What, another article about proteolytic enzymes? Surely there’s nothing more to be said on the subject. After all, in a previous article I referred to LifeLink’s CardioPeptase as a “miracle” microbial enzyme. How can the Poly-Zyme family—or any other combination of proteolytic enzymes—compare to a miracle?

Patience, dear reader. All will be explained. But first let’s take a look at what the Poly-Zymes are.

Poly-Zyme supplements are combinations of enzymes targeted toward specific applications, such as relieving inflammation (Poly-Zyme 021) or enhancing the immune response (Poly-Zymes 022 and 023). Each member of the Poly-Zyme family is composed of a mixture of enzymes, most of them proteolytic, together with other synergistic agents such as thymus extracts and flavonoids.

In case your memory needs jogging, proteolytic enzymes are proteins that cut up other proteins. Some proteolytic enzymes, such as trypsin, chymotrypsin, and the pancreatin complex, are produced in the pancreas where they assist animals and humans with the digestion of food. Others are found in plants, such as bromelain in pineapple stems and papain in papaya. Still others, such as CardioPeptase (also known as serrapeptase), are produced by bacteria or other microorganisms.

As described in more detail in my previous article, proteolytic enzymes have been used as anti-inflammatory agents for many years. In the early 1950s such enzymes were administered intravenously or intramuscularly, but it was later discovered that enterically coated enzymes were equally effective when taken by mouth. A proper enteric coating is needed to ensure that the enzymes can bypass digestion in the stomach and be absorbed in the intestines.

Such is the case for enterically coated Poly-Zyme 021, which can help relieve inflammatory conditions ranging from arthritis, sports injuries, and joint, muscle, and tendon pain to inflammations of the pulmonary, genitourinary, and gastrointestinal tracts ¹. It has also been reported effective for treating leg cramps and edema, sinusitis, chronic skin conditions, and impaired circulation resulting from blood clots, arteriosclerosis, and inflammation of the blood vessels ¹. On top of that, it also makes an excellent digestive enzyme supplement!

If you look at the label, you’ll notice that Poly-Zyme 021 contains four different kinds of proteolytic enzymes in defined amounts—trypsin, chymotrypsin, bromelain, and papain—as well as pancreatin, the enzyme complex derived from pancreatic juice which is the natural source of both trypsin and chymotrypsin. It’s clear there’s some redundancy built into the Poly-Zyme 021 formulation because many of the enzymes appear twice: once as isolated enzymes and once as components of pancreatin. One reason for this has to do with the way that the various proteolytic enzymes synergize with one another. For example, it’s known that adding a small amount of chymotrypsin to trypsin will enhance the intestinal absorption of trypsin ². The mechanism for this enhanced uptake is not known. A possible explanation comes from the fact that chymotrypsin, but not trypsin, forms an irreversible complex with antitrypsin, the primary trypsin inhibitor in the blood ³. By complexing with and tying up antitrypsin (a process known as “suicide” inactivation), chymotrypsin may sacrifice itself to leave more trypsin available in its active state.

In similar fashion, combining bromelain with pancreatin reportedly increases the intestinal absorption of pancreatin ⁴. Hans Nieper, the German physician who developed many innovative enzyme-based treatments for cancer and cardiovascular disease, speculated that the increased absorption of pancreatin was all a matter of electric charge. According to Dr. Nieper, pancreatin is not well absorbed by itself; it tends to stay in the intestines for the purpose of facilitating digestion rather than migrate into the blood stream. In contrast to animal-derived enzymes like pancreatin, plant-derived enzymes like bromelain are much more easily absorbed. However, if bromelain and pancreatin are administered in certain defined ratios, some of the pancreatin will appear in the blood stream. Nieper believed that the presence of bromelain neutralizes the electrical properties of pancreatin and thus temporarily inactivates the blocking mechanism which normally keeps pancreatin from passing from the intestines into the blood ⁴.

Whatever the reason, it’s clear that the synergism between different enzymes results in increased uptake. But that’s not the only kind of synergism at work in Poly-Zyme 021.

In technical terms, each of the four proteolytic enzymes in Poly-Zyme 021 also has a unique “substrate specificity” or preference for molecular targets. This means that each enzyme is picky and likes to attack and chew up proteins only at very particular places. As most people know, proteins are essentially chains of amino acids. The enzyme trypsin likes to cut protein chains immediately after a lysine or an arginine appears in the amino acid sequence. On the other hand, chymotrypsin prefers to cut proteins after an aromatic amino acid (either tyrosine, phenylalanine or tryptophan) or after a large hydrophobic amino acid (such as leucine or methionine). The plant enzymes bromelain and papain belong to a different family of proteolytic enzymes and each one has its own unique substrate preference. For example, papain can cut proteins after an arginine, lysine, glutamic acid, histidine, glycine or tyrosine, although lysine and arginine are the preferred amino acids recognized by papain ⁵.

What all this means is that when the four proteolytic enzymes in Poly-Zyme 021 are combined, the combination has a broader range of molecular targets to attack. As a result the combined enzymes are faster and much more effective than any single enzyme in doing their job—whether that job is degrading inflammatory proteins, reducing the levels of circulating immune complexes (antibody-antigen conglomerates), modifying cell-surface adhesion molecules that guide inflammatory cells to their targets, or cutting apart bradykinin, a messenger molecule involved in pain signaling and inflammation ⁶. An example of this kind of synergism is evident in a Japanese study of inflammatory edema (swelling) induced in experimental animals ⁷. Oral administration of bromelain and trypsin combined was more effective than either enzyme alone in suppressing paw edema caused by injection of an irritant. The enzyme combination also effectively inhibited an increase in vascular permeability (blood vessel “leakiness”) induced by histamine and bradykinin.

Another kind of synergism at work in the Poly-Zyme formulations has to do with the presence of amylase and lipase, which are present both as individual enzymes and also as components of pancreatin. Amylase digests starch into sugars like glucose and maltose and into intermediate length polysaccharides (dextrins). Lipase digests fats into glycerol, mono- and diglycerides, and ultimately fatty acids. It is unknown how these two enzymes synergize with the other enzymes in the Poly-Zyme formulations, but synergize they do. For example, as we’ll see later, amylase collaborates with bromelain and trypsin to enhance immune activation. It’s conceivable that amylase does so by modifying the carbohydrate portions of immune cell glycoproteins, although such an effect has not been previously reported. A similar mechanism would account for enhanced anti-inflammatory effects of amylase as well. As for lipase, oral doses have been used as part of a treatment regimen for arteriosclerosis. The combination of proteolytic enzymes with lipase is thought to be effective in attacking both the fibrous and lipid components of plaque in clogged arteries.

There’s still at least one more synergism in Poly-Zyme 021 that deserves to be mentioned, and that’s between the proteolytic enzymes and rutin. Rutin is a plant-derived flavonoid (actually a flavonoid glycoside, meaning that it has a sugar molecule attached). Like all flavonoids rutin has both antioxidant ⁸ and anti-inflammatory ⁹ properties. Furthermore rutin is metabolized in the gut to quercetin, which itself is notably anti-inflammatory ^9, 10. Thus rutin naturally collaborates with proteolytic enzymes via a parallel but independent pathway to inhibit inflammation.

Because flavonoids like rutin and quercetin are also known to strengthen the integrity of blood vessels, they tend to inhibit inflammatory edema associated with increased vascular permeability. As a result Poly-Zyme 021 is useful in treating conditions such as leg cramps and swelling associated with chronic venous insufficiency (CVI). Rutin not only helps decrease capillary permeability, it also improves venous tone, venous capacity and venous distension as well as activating fibrinolysis (breakdown of fibrous deposits and clots) in CVI ¹¹. The proteolytic enzymes are of course well known for their ability to activate fibrinolysis ⁶, a mechanism which appears to depend on the conversion of plasminogen to plasmin in the body as much as on the innate ability of the proteolytic enzymes to dissolve fibrin directly. Combining the Poly-Zyme enzymes with rutin thus produces a powerful synergistic effect on CVI, and indeed on many other circulatory disturbances such as varicose veins and arteriosclerosis.

Years of clinical trials have confirmed the efficacy of the Poly-Zyme 021 formulation in many different circumstances. Poly-Zyme 021 is essentially a generic version of Wobenzym N, the most popular over-the-counter medication in Germany. This tried-and-true formula has proved beneficial in the treatment of osteoarthritis ¹², rheumatoid arthritis ¹³, inflammatory kidney disease (glomerulonephritis) ¹⁴, chronic autoimmune prostatitis ¹⁵, and mastopathy (hardening of the mammary glands) ¹⁶. It is effective in relieving post-operative pain ¹⁷, lymphedema following breast surgery ¹⁸, and lymphedema, bruising, and pain following cosmetic surgery ¹⁹. It’s also been reported to help prevent the recurrence of arteriosclerosis and inflammation in patients recovering from a heart attack ²⁰.

The same synergistic principles that make Poly-Zyme 021 so effective are also at work in Poly-Zymes 022 and 023. These formulations have repeatedly proved their worth in assisting recovery from cancer and from viral infections, especially those associated with immunosuppression such as herpes zoster (shingles).

Poly-Zymes 022 and 023 are enzyme combinations which include raw thymus extracts instead of rutin. Both 022 and 023, which are administered differently, are targeted toward immune support. Poly-Zyme 022 contains papain and pancreatin in addition to thymus concentrates, while Poly-Zyme 023 contains larger amounts of these factors plus bromelain and lipase as well. The thymus extracts contain additional proteolytic enzymes that complement bromelain, papain, and pancreatin, but the main purpose of the extracts is to provide a source of thymic peptides and proteins. The thymus gland, of course, is a major control center for the immune system and is richly supplied with immune-stimulating factors.

The immunostimulating effects of Poly-Zymes 022 and 023 don’t just come from thymus extracts, however. The proteolytic enzymes in each formulation are themselves potent modulators of the immune response. Bromelain, for example, markedly enhances T lymphocyte activation. It does so by pruning certain proteins from the T cell surface that regulate the interaction of T cells with other immune cells ²¹. Bromelain can also stimulate the killing of candida by immune cells in both healthy subjects and in patients with immune deficiency disease ²². Bromelain, papain, and amylase (the starch-digesting enzyme in the pancreatin complex) have each been shown to induce cytokine synthesis in peripheral blood mononuclear cells in vitro ^23, 24; cytokines are immune-modulating proteins which include interleukins and tumor necrosis factor (TNF).

Therapy with oral proteolytic enzymes has also been effective in countering herpes zoster eruptions ²⁵, which typically arise as a result of immunosuppression (e.g., following cancer chemotherapy). The effectiveness of proteolytic enzyme combinations against herpes zoster—and also against cases of rheumatoid arthritis and osteomyelofibrosis—appears to be related to the ability of these enzymes to suppress elevated levels of transforming growth factor-beta ²⁶.

Some of the anticancer activities of the Poly-Zyme formulations also derive from regulation of the immune response ^23, 24. This applies not only to Poly-Zymes 022 and 023 but also to the Poly-Zyme 021 formula, which has also been reported effective in stimulating the killing of tumor cells by immune cells ²⁷. But that’s not unexpected, given that many of the same enzymes appear in all three Poly-Zyme combinations.

In addition, the Poly-Zyme formulas have anticancer effects that are independent of immune activation. For example, both Wobe-Mugos (a German preparation similar to Poly-Zyme 022) and Wobenzym N (essentially the same as Poly-Zyme 021) were found to be effective as adjuvant therapy when administered together with chemotherapy in cases of malignant lymphoma ²⁸. Bromelain, a component of Poly-Zymes 021 and 023, has been shown to reduce tumor cell metastasis in humans ²⁹ and animals ³⁰ and to inhibit the invasiveness of glioma cells (a particularly aggressive tumor type) in vitro ³¹. Similar inhibitory effects are likely with papain as well. Even the rutin component of Poly-Zyme 021 has cancer-fighting ability independent of any effects it might have on the immune system, since it is metabolized to quercetin in the gut. Quercetin is well known for its antitumor effects ³².

Given all this information, which Poly-Zyme combination is best suited for which job? I’ve already said that Poly-Zyme 021 is best for reducing inflammation and promoting healing from injuries of all kinds. Like Poly-Zyme 021, Poly-Zyme 022 is enterically coated for oral administration and either or both can be used for boosting the immune response, e.g., against viral infections or cancer. I personally recommend trying both, either together or in alternation, to maximize the synergistic benefits inherent in both formulations.

As for Poly-Zyme 023, it’s the only one of the three that is not enterically coated and hence the only one that will have limited effectiveness if taken orally. Originally developed in Germany, this formula was intended to be dissolved in water and used as an enema. Because the FDA in the United States has not approved the use of enzymes administered in this manner, distributors in the U.S. are forbidden to promote this method of using Poly-Zyme 023. Accordingly, anyone interested in experiencing the benefits of this potent enzyme combination should take it upon themselves to find their own method of use.

At the beginning of this article, I raised the question of how CardioPeptase—an enzyme with powerful fibrinolytic and anti-inflammatory properties—could stack up against the Poly-Zyme formulations. As mentioned in my previous article, a study comparing CardioPeptase to trypsin, chymotrypsin, and pronase (another microbial enzyme) individually found that CardioPeptase outperformed them all as an anti-inflammatory agent. However, to my knowledge no one has yet compared CardioPeptase to combinations of proteolytic enzymes. CardioPeptase is effective in part because of its broad substrate specificity-but the same is also true for the synergistic enzyme combinations in the Poly-Zymes.

Here’s my best guess: Like Poly-Zyme 021, CardioPeptase has an excellent track record as an analgesic and anti-inflammatory. Both have proved useful for promoting wound healing and surgical recovery, and both are effective at relieving sinusitis, asthma and bronchitis. Because of its pronounced clot-busting activity, however, CardioPeptase may be best suited for inhibiting arteriosclerosis. Even for this purpose, the late great Hans Nieper, MD recommended that CardioPeptase be used in combination with bromelain and other nutritional factors (see my article on CardioPeptase for details). Since Poly-Zyme 021 contains bromelain and is highly beneficial for all vascular conditions including arteriosclerosis, it wouldn’t hurt to take CardioPeptase with Poly-Zyme 021 for their combined (dare I say synergistic?) cardiovascular benefits.

Because of their clot-dissolving (fibrinolytic) effects, the Poly-Zyme formulations and especially Poly-Zyme 021 should be used cautiously by anyone taking anticoagulant medications such as warfarin concurrently. Consult your health-care professional for advice if you are taking any kind of blood thinner.