AN-PEP and other Digestive Enzymes —

[cyclinglady]

Anyone want to still discuss this topic?  It was started under a Pizza Shop thread that we hijacked.  I am not the best volunteer moderator and I am not going move everything, so go to the link if you want to catch up or copy your comments:

I do like a good discussion.  ?

My current position is that digestive enzymes have not been recommended by any leading celiac research center, but I conceded that there some enzymes, specifically AN-PEP, that do show promise.  There are no scientific trials that completely support it.  More studies are needed.    But until then, I stand by a gluten free diet as the only treatment for celiac disease that I am willing to recommend to members.  

National Celiac Associations take:

https://nationalceliac.org/celiac-disease-questions/gliadinx-product-digestive-enzyme-supplement/

and they cited this study:

“Consumption of gluten with gluten-degrading enzyme by celiac patients: A pilot-study”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3793137/pdf/WJG-19-5837.pdf

[Scott Adams]

I don't think anyone here is recommending anything for celiacs other than a gluten-free diet...GliadinX, and as far as I know other enzymes that contain AN-PEP, are gluten-free. ?

The idea, at least for me, has been finding something that can help me live the lifestyle that I prefer, which includes travelling and eating out, and not having to prepare every meal for myself for the rest of my life. For me this was the answer. 

I do think it is a fallacy to assume that if anyone recommends using GliadinX it means they are recommending that they not try to still be 100% gluten-free.

[docaz]

This was a good idea to move this discussion to a separate thread.

I think that it is very important to mention that the choice is not gluten-free diet OR AN-PEP. 

The choice is between a gluten-free/gluten-reduced diet alone or a gluten-free/gluten-reduced diet in combination with GliadinX. The reason I mention gluten-reduced is because it is a generally accepted fact that even for someone who is very cautious the likelihood is very high that contamination or accidental gluten-exposure will happen. 

It is also important to emphasize that enzymes can not cure or prevent celiac disease. Celiac disease is an autoimmune disease and the associate inflammatory reaction in the small intestine is caused by the contact of the proline-rich gliadin molecule. AN-PEP is designed to break down a specific 8-amino-acid segment that is causing the inflammatory reaction. Other enzymes break down gliadin but not that particular segment. This has been proven in multiple comparative studies in humans and in a laboratory.  

The writer on National Celiac Page quotes just one study but that does not mean that there are not many more and in fact there are many more. 

It is certainly true that even if the results of some of the studies are very compelling the investigators are hedging their opinion in the conclusion section. Other conclusions are more straightforward. 

It is also important to note that there is NOT one single study that suggest that AN-PEP is Not effective. 

More to follow ....

[Fenrir]

Nobody is suggesting replacing a gluten-free diet with AN-PEP, that would be an inappropriate use of the product. 

As I stated in another thread, the reason why AN-PEP isn't FDA approved or endorsed by major Celiac organizations has more to do with the financials than if it's effective or not. 

Blood pressure drugs aren't particularly effective in preventing coronary events if people don't change their lifestyle. Flu shots and vitamins are surprisingly ineffective. Statins are not particularly effective without diet changes and even with diet changes also have a lot of side effects. 

The difference between these drugs and AN-PEP is that there is money to be made in those drugs and many more people affected by conditions they treat. 

[docaz]

3 hours ago, Fenrir said:

Nobody is suggesting replacing a gluten-free diet with AN-PEP, that would be an inappropriate use of the product. 

As I stated in another thread, the reason why AN-PEP isn't FDA approved or endorsed by major Celiac organizations has more to do with the financials than if it's effective or not. 

Blood pressure drugs aren't particularly effective in preventing coronary events if people don't change their lifestyle. Flu shots and vitamins are surprisingly ineffective. Statins are not particularly effective without diet changes and even with diet changes also have a lot of side effects. 

The difference between these drugs and AN-PEP is that there is money to be made in those drugs and many more people affected by conditions they treat. 

There is a lot of truth in the post. 

I do think that regardless how effective enzymes are for this application, it is not very likely that with the next 5 years or more they will receive FDA approval for a particular application. For this reason, there is a "verbal dance"  with sensitivity going on because sensitivity is not considered a disease so many clinicians and companies are promoting enzymes for sensitivity. Reality is that recent studies suggest that many gluten sensitivities are actually caused by complex sugars that the body can not break down. This means that AN-PEP works actually better for celiac disease . Clinicians recommend whatever they want because they are not regulated by the FDA and drugs are used all the time completely legally for off-label indications. (I remember during my residency at a major hospital when we used oral versed for sedation long time before it was FDA approved for that application because it was only approved for intravenous applications). At the same time clinicians for good reasons have to be cautious with off -label recommendations. Companies on the other hand are regulated by the FDA and again for very good reasons, they have to be very extra-careful not advertise an intended use that is not approved. Obtaining an FDA approval is very expensive and if the profits might not offset the cost, then it does not make sense go through that and I think that we are exactly in this situation in particular since enzymes without a specific indication do not require any regulatory approval. I think that the data is solid and every piece of research shows how powerful AN-PEP is but unfortunately we are stuck. 

[cyclinglady]

Good grief.  I never thought that an AN-PEP enzyme should replace a gluten free diet.  I do not think any of you thought that either.   I do understand that some people might think this is the case which is one of the many reasons large celiac groups are not recommending it.  Even in conjunction with a gluten free diet to prevent a gluten exposure, I would still not recommend it without the support of leading researchers.  (I get all the FDA requirements, lack of funding for studies, etc. since my family is in bio-medical (medical devices) as well, but not me personally.  I am just a mom who has celiac disease.)  

Anyway, there are several AN-PEP products on the market.  Do you know where the raw materials are obtained?  For example, only China is fermenting the raw materials for ALL antibiotics per my recent research on my thyroid medication and a recent presentation to Congress this last Fall.  Also, is this is grown on some fungus?  This could be an issue for me personally.  I can not tolerate mushrooms.  Food additives like  Xanthan Gum also cause me problems despite having healed from celiac disease.  

Besides Scott and Docaz, has anyone else used a AN-PEP enzyme?  Any reports?  Please do not bring up other “Gluten Busting” enzyme products as those were thoroughly discredited in this study below (read the table to see the manufacturer’s and product names):  

https://journals.sagepub.com/doi/full/10.1177/1756283X17690991

No offense, but please just post if you have celiac disease.  These products seem to work on those with gluten sensitivities and not celiac disease.  (Well, the AN-PEP studies have not been tested on celiacs long enough to draw any conclusions, but again, promising).  

Again, this subject has been educational, that is for sure!  ?

[Fenrir]

4 minutes ago, cyclinglady said:

Good grief.  I never thought that an AN-PEP enzyme should replace a gluten free diet.  I do not think any of you thought that either.   I do understand that some people might think this is the case which is one of the many reasons large celiac groups are not recommending it.  Even in conjunction with a gluten free diet to prevent a gluten exposure, I would still not recommend it without the support of leading researchers.  (I get all the FDA requirements, lack of funding for studies, etc. since my family is in bio-medical (medical devices) as well, but not me personally.  I am just a mom who has celiac disease.)  

Anyway, there are several AN-PEP products on the market.  Do you know where the raw materials are obtained?  For example, only China is fermenting the raw materials for ALL antibiotics per my recent research on my thyroid medication and a recent presentation to Congress this last Fall.  Also, is this is grown on some fungus?  This could be an issue for me personally.  I can not tolerate mushrooms.  Food additives like  Xanthan Gum also cause me problems despite having healed from celiac disease.  

Besides Scott and Docaz, has anyone else used a AN-PEP enzyme?  Any reports?  Please do not bring up other “Gluten Busting” enzyme products as those were thoroughly discredited in this study below (read the table to see the manufacturer’s and product names):  

https://journals.sagepub.com/doi/full/10.1177/1756283X17690991

No offense, but please just post if you have celiac disease.  These products seem to work on those with gluten sensitivities and not celiac disease.  (Well, the AN-PEP studies have not been tested on celiacs long enough to draw any conclusions, but again, promising).  

Again, this subject has been educational, that is for sure!  ?

I have used GliadinX and it seems to work. 

I believe most of the suppliers are in India and China. But since it's also used as a clarifying agent by wine makers it could be available in the states and/or Europe too. 

[docaz]

2 hours ago, cyclinglady said:

Good grief.  I never thought that an AN-PEP enzyme should replace a gluten free diet.  I do not think any of you thought that either.   I do understand that some people might think this is the case which is one of the many reasons large celiac groups are not recommending it.  Even in conjunction with a gluten free diet to prevent a gluten exposure, I would still not recommend it without the support of leading researchers.  (I get all the FDA requirements, lack of funding for studies, etc. since my family is in bio-medical (medical devices) as well, but not me personally.  I am just a mom who has celiac disease.)  

Anyway, there are several AN-PEP products on the market.  Do you know where the raw materials are obtained?  For example, only China is fermenting the raw materials for ALL antibiotics per my recent research on my thyroid medication and a recent presentation to Congress this last Fall.  Also, is this is grown on some fungus?  This could be an issue for me personally.  I can not tolerate mushrooms.  Food additives like  Xanthan Gum also cause me problems despite having healed from celiac disease.  

Besides Scott and Docaz, has anyone else used a AN-PEP enzyme?  Any reports?  Please do not bring up other “Gluten Busting” enzyme products as those were thoroughly discredited in this study below (read the table to see the manufacturer’s and product names):  

https://journals.sagepub.com/doi/full/10.1177/1756283X17690991

No offense, but please just post if you have celiac disease.  These products seem to work on those with gluten sensitivities and not celiac disease.  (Well, the AN-PEP studies have not been tested on celiacs long enough to draw any conclusions, but again, promising).  

Again, this subject has been educational, that is for sure!  ?

You brought up so many points and will address some

AN-PEP comes from only one source made by DSM a Dutch company. It was made at first in the Netherlands and now it is made in France. This company holds an international patent specifically for celiac disease. 

The study that you quoted, specifically says that AN-PEP is promising!! It discredits some that do nothing but this Tolerase G is SPECIFICALLY mentioned as being able to break at least down small amounts of gluten. This is a quote from the publication:

"Finally, Tolerase G, a commercially available dietary supplement sold by DSM (Kaiseraugst, Switzerland) that contains Aspergillus niger derived prolyl endoprotease (AN-PEP), has had very promising in vitro, ex vivo, and in vitro initial results.^8,9 "

It says further Tolerase G, the AN-PEP-based supplement, was not evaluated in this study because it was not found via the search methods used. This is likely a result of the time at which the searches were conducted, the search terms used, and the Google search algorithm. Tolerase G became commercially available in June, approximately 1 month prior to when the searches were conducted, which may have contributed to the apparent low visibility through the Google searches.

Then further it quotes a publication that is more critical but there are so many that I posted and why you do not consider these valid I do not know. 

Products made from fungi are ubiquitous including every single item that has citric acid which is in a zillion foods and almost all carbonated drinks. 

 

 

[cyclinglady]

@docaz

Thank you for answering my questions!  ?

[Fenrir]

For the record, I've been testing GliadinX a little on myself.

I've gone to restaurants I've previously head reactions at:

Pizza Ranch

Dominos

Denny's

Applebee's

When I first was diagnosed and didn't know better I thought that gluten-free options at these places were safe and I had reactions to the food, presumably from cross contamination because the items I ordered were made from things without gluten in them. 

Over the last month and a half I've eaten Domino's gluten-free pizza twice, Pizza Ranch gluten-free pizza once, Denny's gluten-free Skillet once, and Applebee's Fiesta Lime Chicken once. I took one GliadinX pill immediately before eating the meals each time and didn't have a reaction to any of them. 

Only one time I had heartburn but I think that's simply from the fact that I ate too much spicy stuff that day. 

[cyclinglady]

Hey guys!  

Did you see this new research?  Now researchers might be able to test on mice who have developed celiac disease (and can heal) instead of people, thus not potentially causing harm.  Good news indeed!  

http://news.uchicago.edu/story/breakthrough-mouse-model-celiac-disease-could-lead-new-treatments

[Fenrir]

12 minutes ago, cyclinglady said:

Hey guys!  

Did you see this new research?  Now researchers might be able to test on mice who have developed celiac disease (and can heal) instead of people, thus not potentially causing harm.  Good news indeed!  

http://news.uchicago.edu/story/breakthrough-mouse-model-celiac-disease-could-lead-new-treatments

It's good that they are finding a way to research without using humans but research done on mice (for practically anything) has been pretty unreliable when studies move on to testing things in humans. 

 

[docaz]

5 hours ago, cyclinglady said:

Hey guys!  

Did you see this new research?  Now researchers might be able to test on mice who have developed celiac disease (and can heal) instead of people, thus not potentially causing harm.  Good news indeed!  

http://news.uchicago.edu/story/breakthrough-mouse-model-celiac-disease-could-lead-new-treatments

This is actually a very important study because if the model works well, a lot of the work is easier applicable to humans than many other animal studies. Dr. Jabri spoke recently at an informal meeting of the Chicago Celiac Center and there is hope that this might speed up some of the research. Unfortunately, the results are still decades away. 

[Fenrir]

13 hours ago, docaz said:

This is actually a very important study because if the model works well, a lot of the work is easier applicable to humans than many other animal studies. Dr. Jabri spoke recently at an informal meeting of the Chicago Celiac Center and there is hope that this might speed up some of the research. Unfortunately, the results are still decades away. 

Also, using mice doesn't eliminate the need for human trials as well. From what I've been told is that mice are great for a first line screening. Mice are smaller animals than humans (obviously) and physiology not quite the same. Many drugs tested on mice (even scaled to size) tend to be more effective in mice than humans. However, what using mice allows them to screen out things that don't work or may be dangerous pretty quickly. If it doesn't work in mice, it probably won't work in humans (we're more able to metabolize things than mice are). If it's dangerous to mice then it may not be to humans but at least they know what to watch for in human trials. 

[docaz]

Hi,

This is one of the most recent peer reviewed papers that lists the many gliadin epitopes that cause an inflammatory reaction (see Table 1) and the author describes the reduction in immunoreactive gluten content by AN-PEP (Table 3)  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020197/

Many people are going to extremes to eliminate all gluten in their diet (rightfully so) by bringing food to restaurants, and live a life with significant negative social implications. All experts agree that contamination is almost unavoidable and here is something that is right in front of our eyes, with publications by clinicians from all over the world and costs 50 cents per dose but possibly out of principle (I am not sure what principle) they refuse to consider AN-PEP/GliadinX as an extra step of precaution. 

[Fenrir]

Yes, it's well worth the 50cents a pill. I don't use it every time I go out to eat but I have it with me everywhere. I have some in my drawer at work, at home, and I keep a few in my coat pocket. So far since discovering this I haven't had a massive exposure so I don't know how well it would work at reducing symptoms for something like that. 

However, I have tried eating french fries at places I previously wouldn't, I was able to eat a restaurant I wouldn't have tried to before. I have less anxiety when I go out with my group of friends about having to be the bummer in the group basically limiting the places we go to 1 restaurant.  Granted, I still avoid anything with gluten in it and if I'm sure there is cross contamination. Before I had to avoid almost every place where cross contamination was possible but now I can go to a few more places where cross contamination is possible but would be very small amounts. 

I don't eat out a lot (maybe twice a month) but for example this past weekend my Mother-in-law turned 80 so the whole family wanted to take her out for a meal. She wanted to go to a small steakhouse that isn't really celiac friendly due to cross contamination. They sometimes brown toast on the grill the cook steaks. I ordered a steak, salad and baked potato with butter on it. Took GliadinX before (1 pill) and had zero reaction. I've been there three times now since getting GliadinX and have had no reactions. I had previously had a reaction at this place.