Gluten-Free and Nutritious Too!

Bottom line: A very small number of published studies report finding peptides in exceedingly small amounts (measured in parts per billion) in human breast milk. If dairy cows are fed wheat, barley, and rye grain (not a common occurrence from what I’ve been told) and if they have the same difficulty digesting (breaking down) gluten protein as humans, it is reasonable to wonder if gluten peptides may be found in cow’s milk too. However, based on testing, no significant amounts of gluten peptides have been detected in cow’s milk. As a result, individuals with celiac disease should not be concerned that cow’s milk contains harmful amounts of gluten.

Background: Over the past two years there have been numerous blog posts about “high” amounts of gluten in human breast milk. This has led to some speculation (as well as outright “this is fact” statements) that cow’s milk may contain gluten. Consequently, I have received questions regarding whether this is true.

Research articles on gluten in human breast milk: Based on searches of Pub Med there appear to be only two original research articles (plus a chapter in a thesis) on the topic of gluten in breast milk.

• Chirdo et al. Presence of high levels of non-degraded gliadin in breast milk from healthy mothers. Scand J Gastroenterol. 1998;33:1186-1192. Available at: http://www.ncbi.nlm.nih.gov/pubmed/9867098
• Troncone et al. Passage of gliadin into human breast milk. Acta Paediatr Scand. 1987;76:453-456. Available at: http://www.ncbi.nlm.nih.gov/pubmed/3300148
• Hopman et al. Presence of gluten protein in breast milk: implications for the development of celiac disease In Gluten intake and gluten-free diet in the Netherlands. 2008 (thesis). Available at: http://tinyurl.com/836j4a2  Note: this research was never submitted to a peer-reviewed journal for publication.

Research findings: For the first two cited articles, I have read only the abstracts. While I do not believe in commenting on articles I have not read in full, it is important to point out that despite the title of the first article (i.e., “Presence of high levels of non-degraded gliadin in breast milk…”), the mean amount of gliadin found in the human breast milk samples was 178 ng/ml which is 178 parts per billion or 0.178 parts per million. In my opinion this is NOT a large amount of gliadin. In the second cited article, gliadin was found in breast milk in amounts ranging from 5 to 95 ng/ml or 5 to 95 parts per billion or .005 to .095 ppm.

In the Hopman thesis, researchers used a competitive assay (used to assess gluten fragments) to determine the amount of various gliadin and glutenin peptides, including an epitope that is part of the celiac toxic 33-mer. As with the two other studies cited, peptides were found in breast milk in exceedingly small amounts measured in ng/ml (parts per billion). The mean levels of the three gliadin peptides were 0.132 parts per million; 0.129 parts per million; and 0.404 parts per million. The mean level of glutenin peptide was 0.045 parts per million.

In other words, human breast milk may contain exceedingly small amounts of gluten peptides.

Note: For those of you concerned about the implications of breast feeding on the development of celiac disease, this is the concluding statement from Hopman, “In the present study we show that low amounts of T cell stimulatory epitopes of gluten, both from gliadin and glutenin, are present in breast milk of mothers on a normal diet. Since oral tolerance to food antigens is induced early in childhood, in the period infants are breast-fed, these peptides might be involved in the induction of gluten tolerance.”

In other words, the tiny fragments of gluten that may be found in human breast milk may serve a protective role in preventing celiac disease.

It is very important to point out that the gluten peptide content of human breast milk has been studied very little. One of the above mentioned studies used a sandwich assay to detect peptide fragments. The other study and the thesis used competitive assays. The sandwich assay is not ideal for detecting peptide fragments. The competitive assays used in these publications have NOT been formally validated (defined as having undergone a multi-laboratory performance evaluation with results published in the peer-reviewed scientific literature). As a result, more research is needed in this area before any definitive statements can be made about the gluten peptide content of breast milk.

Research articles on gluten in cow’s milk: Based on a review of Pub Med, only one study has been conducted on the gluten peptide content of cow’s milk (Dekking et al. Intolerance of celiac disease patients to bovine milk is not due to the presence of T-cell stimulatory epitopes of gluten. Nutrition. 2009;25;122-123). Researchers fed dairy cows increasing amounts of wheat. They then tested milk samples for gluten and gluten derived peptides at levels down to detection limits of 1 to 3 ppm gluten. The study authors concluded that “no gluten or gluten fragments could be detected above background in any of the bovine milk samples.”

The competitive assay used in this study has not been formally validated. The sandwich assay (i.e., R5 ELISA) used in this study has been formally validated.

Conclusion: Please continue to enjoy your milk!

I would like to thank the cereal chemists and researchers consulted for this article.

© 2012 by Tricia Thompson, MS, RD. All rights reserved. This article may not be reprinted, reposted, or republished without the express written permission of Tricia Thompson

Over the Holidays you may have come across the Health Day article entitled, “Some Gluten-Free Beers Really Aren’t: Study.” This is an unfortunate title that has led to some confusion. The article is available at: http://www.nlm.nih.gov/medlineplus/news/fullstory_120196.html

The study behind the article

Colgrave ML, Goswami H, Howitt CA, Tanner GJ. What is in a beer? Proteomic characterization and relative quantification of hordein (gluten) in beer. J Proteome Research. October 2011. The study is available at: http://pubs.acs.org/doi/suppl/10.1021/pr2008434

Study authors tested three types of beer: regular beer made with barley malt; gluten-free beer made without barley malt; and what the study authors call low gluten beer. This last type of beer, which the authors state is classified as containing less than 10 parts per million of gluten, is made with barley malt using proprietary methods that reportedly reduce the level of hordein (the problematic protein in barley).

Investigators found that of the beers included in the study, all regular varieties made with barley malt contained hordein; none of the gluten-free varieties made without barley malt contained hordein; and both of the so-called low gluten beers contained hordein.

This study was conducted in Australia which may explain some of the word choices that led to confusion. In the United States, beer containing barley malt is regulated by the Tobacco Tax and Trade Bureau (TTB). In January 2011, I was told by the TTB that, “the Bureau considers labels that declare a product to be “gluten free” or lead to the impression that a product is safe for those who suffer from celiac disease as making health claims, which are prohibited.” In other words, what the study calls “low gluten beers,” meaning those beers made using barley malt but reportedly processed to reduce gluten content, can not be labeled gluten-free in the US.

Note: Many of you are probably aware of a Spanish import made using barley malt with packaging that inferred (maybe still infers) gluten-free status (gluten-free neck tag, bottle cap with a crossed out stalk of wheat). Sometimes products slip through the cracks. Undoubtedly, this also is contributing to the confusion.

What those of us in the gluten-free community generally refer to as “gluten-free beer” does not contain barley malt. Therefore it is not considered a malt beverage under TTB regulations and instead is regulated by the FDA. “Beer” regulated by the FDA can be labeled gluten-free but it can not contain barley malt.

Hopefully this all makes sense. It can be rather confusing when there are two regulatory agencies involved!

©Copyright 2012 by Tricia Thompson, MS, RD. All rights reserved. No part of this article may be reproduced without the prior written permission of Tricia Thompson.

Come see what products are being tested. http://www.facebook.com/pages/Gluten-Free-Watchdog-LLC/258784214186574

This alert is available on the Gluten Free Watchdog site at http://www.glutenfreewatchdog.org/blog.php?id=7

Thanks so much for your support!

Hopefully many of you submitted comments to FDA regarding gluten-free rulemaking. The comment period has now closed.

I am posting both the letter FDALetter and product testing information FDAAttachment2SummaryFindingsGFWRN from Gluten Free Watchdog, LLC (www.glutenfreewatchdog.org) recently submitted to FDA (manufacturer names redacted).

Please see http://www.glutenfreewatchdog.org/blog.php?id=7

Hopefully everyone has taken the time to read the Federal Register Notice. If not it is available at http://www.gpo.gov/fdsys/pkg/FR-2011-08-03/pdf/2011-19620.pdf. Here are a few things to consider: 

• In 2007, the FDA released a proposed rule for labeling of foods as gluten free. The preamble to this rule listed two methods that could be used to establish a gluten threshold level—an analytical methods-based approach and a safety assessment-based approach.
• Under the analytical methods-based approach the gluten threshold would be based on the sensitivity of the validated tests used to assess foods for gluten content (the sensitivity of an assay refers to the level at which gluten can be accurately detected or quantified). Under the safety assessment-based approach the gluten threshold would be based on a daily intake of gluten considered “safe” for the vast majority of individuals with celiac disease.
• The safety assessment found the tolerable daily intake (TDI) for gluten to be 0.4 milligrams per day for adverse effects on the intestinal mucosa and 0.015 milligrams per day for adverse effects on clinical symptoms.
• If these TDI numbers are accurate it means that a person with celiac disease would have to limit themselves to less than a 1 ounce slice of bread containing 20 parts per million* of gluten each day to prevent intestinal damage; far less to prevent clinical effects.

*20 parts per million means 20 milligrams per kilogram of food

• Regarding use of the safety assessment-base approach, The Federal Register states the following, “FDA tentatively concludes that, based on the LOCs (level of concern)* identified in the safety assessment-based approach, the Agency should not use that approach in defining ‘‘gluten-free’’ because the estimation of risk to individuals with celiac disease associated with very low levels of gluten exposure may be conservative and highly uncertain.“

*For more information on LOCs, please see the Health Hazard Assessment for Gluten Exposure in Individuals with Celiac Disease available at: http://tinyurl.com/3b22eto

• In the Federal Register Notice the FDA tentative proposes to use an analytical methods-based approach to adopt a gluten threshold level of <20 parts per million as one of the criteria for labeling food gluten free.
• It is further stated in the Federal Register Notice that, “At the current time, FDA is not aware of any analytical methods that have been validated to reliably and consistently detect gluten below 20 ppm.”

My thoughts

You are not alone if you are confused by the disconnect between the findings of the safety assessment-based approach and the analytical methods-based approach. I have wondered how the FDA was going to reconcile the findings of the safety assessment with the level of gluten listed in the proposed rule (< 20 ppm) for the past three years—ever since I reviewed the safety assessment in 2008. If you would like to read blinded reviewer comments from the External Peer Review of the FDA/CFSAN the Draft Health Hazard Assessment for Gluten Exposure in Individuals with Celiac Disease, please see http://tinyurl.com/3g9exay. Reviewers include David Bellinger, PhD; Donald Kasarda, PhD; Michael Luster, PhD; Joseph Murray, MD; Tricia Thompson, MS, RD; Nga Tran, DrPH.

As I wrote in my review comments at that time, “Many of the TDI (tolerable daily intake) estimates are ridiculously low and do not make sense. The TDI for subchronic gluten exposure for morphological effects is listed as 0.4 mg/d. The TDI for acute, subchronic, and chronic clinical effects is listed as 0.015 mg/d. The FDA’s proposed rule on gluten-free labeling would allow a food to be labeled gluten free if contained less than 20 parts per million of gluten. Codex allows foods to be labeled gluten-free if they contain no more than 20 parts per million of gluten. If a person with CD ate just one ounce of a product containing 20 parts per million of gluten, they would be ingesting 0.57 mg of gluten (greater than the TDI values listed above). If these TDI values are disseminated to the public, persons with celiac disease will be afraid to eat.”

Minds much smarter than mine conducted the safety assessment. While I can point out issues that are confusing or do not make sense, I do not pretend to be an expert on safety assessment methodology. From my perspective, what would be most helpful is clarification from FDA on how they got from the findings of the safety assessment to what is written in the Federal Register notice.

For example, it would be helpful to know how FDA feels about the tolerable daily intake values in the safety assessment. Like the LOCs, do they also believe the TDI levels to be “conservative and highly uncertain?”  If so, it would be very helpful for them to explain why to help calm fears among individuals with celiac disease.  

If, on the other hand, FDA believes the tolerable daily intake values to be accurate, it would be helpful for them to explain why they are continuing to propose a threshold level of gluten of < 20 ppm. If they truly believe that gluten can not be reliably and consistently detected at levels below 20 ppm* then they should not allow certifying agencies to have lower standards of 10 ppm and 5 ppm.

*It is worth noting that when I discussed the level at which the R5 ELISA had been validated with Dr. Enrique Mendez (developer of the R5 ELISA) he referred me to the sensitivity levels. The sandwich R5 ELISA has a limit of detection for gluten of 3 ppm and a limit of quantification for gluten of 5 ppm. 

If they believe lowering the standard to 15, 10, or 5 ppm will prevent industry from being able to manufacture gluten-free food, this belief appears to be unfounded. Based on testing done by Gluten Free Watchdog (www.glutenfreewatchdog.org), the majority of food is testing below 5 ppm gluten* and most of the products testing this low do not carry any specialty certification.

*As stated above, 5 ppm is the lower limit of quantification for gluten. 3 ppm is the lower limit of detection. There are no validated tests that test to zero.

It is the case that the methodology utilized in the safety assessment is generally used to assess the safety of substances that are toxic to all individuals not just certain individuals with a given medical condition. For example lead is toxic to all individuals; gluten is not. As stated in the Federal Register Notice, “FDA’s assessment of the adverse health effects of gluten exposure in individuals with celiac disease presented in the Gluten Report followed established hazard assessment components used within the Center for Food Safety and Applied Nutrition to determine TDIs for chemical and natural toxin contaminants in food.”

As a result, it may simply be the case that the safety assessment as currently conducted is not the best approach for determining safe levels of gluten for the approximately 1% of the US population with celiac disease. 

Ideally, the upper limit of gluten allowed in foods labeled gluten free would be based on what is considered safe for the majority of individuals with celiac disease. However, one of the more important points to stress is just because a labeled gluten-free food is allowed to contain up to (but not including) 20 ppm gluten does not mean it contains that much.  

What I would like to see

• It would be extremely helpful if the FDA would develop a Q & A or consumer/healthcare practitioner bulletin to address issues surrounding the safety assessment.
• It also would be helpful to have this available before the comment period is closed (or to perhaps extend the comment period).

The following is from http://tinyurl.com/3ok27gd

The FDA encourages members of the food industry, state and local governments, consumers, and other interested parties to offer comments and suggestions about gluten-free labeling in docket number FDA-2005-N-0404 at www.regulations.gov¹. The docket will officially open for comments after noon on Aug 3, 2011 and will remain open for 60 days.

To submit your comments electronically to the docket go to www.regulations.gov²

1. Choose “Submit a Comment” from the top task bar
2. Enter the docket number FDA-2005-N-0404 in the “Keyword” space
3. Select “Search”

To submit your comments to the docket by mail, use the following address:

The Division of Dockets Management
HFA-305
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852

Include docket number FDA-2005-N-0404 on each page of your written comments.

Individuals with celiac disease have long worried about ingredients that are sometimes (rarely in the US) made from wheat starch, including wheat-based caramel color, wheat-based glucose syrup, wheat-based maltodextrin, and wheat-based dextrin. Under proposed FDA regulations for labeling food gluten free, wheat starch and ingredients made from wheat starch can be included in labeled gluten-free foods as long as the final food product contains less than 20 parts per million of gluten.

But what about foods not labeled gluten free that contain these ingredients? For example, if wheat-based maltodextrin is the only “suspect” ingredient in a food product not labeled gluten free is it okay to eat? While many (and I know not all!) dietitians and people following gluten-free diets have moved the ingredients caramel, glucose syrup, and maltodextrin into the “safe” column regardless of what they are made from, wheat-based dextrin (in foods not labeled gluten free) remains in the “unsafe” category. The question is whether this is necessary.

Background

Wheat starch is not wheat grain and it is not wheat protein. It is not intended to contain any gluten. Nonetheless it is difficult to completely separate the starch and protein components of wheat and small amounts of gluten remain.

The European Food Safety Authority (EFSA) has investigated wheat starch hydrolysates (e.g., wheat-based glucose syrup, wheat-based maltodextrin) as part of its allergen labeling program. According to the EFSA, testing done on wheat starch using the R5 ELISA found gluten in amounts up to 279 ppm. Wheat starch hydrolysates undergo many purification steps designed to remove protein. While wheat starch hydrolysates were found to contain intact gliadin and gluten peptides, the amounts were very low (< 5 ppm gluten for maltodextrin and up to 25 ppm in the glucose/dextrose samples).

In 2007, As a result of these findings along with a commitment from the starch industry that wheat starch hydrolysates would be purified to a maximum level of 20 parts per million of gluten, these ingredients were given permanent exemption from allergen labeling in the European Union (this is not the case in the US—in the US, under FALCPA, if any ingredient in a packaged food product regulated by the FDA contains wheat protein, the word “wheat” must be included in the ingredients list or Contains statement). Wheat starch and modified wheat starch were not exempted from allergen labeling in the European Union.

Okay, So What about Dextrin?

Dextrin also may be derived from wheat starch and if so would be considered a wheat starch hydrolysate. As many of you know, Benefiber sold in the United States uses wheat dextrin as its fiber source. Nonetheless, the product is labeled gluten free and product packaging states that it is tested to below 20 parts per million of gluten. This is the only information on the gluten content of dextrin I have been able to find. This ingredient does not appear to have been tested by EFSA.

Based on a subscriber request, Benefiber was recently tested by Gluten Free Watchdog, LLC (www.glutenfreewatchdog.org). The product was analyzed for gluten using both the sandwich and competitive R5 ELISAs. The competitive ELISA was used to detect any gluten peptide fragments in the product that might not be measured using the sandwich ELISA. Results of this testing indicate that wheat dextrin, especially when it is one of many ingredients in a food product, would be exceedingly unlikely to cause an otherwise gluten-free product to contain 20 parts per million or more gluten. Granted this is limited testing but it was done on a product containing one ingredient; 100% wheat dextrin.

Just a little food for thought…

Copyright © Tricia Thompson, Gluten Free Dietitan, July 2011. All Rights Reserved.

If you would like more information on testing done by Gluten Free Watchdog please read the FAQ at http://www.glutenfreewatchdog.org/faq.php

For more information on EFSA and maltodextrin, please see:

http://www.efsa.europa.eu/fr/scdocs/doc/487.pdf

For more information on EFSA and glucose syrup, please see:

http://tinyurl.com/3jzbb5m

For more information on the use of wheat starch hydrolysates in gluten-free foods in the EU, please see:

http://www.aaf-eu.org/pdf/AAF_02-2009_Communication_on_EU_allergen_labelling.pdf

There are now four gluten-free certification organizations in North America, namely programs run by the Celiac Sprue Association, the Gluten Intolerance Group, the National Foundation for Celiac Awareness, and the Canadian Celiac Association.  Click on the link to view a chart comparing these programs. The chart was reviewed for accuracy by each of the certifying organizations. The various seals and marks included below are from left to right: NFCA, CCA, GIG, CSA

BLOGGlutenFreeCertificationsTABLEJuly14