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-   -   Clarity-Ferm, Gluten Testing, and Gluten Sensitivity (http://www.homebrewtalk.com/f164/clarity-ferm-gluten-testing-gluten-sensitivity-354908/)

igliashon 09-17-2012 04:17 PM

Clarity-Ferm, Gluten Testing, and Gluten Sensitivity

This keeps coming up in discussions here, so I'm hoping I can clarify some things about clarity ferm and "reduced-gluten" beers, such as Omission and Daura.

Background: I'm an acupuncturist in California, where an acupuncture license requires a 4-year education, culminating in a Master's of Science, which covers enough mainstream medicine to allow us to be licensed as primary care providers. We can order and read lab tests, and refer appropriately to specialists. I'm not a doctor, but I know an awful lot about pathophysiology, and I've spent a long, long time surveying the scientific literature on gluten testing, gluten sensitivity, and specifically gluten in beer. I am always continuing my research, and expect that I may need to update this periodically.

So, for starters, let me say that "gluten intolerance" is a tremendous and unfortunate misnomer, as the intact gluten and gluten-like proteins are NOT the culprit in any known pathology included under this umbrella term. Rather, the culprit is prolamine molecules like gliadin, hordein, secalin, and occasionally avenin, and in the case of celiac disease, specific peptide sequences found in those molecules.

Let's break down the variety of pathophysiological mechanisms by which proteins from wheat, barley, rye, etc. can cause gastrointestinal symptoms. Celiac disease is the best-known and most-studied. While it is commonly stated that celiac disease is caused by a reaction to gluten and gluten-like compounds called prolamines, it is ultimately caused by a handful of peptides within those proteins. Specifically it appears to be a handful of "glutamine residues" being acted upon by tissue transglutaminase, an enzyme naturally occuring in the gut, turning them into a compound that provokes an immune response. All prolamines contain both proline and glutamine--that is the source of their name, PROline-glutAMINE. In other words, it's not the whole gluten molecule that is the problem, it's a small component of it. Sources: http://jem.rupress.org/content/195/5/643.abstract

But I'm getting ahead of myself. Celiac disease is but one of a few pathologies responsible for wheat/barley-related gastrointestinal distress. Non-celiac gluten intolerance is another one, which is studied and understood rather poorly compared to celiac disease. One thing is known for certain, and that is that gliadin--a component of gluten--does alter the permeability of intestinal mucosa in certain patients, which can increase exposure to any number of antigens that may be present in the diet (but which would not be problematic were the intestinal barrier functions intact). There are also as-of-yet untested hypotheses that gluten can alter intestinal motility in sensitive patients and generate IBS-like symptoms. Alcohol is known to exacerbate these effects.
Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480312/

However, there is another pathology--the allergic response--which is an important consideration as well. While gluten and gliadin specifically can trigger allergic responses to wheat, the main protein in barley that seems to trigger the allergic response is known as Lipid Transfer Protein 1--the same protein that is responsible for rendering barley-based beers "heady". If you get a rash following shortly after consuming a barley-based beer, and it goes away within a day, that is a sign of an allergic reaction. The rash associated with celiac disease, dermatitis herpetiformis, does not come and go that quickly, and can take up to two years to resolve after the adoption of a gluten-free diet.
Source: http://www.ncbi.nlm.nih.gov/pubmed/11590395

Now, what does all this have to do with Brewer's Clarex, aka ClarityFerm? ClarityFerm is what is known as a "proline-specific endoprotease", meaning it is an enzyme that hydrolyzes ("cuts apart") proline specifically, while sparing other proteins. Proline is the main protein implicated in the formation of "chill haze" in beer, and Brewer's Clarex hit the market originally as a way to ensure beer remains clear after sitting in the fridge for a long time. It hydrolyzes hordein by breaking apart the proline into its component peptide groups--break the proline, break the hordein. Simple. So far in my research, nothing I've read suggests that a proline-specific protease will hydrolyse glutamine. HOWEVER, malted barley itself contains an enzyme capable of hydrolyzing glutamine, EP-B2, which has been isolated and marketed as a supplement "Glutenase" to help protect celiac sufferers from inadvertent exposure (see here). Why this enzyme does not naturally render all beer safe for celiacs, I haven't figured out yet; I suspect it has something to do with temperature and/or the solubility of prolamines. But it is the case that compared to unmalted barley flour, flour made with barley malt is SIGNIFICANTLY lower in hordein. This is explained in greater detail in this study. In any case, it seems as though a long protein rest should have comparable effect to using Brewer's Clarex.

Hydrolysis of gliadin, hordein, and secalin can render them undetectable under certain testing methods--namely, the once-popular R5 sandwich ELISA test--and this has caused controversy in the past as studies have demonstrated that this form of ELISA test can give false negatives, thus allowing a "gluten-free" label to go on a harmful product. See this study. The more recent R5 competitive ELISA can detect hydrolyzed fragments of hordein, and specifically the peptide sequences known to trigger an autoimmune response in celiac sufferers. This is the test that Omission uses.

To make their beer, Omission uses a combo of a special cultivar of barley with a very low production of hordein, as well as brewer's clarex, producing the beer on equipment that has been fully sanitized. See here. No mention about centrifuges or anything, so I think we can put to rest the myth that they somehow "centrifuge out" the gluten. In any case, nothing in their methodology explains to me how their beers can pass the R5 competitive ELISA, but apparently they do, as every bottle is tested.

However, It is worth noting that while the R5 competitive ELISA is theoretically sound, it is not to my knowledge clinically verified. That is to say, clinical trials have yet to be done to show that any food which passes the test will be safe for celiacs. The test's threshold is 3 PPM of the relevant peptides, and Omission admits that the safety of their product is not guaranteed (though they happily still label it "gluten-free" in the state of Oregon--a bit hypocritical, if you ask me).

It is also worth noting that on the spectrum of gastroenterological disorders that can be associated with consumption of certain cereal grains, celiac disease is the only one for which it has been decisively proven that the pathogenic antigen lies within the gluten molecule. If you have a barley allergy, then the antigen of interest is NOT in the gluten molecule, and is not going to be affected *AT ALL* by Brewer's Clarex. In fact, that's one of the selling points of Brewer's Clarex, that it does not denature the LTP1 protein responsible for head formation. In the case of non-celiac gluten sensitivity, it has not been established which peptides are the culprit in provoking a response, or if it is in fact the gluten that is responsible at all, since grains contain a host of additional proteins.

So what's the take-away here? When it comes to barley-related gastroenterological disorders, there is much we still don't know. If you have a barley allergy, your problem is not gluten and beers like Omission are decidedly NOT safe. Some people, including myself, continue to have mild-to-moderately-severe reactions to beers like Omission and Daura; whether our symptoms are due to allergy, to a response to some other protein, to psychosomatics, or to some as-yet undiscovered pathology, no one can say. On the other hand, some people can drink Omission without any symptoms at all. Further studies and clinical trials must be conducted, but in the meantime the only way to be 100% safe is to avoid anything made with wheat and barley, regardless of how it is processed. Experiment at your own risk, and do so under a doctor's supervision, as your disease may return asymptomatically at first.

igliashon 09-20-2012 05:23 PM

Bumping this...does anyone think this would be worth making a sticky?

BBBF 09-20-2012 05:49 PM

I do. I still can't belive that they are allowing beer made with barley to say Gluten Free on the label.

mloster 09-20-2012 06:44 PM

Yeah, this is definitely sticky worthy

DougmanXL 09-20-2012 06:46 PM

I dunno if anyone else has seen this, but my LHBS gave me a brochure from White Labs advertising using Brewers Clarex to make gluten free beer from barley/etc... but he knew I had tried that, so he told me to "give them hell" for it, but I havent gotten around to it yet...

major67986 09-21-2012 03:33 PM

Actually, there is a new test that is available through R-Biopharm that was designed specifically for fermented beverages. It has a limit of testing to 10 ppm, but sounds like it may be testing for the smaller proteins. Here's the link to the literature on their website: http://www.r-biopharm.com/product_si...ed%20Analysis&.

I also recently received a brochure from my LHBS on White Labs clarity ferm. Mine did NOT say it was for making gluten free beer, but for making gluten reduced beer. Might want to double check your brochure...

Nonetheless, I recently brewed an all (barley) grain pumpkin ale and put the Clarity Ferm in it. I have a lab here in Boulder, Microbac, that will do this new test for me for $80 on 1 bottle of beer. I plan to take it up there to see what the results are. This lab also does the testing (I believe) for New Planet and one of the distributors here had the tests performed on Greens, Redbridge, Bard's and Brunhaut (Amber & Blonde). All were <10 ppm.

A bit about my background...I was diagnosed with celiac disease about 5 or 6 years ago. I am also on the board of the Gluten Intolerance Group of Colorado (local branch of the national Gluten Intolerance Group). This is the group that offers the "GF" certification in a circle you see on many products these days. I have NO medical training or background, but being celiac myself and supporting our members do my best to make sure I only speak what I know to be the truth because there are a lot of people out there, even IN the medical field, that do not have all of the facts or maybe just don't believe them, and put a lot of INCORRECT information out there.

With that said, I wanted to clarify a few things said about celiac disease and gluten intolerance:
  • There are MANY forms of celiac disease and NOT all show signs of nutrient deficiency.
  • Classical or typical celiac disease is the type that presents the GI and nutritional problems. Some in the medical field believe this could be the lowest percentage of those suffering from celiac.
  • Nonclassical or atypical CD causes problems primarily outside of the GI and nutritional problems. There is several research articles out there of cases where people were misdiagnosed with MS, Parkinsons, or other neurological diseases, and in fact had CD.
  • Silent CD occurs in the absence of any related symptom or nutritional deficiency and are typically found only through screening
  • Latent CD is when the blood tests are positive but there is no intestinal damage
  • Celiac Disease is a form of Gluten Intolerance.
  • Non-Celiac Gluten Intolerance does NOT have a single, widely agreed upon definition. But, most leaders in the field refer to this when an individual exposed to gluten, develop symptoms but lack a significant immune response. In other words, they don't feel well but their blood tests are negative or inconclusive and the biopsy shows no damage. Symptoms for the non-celiac gluten intolerant can be just as severe, but there is not enough research in this area to suggest there will be any long term complications if it were to go untreated (as it can in CD).
  • Symptoms for both CD and non-celiac gluten intolerance are a lot more diverse than just GI issues and nutritional deficiencies. Some people experience neurological symptoms such as migraines, brain fog, depression, fatigue and even seizures. Some have dermatitis herpetiformis. Some have experienced reproductive issues.

If you want more information on this topic, the best place (IMO), is to start by reading "Real Life with Celiac Disease" by Melinda Dennis and Daniel Leffler. This book is probably the most up-to-date research and very informative! Another great resource is Dr. Stephen Wangen (aka "The Gluten-Free Doctor"). He is widely known in the community and has several books out as well. Not to plug my group, but our Nat'l website also has a lot of great links/resources: http://www.gluten.net/.

Also, I wanted to point out...I do not believe beers that are brewed with barley (or anything else with gluten) can be labeled "Gluten Free", unlike food products. They can only be labeled gluten free if all of the ingredients used to make it were gluten free. The ones like Omission, Brunhaut and Daura, at least the ones I've seen at the store, have never been labeled this way. Some have a tag hanging on the bottle that state the gluten content (e.g. "<5ppm").

Bottom line is, yes, everyone is different and their tolerances are different. Unfortunately, there is not a test yet to tell an individual what their tolerance is, so that is choice each person has to make for themselves.

BBBF 09-21-2012 06:08 PM

The last time I checked, Two Brothers had gluten free on their packaging of Prairie Path. It looks like they are using the test you mentioned and it is coming in as less than 5ppm. However, I still feel that it is wrong to label it as gluten free. There should be some sort of separation between natually gluten free and gluten reduced/removed.


major67986 09-21-2012 09:17 PM

Alcohol and Tobacco Tax and Trade Bureau ruling in May 2012

Originally Posted by BBBF (Post 4433232)
The last time I checked, Two Brothers had gluten free on their packaging of Prairie Path. It looks like they are using the test you mentioned and it is coming in as less than 5ppm. However, I still feel that it is wrong to label it as gluten free. There should be some sort of separation between natually gluten free and gluten reduced/removed.


Here's the ruling from the Alcohol and Tobacco Tax and Trade Bureau

Not sure how they are enforcing this if at all yet...

igliashon 09-22-2012 01:00 AM

Thanks, major! That's definitely some good info. That new test is very exciting, and I'm very curious what the results will show. I wonder if it's the same test that was used in this study?

pintail78 09-22-2012 02:35 PM

I developed celiacs, diagnosted 5 years ago, I had nutrient deficiency, and small insestine problems. GF works good for me, but I'm not terribly sensitive, example I can drink 1 or 2 coronas with no reaction. For clarity ferm, I use up to 2# of malted barley grain in my recipes with sorghum base. It tests non-detect for gluten with the Elisa (with respect that it may still have smaller proteins in it), and I have no reaction and drink it regularly. This allows me to make almost any style pretty well.

Conclusion: This works for me, but may not for everyone else. CD is still poorly understood, the info I read above is pretty correct with current science.
Background: I am a college level science professor.

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