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

March 13, 2013 in FAQ, FAQ, Foods in Moderation, Gut Health, The Autoimmune Protocol, The WHYs of the AIP

The Paleo Approach by Sarah BallantyneIn my research for The Paleo Approach, I feel that it is important to provide scientific references for every single statement I make.  This has me doing a great deal of fact checking, scouring the medical literature to verify information often gleaned from other paleo authors and bloggers.  Most of the time what I find out just helps reinforce concepts, filling in blanks, and typically making a strong case for my assertions.  But, every once in a while, I find information that makes me completely reevaluate a concept and sometimes even an aspect of the autoimmune protocol.

The update for this blog post comes from my further examination into the science behind gluten cross-reactivity.  While there are plenty of papers confirming how cross-reactive antibodies can be formed, I could not find any published studies confirming the results from Cyrex Labs (and my motto with the paper is if I can’t cite it, I don’t say it).  I contacted the company to request further information (I was particularly interested in the reported cross-reactivity to tapioca as I was trying to decide whether or not tapioca starch and/or pearls should be included in The Paleo Approach).  Cyrex labs responded quickly and informatively and my level of esteem for that company (which was high to begin with) elevated another couple of notches.  While they were unwilling to share proprietary data with me, they were able to point me to a recent publication that evaluated gluten cross-reactivity and share a summary of their proprietary findings (the paper did not show up on my PubMed searches).  As I devoured the paper (figuratively, not literally), I realized that an update to this post was required.  This is not an excerpt from The Paleo Approach but it is a direct result of my research for the book and much of the information that follows is still presented in it.

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 intolerant or have celiac disease, i.e., have formed antibodies against gluten.

A recent study evaluated the potential cross-reactivity of 24 food antigens.  These included:

  • Rye
  • Barley
  • Spelt
  • Polish Wheat
  • Oats (2 different cultivars)
  • Buckwheat
  • Sorghum
  • Millet
  • Amaranth
  • Quinoa
  • Corn
  • Rice
  • Potato
  • Hemp
  • Teff
  • Soy
  • Milk (Alpha-Casein, Beta-Casein, Casomorphin, Butyrophilin, Whey Protein and whole milk)
  • Chocolate
  • Yeast
  • Coffee (instant, latte, espresso, imported)
  • Sesame
  • Tapioca (a.k.a. cassava or yucca)
  • Eggs

They did not find cross-reactivity with all of these foods (as is implied by the Cyrex Labs gluten cross-reactivity blood test, a.k.a. Array 4).  But, they did find that their anti-gliadin antibodies (antibodies that recognize the protein fraction of gluten) did cross-react with all dairy including whole milk and isolated dairy proteins (casein, casomorphin, butyrophilin, and whey)—this may explain the high frequency of dairy sensitivities in celiac patients—oats, brewer/baker’s yeast, instant coffee (but not fresh coffee), milk chocolate (attributable to the dairy proteins in chocolate), sorghum, millet, corn, rice and potato.

While not all people with gluten sensitivities will also be sensitive to all of these foods, they should be highlighted as high risk for stimulating the immune system.   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 corn used in so many foods and even the trace milk proteins that can be found in ghee.

Beyond this gluten contamination is common in the food supply and many grains and flours that are inherently gluten free may still contain gluten once processed.  Commonly contaminated grain products include millet, white rice flour, buckwheat flour, sorghum flour, and soy flour.  As these are commonly used ingredients in commercial gluten-free baked goods, extreme caution should be exercised.

Cyrex Labs offers a simple blood test that is referred to as their gluten ross-reactivity panel, a.k.a. Array 4.  It tests for reactions to the gluten cross-reactors mentioned above as well as the non cross-reactors evaluated in the paper.  Cyrex Labs reported to me that they see positive sensitivities frequently (many as high as 25%) in many of those foods in people with diagnosed gluten sensitivity.  This may reflect that when you have a leaky gut, food intolerances are quite easy to form.

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.

When I first wrote this blog post, it made so many pieces of the puzzle come together.  I stopped eating chocolate (I had already given up coffee), fermented foods like sauerkraut and kombucha (because of the yeast content), eggs, and tapioca.  Over the months that followed, I was able to definitely discern that I am very sensitive to chocolate (perhaps because it is extremely high in phytic acid, discussed in this post) and eggs (discussed in this post).  I have successfully reintroduced fermented foods and have not been particularly inspired to test my sensitivity to tapioca (I test by eating a bit and seeing if I have a reaction, most typically my reactions are acne, but sometimes trouble sleeping, mood issues, joint aches, or increased itchiness and redness of my lichen planus lesions).  So, will I give coffee a try now?  Maybe, once in a while as a special treat, but removing gluten cross-reactivity from the list of ways coffee is suboptimal, really only removes one potential problem.  Coffee still has effects on cortisol and still correlates with increased inflammation.  Oh well.  Whether I can drink coffee again or not, I am glad to be able to share this updated information with all of you!

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

A. Vojdani and I. Tarash, “Cross-Reaction between Gliadin and Different Food and Tissue Antigens,” Food and Nutrition Sciences, Vol. 4 No. 1, 2013, pp. 20-32.  http://www.scirp.org/journal/PaperInformation.aspx?PaperID=26626

Thompson T et al. Gluten contamination of grains, seeds, and flours in the United States: a pilot study. J Am Diet Assoc. 2010 Jun;110(6):937-40. doi: 10.1016/j.jada.2010.03.014.

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The WHYs behind the Autoimmune Protocol: Alcohol

November 8, 2012 in Foods in Moderation, The WHYs of the AIP

Alcohol is restricted in the paleo diet autoimmune protocol; and for those of us with autoimmune disease, it can feel like there are no pleasures left!  My inner monologue goes something like this “Seriously, first I give up grains, legumes, dairy, modern vegetable oils and refined sugar.  THEN, I give up eggs, nightshades, nuts, seeds, coffee and chocolate.  And NOW you want me to give up my wine?!  I thought red wine was supposed to be good for me! Waaaaaaah”

Moderate consumption of alcohol (not just red wine) seems to provide diverse health benefits; including reducing the risk of cardiovascular disease 1, reducing the risk of developing type II diabetes 2, preventing Alzheimer’s disease 3, and it may even reduce the risk of some cancers 4. (Don’t get too excited about the cancer prevention piece… moderate alcohol consumption also increases the risk of other cancers.)  While alcohol is not technically paleo, there is certainly evidence that prehistoric man would have imbibed fermented fruit and probably got pretty darned stinkin’ drunk from time to time.  Almost every version of the paleo diet condones low to moderate consumption of alcohol (usually restricted to gluten-free alcohols, so mainly wine and spirits), including Prof. Loren Cordain and Robb Wolf.   It is a Neolithic pleasure that most people following a paleo diet still enjoy.

So, with all the research supporting that moderate consumption of alcohol (especially wine) is healthy, why is it then a problem for those with autoimmune disease?  Once again, it boils down to the fact that those with autoimmune disease have more sensitive systems and face more challenges to healing a leaky gut than others.

Alcohol consumption directly causes an increase in intestinal permeability (i.e., a leaky gut) 5.  Alcohol unravels the tight junctions and adherens junctions that glue the cells that line the gut (called gut epithelial cells or enterocytes) together to form the  barrier between the inside of the gut where undigested food and bacteria live and the inside of our body.  Effectively, alcohol creates little holes between the gut epithelial cells.  It does this through several mechanisms 5.  Importantly, the “holes” that alcohol makes in the gut epithelial barrier are known to be big enough to allow some very large molecules into the body, most notably endotoxin.  Endotoxin is a toxic protein derived from the cell walls of gram-negative bacteria, such as E. Coli, which live in our guts (usually in the large intestine, but often in the small intestine in those people with autoimmune disease).  As these bacteria die (as part of their normal life cycle), endotoxin is released.  If it gets into the blood stream, it stimulates systemic inflammation, stimulates the immune system, and damages the liver 5.

Normally the majority of bacteria that grow in our guts are gram-positive bacteria (although some gram-negative bacteria is normal).  What does gram-negative and gram-positive mean?  This refers to a staining technique that differentiates between these two major classes of bacteria.  Basically, gram-negative bacteria have more complex cell membranes/walls and these tend to be pathogenic (i.e., they cause disease).  E. coli is an example of a gram-negative bacteria.  Lactobacillus (the probiotic found in supplements, yogurt and fermented vegetables) is an example of a gram-positive bacteria.  So, here’s the kicker:  alcohol consumption feeds gram-negative bacteria such as E. Coli to create bacterial overgrowths of these more toxic bacteria and therefore excess endotoxin production in the gut.  Excessive alcohol consumption is also correlated with gram-negative bacteria growing very high up the digestive tract, in the duodenum and sometimes even the stomach 5,6.

So, alcohol increases the production of endotoxin within the gut and increases intestinal permeability to endotoxin.  Another toxin that is produced by both gram-negative and gram-positive bacteria is called peptidoglycan (another component of the cell wall that is released into the gut when the bacteria die).  There is evidence that alcohol increases the permeability to peptidoglycan and that this toxin is very effective at stimulating the immune system and causing inflammation 5.

And that’s not all.  Even fairly small amounts of alcohol can damage the lining of the gut; specifically, alcohol leads to “mucosal damage in the upper small intestine with a loss of epithelium at the tips of the intestinal villi, hemorrhagic erosions and even hemorrhage in the lamina propria” 5.  If that sounded bad, that’s because it is.  It’s similar to the damage caused by gluten in celiac patients.

Most of the current understanding of the link between alcohol consumption and increased intestinal permeability (a.k.a. leaky gut) comes from studies of chronic alcohol consumption.  But, there are studies to show that this damage occurs even from a single drink.  Occasional drinkers basically don’t damage their intestines as much because they don’t consume as much alcohol at one time and they have more time for the guts to heal in between drinks.  This might lead to some adaptive mechanisms, which might be part of how low-to-moderate alcohol consumption can actually provide a health benefit.

So, what does this mean for those with autoimmune disease?  If you have autoimmune disease, you have a collection of genes that makes you more susceptible to developing a leaky gut and to having an exaggerated immune reaction to substances that leak out.  This means that anything that increases intestinal permeability should be avoided.

There’s some good news.  If you are being very strict with the autoimmune protocol, you are likely to tolerate an occasional drink (make sure to stay away from any grain-based alcohols though, especially beer and ale which contain gluten).  Chris Kresser puts the limit on one 5oz glass of wine twice per week (or equivalent amount of hard alcohol that is not derived from grains such as rum, tequila, sherry, cognac and brandy).  However, I advise avoiding all alcohol until you are starting to see some success on the autoimmune protocol. 

There’s some other good news.  It’s actually the alcohol that is the problem here, which means that cooking with wine or hard liquor (where the alcohol is burned off in the cooking process) is totally okay.  Well, with one more caveat:  some people are can be sensitive to the yeast content of wine (the yeast used in wine fermentation is a potential gluten cross-reactor) or can be sensitive to the the sulfites found in wine.

In summary, alcohol is not good for anyone dealing with leaky gut issues.  However, an occasional drink once your body is healing is probably okay.  Cooking with alcohol is also probably okay for most people, even if you don’t tolerate an actual drink.  But once again, I do urge caution as you experiment to find where your individual line is.

1 http://www.sciencedaily.com/releases/2011/02/110222192913.htm

2 Mekary RA et al “Joint association of glycemic load and alcohol intake with type 2 diabetes incidence in women” Am J Clin Nutr December 2011 ajcn.023754

3 http://www.jsonline.com/features/health/50590097.html

4 http://www.theatlantic.com/health/archive/2012/01/the-truth-about-breast-cancer-and-drinking-red-wine-or-any-alcohol/251171/

5 Purohit V et al “Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences” Alcohol. 2008 August; 42(5): 349–361.

6 Sekirov I et al “Gut Microbiota in Health and Disease” Physiol Rev, 2010 July; 90( 3): 859-904

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The Great Dairy Debate

October 13, 2012 in FAQ, Foods in Moderation, The WHYs of the AIP

The value (or lack thereof) of dairy products is the second most fiercely debated topic within the paleo community (after carbohydrate intake).  Opinions vary dramatically from consumption of no dairy whatsoever, to only consuming dairy fat (such as ghee, butter and heavy cream), to only consuming raw grass-fed dairy, to only consuming fermented dairy or aged cheeses, to including any dairy on a regular basis.

The reason for this diversity of opinions is that the science is not clear cut.  There are strong arguments to be made both for and against.

Let’s start with the arguments against dairy.  Prof. Loren Cordain dedicates an entire well-cited chapter in his most recent book The Paleo Answer (a fantastic book for describing the nitty gritty scientific details behind the paleo diet) to the many reasons why milk should not be consumed in any form.  To summarize, what I view the strongest parts of this argument:

  • Milk is not as nutrient-dense as meat, fruits and vegetables.
  • Milk is highly insulinogenic, meaning it causes a large spike in blood insulin levels, disproportional to the amount of sugar and protein in milk.  This may contribute to the development on insulin resistance, at least in the context of a high carbohydrate diet.  Insulin is also pro-inflammatory.
  • Milk contains active bovine (cow) hormones which have the potential to alter our hormone levels.  The effects of dietary intake of most of these hormones have not been studied.  However, other hormones have been studied.  For example, the milk hormone Insulin-like Growth Factor-1 (IGF-1) has been linked to risk of breast, colorectal and prostate cancer, with the strong indication that consumption of dairy protein is a large contributor to blood IGF-1 levels 1.
  • Milk contains protease inhibitors which may contribute to the development of a leaky gut (see this post for a more in depth explanation as to why)
  • Milk increases mucus production.  This may aggravate conditions such as asthma but also creates excess mucus in the gastrointestinal tract which may irritate the gut lining and inhibit nutrient and mineral absorption.
  • Lactose is poorly tolerated by adults.  Approximately 25% of Caucasians (American and European) are lactose intolerant.  97% of Native Americans are lactose intolerant.  This argument does not apply to drinking raw milk since raw milk contains enzymes to help digest lactose.
  • Dairy is highly allergenic.  This is where I believe the chief argument against dairy lies and I will discuss this further below.

There are also some very compelling arguments for including dairy products in our diets.  Studies have shown that consumption of dairy, especially full-fat dairy products and fermented dairy products, can protect against Metabolic Syndrome (cheese, full-fat dairy, and fermented dairy), Type II Diabetes (fermented dairy only) and Cardiovasular Disease (cheese, full-fat dairy, and fermented dairy) 2-6.

Grass-fed dairy, especially the fat from grass-fed dairy, is an excellent source of fat-soluble vitamins and Conjugated Linoleic Acid, an anti-inflammatory and healing fat.  Fermented dairy is an excellent source of probiotics.  There are also some valuable proteins in dairy, such as glutathione (very important for reducing inflammation and protecting against oxidative stress) and whey (which may help prevent cancer).

There is also evidence that dairy proteins are beneficial for children due to their growth-promoting effects.  Traditionally, children would have received some breast milk until approximately 5 years of age.  In our current society, most children are weaned by age 1.  The current scientific view is that, provided cow’s milk is not introduced too early, it is a good substitute for human milk in terms of its growth promotion 7.

Yes, the science is not clear, although there seems to be a good case for including dairy fat in our diets.  This is why the standard paleo diet allows for ghee and butter, and in many cases heavy cream and full-fat sour cream.  Many people also include fermented dairy in their diets with great success.

However, one thing that is abundantly clear is that milk allergy is common.  Beyond lactose-intolerance, which can be treated with the aid of digestive enzymes or consumption of raw milk, allergy to milk proteins is very common.  Epidemiological reports of cow’s milk allergy (IgE antibody reactions to cow’s milk proteins) range between 1 and 17.5% in preschoolers, 1 and 13.5% in children ages 5 to 16 years, and 1 to 4% in adults 8.  It is not known how prevalent cow’s milk sensitivities are (IgA and IgG antibody reactions to cow’s milk proteins).  It’s important to note that goat’s milk is not as allergenic as cow’s milk.

Cow’s milk proteins are also known gluten cross-reactors, which means that those with gluten intolerance may produce antibodies against gluten that also recognize dairy proteins.  For these people, eating dairy is the same as eating gluten (more information in this post).  Very importantly, for people with allergy, intolerance or gluten cross-reactions to dairy proteins, even the trace dairy proteins in ghee can be a problem.

So, what do I recommend?  Caution.  I believe that dairy is probably okay for many healthy adults, especially full-fat, grass-fed dairy.  In fact, for healthy individuals, the benefits likely outweigh the risks.  However, for those battling autoimmune disease or other conditions where a leaky gut is a potential contributing factor, it makes the most sense to omit dairy from your diet for now.  As is my standard recommendation for all of the gray-area foods, I suggest leaving it out of your diet for at least 1 month, then try reintroducing it and see if you notice any obvious symptoms (this is the best way to determine if you are allergic or sensitive).

I am still trying to gauge my own tolerance for grass-fed butter.  My daughters both seem to do better without cow’s dairy in their diets (except grass-fed butter, which seems okay), but I have reintroduced grass-fed goat mineral whey protein powder into their diets and they seem to do really well with that (especially my oldest).  I also have intentions to try them with some grass-fed goat’s whole milk.  This is another highly individual aspect of a paleo diet and you really don’t know whether or not milk is good for you until you try living without and then try living with.

1. Crowe FL et al “The association between diet and serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in the European Prospective Investigation into Cancer and Nutrition.” Cancer Epidemiol Biomarkers Prev. 2009 May;18(5):1333-40.

2. Louie JC et al “Higher regular fat dairy consumption is associated with lower incidence of metabolic syndrome but not type 2 diabetes.” Nutr Metab Cardiovasc Dis. 2012 Sep 26. pii: S0939-4753(12)00193-7. doi: 10.1016/j.numecd.2012.08.004. [Epub ahead of print]

3. Warensjö E, et al. “Biomarkers of milk fat and the risk of myocardial infarction in men and women: a prospective, matched case-control study.” Am J Clin Nutr. 2010 Jul;92(1):194-202. Epub 2010 May 19.

4. Sonestedt E et al. “Dairy products and its association with incidence of cardiovascular disease: the Malmö diet and cancer cohort.” Eur J Epidemiol. 2011 Aug;26(8):609-18. doi: 10.1007/s10654-011-9589-y. Epub 2011 Jun 10.

5. Sluijs I et al “The amount and type of dairy product intake and incident type 2 diabetes: results from the EPIC-InterAct Study.” Am J Clin Nutr. 2012 Aug;96(2):382-90. Epub 2012 Jul 3.

6. Bonthuis M et al. “Dairy consumption and patterns of mortality of Australian adults” European Journal of Clinical Nutrition (2010) 64, 569–577; doi:10.1038/ejcn.2010.45; published online 7 April 2010

7. Agostoni C and Turck D. “Is cow’s milk harmful to a child’s health?” J Pediatr Gastroenterol Nutr. 2011 Dec;53(6):594-600.

8. http://www.worldallergy.org/publications/WAO_DRACMA_guidelines.pdf

Chris Kresser has a terrific post Dairy: food of the Gods or neolithic agent of disease?

The Paleo Answer by Prof. Loren Cordain is an excellent resource.

 

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

October 4, 2012 in FAQ, FAQ, Foods in Moderation, Gut Health, The Autoimmune Protocol, The WHYs of the AIP

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

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