19 Gluten Cross-Reactive Foods Busted Myth

19 Gluten Cross-Reactive Foods Busted Myth

19 gluten cross reactive foods busted myth Christina Graves

Grain Free Diet Research

Graves, C.L. (2019). 19 Gluten Cross-Reactive Foods Busted Myth. Grain Free Research. The Paleo Foundation.

Busted Myth 19 Gluten Cross Reactive Foods

Grain Free Diet Research

Graves, C.L. (2019). 19 Gluten Cross-Reactive Foods Busted Myth. Grain Free Research. The Paleo Foundation.

Busted Myth 19 Gluten Cross Reactive Foods

November, 2019

GRAIN FREE RESEARCH

19 Gluten Cross-Reactive Foods Busted Myth

Christina L. Graves Ph. D  ¹  ORCID logo

 

¹ University of North Carolina at Chapel Hill | UNC · Department of Biology

 

Correspondence

Karen E. E. Pendergrass
 Department of Standards, Paleo Foundation, Encinitas, CA

Email: info@paleofoundation.org

 

Contact
¹ Twitter: @clgraves129

ABSTRACT

1. Numerous online blog articles report  ”19 Gluten Cross-Reactive foods. “

2. Close inspection reveals questionable conclusions and significant overstatement and extrapolation from the original sources of information.

3. Alternate conclusions presented within this blog article would call into question the existence of many blog-reported gluten cross-reactive foods.

4. Lessons about rigorous research and reporting of scientific data can be learned.

 

KEYWORDS

Cross Reactivity, Gluten

1 |   INTRODUCTION

 

There There have been a number of warnings issued about ’19 Gluten Cross-Reacting Foods’ repeatedly featured on a variety of popular and trusted health and diet blogs. [ 1, 2, 3 ]   The sheer number of articles that are circulating with the same information gives readers, naturopathic healthcare practitioners, patients, and the general public a sense of informational credibility and reliability. 

The basic gist of these articles is that there are approximately 19 foods that “cross-react” with gluten— that these other foods can mimic gluten.  This leads to your body reacting to these “cross-reactive foods” as if they were gluten, making these foods problematic for anyone who has a sensitivity to gluten (either Celiac disease or non-Celiac gluten sensitivity). In other words, if you are making antibodies to gluten, those same antibodies recognize other food proteins.

However, because there were 207 internet bloggers who have blogged about “gluten cross-reactive foods”, it must have been independently verified 207 times.  Instead, it appears that this did not happen, and that these are examples of blatant regurgitation and misreporting without scrutiny.

 

2    |   CROSS REACTIVITY

Cross-reactivity in immunology has been defined as the ability for antibodies or self-reactive immune cells to recognize and bind different but similar antigens. So, if proteins in one substance are very similar to the proteins in another substance, there can be an immunological reaction to both.  A good example of this is the Havein-like protein domains found in latex and bananas.  People who develop sensitivity to latex are often also sensitive to bananas because they contain similar proteins. [4

In the case of  “gluten cross-reactive foods,” the argument is that antibodies or cells recognizing wheat or gluten can also recognize other foods, such as eggs, chocolate, or coffee.

3    |   CELIAC DISEASE (CD) AND NON-CELIAC GLUTEN SENSITIVITY (NCGS)

About 1 in 133 people have Celiac disease, an autoimmune disease that damages the intestine. [5] The autoimmune reaction generates cells and antibodies which recognize gluten or gluten complexed with tissue transglutaminase (tTG)

The most common portion of the wheat gluten protein that is recognized is called α-gliadin. As a result of this, individuals with CD have cells which make anti-α-gliadin and anti-tTG antibodies (among others), and these are detectable using blood tests. CD is diagnosed with these blood tests along with a confirmatory intestinal biopsy.

Non-Celiac Gluten Sensitivity  (NCGS) is different.  In general those with NCGS test negative for these autoantibodies —  there is currently no biomarker or blood test to diagnose NCGS.  The paper discussed here specifically deals with antibodies specific to α-gliadin peptide. Therefore, this paper can potentially only apply to individuals with CD and NOT those with NCGS. You can’t have “gluten cross-reactive” antibodies without anti-gluten or anti-tTG antibodies to start with. Though the authors use the term “gluten sensitivity” in the paper discussed below, they are not referring to those with NCGS, and instead are using the term somewhat synonymously with CD. 

4    |   GLUTEN-ASSOCIATED CROSS REACTIVITY

The “gluten-associated cross-reactive” foods list has been compiled from the Cyrex Labs Array 4. The Chief Scientific Officer of Cyrex, Aristo Vojdani, also used the specific foods listed in the array as antigens in a publication assessing their reactivity to α-gliadin antibodies (Vojdani & Tarash 2013).

Most of the articles on gluten cross-reactive foods list all 18 foods covered on the Cyrex panel, extrapolating to say that all are or can be cross-reactive to gluten.  However, not all of these foods were determined to be gluten cross-reactive in their studies.  For example, hemp and potatoes were never demonstrated to be cross-reactive, or have the potential for cross-reactivity. 

In addition to these reporting errors, some individuals have added foods to this “gluten cross-reactive” list that doesn’t even show up in the conclusions of the original paper and have no additional citations, including sugar, “chemicals,” and GMO’s.

Further,  the panel does not appear to assess reactivity of α-gliadin specific antibodies to other foods, but rather measures direct IgG antibody production against those foods.

5    |   VOJDANI & TARASH 2013, CYREX LABS ARRAY 4

The following are the main highlights and conclusions of Vojdani & Tarash 2013 which deal with the “gluten cross-reactive foods” found on the Cyrex Labs Array 4.

RATIONALE

1. Some CD patients (~30%) continue to experience symptoms despite adopting a gluten-free diet (GFD).   [Note: they did not study those with NCGS]

2. The authors hypothesized if continued symptoms despite the adoption of a GFD could be caused by cross-contamination with gluten-containing foods or with cross-reactivity between α-gliadin (the main immunogenic epitope of wheat in celiac disease).

3. This study measured the reactivity of α-gliadin antibodies (both polyclonal and monoclonal) against α-gliadin and other food antigens using ELISA and dot-blot.

Cross-Reactive Foods and Food Antigens

METHODS

1. Purchased foods from the supermarket and processed them for study.  The left side of [TABLE 1] shows foods that were used for antigen testing. Note that the foods used are identical to the foods contained in the Cyrex Array 4 which then show up on every “19 gluten cross-reactive foods list.”

2. Polyclonal rabbit anti-α-gliadin antibodies were made from rabbits injected with α-gliadin.

3. Highly specific monoclonal mouse anti-α-gliadin antibodies were purchased from a commercial source.

4. Used indirect ELISA and dot blot analysis to assess cross-reactivity of polyclonal and monoclonal anti-α-gliadin antibodies to food proteins.

RESULTS

In FIGURE 1 and 2 (using polyclonal and monoclonal antibodies respectively), the authors asked whether certain food proteins would be recognized from antibodies specific for anti-α-gliadin. They found high binding against α-gliadin (positive control).

They also found binding “…against α– + β-casein, followed by yeast, casomorphin, oat cultivar #2, fresh corn, milk, millet, milk chocolate, instant coffee, rice, milk butyrophilin, and whey protein.” They did not find binding of oat cultivar #1, sesame, buckwheat, sorghum, hemp, amaranth, quinoa, tapioca, teff, soy, egg, and potatoes — foods commonly cited as “gluten cross-reactors.“ Note that only the mean for the assays (stated to be performed in quadruplicate) are reported, that “error bars” are not included, nor is there comment on whether the results were significantly different from the control.

By this standard, I could flip a coin, get tails 3/4 times, and conclude tails is 3 times as common as heads.

Scientific conclusions can only be trusted when tested to be true with statistical significance (typically p≤0.05).

no inhibition of soy no gluten cross reactivity

RESULTS ABSORPTION/INHIBITION STUDIES

The authors asked: can food proteins displace binding of the α-gliadin-specific antibody to α-gliadin? 

 

They used high (10mg/ml) and low (150 ug/ml) concentrations of the proteins.  At the high concentration, α-gliadin inhibited anti-α-gliadin antibody binding to plate-bound α-gliadin at 79% (this is the positive control). At the low concentration, no displacement was observed.  At higher concentrations, yeast, instant coffee, and casein appear to promote displacement of anti-α-gliadin antibodies to α-gliadin.  They also report no inhibition from soy at any concentration.

“The absorption with corn, yeast, millet, α– + β-casein, instant coffee and rice antigens inhibited the binding of α-gliadin 33-mer peptide to anti-α-gliadin 33-mer peptide by 27%, 26%, 23%, 21%, 16%, and 15%, respectively.”

 

STATISTICAL SIGNIFICANCE

While the authors report differences in the means, are they actually significant differences?  First, we need to evaluate what the specific hypotheses for this particular experiment are.

1. Null hypothesis: (Food) antigen X does not inhibit α-gliadin antibody binding relative to control.

2. Alternate hypothesis: (Food) antigen X inhibits α-gliadin antibody binding relative to control

Biologists typically use a threshold value of p ≤ 0.05, which is considered to be statistically significant, and p ≥ 0.05 as non significant (this threshold value may change depending on the application and appropriateness for a given assay). A p ≤ 0.05 means that if we assume the null hypothesis (no effect) to be true, the chance of getting a result at least as large as what was observed, is equal to (or less than) 5%. Therefore, if we get a very small p-value (under 5%), we can reject the null hypothesis because the frequency of seeing such results under this hypothesis is so small that it’s incompatible. Meaning these results are unlikely to occur under the null hypothesis/model. The smaller the p-value, the less consistent the results are with the null hypothesis. Therefore, we might accept the alternative hypothesis, which is likely to be more compatible with the observed results.

Observing  the “p-values” reported in Table 2:

Using the p ≤ 0.05 threshold, we can reject the null hypothesis for α-gliadin (outlined in blue, positive control). If we’re generous and we increase our threshold to p ≤ 0.1 (meaning the frequency of getting results at least this large under the null hypothesis is less than or equal to 10%), we can include yeast, millet, and corn.

p = 0.5 means that there is a 50% chance of getting results at least as large as what was observed under the null hypothesis of no effect. In other words, if we repeated this experiment several times, half of the time, we’d see differences at least this big, even if there was no actual effect.

This calls into question the interpretation of the results, because the results are so consistent with the null hypothesis of no effect. While the means of the assays (reported as a % inhibition) may have been reduced (indicating binding), there was apparently such high assay variability that it was not a significant difference from the control. Therefore, these results are consistent with the hypothesis of no effect, and consistent with the idea that the differences we see are due to chance. 

Dot blot analyses (Fig 8 and Fig 9 of the paper, using polyclonal and monoclonal antibodies respectively) showed slight staining (possibly indicating antibody reactivity) against instant coffee, corn, yeast, milk, α– + β-casein, millet, rice, milk butyrophilin and oats.

 

6    |   VOJDANI & TARASH 2013 CONCLUSIONS

No staining was observed with casomorphin, egg, pure coffee bean, cocoa, and sorghum.  A note on the dot blot experiment: polyclonal antibodies (used in Fig. 1 and 8) are notorious for yielding high background (i.e. not real) signal. [6]

 

Secondary lactose (milk sugar) intolerance is common  in people with CD. [7]  It has also been demonstrated that about 50% of CD patients (who do not get better on a GFD alone) can have a specific mucosal response to cows milk, with casein being the likely culprit. [8]

Antibodies to milk proteins can be elevated for some people; these responses have not been demonstrated to be due to mimicry or cross-reactivity. [9] As Vojdani & Tarash 2013 cite, there is some computational data to suggest that these antibodies may cross-react, and some of their own data might also suggest that is the case. [10]

 

COFFEE

Instant coffee often contains gluten. Be aware of labels which state “may contain traces of gluten.”

 

OATS

Some oats contain gluten. We already knew this, since, though they are different plants, and oats do not contain gluten, they are processed together, and therefore are often contaminated with wheat/gluten/α-gliadin. If you do eat oats, you should make sure they are tested to be gluten-free; even being processed in an oat-only facility may not be enough. [11]

People with Celiac disease may also have T-cell specific reactions to the oat prolamine avenin.

Monoclonal antibodies against γ-gliadin (not α-gliadin antibodies like are used in this study) can react to oat avenin. [12]

However, avenin is not proline-rich like gliadin and therefore is able to be better degraded by GI tract enzymes, and this lessens potential immune reactions. Additionally, studies looking at immune activation in the small intestines of Celiac disease patients (following a GFD) failed to show histological consequences of immune activation following oat consumption. [13]

However, some studies do demonstrate oat-specific responses particularly in patients with complicated Celiac disease, although these are typically not large or randomized studies. [14]  Moreover, the variety of the oat can make a difference, and this was reported in Vojdani & Trash 2013. [15]

 

YEAST

Vojdani & Tarash 2013 conclude that they “don’t know” whether the reaction they observed is a true cross-reaction or if the yeast used is contaminated with gluten. In these experiments, Brewer’s and Baker’s yeast appear to be combined when cross-reactivity was assessed.

 

CHOCOLATE

Reactivity was noticed with milk chocolate (see results from milk section). There was no reaction with pure cocoa or milk-free dark chocolate. Note that many milk chocolate products can be cross-contaminated with wheat, so it’s important to purchase chocolate that has been certified grain-free and gluten-free.

SOY

As indicated in Figure 3, there was no inhibition of anti-α-gliadin antibody binding when soy was added. However, the dot blots and other data are potentially suggestive. The inconsistency of reported results (i.e. which foods are “gluten cross-reactive?”) is concerning.

Note that milled soy flour may be contaminated by gluten (the linked pilot study found more than 2,900 ppm of gluten in one product). [16]

 

MILLET

Vojdani & Tarash 2013 conclude (based on Figures 1 & 2 and 4 & 5) that “millet may not be a good substitute for gluten-containing grains for some individuals” suggesting that this is due to “gluten cross-reactivity.” It is important to note that milled millet often contains contaminating gluten — even on those products listed as gluten-free, or “naturally gluten-free.” [17]

This makes millet often unsuitable due to contaminating gluten, and not necessarily due to cross-reactivity. The authors note a reference stating “amylase inhibitor from barley had significant homology with millet” however this does not appear to have any direct bearing on the antibodies specific for anti-α-gliadin used in this study.

 

CORN AND RICE

These are briefly discussed in the conclusions of Vojdani & Tarash 2013, only to state that “We also obtained fresh corn on the cob and various rice

grains and observed significant immune reactivity…” and make mention of a lipid transfer protein with ” high cross-reactivity rate with various grains and vegetables.”

The cited studies appear to be specific for allergic (IgE-mediated) type reactions. Other studies have suggested that corn might be a problem for some people with Celiac disease, and some zein moieties are computationally predicted to have sequence similarity to α-gliadin. [18]

However, CD-specific antibodies don’t appear to cross-react to corn zein. The rice/gluten cross-reactive study cited by Vojdani & Tarash 2013 is specific for IgE mediated responses, whose dominant epitopes are different than the epitopes recognized by anti-α-gliadin antibodies presented in this study. [19]

 

7    |   DISCUSSION

Because extra-intestinal symptoms of CD have been reviewed in the scientific discourse [21], I will not be commenting on the portions of this paper discussing reactivity to tissue antigens.

 

8    |   CONCLUSIONS

Patients on a gluten-free diet should adhere to a zero-tolerance poicy. This requires not only abstinence even from ‘gluten-free’ foods, but also

reading labels carefully, checking for the country of manufacturing origin, and on-label statements such as “produced in a factory that also processes wheat, gluten, and dairy”.

However, The Celiac Disease Center does not currently recognize Enterolabs or Cyrex stool tests for cross-reactivity (or for CD for that matter). [20] Simply, they are “not sensitive or specific enough” and just haven’t held water (yet) in the scientific arena.

 

9   |   NOTE FROM THE AUTHOR

I would like to plead with the audience to take this post for what it is: a critical review of an article which has been misinterpreted and has spread throughout the blog-o-sphere like wildfire; it is intended to start a conversation. 

It is not a personal attack on the authors of the study, Cyrex labs, practitioners who use Cyrex labs, nor is it an attack on The Paleo Mom, whose work I very much appreciate and admire.  I am very much open to continued discussion on the methods, conclusions, and results of the particular paper discussed here, as well as links to any scientific and peer-reviewed articles. I also don’t want this post to detract from legitimate arguments concerning the avoidance of some of the foods on the Cyrex Array 4 list. I believe it is true that “gluten-free isn’t always enough” and this is true for those with CD as well as NCGS.

There are many reasons to avoid other foods than gluten, and it is relatively easy (and cheap) to determine other foods you are sensitive to using a food journal and food rotation diet.  I myself am

diagnosed with NCGS, and have found symptom relief from several autoimmune and autoinflammatory diseases with a gluten-free diet and also with the avoidance of sugar, non-gluten-containing grains, alcohol, and other foods – some of which are on the Cyrex Array 4.

My only purpose is to highlight the importance of being rigorous with our own research and reporting within the ancestral health community and to highlight that the rationale for the avoidance of some foods may have arrived through the inflated interpretation of inconclusive results.

Scientific research is only beginning to reveal the intricacies of “leaky gut” and how it may promote the development of or exacerbate autoimmunity — and only time, clever questions, and intelligently designed experiments will yield fruitful results to push forward clinical and scientific dogma.

 

10   |   REFERENCES

1. Ballantyne, Sarah. (March 13, 2013). Gluten Cross-Reactivity: How your body can still think you’re eating gluten even after giving it up. Retrieved from https://www.thepaleomom.com/gluten-cross-reactivity-update-how-your-body-can-still-think-youre-eating-gluten-even-after-giving-it-up/

2. Myers, Amy. (N.D.) Are You Not Healing Because Your Body Thinks Coffee, Chocolate & Cheese Are Gluten?  Retrieved from https://www.mindbodygreen.com/0-7875/are-you-not-healing-because-your-body-thinks-coffee-chocolate-cheese-are-gluten.html

3. Perlmutter, David. (N.D) Gluten Associated Cross Reactive Foods. C https://www.drperlmutter.com/eat/foods-that-cross-react-with-gluten/

4. Frank SA. Immunology and Evolution of Infectious Disease. Princeton (NJ): Princeton University Press; 2002. Chapter 4, Specificity and Cross-Reactivity. Available from: https://www.ncbi.nlm.nih.gov/books/NBK2396/

5. Adams, Jefferson. (March 30, 2009). Celiac Disease Statistics. Retrieved from https://www.celiac.com/articles.html/celiac-disease-statistics-r1147/

6. Abcam. (N.D) What are polyclonal, monoclonal and recombinant antibodies? Retrieved from https://www.abcam.com/protocols/a-comparison-between-polyclonal-and-monoclonal

7. Plotkin, G. R., & Isselbacher, K. J. (1964). Secondary Disaccharidase Deficiency in Adult Celiac Disease (Nontropical Sprue) and Other Malabsorption States. New England Journal of Medicine, 271(20), 1033–1037. doi:10.1056/nejm196411122712003 

8. Kristjánsson, G., Venge, P., & Hällgren, R. (2007). Mucosal reactivity to cow’s milk protein in coeliac disease. Clinical & Experimental Immunology, 147(3), 449–455. doi:10.1111/j.1365-2249.2007.03298.x 

9.  Scott HFausa OEk JBrandtzaeg P. (1984). Immune response patterns in coeliac disease. Serum antibodies to dietary antigens measured by an enzyme linked immunosorbent assay (ELISA). Clin Exp Immunol. Jul;57(1):25-32.

10.  Darewicz, M., Dziuba, J., & Minkiewicz, P. (2007). Computational Characterisation and Identification of Peptides for in silico Detection of Potentially Celiac-Toxic Proteins. Food Science and Technology International, 13(2), 125–133. doi:10.1177/1082013207077954 

11.  Thompson, T. (2004). Gluten Contamination of Commercial Oat Products in the United States. New England Journal of Medicine, 351(19), 2021–2022. doi:10.1056/nejm200411043511924 

12.  Mitea, C., Kooy-Winkelaar, Y., van Veelen, P., de Ru, A., Drijfhout, J. W., Koning, F., & Dekking, L. (2008). Fine specificity of monoclonal antibodies against celiac disease–inducing peptides in the gluteome. The American Journal of Clinical Nutrition, 88(4), 1057–1066. doi:10.1093/ajcn/88.4.1057 

13.  Srinivasan, U., Jones, E., Carolan, J., & Feighery, C. (2006). Immunohistochemical analysis of coeliac mucosa following ingestion of oats. Clinical and Experimental Immunology, 144(2), 197–203. doi:10.1111/j.1365-2249.2006.03052.x 

14.  Arentz-Hansen, H., Fleckenstein, B., Molberg, Ø., Scott, H., Koning, F., Jung, G., … Sollid, L. M. (2004). The Molecular Basis for Oat Intolerance in Patients with Celiac Disease. PLoS Medicine, 1(1), e1. doi:10.1371/journal.pmed.0010001 

15.  Comino, I., Real, A., de Lorenzo, L., Cornell, H., Lopez-Casado, M. A., Barro, F., … Sousa, C. (2011). Diversity in oat potential immunogenicity: basis for the selection of oat varieties with no toxicity in coeliac disease. Gut, 60(7), 915–922. doi:10.1136/gut.2010.225268 

16.  Thompson, T., Lee, A. R., & Grace, T. (2010). Gluten Contamination of Grains, Seeds, and Flours in the United States: A Pilot Study. Journal of the American Dietetic Association, 110(6), 937–940. doi:10.1016/j.jada.2010.03.014 

17.  Thompson, T., Lee, A. R., & Grace, T. (2010). Gluten Contamination of Grains, Seeds, and Flours in the United States: A Pilot Study. Journal of the American Dietetic Association, 110(6), 937–940. doi:10.1016/j.jada.2010.03.014 

18.  Cabrera-Chávez, F., Iametti, S., Miriani, M., de la Barca, A. M. C., Mamone, G., & Bonomi, F. (2012). Maize Prolamins Resistant to Peptic-tryptic Digestion Maintain Immune-recognition by IgA from Some Celiac Disease Patients. Plant Foods for Human Nutrition, 67(1), 24–30. doi:10.1007/s11130-012-0274-4 

19.   Denery-Papini, S., Bodinier, M., Larré, C., Brossard, C., Pineau, F., Triballeau, S., … Moneret-Vautrin, D.-A. (2012). Allergy to deamidated gluten in patients tolerant to wheat: specific epitopes linked to deamidation. Allergy, 67(8), 1023–1032. doi:10.1111/j.1398-9995.2012.02860.x 

20.   Celiac Disease Center. (2013) Frequently Asked Questions. Retrieved from http://www.cureceliacdisease.org/faq/why-dont-you-recognize-tests-stool-tests-or-otherwise-for-gluten-sensitivity-that-are-currently-available-through-companies-like-enterolab-or-cyrex/ 

21.   Hadjivassiliou, M., Williamson, C. A., & Woodroofe, N. (2004). The immunology of gluten sensitivity: beyond the gut. Trends in Immunology, 25(11), 578–582. doi:10.1016/j.it.2004.08.011 

Comments

comments

42 Responses

  1. B says:

    Thank you, that was an awesome read!

  2. Follydarling says:

    Here is something no one ever documents people with Ornithine Transcarbamylase Deficiency (an inborn error of metabolism) suffer from damaged villi just like people with Celiac Disease. OTCD patients are unable to properly digest proteins efficiently including gluten. Therefore gluten causes us digestive problems. People many not know they have OTCD and may be gluten intolerant.

    I wish if people are going to write about gluten and list the related disorders they would list OTCD that also damages the villi. I have the disorder and the problems that occur are quite frustrating and documented very well in scientific papers.

  3. Christian Wernstedt says:

    Great analysis!

  4. Thanks – a great analysis.

  5. Dame Liberty says:

    Well done! Now, could you please tackle ‘adrenal fatigue’? It’s all over the paleosphere with hardly a legit citatation in sight.

  6. Dear Ms. Graves;

    First, I would like to compliment you on the fantastic job you did in bringing to light the rampant misinterpretations that have been flooding the internet regarding my work.

    As a doctoral candidate and an internet blogger yourself, you must know that there is a vast difference between an internet blog and a publication in a peer-reviewed scientific journal. I presume you are aware of the rigors involved in successfully submitting a manuscript to a scientific journal.

    I stand with you in cautioning sufferers that merely because 207 bloggers agree on something doesn’t necessarily make that thing true. I would advise the discerning reader to not be satisfied with mere summaries, but to go the extra mile and follow the links offered by these helpful bloggers as arrows pointing them to the actual source material, and to read them themselves.

    And as the primary author of the scientific article you adroitly summarized in your blog, and a member of the editorial boards of six different peer-reviewed scientific journals, I stand firm on everything I said in my article. It is one of almost 150 that I have published in peer-reviewed scientific journals and magazines in my 45 years of work on the role of environmental triggers in autoimmunity. As you actually point out in your blog, nowhere in my actual article do I ever actually claim that foods other than dairy, yeast, corn, oats, millet and rice were positively found to be cross-reactive with alpha-gliadin 33-mer. And to my knowledge, neither has Cyrex. In fact, I just recently applied the same monoclonal and polyclonal antibodies against alpha-gliadin 33-mer to an additional 150 different food antigens, and I can tell you that we found no additional cross-reactivities. It should be remembered that for the article being discussed we examined the cross-reactivity with antibodies made specifically against alpha-gliadin 33-mer, and we have no way of knowing what foods will cross-react with gamma-gliadin, omega-gliadin, glutenin, and gluteomorphins. For this, additional research is required.

    As scientists we have a moral responsibility to ensure that the research and conclusions we present is based on scientific evidence and fact. That is why you will see the words “may” and the phrases “evidence indicates” and “more research is required” in the conclusions of many scientific articles. The very nature of a blog allows for the introduction of personal opinion, bias and speculation to a degree that could never be tolerated in any scientific journal. I authored this article, for no monetary recompense and at no small expense, as I did my other articles, out of a desire to help sufferers of disease. I imagine bloggers have a similar motivation, and so, rather than being dismissive of blogs I would urge the happy balance of taking what the bloggers have to offer and then, as I have already said, reading the source material ourselves. To this end I advise readers to seek out my actual article on the internet, where it is freely available. And since, Ms. Graves, you never presented it in your blog, I advise readers to read the actual conclusions section from my article:

    Conclusions
    If a subgroup of patients on a gluten-free diet does not show improvement in their GI or other symptoms, attention should be given to dairy and other cross-reactive foods, such as yeast, corn, oats, millet and rice, as shown in the present study. If after adherence to a strict gluten-free diet and the elimination of cross-reactive foods symptoms still persist, further investigation for other food intolerances should follow.
    In the absence of the proper dietary elimination of gluten, the present study supports the hypothesis that if the high prevalence of antibodies against dietary proteins and peptides and their cross-reaction with various tissue antigens are not taken seriously, and if proper measures are not implemented, the result may be the development of autoimmunity in the future.

    Now look at this and, in fact, at the whole article, and tell me where it says we found 19 foods positively cross-reactive with gluten. Celiac disease, NCGS and autoimmune diseases are cause enough for confusion and distress already. Let us not add fuel to the fire but rather be discriminating, cautious and thorough in our quest for knowledge.

    • Gratitude says:

      We all owe you a debt of gratitude for your service to humanity. As a practitioner and a personal beneficiary of your life’s work, I stand witness to the benefits of your knowledge.

    • Marsha says:

      Thank you for your work and your comments here. Do you know if fermented dairy such as yogurt or fermented cheeses, or full-fat dairy like heavy cream are cross reactive? Everything I have read on this issue lumps all dairy together.

  7. Melissa says:

    This is a great post, thanks for writing something like this! I don’t see people questioning this stuff enough. I have seen this research cited improperly in a ton of blogs and sadly even some paleo books.

  8. Wendy Good says:

    Thank you for writing this out. The more dialog and intelligent challenging of accepted norms – whether for or against any issue – the more people will be driven to find the truth. Many people react negatively when something they believe is challenged. It is always best to challenge why we believe what we believe, regardless of what it is. Sometimes the answers may be a surprise.

  9. Krista says:

    Christina Graves, how about a response to the comment of Dr. Vojdani?

    • Christina Graves says:

      Hi Krista, I did not publicly respond to Dr. Vojdani’s comment because I did not (and still do not) feel that it requires a public response. I greatly appreciate the perspective that his comments and clarifications add to the discussion.

  10. Cristin says:

    Thank you so much for taking the time to compile this article.

  11. Rebecca says:

    Hi Krista,

    Great article. Can you recommend any resources for interpreting the results of Cyrex Array 2 – intestinal permeability screen?

  12. Rebecca says:

    Sorry, I meant to address the question above to Cristina graves.

    • Christina Graves says:

      Hi Rebecca,

      For readers who are unfamiliar, the Cyrex Array 2 (Intestinal Antigenic Permeability Screen) Includes results for circulating (i.e. in the blood):
      Actomyosin IgA
      Occludin/Zonulin IgG
      Occludin/Zonulin IgA
      Occludin/Zonulin IgM
      Lipopolysaccharides (LPS) IgG
      Lipopolysaccharides (LPS) IgA
      Lipopolysaccharides (LPS) IgM

      The only reference I can find to these tests are here, a recent paper by Vojdani.

      http://www.hindawi.com/journals/crigm/2012/265052/

      I can find no other peer-reviewed references to these tests, or any peer-reviewed publications which validate these tests against known markers of intestinal permeability.

      Circulating antibodies against food antigens and commensal bacterial products are found in healthy, normal individuals (http://www.pnas.org/content/84/8/2449.full.pdf) and what an “elevated” response is remains unclear. Moreover, IgA antibodies are often involved in tolerance, further complicating what an increase in these may be. If you have an antibody response to an antigen, it means you have had exposure to it. In some cases, inappropriate antibody responses can result in tissue damage (as in the case of an autoimmune disease).

      I can find no reference for Actomyosin IgA being associated with intestinal permeability (except for the previously linked paper). Actomyosin contractile ring is a component of the tight junction of the intestine (but it’s expression is not limited to the intestine), and the food that you eat or commensal bacteria in your gut can change expression of tight junctional proteins (which can then affect intestinal permeability). (ref: http://jn.nutrition.org/content/141/5/769.full)

      I can find no reference to antibodies against actomyosin (IgA or otherwise) as related to intestinal permeability, although it is documented to occur in patients with myasthenia gravis who also have thyoma (http://uh7qf6fd4h.search.serialssolutions.com/?sid=Entrez:pubmed&id=pmid:2323065).

      In my opinion, these tests are not the standard (or even validated) methods to test intestinal permeability. Verified measures of intestinal permeability include total serum LPS, lactulose/mannitol excretion (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2802677/), or circulating zonulin expression. Note that increased circulating LPS and zonulin and direct measures of these proteins are quantified and not the antibody responses to them (as is proposed in the Cyrex 2 array).

      My guess is that an antibody array (i.e. LPS IgA, Zonulin IgG, etc.) was chosen because most people will be “positive.” And that’s good for business. Again, in my opinion, what elevated antibody responses actually mean and whether they are true, validated measures of intestinal permeability remains unclear. (This is of course excepted for diseases for which these measures have been validated, such as antibody production against Ttg in Celiac Disease).

      If anyone has additional references either for or against these, please feel free to link. I am here to learn, as well, and am not afraid to recant incorrect statements. Moreover, I am not a practitioner – so I have never run these tests or used them to assess an ill patient.

  13. Susan92065 says:

    Is it also possible that gluten sensitive people may have harmed their intestines yo the point where digestion is simply impaired?

  14. dan says:

    Hi Christina,

    Thanks so much for this article. I recently read about these 19 cross-reactive foods, and was dreading trying to avoid them all.

    I have a question for you. Since being diagnosed with celiac disease 5 years ago, I have consistently tested positive for IgA antibodies every time I go to the doctor. the numbers are usually in the 30s or 40s. I am baffled by this as I am very strict about the GF diet, prepare my own meals from whole foods – meats, fish, vegetables, when I very rarely have to eat out I get steamed chicken and vegetables with no seasonings. I also strictly avoid dairy. I am out of ideas as to how to be more gluten free. Do you have any advice, or good resources you can point me towards? Thanks.

    Dan

    • Christina says:

      Hi Dan, first and foremost I am not a medical doctor so I can’t give medical advice. Is this testing done through a gastroenterologist or is this a stool test done through a naturopath’s office? (Many of the antibody tests that are marketed to naturopaths are not well validated). Are you having symptoms or just elevated antibodies? If you are still having symptoms, if were you I would also discuss the idea of Refractory Celiac Disease with your doctor, particularly if you went a very long time undiagnosed (i.e. you are middle aged and have had symptoms for a very long time). Also, the guys over at SCD lifestyle seem to be very knowledgeable in this arena – Jordan Reasoner has a similar story as you. http://scdlifestyle.com/

  15. Kristy says:

    This article is exactly what I was looking for.

    I finally managed to track down the original research as published by Vojdani & Tarash (coincidentally coming across the researchers’ names in a commenter’s post on a blog article), having felt pretty skeptical of the unsourced claims of various bloggers.

    I wasn’t really convinced. The research seemed pretty weak, and their conclusions didn’t hold much conviction.

    I’m glad to see that someone aware of statistical significance and research design agreed.

    The problem is that I’m not a biology major, and quite frankly had a hard time really understanding the methods the researcher’s were using or what they implied. Your breakdown assured me that my skepticism was warranted.

  16. Cristin says:

    Paleo Mom posted today on her FB page https://www.facebook.com/pages/The-Paleo-Mom/306461856045017 that potato is a gluten cross-reactor. Do you still disagree? When I questioned her on it, she pointed to this article she wrote: 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 I’m hoping to keep potatoes in my diet, and all the conflicting data is really confusing me.

    • Christina says:

      The ELISA data from the paper did not find that the potatoes cross reacted to alpha gliadin. The mean was less than 1 SD different from the negative control (not significantly different). Moreover, it does not state or imply in the paper that potatoes are cross reactive. Again, even if you accept the data presented in this paper, a true immunological cross reaction only applies if you are actively making antibodies and cell specific immune responses to alpha gliadin to begin with (i.e. celiac disease), and it doesn’t apply to NCGS, which there are no medically accepted tests for. From the paper: “…..while the immune reactions against oat cultivar #1, sesame, buckwheat,
      sorghum, hemp, amaranth, quinoa, tapioca, teff, soy, egg,
      and potatoes were less than 1 SD above the mean of the ELISA background OD”

  17. Dan says:

    Thanks. Great article. I confess to not understanding the science behind the claims or your analysis but I do painfully understand symptoms. I suffer dermatitis herpetiformis (or so the theory goes) and follow a strict gluten free paleo diet. After much trial and error I know that rice and corn are definite triggers and cross contamination with gluten is not the issue. I have no idea of the mechanism behind it… just the symptoms. n=1 is the only approach that has worked for me. While I do not understand the science I greatly appreciate those of you who do continuing to pursue this, as it is frustrating that the research is so scant..

  18. Linda says:

    Thanks for this article and all the research behind it. I have been personally involved in the whole food intolerance problem for many years and more recently with my son who had severe gastrointestinal problems as well as long term ezcema. The cross-reactive foods scenario was totally depressing when we were going through an elimination diet and so I ignored it. My experience is that if you have a leaky gut you will respond to other foods especially if used frequently. When we gave up dairy we consumed a lot more almond and cashew nut/ products and my son started to react to those but I did not. I stress in my blog that everyone has to find their own reactive foods and retest occasionally once the gut is healed. (But not gluten!)

  19. poll says:

    Thes a great analysis.

  20. A million thanks for this. I’m willing to be that voice in the Celiac community to say something. Tired of people scaring others to believe in lies!

  21. JosieJake says:

    Interesting, however, I am gluten and lactose intolerant. After eating eggs and rice I immediately have to lie down for several hours. It’s the same reaction I have to gluten and lactose only those items affect me the next day.

  22. I am embarrassed to say this is one of the first times to this site. If this is how you write, I am so in. I am impressed with the quality and information and will share this with my followers as well. I see my work plagiarized all of the time, so I get it. The information your brought forth is important, not only for the information itself, but also to caution people to do their own due diligence when choosing what they eat and eliminate from their diet. Many thanks for this excellent article. Excuse me now… I am going to have a cup of coffee.

  23. Susie says:

    It was my understanding as a user of the Cyrex 4 array, that I was also being tested for ingredients that I would use instead of the obvious wheat products. Like eggs and tapioca are used in place of wheat flour when you bake. Some of the items I tested for had nothing to do with cross-contamination. I am just a user of the test and through the test found out I couldn’t have quinoa and casein. I was pleased with my results. Would have never guess that I had a problem with quinoa.

  24. bevy says:

    I don’t have a very varied diet at this point. Gluten sensitive b’c of Hep C and allergic to dairy, chocolate (in any form), sugar and can only tolerate maple syrup and lots of honey. 🙂 But reading and starting to believe that the 19 foods would have to be avoided too would be too much for me. Mainly b’c what else can I eat??? I know – that’s ridiculous of me … but thanks for casting some dispersions on the so called research.
    🙂

  25. Maria Andreina says:

    Hi! English it is not my first language and i get lost with some details, I just want to know if Millet has a cross-reactivity with gluten. Can you please, help me? Thank u so much

  26. Maria Andreina says:

    Hi! English it is not my first language and i get lost with some details, I just want to know if Millet has a cross-reactivity with gluten. Can you please, help me? Thank u so much… HELP HELP

  27. Sasha says:

    Hi Christina,
    Thank you for the article and explaining to readers p-values and statistical significance. I work in statistical analysis myself and therefore I think some knowledge of statistics is very beneficial to everyone. It’s important to always question any claims made, especially if it’s a random blog, otherwise you can end up eliminating some great foods when it’s not necessary or spending tons of money on ineffective supplements.
    Also if you continue to have symptoms that often get blamed on gluten – such as brain fog, fatigue, muscle pains, I think it’s important to get tested for autoimmune disease. I had a lot of symptoms and was tested for celiac disease. The results were inconclusive but later on I also found out that I had Anti-Tg and Anti-TPO antibodies. I was then diagnosed with Hashimoto’s thyroiditis and later on with Hashimoto’s Encephalitis (this disease is quite rare). I did adopt AIP diet which helped me, but I was also treated with high dose Solu-Medrol IV and this treatment improved my symptoms. If I would not have known about the antibodies, I would not know which treatment I needed, therefore it’s very important to investigate your condition!

  28. Rob says:

    Thanks everyone for doing good science and solid interpretations and reviews of the data. I have CD and despite being on a GFD I get headaches, stomachaches, and skin problems when I eat corn, rice and dairy. This study backs up how I feel so I can now be more confident on what I can consume and what must be avoided.
    Cheers,
    Rob

  29. […] do discover a sensitivity to yuca and all derived products, but don’t mistake that for the debunked idea of “gluten-cross reactivity” – food sensitivities can exist without […]

  30. […] 2014, scientist Christina Graves, wrote an article for Paleo Foundation, entitled: 19 Gluten Cross-Reactive Foods: Busted Myth? Here are her […]

Leave a Reply

Your email address will not be published. Required fields are marked *