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Gluten-Free Beer: Does Omission Beer Deliver the Goods? — A Simple Guide for the Non-Biochemist

By: Peter Olins, PhD, on July 25, 2013

Unlike other breweries, Omission Beer (from Craft Brew Alliance) starts with barley malt, but then uses an enzyme technology that aims to destroy hordein—a protein similar to wheat gluten, which is toxic to people with celiac disease.

Last October, I wrote an article entitled “Is Gluten-Free Beer Made From Barley Malt Safe for Celiacs?” Since then, I have been amazed by the amount of controversy and confusion about this topic on the Internet, so I decided to write an update, which I hope will clarify the issues. I suspect that the problem is that a typical beer-drinker wants a simple yes/no answer to the question, ‘Is this safe or not?’, but the reality is not always so straightforward.

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Detecting substances like salt in food is very easy: salt is a simple molecule can be accurately measured in laboratories around the world. The same goes for single toxic contaminants in our food, like arsenic or mercury. Gluten is different, however, because it is a very complex mixture of proteins, and there is no simple way to measure it directly. Instead, detecting gluten relies on a small peptide segment (a kind of tag), in order to estimate how much gluten may be present. This is very convenient, but it has three major problems.

Key Take-Home Messages About Gluten-Free Beer Made With This Process:

  • Currently, there is is no reliable way to predict if the residual gluten present in fermented foods, such as beer, is safe for people with celiac disease.
  • A new assay for gluten, called the “R5 Competitive ELISA”, has been developed, but has not been validated.
  • The new assay is likely to cause confusion, and “ppm” gluten values obtained with it could create a false sense of security for celiacs, who are highly sensitive to gluten contamination.

What is Gluten?

The answer is not as simple as you might think. Gluten is the main protein present in wheat; but what most people don’t know is that it is actually a very complex mixture of over 100 different proteins. This means that there is no single substance called “gluten”—it’s just an umbrella term. What’s worse, different varieties of wheat, grown in different parts of the world, contain varying amounts of the different components of gluten. So the challenge has been to find some general way to estimate the total amount of gluten in a wide range of foods.

A little background on proteins—for the non-biochemist.

Proteins are simply strings of small components called amino acids. Gluten proteins typically contain about 300-1100 amino acids. Strictly-speaking, “gluten” only refers to the mixture of proteins from wheat. However, grains such as barley and rye also contain related proteins. For the sake of simplicity, they are often grouped together under the umbrella term of “gluten”, since these proteins are also toxic to people with celiac disease. “Hydrolysis” is just a fancy name for cutting up a protein into small fragments, called peptides, and is carried out by specialized proteins called enzymes.

Current Method for Estimating Gluten Levels in Foods

The most widely accepted assay for detecting gluten in food is called an ELISA. One commercial test is called the “R5 Sandwich ELISA” (nothing to do with edible sandwiches…), and involves the detection of a small peptide segment or tag composed of a string of five amino acids (QQPFP): this sequence of amino acids is present in a wide variety of gluten proteins. This assay is easy to perform, cheap, and highly reproducible.

Peptide Tags Are a Bit Like Store Security Tags

We are all familiar with the little plastic tags attached to clothing to prevent shoplifting: the tag is used as convenient way to detect something important, even though the tag itself has little value. This is a bit like the peptide tag that is commonly used for measuring gluten: the peptide tag itself is not toxic to humans, but it is present in most of the different proteins in gluten. By measuring the amount of peptide tag present in a food, we can get an estimate of the overall amount of gluten present.

What Happens When We Remove the Tag or Destroy It?

In the case of a store security tag, it’s sometimes possible for a shoplifter to remove it, and the store owner does not realize that the clothing is missing. A similar thing is true for the tags used to detect gluten: if the gluten protein is cut into pieces by an enzyme, the tag is no longer connected to the rest of the gluten protein. In extreme cases, the tag itself could be destroyed, even though other toxic fragments of gluten might remain intact.

What does 20 ppm gluten mean?

The term, “ppm”, is an abbreviation for “parts per million”: 20 ppm gluten contamination is really a tiny amount—imagine one teaspoon of gluten divided evenly between 250 liter-sized bottles of water! In many parts of the world, a “Sandwich ELISA” is used to measure trace levels of gluten in a food, and regulators have decided that 20 ppm is an acceptable level of residual gluten for people with celiac disease. In the U.S. we are still waiting for a final regulation from the government, but the latest public draft FDA regulation for gluten in food also sets a cutoff value of less than 20 ppm for a food labeled as “gluten-free”.

It’s Hard to Test for Gluten in Beer

As explained above, when gluten is broken down into peptide fragments, the peptide tag becomes separated from the rest of the gluten, and can result in a false-negative result using the current test (R5 Sandwich ELISA).

In order to overcome this problem, scientists recently developed the “R5 Competitive ELISA”. However, this assay has not been formally accepted for measuring the level of gluten in food. Researchers have attempted to “validate” this assay for detecting hydrolyzed gluten in foods. Simply stated, the word “validation” is used by biochemists to describe how consistently they get the same result using the same food substance and the same reference material. For the following reasons, I question if this scientifically meaningful:

  • The reference material used in the new assay is prepared by artificially hydrolyzing a mixture of known proteins from different grains, to produce a mixture of peptide fragments. However, the peptides present in reduced-gluten beer are not the same as those in the reference material.
  • Differences in the process used by the brewer will probably result in a different range of peptides, either between different brewers, or from batch to batch.
  • Biochemical validation is not the same as safety validation. In the case of gluten assays, biochemical validation measures the amount of peptide tag detected in a food, but it does NOT measure how safe the food will be.

Gluten-Free Beer Safety

What Does This Mean For Gluten-Free Beer?

As I described in my article last year, there are two approaches for making gluten-free beer: 1) starting with ingredients that lack gluten to begin with, or 2) starting with gluten-containing ingredients (such as wheat or barley malt), and then hydrolyzing the final product with an enzyme to reduce the amount of intact gluten. “Omission” beer (made by Widmer Brewery, owned by Craft Brew Alliance) and “Daura” (made by Estrella Damm) are examples of beers that use an enzyme to help reduce the gluten content of their products. My article went into more depth about the technology for gluten removal, the assay for gluten and the current U.S. regulations regarding gluten in beer. In principle, the use of gluten-degrading enzymes is a great concept, but as we have seen from the discussion above, there is NO reliable way to predict the safety of the final product.

I consider the R5 Competitive ELISA assay to be more of a warning signal, rather than a predictor of safety. In other words, any beer that gives a positive signal in the R5 Competitive ELISA would definitely be suspect, but a negative signal should not be taken as reassuring. Unfortunately, from some of the comments that I have seen on the Internet, many people are confused by what the R5 Competitive ELISA means, and mistakenly believe that it is a measure of safety.

Really technical stuff about toxic peptides in gluten—for those who would like to delve deeper.

There are an amazing number of small peptide segments within different gluten proteins that provoke an immune response in people with celiac disease. These stimulatory peptides vary from person to person, which means that different varieties of wheat and related grains will probably differ in their effect on different people. The range of biologically active peptides has only been investigated in a few people, and this list continues to grow. We are only just starting to learn which peptides are important, and chances are that the story will become even more complicated in the future!

A second kind of peptide present in gluten is directly toxic to cells, triggering what is called the “innate immune system“. Much less is known about this kind of toxic peptide, and no routine test has been developed to measure its effects in wheat-containing foods.

Future Possibilities

  • Ultimately, the best way to be confident that beers like “Omission” are safe for celiacs would be to test them directly for their biological activity in a research study, possibly using biopsy samples from celiac disease patients. However, this would be a complex and expensive process.
  • It would be great if brewers such as Craft Brew Alliance would release any research data that it may have about the peptide composition of its “Omission” beer.
  • There have been several anecdotal reports on the Internet that some celiacs have had a bad reaction to “Omission” beer: perhaps the brewers might approach these folks directly in order to get more information about their experiences.

Final Conclusions

  • Current assays that have been validated to measure gluten in foods are poor at detecting toxic peptide fragments in hydrolyzed foods, such as beer.
  • A newer assay designed to detect fragments of gluten is not suitable for measuring the potential toxicity of these peptides in people with celiac disease.
  • It is not meaningful or valid to compare a “20 ppm” gluten value obtained in the current “R5 Sandwich ELISA” assay with a “20 ppm” value in the newer “R5 Competitive ELISA”.
  • Using the R5 Competitive ELISA as an indicator of safety is likely to mislead the general public, who will not understand the distinction.

The Tobacco Tax and Trade Bureau (TTB) regulates the beer industry in the U.S. Based on available knowledge, it has ruled that claims about actual levels of gluten content in all advertising and labeling of barley-based beers is prohibited, quote:

“Because the current tests used to measure the gluten content of fermented products have not been scientifically validated, such statements may not include any reference to the level of gluten in the product.  TTB believes that the qualifying statement is necessary to avoid misleading consumers about the gluten content of these products because of the serious health consequences associated with the consumption of gluten by individuals with celiac disease”
 I strongly agree with this precaution, especially since most people do not have the technical expertise to interpret the subtleties of different kinds of gluten tests. Sadly, many articles and websites fail to stress this critical information.

I have tried to make these issues clearer for the non-biochemist, but please let me know if you have questions or comments  — Peter.

Update, August 2, 2013

Today, the FDA released its official regulation for gluten-free labeling of foods: http://goo.gl/diqHvN. This is effective today, and compliance is required by August 4, 2014.

There are few surprises in the final regulation, which is very similar to the draft version that has been available for about two years. The situation with beer and hydrolyzed foods is complicated, since the regulation of beer and similar beverages is divided between the FDA and the TTB (Tobacco Tax and Trade Bureau). Currently, the FDA regulates malt beverages that lack hops, or beers made with hops but from grains other than barley or wheat! Traditional barley-hops beers are regulated by the TTB.

The FDA reaffirmed its earlier position that there is currently no valid assay for measuring “gluten” in hydrolyzed foods, such as beer, including the R5 Competitive ELISA. For now, the Sandwich ELISA will remain as the standard for gluten-free labeling. The FDA plans to update these regulations as soon as a valid approach can be identified for hydrolyzed proteins.

It remains to be seen whether the TTB will remain strict in prohibiting labeling of “gluten-free” beer in the absence of a valid assay for hydrolyzed proteins, or whether it will relax its standards.

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