Proteolytic Enzymes

Nutrients that Accelerate Healing: Proteolytic Enzymes by Luke R. Bucci, Ph.D.

Injuries are inevitable. At some point in time, everyone will sprain an ankle, skin a knee, bruise a shin or perhaps break a bone. Carried to the extreme, injuries are the number one cause of death for young and middle–aged people (from car wrecks, falls and other accidents). Fortunately, our bodies are prepared for Injuries and possess a complex, elaborate and fascinating way to reverse effects of injuries – healing.

Factors Affecting Healing

Table 1 lists some of the more important factors influencing the healing process. As can be seen, there are many factors to consider when one is trying to optimize healing. Imagine yourself trying to find ways to improve and accelerate healing safely. It is impossible to control all the factors affecting healing, especially in people. The simplest way to study effects of nutrients on healing would be to add enough of that nutrient to affect its metabolism beneficially, and then see what happens. This type of research has been performed for some nutrients, but many remain untested. This article will focus on one nutrient that has been extensively tested and found to aid the healing process – proteolytic enzymes.
Table 1

Factors Influencing the Healing Process
Injury severity
Dietary intake
Nutritional status
Environmental temperature
Oxygen content
Mental state
Underlying diseaes

Proteolytic Enzymes

Just as their name implies, proteolytic enzymes are proteins that can digest and break down other proteins. If this sounds familiar, it is, because these proteolytic enzymes are also digestive enzymes secreted by the pancreas after meals. Thus, Trypsin and Chymotrypsin are derived from hog or beef pancreas commercially. Cruder grades are known as pancreatin. Bromelain (from pineapple stems), Papain (from green papaya latex), and ficin (from fig tress) are examples of proteolytic enzymes from plants, suitable for strict vegetarians. Also, proteolytic enzymes from bacteria or fungi are available.

Proteolytic Enzymes and Injuries

To make a long story short, under the right conditions, proteolytic enzymes are able to accelerate the healing process in a beneficial manner. This makes perfect sense, since proteolytic enzymes are involved in all aspects of healing. In fact, proteolytic enzymes are a major control mechanism for most, if not all, bodily processes. For example, blood clotting or cell killing by immune cells is dependent on many proteolytic enzymes. This fact is largely unappreciated. When taken in dietary supplements, proteolytic enzymes can substitute for other proteolytic enzymes normally used by the body to control the healing process. Thus, proteolytic enzyme supplements are not drugs, because they are used to replace or supplement the body's own proteins.

Proteolytic Enzymes How They Work

Proteolytic enzymes help to reduce inflammation and accelerate healing by many ways as seen in Table 2. Most of these effects are also performed normally by proteolytic enzymes the body already possesses. Unfortunately, when an injury occurs, bodily proteolytic enzymes are unable to keep pace with demands for their presence. At first thought, many people are worried that adding additional proteolytic enzymes will be harmful by causing too much breakdown of proteins in the wrong places. In fact, if all of our endogenous proteolytic enzymes were activated at once, we would dissolve into a pool of goo in minutes. Fortunately, our bodies are loaded with protease inhibitors, especially in the blood, so that proteolytic enzymes will not run amok and harm other systems. After all, during digestion, proteolytic enzymes digest food and not ourselves. This gives the reader an idea of how proteolytic enzymes are well-controlled.

Table 2

Mechanisms Describing How Proteolytic   Enzymes Work
Replace or substitute for endogenous
proteolytic enzymes
Activate other endogenous proteolytic enzymes
Inactivate substances that cause
inflammation (bradykinins)
Decrease pro-inflammatory prostaglandins
Increase anti-inflammatory prostaglandins
Break down proteins leaked from
damaged cells to improve fluid flow
Break down excess fibrin (clot)
to improve fluid flow

To fulfill their promise, proteolytic enzymes must be absorbed intact into circulation with activity preserved when given orally. But proteolytic enzymes are themselves proteins. How can proteins be absorbed and exert an anti-inflammatory effect? Won't they be completely broken down into amino acids in the gut like other proteins? This question has been examined over three dozen times in the literature and almost overwhelming support is found for absorption of proteolytic enzymes. Although only a small amount of active enzyme is absorbed (0.01-10% of total) after oral administration, this amount appears to be sufficient to account for the mechanisms and effects seen in Tables 2 and 3. Remember that proteolytic enzymes are enzymes, meaning they are catalytic (one enzyme molecule can catalyze hundreds of thousands of reactions in a very short time).
Table 3

Comparison of Anti-inflammatory Effects Between
Proteolytic Enzymes and Drugs for Five Types of Inflammation

Agent Type                                                   % Inhibition of inflammation*      

  1 2 3 4 5
Pancreatin Proteolytic 35 32 39 11 38
Enzyme Bromelain 45 22 46 43 41
Papain 14 10 13 12 24
Ficin 31 37 53 22 35
Aspirin Salicylate 36 23 34 58 74
Hydrocortisone Corticosteroid 29 19 31 43 53
Indomethacin NSAID 17 20 23 40 36
Phenylbutazone NSAID  27 20 11 31 59

* Inflammation (edema) induced in rat paws after injection of:
(1) serotonin: (2) egg white: (3) dextran; (4) brewers yeast; and (5) carageenan.

Proteolytic Enzymes How Well They Work: Anti–inflammatory Effects

During the 1960s, proteolytic enzymes were prescription drugs for reduction of inflammation and acceleration of healing for injuries. After corticosteroids and non–steroidal anti–inflammatory drugs (NSAIDs) were discovered, proteolytic enzymes rapidly fell out of favor. This does not mean that proteolytic enzymes are useless, but rather, reflects the financial and political vagaries of the pharmaceutical business. In fact, animal studies using standard experimental models of inflammation have compared proteolytic enzymes to NSAIDs and corticosteroids. In 1972, the Department of Pharmacology from the Milan University School of Medicine in Italy studied oral doses of pancreatin, Bromelain, Papain and ficin along with oral aspirin, indomethacin (Indocin), phenylbutazone (Butazolidin) and hydrocortisone. Five different kinds of inflammation were studied. Results are shown in Table 3. Pancreatin, Bromelain and ficin were as effective as the drugs against most kinds of inflammation. lnterestingly, except for aspirin, tested drugs were effective only for two or three types of inflammation, meaning proteolytic enzymes are actually more useful for reducing inflammation than most drugs in current widespread use.

Proteolytic Enzymes How Well They Work: Acceleration of Healing

Unlike drugs, proteolytic enzymes can actually speed healing from injuries. In fact, most anti–inflammatory drugs either delay healing or have no beneficial effects on times to heal. This is well–known among scientists and drug companies, but not among clinicians and patients. Again, to illustrate the promotion of healing found with proteolytic enzymes, one representative report will be singled out and examined in detail.

In 1965. a medical doctor explored the use of a prescription proteolytic enzyme product on injured football players from the University of Pittsburgh with a double-blind study. Two tablets four times per day of Orenzyme (containing pancreatin) or placebo were given immediately after an injury until return to play. Standard physiotherapy was also given to each injured athlete. Injuries ranged from contusions (bruises) to sprains and fractures. Time before return to play was estimated by three sports medicine doctors and compared to the time each player actually returned to play. The most common time for return to play for the proteolytic enzyme group (11 players) was 33% (one–third) of that predicted, while that for placebos was 73% (almost three–fourths). Thus, in a double-blind study with proper statistical analysis, proteolytic enzymes were associated with faster healing times. This type of finding was also seen for over two dozen other studies on sports injuries alone.

Proteolytic Enzymes and How To Use Them

Although clinical trials of proteolytic enzymes appear very dramatic, there are a few guidelines for proper use that will ensure best results. Less than optimum use will mean that best results may not be achieved. Table 4 lists these guidelines. It must be emphasized that proteolytic enzymes seem to work best on acute injuries, and less on chronic injuries. Also, it is very important to start supplementation as soon as possible after an injury. For those conditions where a person knows an injury will occur (such as boxing), supplementation may start a day before the traumatic event. In fact, several studies on boxers and proteolytic enzymes found 50% reductions in swelling and time to recovery when enzymes were given before, during and after about.

Table 4

Guidelines for Use for Proteolytic Enzymes
Start supplementation as soon as possible after injury
Initial loading dose: 5-10 tablets
Daily doses: 2-8 tablets four times per day
Take daily doses between meals on an empty stomach
Continue until healing improves or one week

The major drawback to use of proteolytic enzymes is patient compliance. Taking a large number of "pills" several times per day on an empty stomach is difficult to remember for the average consumer, but consistent supplementation is a must.

Table 5

Considerations for Choosing Proteolytic Enzyme Products
Enteric coating desired
Highest activity possible (difficult to determine)
Multiple proteolytic enzymes preferred
Strict vegans should avoid pancreatin, trypsin, chymotrypsin; bromelain, papain, ficin are suitable
Manufacturers reputation somewhat reliable
Choose companies with small batch sizes
(will increase shelf life and potency)
Small tablets preferred will release enzyme quicker
than large tablets and allow for more flexibility)

Proteolytic Enzymes Product Choice Factors

Table 5 lists the various factors which can determine which proteolytic enzyme product is more beneficial than others. Unfortunately, the average consumer will not have access to product potency information. Even the label claims are next to meaningless. Different products use different assay systems to define proteolytic enzyme activity, which confuses label comparisons. Thus, it is impractical to rely strictly on label claims. This author and his co-workers have tested the actual activities of many proteolytic enzyme products, including prescription drugs. It was found that the majority of the products possessed very low potency (including the prescription drugs). The measured potency did not correlate with the label claim, so it is impossible to predict which supplement is the most potent. Surprisingly, the most potent tablets were among the smallest tablets.

Thus, the bottom line on choosing a supplement is to try one. If it does not appear to help, then try another, and so on. Eventually, one product will work. Until common industry standards are agreed upon, it will be difficult to compare potencies of proteolytic enzyme products.


In conclusion, proteolytic enzymes represent a powerful type of supplement which were previously a first-line pharmaceutical anti-inflammatory. In fact, proteolytic enzymes, when used properly, are one of the few nutritional supplements that can show visible overnight results in many cases. It is of prime importance to use proteolytic enzymes for acute injuries. Chronic injuries do not seem to respond as well as acute injuries. Fortunately, there are other supplements which are more useful for chronic injuries, such as chondroitin sulfates. Also, proteolytic enzyme products are tremendously safe. No reports of side effects from oral use have been reported. Other than potential allergic reactions to the source of the enzymes, no side effects are expected.

Proteolytic enzymes are able to reduce inflammation and speed healing of acute injuries, especially sports injuries. An extensive and favorable body of literature supports the efficacy and safety of proteolytic enzymes for these purposes.

Luke R. Bucci, Ph.D. received his degree in Biochemistry/Cell Biology from the University of Texas Graduate School of Biomedical Sciences at Houston. A postdoctoral appointment on effects of chemotherapy and radiotherapy on normal tissues at M.D. Anderson Hospital followed before he became Research Director for Biotics Research Corp. in Houston; he is also a technical consultant for Sports Research Corporation. Dr. Bucci has lectured extensively on anabolic steroid abuse and nutritional steroid alternatives.

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