Proteolytic Enzymes: Definition, Natural Sources, Therapeutic Dosages, Mechanism of Action, Side Effects and Interactions

They are essential for many critical processes to take place in the body.

Proteolytic enzymes are also known as proteases, peptidases, or proteinases.

Proteolytic enzymes are produced in the human body by the pancreas and stomach.

Although proteolytic enzymes are best known for their role in digesting consumed proteins, they also perform many other vital functions.

Proteolytic enzymes are essential in the process of cell division, blood clotting, immune function, and the recycling of proteins, among other vital methods.

Proteolytic enzymes are grouped into families and clans according to sequence relationship and are classified by their substrate specificity or by their enzymatic mechanism of action.

In many situations involving protein degradation, proteases of various classes and substrate specificities work together to degrade protein substrates.


Proteases can be classified according to the mechanism of action; the significant classes of independently acting proteases include serine, cysteine, aspartic, and metalloproteases.

The optimum pH for proteolytic enzymes spans the entire range, which is why some are also classified as acidic, neutral, or alkaline proteases (although these terms are sometimes used about the pH of the enzyme).

The optimum pH can reflect the subcellular location.

Natural sources of proteolytic enzymes

Proteolytic enzymes (proteases) help in the digestion of proteins in food.

The body produces these enzymes in the pancreas, called trypsin and chymotrypsin. Still, certain foods also contain proteolytic enzymes and have been manufactured to replace them in cases of deficiencies.

There are two rich plant food sources of proteolytic enzymes: papaya and Pineapple.

Papain is a powerful proteolytic enzyme, which is known as papaya proteinase. This enzyme is located in the leaves, roots, and fruits of the papaya plant.

Papain has been used for many years due to its ability to break down proteins as a meat tenderizer.

On the other hand, Pineapple contains a powerful proteolytic enzyme called bromelain.

Bromelain is found in the fruit and has been used for centuries by the indigenous peoples of Central and South America as a natural treatment for various things like;

  • Improve digestion
  • Reduce inflammation.
  • Promote the healing and recovery of a sick person.
  • Reduce muscle pain.

Generally, the primary use of proteolytic enzymes is to support the digestion process.

However, according to recent research, proteolytic enzymes can also be used to solve a wide range of health problems.

Symptoms of a deficiency in proteolytic enzyme production

It is usually unnecessary to obtain proteolytic enzymes from food because the body produces them, mainly trypsin and chymotrypsin.

However, alternative therapies are necessary for the event of deficiencies of these proteolytic enzymes in the body, which generally result from diseases of the pancreas (pancreatic insufficiency).

Symptoms of proteolytic enzyme deficiencies are abdominal discomfort, flatulence, indigestion problems, poor absorption of nutrients, and the passage of undigested food into the large intestine.

Therapeutic doses of proteolytic enzymes

The amount of proteolytic enzymes is usually expressed in grams or milligrams. Still, international units are also used, which refer to the potency of the enzyme, specifically, the power to aid digestion that they possess.

The recommended doses of proteolytic enzymes will vary according to the formula used, and due to the variability of procedures, the product indications must be followed.

Proteolytic enzymes can be broken down by stomach acid. But to prevent this from happening, the supplemental enzyme capsules are coated with a compound that dissolves when it reaches the small intestine. This preparation is called an enteric coating.

The typical dosage is one to three capsules 10 to 20 minutes before meals or on an empty stomach when non-digestive effects are desired. If taken as a digestive aid, it can be taken just before meals.

Mechanism of action of proteolytic enzymes

Proteolytic enzymes assist the body in digestion and convert proteins into their constituent amino acids.

Enzymes are necessary to facilitate many diverse chemical reactions in the body.

Proteolytic enzyme supplementation enhances many metabolic functions performed by endogenously produced enzymes.

Maintaining optimal enzyme function is a critical factor in supporting health and well-being.

One of the outdated arguments against the effectiveness of orally administered proteolytic enzymes was that they were either not digested or too large to be absorbed.

Absorption studies with the various proteolytic enzymes have confirmed that they are absorbed intact. They appear to be actively transported through the intestinal wall.

Since stomach acid can destroy proteolytic enzymes, the best formulas are “enteric-coated” tablets or “delayed-release” capsules.

Enteric coating means that the pills have a coating around them that prevents the drug from breaking down in the stomach.

The enteric-coated pill passes into the small intestine without dissolving, and it is there that, due to the change in pH, it breaks down.

One of the problems with an enteric coating is that unwanted synthetic compounds are often used in making the cover film.

A better approach is to use “delayed-release” vegetarian capsules that use natural dietary fibers that also resist stomach acid to achieve enzyme-targeted delivery to the upper small intestine.


There are many combinations for the production of proteolytic enzyme compounds.

Protease can be derived from various sources, such as fungal sources that exert an action similar to those found in animal sources (pancreatin from pig pancreas or ox bile) such as chymotrypsin and trypsin.

Proteases are a type of enzyme whose catalytic function is to hydrolyze (break) the bonds of proteins. Proteases differ in their ability to hydrolyze various peptide bonds.

Papain and Bromelain

Bromelain is a family of proteolytic enzymes derived from the pineapple plant. Bromelain has a variety of physiological mechanisms through which it exerts its effects.

Papain is a proteolytic enzyme derived from immature papaya and traditionally used in combination with bromelain.

They are proteolytically derived from papaya and Pineapple, respectively, and are also used in the composition of this enzyme therapy.


This proteolytic enzyme is more potent than the proteolytic enzymes produced in the pancreas, chymotrypsin, and trypsin.

Serratiopeptidase is derived from a bacterium that resides in the intestines of silkworms. It is also called the “silkworm” enzyme, as it is the enzyme used to break down the silkworm’s cocoon.

Bacterial proteases are generally optimally active under alkaline conditions, fungal proteases under more acidic conditions, and neutral (bacterial) proteases are active at neutral pH.

Fungal amylase is an enzyme derived from the fungus Aspergillus Oryza. It breaks down carbohydrates, such as starch and glycogen.

The advantages are that fungal sources are more stable, exert a more gradual range of activity at different pH levels, and exercise more excellent proteolytic effects.

Indications of use

Proteolytic enzymes (or proteases) refer to the various enzymes that digest (break down into smaller units) proteins.

Proteolytic enzyme preparations are helpful in the following situations:

  • Vegetarian proteolytic enzymes support digestion, muscle, joint, and general health such as inflammation, sports injuries and trauma, rheumatoid arthritis, multiple sclerosis, and other autoimmune disorders.
  • Proteolytic enzymes assist the body in digestion and convert proteins into their constituent amino acids in cases of pancreatic insufficiency. Proteases, fungal amylase, and lipase are added to facilitate the digestion of various foods.
  • Enzymes are necessary to facilitate chemical reactions throughout the body.
  • They are recommended for cancer, fibrocystic breast disease, food allergies, hardening of the arteries (atherosclerosis), hepatitis C, herpes zoster (shingles), sinusitis, asthma, bronchitis, and chronic obstructive pulmonary disease.


Proteolytic enzymes have a long history of use in the treatment of cancer. In 1906, John Beard, a Scottish embryologist, reported on the successful treatment of cancer using a pancreatic extract.

Numerous alternative medicine practitioners have promoted proteolytic enzymes for many years.

Current clinical research on proteolytic enzymes suggests significant benefits in treating many forms of cancer.

Specifically, these studies have shown improvements in patients’ general condition, quality of life, and moderate to significant gains in life expectancy.

These studies have been carried out in patients with cancer of the breast, lung, stomach, head and neck, ovaries, cervix, and colon, and in lymphomas and multiple myeloma cases.

These studies included using proteolytic enzymes in conjunction with conventional therapy (surgery, chemotherapy, and radiation), indicating that proteolytic enzymes can be used safely and effectively with these treatments.

Proteolytic enzymes are not recommended for at least two days before or after surgery, as they can increase the risk of bleeding.

Proteolytic enzymes are pretty helpful in speeding up post-surgical recovery and alleviating a complication from surgery and radiation known as lymphedema.

The use of enzyme preparations to support proper digestive function is used in conventional medicine for pancreatic insufficiency (characterized by digestion problems, malabsorption, nutrient deficiencies, and abdominal discomfort) and cystic fibrosis (a rare inherited disorder).

The benefits in some inflammatory conditions appear to be related to helping the body break down immune complexes formed between the antibodies produced by the immune system and the compounds they bind to (antigens).

Conditions associated with high levels of immune complexes in the blood are often called “autoimmune diseases” and include rheumatoid arthritis, lupus, scleroderma, and multiple sclerosis.

Higher circulating immune complexes are also seen in ulcerative colitis, Crohn’s disease, and AIDS.

The list of conditions benefited by pancreatic enzyme supplementation seems to be growing. For example, one potential use is in treating diseases related to the virus, including hepatitis C and herpes simplex infections.

In a study on herpes zoster (shingles) treatment, a proteolytic enzyme preparation taken by mouth was more effective than standard drug therapy (acyclovir).

In a study in patients with hepatitis C, proteolytic enzymes were slightly superior to alpha-interferon in improving symptoms and laboratory values.

Proteolytic enzymes also appear to be quite helpful in recovery from surgery, fibrocystic sinus disease, acute and chronic sinusitis and bronchitis, and chronic obstructive pulmonary disease and asthma.

To take full advantage of proteolytic enzymes, it is essential to use a high-quality product inadequate dosage.


Most proteolytic enzymes have well-established guidelines and contain the following enzymes per two delayed-release capsules:

  • Bromelain 1200 GDU.
  • Protease 130,000 HUT.
  • La Papaína 3,000,000 PU.
  • Serrapeptase 80,000 SPU.

Side effects

Proteolytic enzymes are generally well tolerated and are not associated with significant side effects. Even in people with presumably normal pancreatic function, taking proteolytic enzymes did not produce adverse side effects or reduce the ability of these subjects to make their pancreatic enzymes.

Although no significant side effects have been observed with any proteolytic enzymes, allergic reactions can occur (as with most therapeutic agents).

People with allergies should not use pancreatic enzymes to pork, bromelain should not be used in people allergic to Pineapple, and papain should not be used in people sensitive to papaya.


You may need additional folic acid when the proteolytic enzyme pancreatin is given.

The proteolytic enzymes papain or bromelain can cause interactions with medications such as warfarin (Coumadin), so they should not be administered except under medical supervision.

Bromelain should not be taken with sedative medications.