Systemic enzyme therapy | Science-based medicine (2023)

One of the recurring themes in alternative medicine is the practice of simplifying complex medical problems and then offering equally simple solutions that are still within the realm of science. This approach allows the doctor to ignore all the complexities and difficulties of practicing real medicine and still offer drugs that sound legitimate at first glance. Even scientifically.

I've already discussed this in Unscientific Approaches to Treating Food Intolerance if that makes senseclinically useless IgG blood tests, ordeclares gluten a universal food enemy. David Gorski dealt with the same topic a few days agorelated to cancer treatment, which contrasts the simplistic views of alternative medicine providers with the facts of cancer research. Cancer is incredibly complex - each of the hundreds of different variants of the disease. I am always amazed when I talk to oncologists about how the treatment regimens are established. They describe how the results of dozens of clinical trials, conducted by different study groups around the world, have helped define the current "best" therapies for each cancer: the appropriate drugs, doses, treatment intervals and intensities. Good evidence speaks all languages, and as new data emerges, practice changes rapidly to be based on new evidence. The complexity of treatment is constantly increasing. When you overlay the genetic and genomic complexities described by David, you get a sense of the challenges (and opportunities) cancer researchers face in enabling science to continue to improve outcomes for cancer patients.

Therefore, it is somewhat shocking when one pays attention to the "literature" of alternative medicine, where there are many simple solutions. What is particularly popular with the patients I talk to, especially those of European descent, is the use of what are known as systemic enzymes - enzymes that are taken orally to have an effect throughout the body. These products do not belong to "conventional" medicine, but are popular dietary supplements recommended by naturopaths. I was recently asked about the product Wobenzym N, a product with German rootsannounced with the following conditions[PDF]:

Taking Wobenzym®N as directed helps several key systems in your body. This product supports the musculoskeletal system by promoting joint and muscle health and mobility, and has been used for decades. Wobenzym®N supports the circulatory system by promoting vein health. This product also supports respiratory and sinus health. Many people use Wobenzym®N to support a balanced immune system and promote healthy aging. Wobenzym® is safe and effective and has been used by over 100 million people worldwide for over 40 years.

Vague and vague claims, and they existQuacksalber Mirandawarning there too. But what does Wobenzym N actually do?Again? Other sites that promote its usethey go much further in their healing claims, which describes its use in conditions ranging from Alzheimer's disease and angina pectoris to multiple sclerosis, prostatitis, respiratory infections and uveitis. Some mention the utility icancer treatment. What connects all these different relationships? There is, as David Gorski says, a real cause. When using systemic enzymes, your "OTC" for all ailments is inflammation.

Redness, heat, pain, tumor

Inflammation is our body's response to infection and injury and is part of the healing process. Diseases with an inflammatory component are common and have huge health implications—think asthma, arthritis, and inflammatory bowel disease, all common, chronic diseases that affect millions of people. Mild inflammation associated with obesity can cause numerous obesity-related complications. But "inflammation" does not exist in one form. There are several mediators, such as cytokines and eicosanoids. There is a wide spectrum of cellular responses. AsPeter Lipson has already explained this:

Inflammation is a medical term that refers to a series of complex physiological processes mediated by the immune system. The old name "inflammation" comes from the obvious physical signs of inflammation:Redness, heat, pain, tumoror redness, warmth, pain, and swelling. As vitalistic ancient medical beliefs gave way to modern science, it was realized that inflammation is far more complex than just these four outward characteristics. The cellular and chemical reactions of inflammation are not only a response to injury and disease, they can also cause disease. For example, asthma and food allergies are called a type of immune responseType I hypersensitivityit causes a harmful type of inflammation. Coronary artery disease, the leading cause of death in Americans, is believed to be presentan important inflammatory component.

Although there may be an inflammatory component to many different diseases, it is an oversimplification to think that we can treat all forms in the same way until there is evidence that this is the case. Both asthma and arthritis have inflammatory elements, but they are different diseases with different treatments. However, simplify the terms to "inflammation" and you can introduce an equally simple solution. Solution?Systemic enzyme therapy:

Wobenzym®N provides "systemic enzyme support," which describes a process that uses enzymes to support the body's various regulatory and communication systems, especially the immune system.† A balanced immune system is essential to maintaining overall health. Active enzyme molecules must be readily available in the small intestine to ensure systemic enzyme action.

Enzymes play a vital role in the body and are involved in a surprisingly large number of metabolic processes. Scientists assume that up to 15,000 enzymes work in our body every day. Enzymes are involved in a number of bodily processes including: respiration, growth, digestion, energy production, transmission of nerve impulses, blood clotting, recovery after exercise or balancing the complex processes of the immune system.

Enzyme supplements can be scientifically based. Its application is common in diseases of the pancreas, as well as in diseases such as cystic fibrosis. However, these are not applications where the enzymes must be absorbed from the gastrointestinal tract. Systemic enzyme replacement is different.

When I learned about it, I first came up with the idea of ​​huge enzyme superdosesGonzalez regime, an alternative cancer treatment regimenwhich Kimball Atwood has discussed at length in previous posts. Treatment includes coffee enemas and hundreds of pills of pancreatic digestive enzymes a day. The drug itself was based on speculations about the causes of cancer, which have now been definitively disproved. A clinical trial of Gonzalez's therapy was funded by the National Center for Complementary and Alternative Medicine (NCCAM), to which i.a. belonged toa large number of pancreatic enzymes. The results of the study were remarkable, but not positive for the "alternative" approach: conventional chemotherapy for the treatment of pancreatic cancer wasthree times betterEnd the Gonzalez regime.

Our pancreas secretes enzymes that help digest food. Is it to be expected that the used enzymes will be absorbed by the body? Enzymes are large proteins that act as catalysts for biochemical reactionsthrough the body– Many chemical transformations are catalyzed by enzymes. Many parameters can affect enzyme activity, including pH and temperature and the presence of activators and inhibitors. Given the importance of enzymes in the body, genetic disorders can occur that affect enzyme production and functioncatastrophic consequences. We would also expect that the production and distribution of enzymes in the body would be fairly tightly controlled with respect to possible effects and that the food we eat would also contain its own share of naturally occurring enzymes.

The use of proteins as therapeutic agents to act on diseases is of great research interest. The challenge with getting protein into the body is that most of it is quickly removed from the circulation, either by biotransformation by enzymes or by renal filtration. Very high doses may be required, increasing the risk of non-specific toxicity and even allergic reactions. The most common therapeutic use of protein is by injection, since large chemical molecules are generally either destroyed by our endogenous digestive enzymes or, if they survive, cannot cross membranes into the bloodstream.

Therefore, the concept of oral application of enzymes and achieving significant therapeutic effects in the body is a concept with significant obstacles for drug development. occurs? Looking at Wobenzym N,Each gastro-resistant tablet contains::

  • Bromelain 45 mg
  • Kimotripsin 1 mg
  • Pankreatin 100 mg
  • Papain 60 mg
  • Rutin 50 mg
  • Trypsin 24 mg

The recommended dose is 3 tablets twice a day 45 minutes before meals. Before looking at the clinical data, I wanted to better understand the formulation and dosage while considering design and application issues.


Each Summary of Product Properties ("Monograph") has the same section. The abbreviation ADME stands for absorption, distribution, metabolism and elimination. This section summarizes the behavior of the chemical in the body. This is not a clinical section describing therapeutic effects. It simply characterizes how extensively and quickly a drug is absorbed from the gastrointestinal tract, where it is distributed in the body ('volume of distribution'), how and whether it is broken down or 'biotransformed' to facilitate elimination, and how quickly it is eliminated from the body. (I have described this process in more detailin the previous post about generics.) I want to see this chart or get enough data to understand what it looks like.

Plasma drug level curve

It is the basic pharmacological work done on a drug that gives us information to understand its properties in the body. There is no point in conducting clinical trials with a chemical packaged as a pill if we cannot confirm that the active ingredient is actually absorbed when swallowed. Clinical trialsconsequencesbasic pharmacological work. If a drug treats different conditions, we may need to study different doses to determine the MEC for each condition. (For example, you need to take a lot more anti-inflammatory drugs to treat rheumatoid arthritis than to treat headaches.)

This is a pharmacokinetic study and allows us to determine how the drug should be dosed and delivered to the body. Is it eliminated slowly so that intake can be infrequent - daily or even weekly? Is it cleared from the body quickly, meaning we have to dose it multiple times a day to stay in the optimal therapeutic range? How is it removed from the body? Does the liver convert it? What is the effect of changing the dose on the excretion of the product? What dose range studies have been performed on the product to determine the appropriate dose? And how does that dose change depending on the disease being treated?

My reason for elaborating on this point is that an understanding of ADME is essential to the rational use of any drug, dietary supplement, or chemical of any kind. As far as herbs are concerned, this is the difference between herbal medicine andpharmacognosy. Without them, product dosing is empirical — testing in the dark. Back to Wobenzym N: We have a combined product with six different ingredients. The dosage instructions are very specific: 3 enteric-coated tablets, twice a day, 45 minutes before meals. This also applies to all purposes described. But why this dose? Why 3 pills? Why twice a day? What happens if you take more or less? Different ingredients usually have their own physicochemical properties. What are the effects of each? I looked at each ingredient firstComprehensive Natural Medicine Database(NMCD) and then in the primary literature itself. Here's what I was able to find:

  • Bromelainis an expression for aA collection of enzymesisolated from pineapple. While evaluating itNMCDBecause it is "possibly effective" for osteoarthritis, the data conflict with some studies suggesting thisno effect on osteoarthritis. Bromelain has not been proven to reach anyoneclinically significant concentrationin the blood. These are large protein molecules andIt is not clear how effectively they are absorbed- Doses of 3000 mg/day appear to result in low, albeit measurable, blood levels. blood plasma componentscan inactivate absorbed bromelain, but half-lifeare described[PDF]. All in all, the data is not impressive.
  • chymotripsinis a protein-digesting enzyme synthesized and secreted by the pancreas. I could not find any published efficacy of a single-ingredient chymotrypsin supplement for any condition. It is not clear what an additional dose of a few milligrams would do. I could not find any data characterizing its ADME.
    Pancreatinis a mixture of digestive enzymes including lipase, protease and amylase that is used as a prescription medicine to treat pancreatic insufficiency in conditions such as cystic fibrosis. High doses are associated with increased blood/urine uric acid levels. There is no proven use of oral pancreatin for any purpose other than pancreatic inefficiency. Again, little information is available to describe ADME.
    Papainis a combination of enzymes obtained from papaya. I could findone study(in German), which favorably compared oral nutritional supplements with acyclovir for herpes zoster pain. Due to the limited data in the abstract, a more extensive data evaluation is not possible. Few data are available to characterize ADME.
    Rutinis a flavenoid classified as "possibly active" in osteoarthritis based on aA single double-blind trial of an enzyme product (bromelain, trypsin and rutin) versus diclofenac. Rutin does not appear to be absorbed intact as it appears to increase plasma quercetin levels and appears to have an effectEffects on the absorption of other drugs. Again, little information is available to understand pharmacokinetics.
  • trypsinis another enzyme produced in the pancreas to help digest protein. Apart from the routine study, I could not find any published studies examining its effectiveness in other conditions. limitedinformation is availabledescribe ADME.

As I noted, large proteins are absorbed like enzymesThe drug design challenge. It is also unclear how large molecules, even if absorbed, would escape rapid metabolism and elimination. There appears to be some data on the ingredients of Wobenzym N that suggest that some components enter the bloodstream. And there are some studies on individual ingredients - but nothing that unequivocally proves a significant effect. With that in mind, I looked for studies using a combination of Wobenzym ingredients.


I stared at the reviewComprehensive Natural Medicine Database(NMCD). About Wobenzym N it is partially written:

Wobenzym N is designed to reduce inflammation and edema and accelerate recovery from certain injuries. It is commonly used by people with arthritis and athletes, including some professional and Olympic athletes. The enzymes in this product are believed to activate macrophages that attack inflammatory circulating immune complexes. Rutoside, an additional ingredient, acts as an antioxidant. To date, there is no convincing clinical evidence that Wobenzym is effective for these purposes. Because these enzymes do not affect the synthesis of prostaglandins, Wobenzym N is also considered free from many of the side effects associated with non-steroidal anti-inflammatory drugs (NSAIDS). Side effects reported after oral administration include loose stools, increased flatulence, and skin reactions.

NMCDwarns that the product can also affect blood clotting.

Are there clinical trials with Wobenzym? Yes, but only a few are in English, which makes it difficult to review. I couldn't find any evaluable studies in PubMed, but other websites list studies under conditions likepelvic inflammatory disease, cancer and multiple sclerosis (URL Removed - Malware Site! -Webmaster). Some therapeutic improvements have been attributed to taking Wobenzym (egDiabetes,after a heart attack), but the studies are preliminary, sometimes unblinded, and do not appear to have been replicated. One of the rare English newspapersappeared in Medical Hypotheses,Not a good sign for someone looking for science-based medicine. In a study published in Russian, there is an uncontrolled study of bronchitis in children. Other studies were published in Czech, Ukrainian, Latvian and Russian. OneA German systematic reviewstated: "Oral therapy with proteolytic enzymes does not offer a valid alternative in the anti-inflammatory treatment of rheumatic diseases compared to NSAIDs." for whose treatment it is used. Overall, the product's safety profile appears acceptable, however, it is not clear how extensive safety data have been collected in these small studies.

There are several trials of a similar product, Phlogenzyma (Rutoside, Bromelain and Trypsin). Onedid not show impressive resultsfor ankle extension. A study examining the same combination in osteoarthritis of the hip suggestsNon-inferiority to diclofenac, i aOpen study for osteoarthritisknees also resulted in non-inferiority. I even found a small study that found it effectivetreatment of pediatric sepsis, which made me wonder if there are any research ethics committees in India.

There is also the interesting case of enzymesSerrapeptaza, is also sold as an anti-inflammatory. It has been sold by the pharmaceutical company Takeda since 1968 for asthma and bronchitis, and is advertised as an anti-inflammatory enzyme for various other purposes.It was withdrawn from the Japanese market in 2011, after double-blind studies concluded that it had no therapeutic effect.

Overall, I was not impressed when I looked at the data for the systemic enzymes. Despite general claims of effectiveness, there are so many limitations in the data itself that it is not clear whether we can conclude that treatment effects are real. In the absence of data on the absorption, distribution, metabolism and excretion of Wobenzym, it is unclear whether this product is even absorbed to any significant extent and available in the body for systemic effects. Because there is no objective measure of effectiveness, it is unclear whether supplementation will have a beneficial therapeutic effect in any chronic or other condition. You may feel better when you take it, but there is still no conclusive evidence that it has any significant effect.

This stone keeps tigers away

It would be an amazing discovery - worthy of a Nobel Prize - if there was an oral therapy that was shown to have a beneficial effect on a range of chronic diseases, with no evidence of toxicity. It would be remarkable even to show that large protein molecules can be taken orally and released into the bloodstream in significant quantities. Unfortunately, none of this has been conclusively proven with Wobenzym or other "systemic" enzyme treatments. Science is complicated, and simple solutions can be attractive, but they can also be wrong. Given the poor clinical and pharmacokinetic data for this product, I expect that if more research is conducted, it will follow the same evidence trajectory as many other dietary supplements with an implausible premise: as research studies increase in size and methodological rigor, treatment improves effects disappear. In the absence of better evidence on the effectiveness and safety of systemic enzyme therapy, its use cannot be considered scientifically based.

  • Scott Gavura

    Scott Gavura, BScPhm, MBA, RPh is committed to improving the way medicines are used and examining the pharmaceutical profession from the perspective of science-based medicine. His professional interest is improving the cost-effectiveness of drug administration at the population level. Scott holds a bachelor's degree in pharmacy and a master's degree in business administration from the University of Toronto, and completed an accredited Canadian Hospital Pharmacy Residency Program. His professional experience includes working in both community and hospital pharmacy. He is a registered pharmacist in Ontario, Canada. Scott has no conflicts of interest to disclose. Disclaimer: Any views expressed by Scott are solely his own and do not represent the views of any current or former employer or organization with which he may be affiliated. All information is provided for discussion purposes only and should not be used as a substitute for consultation with a licensed and accredited health care professional.

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