Proteolytic Enzymes

List of Proteolytic Enzymes and the Benefits of Protease Supplements

What are Proteolytic Enzymes?

Proteolytic enzymes work to clean the bloodstream and soft tissues and promote healthy digestion by breaking down harmful proteins. Enzymes are proteins themselves, but their function is speed up chemical reactions within the body. Normally there are tens of thousands of enzymatic reactions occurring in the body at once, all working to sustain life. Although there are thousands of enzymes, only a small subset of those are proteolytic enzymes, and their function is to improve all metabolic facets in the body, ranging anywhere liver function to immune support. These microscopic enzymes are found in a variety of foods as well as supplements. A large portion of proteolytic enzymes are produced by the body itself during the digestion process.

How do Proteolytic Enzymes Work?

Each type of proteolytic enzyme has particular functions to assist in chemical reactions, but in a broad sense they work by breaking down harmful proteins that may cause illness or allergies. They do this by breaking down the defense mechanisms that dangerous cells and proteins have that would ultimately cause harm to your body. These enzymes often work by breaking down large circulating immune complexes that are taken into the body via foods like wheat, corn, dairy, and soy that the body may recognized as allergens. By doing this, proteolytic enzymes make up for any dietary issues that a person may have, and then the by products are filtered by the lymphatic system and kidneys.

Proteolytic enzymes, also called proteases, can be broken down into six broad categories: Serine protease, Threonine protease, Cysteine protease, Aspartate protease, Glutamic acid protease, Metalloproteases. All these types of proteases work by breaking peptide bonds, although sometimes by different mechanisms.

Proteolytic Enzymes Benefits and Uses


The anti-inflammatory and analgesic properties of the enzyme bromelain make it a safe alternative to other medications designed to treat arthritis and joint pain. Its first recorded use in a 1964 study showed that bromelain is effective in reducing pain and inflammation caused by both rheumatoid arthritis and osteoarthritis. Numerous subsequent studies confirm these results, particularly studies that examine arthritis in the knee and shoulder joints. These studies were performed to determine the mechanism by which bromelain works to treat arthritis. A 1988 study showed that bromelain works by reducing edema and pain in the joints, which can provide relief for patients with arthritis. At least five other studies spanning the 1990s and early 2000s show that bromelain works by modulating certain immune cell surface adhesion molecules which all play a role in the pathogenesis of arthritis. The studies are of limited quality and most are performed on mice, so further research is needed to confirm how bromelain works when used to treat arthritis. A human study performed in 2004 showed that the compounds rutin and trypsin that are present in bromelain treatments may also work to improve the condition of osteoarthritis. This is our Favorite Proteolytic enzyme for Arthritis.


Early studies on bromelain treatment from the 1960’s show that this proteolytic enzyme can reduce inflammation and swelling caused by edema proceeding injuries, minor procedures, and dental surgery. Bromelain’s analgesic properties lends itself to be used as an anti-inflammatory medication, and several studies support this use. In a 1981 study, edema was induced in the hindleg of mice, and an oral treatment of bromelain showed to decrease the swelling. Bromelain given to mice in a 2008 study also showed to reduce inflammation by reducing the migration of neutrophil (a type of white blood cell) to the inflamed area by 50-85%. A study performed in 1988 showed that one mechanism by which bromelain possibly works to reduce inflammation is by producing bradykinin, a peptide that causes blood vessels to dilate, blood pressure to fall, and in turn reduces inflammation. Another proteolytic enzyme, seaprose, also showed to reduce inflammation in the lungs in patients with chronic bronchitis. This study performed in 1993 worked by giving patients 90 mg of seaprose a day and then resulted in patients not only having reduced inflammation, but less mucus build-up as well. This is our Favorite Proteolytic enzyme for Inflammation.


Proteolytic enzyme therapy for cancer patients has shown to work in numerous experimental studies and clinical trials. In one study conducted in 2008, enzyme therapy given to patients suffering from breast cancer, colorectal cancer, and plasmacytoma improved the symptoms of nausea, gastrointestinal complaints, fatigue, weight loss, and restlessness caused by the tumors and alternate cancer therapies as well. Those patients suffering from plasmacytoma that were given proteolytic enzymatic treatments showed an increase the response rates, the duration of remissions, and the overall survival times. Overall, the therapy seemed to stabilize the quality of life for cancer patients. A study performed in 1994 explains why proteolytic enzymatic treatment is effective in treating cancer; certain proteolytic enzymes produce tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1 beta), and interleukin-6 (IL-6), which all aid in resisting cancer cells. Another study performed in 2008 on mice showed that bromelain treatment blocks the CD128 chemokine receptor which in turn can inhibit breast cancer stem cells from developing. We recommend a general Proteolytic enzyme supplement for Cancer.


Bromelain’s effectiveness in treating inflammation caused by numerous conditions indirectly makes it an effective anti-pain treatment. Even though most research performed on bromelain is not necessarily looking to treat pain alone, all studies regarding inflammation can be linked to a decrease in the associated pain as well. Another proteolytic enzyme, seaprose, was specifically reported in a 1996 study on 40 people to reduce pain, but again that pain was associated with a condition called thrombophlebitis that causes inflammation. This is our Favorite Proteolytic enzyme for Pain Relief.

Heart Attack

An early study from 1972 on bromelain showed that it can promote healthy blood viscosity and platelet aggregation. Since then a study on rats was performed in 2008 where rats were injected with a 10 mg/kg bromelain solution twice a day for fifteen days in a row. Following the treatment, the rats had improved left heart ventricle function and increased aortic flow, which left the researchers to conclude that a bromelain treatment may be a possible cardioprotective therapy. This is our Favorite Proteolytic enzyme for the Heart.

Blood Pressure

A study performed in 2012 showed that the enzyme nattokinase acts as an ACE-inhibitor which can lower blood pressure by producing a protease enzyme called subtilisin. The researchers further concluded that the benefits of nattokinase can be had just by eating the food natto, from which nattokinase is derived, and patients do not necessarily need supplementation. A larger study performed in 2008 on 86 human participants that ranged from 20 – 80 years old treated high blood pressure using a nattokinase treatment. The experimental group showed significant improvements in both systolic blood pressure and diastolic blood pressure in comparison to the placebo group, which led the researchers to conclude that nattokinase may be used to treat hypertension. This is our Favorite Proteolytic enzyme for Blood Pressure.

Alzheimer’s Disease

A study performed in Taiwan in 2009 showed that the enzyme nattokinase may prevent the onset of Alzheimer’s disease. The process behind this is that nattokinase can break up amyloid fibrils, a type of peptide protein that can build up in the brain and cause cognitive damage that would lead to Alzheimer’s. More research is needed to confirm those results, but this initial work warrants further study. This is our Favorite Proteolytic enzyme for Alzheimer’s.


Bromelain has been recommended for centuries as a folk medicine to treat gout. Although strict experimental studies on the effects of bromelain specifically on gout are lacking, several dietary studies recommend a diet rich in foods containing bromelain (like pineapple) to treat that condition. And we know that bromelain can also be used to treat other varieties of arthritis, so it is reasonable to infer that it can be used to treat gouty arthritis as well. Modern testimonial evidence suggests that if gout is flaring, 500 mg of bromelain taken every three hours until the attack subdues can reduce the duration of the flare up. The same dosage taken twice daily can also prevent the onset of gout symptoms. This is our Favorite Proteolytic enzyme for Gout.


The enzyme Cathepsin K in combination with other experimental treatments was shown in a 2014 study to decrease bone fractures and increase bone density after one year of treatment. Although this treatment is relatively new, researchers are already regarding it as a revolutionizing treatment for the management of osteoporosis. Further research on osteoporosis on post-menopausal women shows that proteolytic enzymes reverse apoptosis, also known as programmed cell death, which allows new bone formation to occur. We recommend a general Proteolytic enzyme supplement for Osteoporosis.


The pain associated with fibromyalgia is cause by a buildup of fibrin, and several studies show that some proteolytic enzymes are capable of breaking down fibrins. A study published in 1969 showed that the enzymes trypsin, elastase, and pronase destroyed a fibrin stabilizing factor in an experimental study. The use of proteolytic enzymes for treating fibromyalgia should be done with caution however. A 2016 case study showed that the enzyme serratiopeptidase, which is known for its fibrinolytic properties, can in some stances lead to severe swelling when used after oral surgery. However, there is numerous testimonial evidence claiming that another enzyme serrapeptase reduces the pain associated with fibromyalgia. We recommend a general Proteolytic enzyme supplement for Fibromyalgia.

IBS (Irritable Bowel Syndrome)

There is conflicting information about the role and use of proteolytic enzymes for irritable bowel syndrome (IBS). A 2007 study shows that patients with IBS release excess proteases trypsin and tryptase, making the patient more sensitive to pain, and those proteases can directly stimulate sensory neurons in the gut. However, two more studies performed in 1999 and 2011 showed that taking an oral proteolytic supplement reduced gas, bloating, and abdominal pain in IBS patients. While this initial research is promising, scientists advise caution when using proteolytic enzymes for this condition because they feel that more research is needed in this area. We recommend a general Proteolytic enzyme supplement for Irritable Bowel Syndrome.


In 1997 a study was performed on guinea pigs to test the effects of proteases on allergic responses. The results showed that those animals given the treatment had heightened antibody responses to other enzymes that would normally cause allergies compared to the control group. The idea behind why proteolytic enzymes work to treat allergies is simple. Allergies are caused by the body’s reaction to particular proteins, and since proteolytic enzymes work to break down proteins, they should theoretically be able to break down proteins that cause allergies. We recommend a general Proteolytic enzyme supplement for Allergies.

Acid Reflux

Studies published in 2006 and 2013 report that among other compounds, proteases may aggravate and, in some instances, even cause acid reflux. However, many herbalists claim the opposite, that proteolytic enzymes may prevent acid reflux by attacking the root of the cause: the digestive system. They report that acid reflux can often be caused by poorly digested foods, and proteolytic enzymes should aid in the digestion by breaking down those food proteins. Testimonial evidence rules in favor of the research with many people reporting a side effect of acid reflux after taking proteolytic enzyme supplements. We recommend a general Proteolytic enzyme supplement for Acid Reflux.


There is some evidence that proteolytic enzymes may be used to treat asthma, as shown in a 2005 study. In this study, healthy non-smoking adults with asthma were given a protease treatment, and those given the treatment were shown to have more enzymatic activity in the saliva and mucous than those not given the treatment. The rational behind this is that many cases of asthma are characterized by inflammation and remodeling of the airways, and previous research shows that proteases have an active role in those issues. We recommend a general Proteolytic enzyme supplement for Asthma.


A large medical review published 2008 explained that a topical treatment containing proteolytic enzymes helped to treat dead tissue on the skin. Their summary shows that collagenase treatments are effective in removing necrotic tissue from ulcers and burn injuries. There is some evidence, although limited, that papain may even treat similar symptoms faster than collagenase. Another five studies ranging from 2002-2012 successfully showed that enzymatic creams and ointments can be used to clean and dress surface wounds. Aside from wound maintenance, a study published in 2007 showed that a proteolytic cream may have cosmetic benefits as a skin moisturizer, and as such it may also be effective at treating rosacea, dandruff, dermatitis, and even eczema. The idea behind why proteolytic enzymes work to treat skin conditions is that it helps to protect compromised skin barriers by reducing water loss and maintaining healthy, hydrated skin. We recommend a general Proteolytic enzyme supplement for Skin.


A study performed in 1995 had two groups of 96 people that were given either a standard shingles treatment or a proteolytic enzyme treatment over the course of 14 days. While both groups showed an improvement in treating the initial outbreak of shingles, the group given the enzyme treatment experienced fewer side effects. Another study published the same year on 90 people over a 7-day period, and that study had similar results. They also reported that in addition to experiencing fewer side effects, enzymatic treatment is less costly to the patient than standard treatment options. Proteolytic enzymes’ anti-inflammatory and immune-protective properties explains how it is able to combat the virus, Herpes zoster, which causes shingles. We recommend a general Proteolytic enzyme supplement for Shingles.


This condition occurs when there are dysfunctions or changes in proteolytic enzymes, cytokines, inflammatory molecules, and vascularization during the normal ovulation cycle, as summarized by a large scientific review published in 2014. Because enzymes are one of the major factors in maintaining a healthy female reproductive system, many herbalists and holistic care practitioners suggest a proteolytic enzyme supplement to help treat or prevent the onset of endometriosis. While a regulated enzymatic treatment is not available, anecdotal evidence reported by customers supports this treatment. We recommend a general Proteolytic enzyme supplement for Endometriosis.


Since many proteolytic enzymes have anti-inflammatory properties, it makes sense that some use it to treat diverticulitis, a condition marked by inflammation and pain associated with the colon and large intestine. Furthermore, some may think that an imbalance in enzymes may be the cause of diverticulitis. However, a study published in 1969 showed that a healthy colon sample and a sample with diverticulitis had similar enzymatic activity. Nonetheless, many holistic and naturopathic care givens suggest a protease supplement to treat diverticulitis. We recommend a general Proteolytic enzyme supplement for Diverticulitis.

Heart Disease

While some may suggest taking protease supplements to treat or prevent heart disease, some research indicates that you should not do so. A study published in 2012 reports that the progression of heart failure can occur due to remodeling of the cardiac tissue, and that remodeling can be heightened by increased protease activity. In order to treat heart disease, it is actually recommended by the scientific community to inhibit the activity of proteolytic enzymes. However, other conditions that are associated with heart disease, like blood clots, can dissipate in reaction to protease treatment if taken in moderation. We recommend a general Proteolytic enzyme supplement for Heart Disease.


While there is not much research on the effects of a protease treatment on candida, it is known that yeast infections are caused by bacteria, and the proteins in that bacteria can be broken down by enzymes. However, several case studies published by naturopathic practices show evidence that a proteolytic enzyme formula can successfully treat candida. For example, in one instance a 71-year-old man was given a proteolytic treatment after candida flared up due to a course of antibiotics, and over the course of several weeks the symptoms dissipated. Even though evidence is limited to case studies like that, those results may warrant actual scientific research.We recommend a general Proteolytic enzyme supplement for Candida.

Blood Clots

A Czech study published in 1995 suggests that unspecified enzyme therapy can potentially dissolve blood clots as well as strengthen the arterial walls and improve the quality of blood itself. A study published the following year on the protease seaprose showed that the enzyme helps to treat thrombophlebitis, a condition characterized by pain and inflammation in the veins which can lead to serious blood clots. In this study, 40 patients were administered 30 mg tablets three times per day over the course of 14 days, and by the end of the trial, symptoms reduced by over 60% in most cases and there were no adverse reactions to the treatment. In my opinion there is definitely some potential for Proteolytic Enzymes to prevent blood clots. This is our Favorite Proteolytic enzyme for Blood Clots.

Lyme Disease

There is no current scientific research on the effects of a proteolytic enzyme therapy on the treatment of Lyme Disease. However, supplements targeted to treat this condition are available, and testimonies shown on those companies’ websites as well as Lyme Disease related anecdotal evidence claim that an enzymatic treatment is more effective than antibiotic treatments in staving off the symptoms of Lyme Disease. We dont recommmend treating Lyme Disease through Proteolytic enzymes but if you want to try, use a general Proteolytic enzyme supplement.

Leaky Gut

Although reliable studies testing proteolytic treatments on Leaky Gut Syndrome have not yet been performed, more descriptive studies do report that proteases somehow play a role in gut health. Research conducted in 2017 reports that an imbalance of proteases the gut contributes to epithelial damage and increased permeability that would lead to leaky gut. They conclude that more research in this area should be conducted in order to create protease targeted therapies aimed in treating the condition. While there are supplements available, testimonial evidence varies on how well those supplements work in treating leaky gut, with some saying it worsened the conditions and others saying they could not survive without them. We recommend a general Proteolytic enzyme supplement for Leaky Gut.

List of Proteolytic Enzyme Supplements and Herbs


Bromelain refers to a combination of two protease enzymes. It has a long history in Europe of being used to treat inflammation. Many studies (as indicated above) show that there is scientific merit to bromelain’s use as a medical treatment. Clinical trials assessing bromelain’s effectiveness in treating osteoarthritis administer 540–1890 mg of bromelain per day.


It works well as a meat tenderizer by breaking down meat proteins, and as such it is a useful digestive enzyme when ingested with food. When it is ingested without food, it travels directly through the bloodstream where it acts as an anti-inflammatory. Doses of 0.325 and 0.75 mg/kg of papain are shown to be on par with strong anti-inflammatory drugs like butadion and indomethacin.


This enzyme is derived from a traditional Japanese food called natto, a type of vegetable cheese made from boiled or steamed soybeans that is then fermented with healthy bacteria. Nattokinase is useful in finding a good balance in the body’s blood clotting ability.


This protein is found in mammalian milk, and the amount of casein in milk varies from species to species, with cow’s milk protein being 80% casein, as compared to human’s, which is only 20-45%. Casein intake can improve cardiovascular health, relieve hypertension, and improve immune system support.


Pepsin is also synthesized in the stomach and is adapted for digesting meat and egg proteins as well as milk, and then the by-products of those proteins (amino acids) can be absorbed into the bloodstream.


Amylase is an enzyme which breaks down starch molecules into smaller carbohydrate molecules through a process called hydrolysis. There are two types of amylase, one which is produced by the salivary glands, and the other which is made by the pancreas. Because amylase can react with starches twice in the body (the mouth and the intestines), those proteins can be broken down more effectively.


This enzyme works well as an anti-inflammatory agent as well as an anti-edema. It can also be used to reduce pain and clear mucous build-up in the lungs. However, there is a downside to using serrapeptase supplements because the quality is often inconsistent, and it is easily dissolved by stomach acid before the body can absorb it.


Chymotrypsin is also secreted in the pancreas and assists other enzymes in breaking down food proteins during the digestive process.


Chymosin is synthesized in the stomach to help digest food, particularly milk digested by an infant animal. Without this protein, milk would not be properly absorbed by the body. It is closely related to the enzyme pepsin.


This enzyme is secreted by the pancreas, and it is designed to breakdown proteins even further in the intestines. The amino acids created during this break down can then be absorbed by the body.

List of Proteolytic Enzyme Foods


This fruit is a great source of bromelain which is found in all parts of the fruit, although it is typically only the stems of the leaves that are used to derive the enzyme.


This fruit contains the enzyme papain which has similar effects to bromelain as an anti-inflammatory agent.


Kiwi berries contain an enzyme called actinidin, which is similar to papain. Because of its ability to break down proteins, kiwi juice is sometimes used as a meat tenderizer. For some people, actinidin is an allergen that can cause an immediate adverse reaction after ingesting.


This fermented dish is rich in many proteolytic enzymes that benefit the digestion process, and since it is not cooked those enzymes are not lost like they are in more traditional dishes. It is important to eat freshly prepared sauerkraut, opposed to canned which will not retain many of the nutrients.


This fermented milk beverage is often rich in casein as well as lesser known proteolytic enzymes that are said to boost the immune system, lower blood pressure, and promote healthy cell growth. It is recommended to ingest kefir with caution in the event it is spoiled, and consult a doctor before talking large quantities of kefir.


Although not an enzyme itself, ginger is often found in many proteolytic formulas because its own anti-inflammatory properties can heighten the same properties found in many enzymes. Ginger works in this way by inhibiting the COX-2 enzyme which causes inflammation.

Proteolytic Enzyme Dosage

With a good diet rich in organic and unprocessed foods, you can take in all the proteolytic enzymes you need. However, this is seldom the case for most people and supplementation is necessary. Many doctors and researchers theorize that the body cannot actually absorb proteolytic enzyme supplements, however, studies show that these theories are often disproven. Supplementation has been proven to work in many instances through simple blood tests.

Unless specified by a doctor to take more or less of particular proteolytic enzymes, most proteolytic enzyme formulas contain a combination of multiple beneficial enzymes in differing amounts. As such, the recommended dosage may vary from company to company. Most companies recommend that for daily maintenance, you should take one capsule three times a day. Doses should be taken between meals.

There are instances where dosages should be altered. If going through a detoxification process, the standard dosage should be doubled, or in some cases tripled or quadrupled until the effects are felt. The detoxification process can range anywhere from 30 days to 24 months. For athletes or anyone undergoing regular intense exercise, a tripled or quadrupled dosage is also recommended.

Proteolytic Enzymes Side Effects, Safety, Dangers and Warnings

As a general warning, most proteolytic enzymes are effective blood thinners (although not all), and as such they can cause nosebleeds, intestinal discomfort, or excess hemorrhoidal bleeding. Since they are also effective blood thinners, there is also a possibility that taking excess proteolytic enzymes can weaken blood vessels and lead to a hemorrhagic stroke.

Bromelain is the most commonly used and studied among proteolytic enzymes, and because of this there is more information known about possible side effects in comparison to other enzymes. Bromelain treatment shows some side effects including diarrhea, nausea, flatulence, headache, tiredness, dry mouth, skin rash, and unspecified allergic reactions. In clinical trials, those given lower doses of Bromelain tend not to have adverse reactions, but larger doses did result in side effects for some people. The effects of long-term use of bromelain has yet to be assessed, but there is some concern that there may be a possible drug interaction with anti-coagulants like warfarin and anti-biotics. Further study is also needed to find the proper dose parameters. If you are allergic to pineapple, from which bromelain is derived, it is not recommended to take it.

While not much more is known about the adverse effects of other enzymes, a few do have some cautions. Papain may interact negatively to blood thinners, and this enzyme has also been linked to instances of miscarriage. Nattokinase can have interactions with anti-coagulating medications. Seaprose is not linked with any side effects, however during one experimental treatment one patient reported diarrhea that improved once the dosage was altered. Serrapeptase has been associated with intestinal distress. Many proteolytic enzymes derived from fruits or vegetables may cause an allergic reaction to people who are allergic to said fruits and vegetables.

If using a topical treatment, like a proteolytic moisturizer, there is a possibility of an allergic reaction that usually takes the form of a rash. However, the use of proteolytic enzymes in the cosmetic industry is relatively new, so concentrations are typically low and of little concern.


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