of your cross reactions causes yours to flare up or is it personal to each individual?
I eat my homemade sauerkraut, kimchi, milk kefir (which I will switch to coconut kefir after reading today), kombucha. I have dehydrated water kefir granules that I will rehydrate and I make spelt sour dough for the kids.
What do you eat/drink to keep your fermented foods up now that you can’t have kombucha or lactofermented vegies? Oh, I hope I don’t react. I have been off yeast for years due to its link with candida in me so it most probably is a culprit.
I am in Australia so will need to see if I can get a Cyrex test.
Once my gut is healed, can I expect cross reactions to disappear or will they be a never more food like gluten? How strong is the link between these proteins and gluten in the long term in a healthy person? I can do no coffee, would prefer to be able to eat my homemade chocolate but my fermented foods……No!
Thankyou

I appreciate the information, as I have been following the AIP diet for over a month and still having flares (though much less frequently). I will be honest and say that I am battling depression over my limited food choices. Just when I start to find foods that I enjoy- they seem to end up later on the do not eat list. I’m not sure if others feel as I do, but I had to throw it out there. I hope I can regain some of my energy to maintain this lifestyle for my health. Today is one of those days where I want to throw in the towel. It would greatly help too if more AIP recipes would not include these items. Thank you.

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