Wednesday 8 March 2017

PERT - Pancreatic Enzyme Replacement Therapy

So what is the deal with all of these enzymes?  There are loads out there - you are very likely to find at least 20 different plant-derived enzymes at your local health food store.  Many are coupled with a cocktail of probiotics and additional nutritional support, labeled with the words vegan, vegetarian and all natural to distinguish them from their porcine-derived cousins.  Many individuals report very positive results from taking these enzymes and probiotics, but the jury is still out as to whether this is a quantifiable test or another well documented case of the placebo effect (which is not bad, by the way - I once recovered from an aggressive bout of bronchitis only after a reluctantly written prescription for the world's weakest and most ineffective antibiotic, just the thought of having medicinal help improved my health almost overnight...).  Certainly a combination of digestive enzymes and probiotics never hurt anyone and in fact, a little digestive help is always appreciated.

The enzymes and probiotics you find in the store are different to those available by prescription - in quite a number of ways!  The first and most obvious difference is the requirement for a prescription (or not), meaning the FDA has become involved.  I was astonished to learn that the first FDA approval for porcine-derived pancreatic enzyme replacement therapy was in 2009!  Until 1991, replacement enzymes sailed along on the free market - and there were loads of them.  Inconsistencies in formulation and quality, resulting in adverse side effects, eventually caught the attention of the FDA.  As of 2012, there are only six FDA-approved replacement pancreatic enzyme formulations:  Creon, Zenpep, Pancreaze, Ultresa, Viokace and Pertyze.

A second, and equally obvious difference between store bought enzymes and prescription enzymes is the price ($$!!).  In order to be approved for use in chronic disease (such as Cystic Fibrosis), pharmaceutical companies must formulate a supplement which delivers the appropriate enzymes in the appropriate amounts at the appropriate time.  This is no small feat.  The internal environment which the supplements must withstand before reaching the duodenum is severe - the pH of stomach acid is between 1 and 3.  Your gastric acid, which can be destructive to other tissues such as your esophagus and intestines,  provides a massive service for the rest of the body.  Not only does it help to break down complex proteins in food (a low pH value is required for this!) but it also serves as a primary defense against bacteria and viruses.  Not many lifeforms can withstand the stomach acid, but one common exception, helicobacter pylori, has been linked to a variety of gastric ailments.  The enzyme supplements therefore must hold up against this acid - many lipases (which help with fat breakdown) are irreversibly deactivated by stomach acid.  This is why replacement enzymes are often prescribed with a proton pump inhibitor (PPI) to help raise gastric pH to the 3 or 4 level.  The price you or your insurance pays towards replacement enzymes is not driven by the enzymes themselves but by the protective (enteric) coating required to ensure proper enzyme concentration in the duodenum.  In addition to completely protected tablet formulation, each tablet contains enzymes which are further encapsulated in microspheres or microbeads.  More enzyme protection means more background R&D which is supplemented by the price of their product.

One final difference between store bought and prescription enzymes is the enzyme source.  Most (but not necessarily all) over the counter digestive enzymes are plant derived.  Prescription enzymes are solely porcine-derived, meaning that there are currently no FDA-approved pancreatic enzymes which are harvested from anything other than pigs.  Why pigs?  It turns out that pigs are a very close model for humans in many ways, including their pancreatic enzyme composition.  Animal-derived enzymes and molecules are commonly used in the production of food and medical therapies.  For example, rennet is a collection of enzymes produced by cows which is used for making cheese.  The commonly prescribed blood thinner Heparin is also derived from cows - although formulations of Heparin may be prepared from other farm livestock, the FDA approved and regulated Heparin is solely bovine-produced.  Porcine and bovine derived products have been deemed safe and effective for human use, but they pose a problem for select groups of people including those allergic to pork or those who do not consume pork or porcine-derived products.  Recently, a few small biopharmaceutical companies have taken up the challenge and have demonstrated production of digestive enymes from yeast (AzurRx MS1819 in phase II clinical trials) and bacteria (Anthera's Sollpura studies).  Although Anthera's bacterially-derived enzymes failed to show improvement over currently available therapies (which meant clinical trial failure), interest in non-porcine derived enzymes has hit the drug development pipeline!

Your enzyme prescription and therapy response rate depend on a number of factors, including diet and lifestyle, weight, underlying condition and often preference of your GI doctor or insurance.  Under dosing can lead to further pancreatic problems including fibrosis and calcifications while over dosing burdens the colon and can result in fibrosing colonopathy.  It is therefore imperative that patients are open and honest with physicians about symptoms (even if the tought of saying them out loud makes you super uncomfortable!) and be diligent about taking the prescribed dosage with meals.  Know that a lot of research hours and intense investigation, along with scrutiny, accompany your tablets to ensure you are safe and experience only minimal side effects.  It feels daunting at first, taking several pills every time you eat, but the payoff is (hopefully) symptom-free dining and enjoyable living!
 

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