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Protease: The Enzyme that Makes Protein & Amino Acids Tick


Protease - Dr. Axe

Maybe we don’t give enzymes enough credit. They are required for literally every single chemical action that takes place in our bodies — from digestion to immune function and blood flow. We are able to see, think and breathe because of protease. What are proteases? They’re enzymes that allow for the breakdown of proteins in the body.

Because of this, proteolytic enzymes are at the cutting edge of biological research, and they have become a major focus for the pharmaceutical industry. According to a scientific review published in the Biochemical Journal, “although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases.” (1)

But what exactly does protease do, and why are proteases so essential for our overall health? These are complex enzymes and researchers are still learning about their role in the human body, but hopefully I can help you to understand their importance.

What Is Protease?

Proteases have been called biology’s version of Swiss army knives, able to cut long sequences of proteins into fragments. A protease is an enzyme that breaks the long, chainlike molecules of proteins so they can be digested. This process is called proteolysis, and it turns protein molecules into shorter fragments, called peptides, and eventually into their components, called amino acids. We need a steady supply of amino acids for proper growth and repair. (2)

Proteins start as a tough, complex, folded structure, and they can only be broken down or disassembled with protease enzymes. The process of digesting proteins starts in the stomach, where hydrochloric acid unfolds the proteins and the enzyme pepsin begins to disassemble them. The pancreas releases protease enzymes (primarily trypsin), and in the intestines, they break protein chains apart into smaller pieces. Then enzymes on the surface and inside of intestinal cells break the pieces down even further, so they become amino acids that are ready for use throughout the body.

When these protease enzymes aren’t present in the body to break down protein molecules, the intestinal lining would not be able to digest them, which can lead to some serious health issues.

Proteases are produced by the pancreas, and they are also found in some fruits, bacteria and other microbes. The digestive tract produces three different forms of protease in our digestive tracts: trypsinogen, chymotrypsinogen and procarboxypeptidase. These three proteases attack different peptide linkages to allow for the generation of amino acids, the building blocks of protein.

What does protease do? Everything! These enzymes allow for the proper function of our digestive and immune systems, kidneys, liver, spleen, pancreas, and bloodstream. Protease plays a part in regulating metabolic function, and it allows for the vitamins and minerals we ingest to work properly. And, on top of that, proteases are needed for hormones to function properly and encourage muscle recovery and tissue healing.

Types of Proteases

Protease enzymes are often classified based on their origins. Some proteases are produced in our bodies, some come from plants and others have a microbial origin. Different types of proteases have different biological processes and mechanisms. (3)

Our digestive systems naturally produce three types of proteases: pepsin, trypsin and chymotrypsin. Here’s a breakdown of these three types of proteases:

Pepsin: Pepsin is a naturally occurring protease that’s found in the gut. It’s essential for breaking down and digesting proteins. Cells in the stomach begin by producing an inactive enzyme called pepsinogen, which changes into pepsin when it enters the acidic environment of the stomach. Then pepsin works to break chemical bonds in proteins, producing smaller molecules that are called peptides. This is the first phase of protein digestion.

Trypsin: Trypsin is a protease enzyme that’s produced in the pancreas in an inactive form called trypsinogen, which then mixes with bile and enters the small intestine, where it is converted to active trypsin. Trypsin works with pepsin and chymotrypsin to break down proteins into peptides and amino acids.

Chymotrypsin: Chymotrypsin is also produced in the pancreas and works as a component of pancreatic juice in the small intestine to break down protein molecules into peptides. Chymotrypsin is activated in the presence of trypsin.

Proteases are also found in certain whole foods, and they are available in supplement form. Two types of plant-based protease enzymes that exist are:

Bromelain: Bromelain is a protease that’s found in the stem and juice of pineapple. Bromelain supplements are typically used for digestive disorders, faster recovery from surgery or injuries, allergies symptoms, sinus infections and joint pain.

Papain: Papain is a protease enzyme that’s found in the latex of papaya, especially when it’s unripe. Papain stimulates digestion and improves the overall absorption of nutrients, which is why it’s often used in digestive enzyme supplements.

Protease - Dr. Axe

Health Benefits

1. Essential for Digestion

Enzymes play a major role in our digestive health, and proper digestion is dependent on protease processes. They have the distinct ability to break down peptide bonds and release amino acids. Proteases are required for the breakdown of proteins so they can be digested, but they also break down other wastes, including toxins. This is important for digestive and immune function because it prevents toxic overload that can make us sick.

Studies show that proteolytic enzymes, especially bromelain, can help to reduce the severity of symptoms related to inflammatory bowel diseases and ulcerative colitis because of their anti-inflammatory properties. (4)

2. Allows Absorption of Amino Acids

Protease allows for the absorption of amino acids, which are vital for building and repairing tissue. A protein consists of a specific sequence of amino acids, and when protease works to break these sequences apart, this allows us to use amino acids for a number of body functions. We need an optimal balance of amino acids for the body to maintain homeostasis because they regulate key metabolic pathways that are necessary for growth, maintenance, immunity and reproduction. (5)

3. Boosts Immune Function

Protease enzymes increase the potency of natural killer cells and degrade pathogenic complexes that can reduce normal immune function. Studies suggest that papain, trypsin and other proteases can prevent or break up existing pathogenic immune complexes, thereby enhancing lymphatic drainage and boosting the immune system.

Although pathogenic complexes are a normal part of the immune system, when they occur in excess, they can cause certain health conditions, including kidney diseases, rheumatologic diseases and nerve inflammations. (6)

4. Prevents Blood Clots and Arteriosclerosis 

Protease improves the quality of our blood cells. These enzymes are responsible for the formation and dissolution of blood clots. They also have anticoagulant, anti-inflammatory and anti-hypertensive effects. (7)

Protease supplements have been developed and used to treat thrombotic disease since the 1970s. Papain, the protease found in papayas, may help to prevent the thickening of blood vessels, a heart condition called arteriosclerosis. Bromelain, the protease found in pineapple, has anticoagulant properties and can reduce the risk of blood clots that lead to dangerous complications like coronary heart disease, pulmonary embolism and stroke. (8)

5. Accelerates Tissue Repair

Proteases have been used to promote tissue repair since ancient times. Trypsin and chymotrypsin help reduce inflammation and promote a speedier recovery of acute tissue injury, according to a scientific review published in Advances in Therapy. The combination of these two enzymes are commonly used in oral proteolytic enzyme supplements to repair traumatic, surgical and orthopedic injuries. Along with their anti-inflammatory effects, protease enzymes also work as anti-infective, antioxidant, anti-blood clot and anti-swelling agents. (9)

6. May Help Prevent Colon Cancer

Research suggests that proteases found in some foods, like papaya, are able to bind to cancer-causing toxins in the colon, keeping them away from healthy colon cells. According to research published in the World Journal of Gastroenterology, protease enzymes are involved in the degradation of cancer invasion and metastasis. Researchers indicate that proteases may serve as potential target molecules for therapeutic agents in the treatment of colorectal cancer. (10)

Protease vs. Proteinase vs. Proteasome

It’s easy to get confused about the many terms that are used when discussing protease. Protease is the general term for enzymes that degrade proteins by hydrolysis of peptide bonds. Researchers realized that there are actually two different types of protease enzymes, even though they are usually grouped together. One group of protease enzymes acts best on intact proteins, while other enzymes show a preference for small peptides as substrates, according to research published in Biochemical Journal. (11)

Proteinase is a type of protease that appears to show preference for intact proteins. Proteinase works to break apart the internal peptide linkages of long peptide chains. It is important in normal physiological functions and used for pharmaceutical purposes.

Proteasomes are also protease complexes that are involved in proteolysis by working to break down proteins in the body. Proteasomes are responsible for the degradation of intracellular proteins. (12)

Protease vs. Amylase vs. Lipase vs. Pepsin

Protease: Protease is the general term that’s used to describe any enzyme that breaks down protein. Pepsin begins this process in the stomach, and trypsin and chymotrypsin are produced in the pancreas and released into the small intestine. These three types of protease work to complete protein digestion, breaking down protein into simple amino acids that are absorbed into your circulation.

Amylase: Amylase is a digestive enzyme that breaks down starch into simple sugars so they can be used for energy. First, amylase is released by your salivary glands so it can begin the digestive process as soon as you start chewing your food. This triggers the start of a domino effect that makes up the digestive process. But, in a nutshell, gastric amylase works to degrade partially digested food into chyme, which triggers the release of the hormone secretin, allowing the pancreas to release pancreatic enzymes that will finish the digestive process.

Lipase: Lipase is a digestive enzyme that splits dietary fats so the intestines can absorb them. Lipase is released mainly by the pancreas as pancreatic lipase, but it’s also found in the blood, gastric juices, intestinal juices and adipose tissues. Bile begins the process of fat digestion by converting fats into small fatty globules. Then lipase converts these globules into fatty acids and glycerol, a simple compound that’s found in all lipids and used by your cells for energy. Because lipase is needed for proper fat digestion, it affects so many bodily functions, including nutrient absorption, cholesterol regulation and metabolism.

Pepsin: Pepsin is a type of protease that’s produced in the stomach. Like all proteases, pepsin breaks down proteins into peptides. It is one of three proteases in the human digestive system — with the two others being trypsin and chymotrypsin. Pepsin is involved in the first phase of protein digestion.

Supplements and Dosage

The FDA has approved a variety of protease drugs that are used as part of treatments for stroke, hemophilia, acute myocardial infarction, sepsis, traumatic bleeding, digestive disorders and muscle spasms. (13)

There are a few different types of over-the-counter protease supplements on the market today. You can find bromelain and papain supplements online or in health food stores, and you can also purchase trypsin, which is typically produced from bacterial, fungal or porcine (pig) sources. Products containing chymotrypsin are also available and usually produced from bovine or porcine sources.

According to information reported in Mayo Clinic Proceedings, in an article meant to inform clinicians about enzyme supplements, the uses and dosage of protease enzyme supplements are as follows: (14)

  • Bromelain: Up to 400 milligrams per day for swelling, burns, inflammation and allergic rhinitis
  • Papain: Up to 1,500 milligrams per day for inflammation, digestion, herpes zoster symptoms, chronic diarrhea and pharyngitis
  • Trypsin: Up to 50 milligrams per day (usually combined with bromelain) for osteoarthritis and digestive enzyme supplementation
  • Chymotrypsin: Up to 100,000 units four times daily for reducing inflammation and edema associated with ulcers, surgery, abscesses or traumatic injury

Proteases are also commonly taken in combination with two other vital enzymes: amylase, which breaks down carbohydrates, and lipase, which breaks down fats. When all three of these digestive enzymes are working properly in your body, your digestive system will work optimally. For people with digestive diseases, age-related enzyme insufficiency, too little stomach acid (called hypochlorhydria), liver disease and nutrient deficiencies, taking a digestive enzyme supplement may be helpful.

Inhibitors and Deficiency

What is a protease inhibitor? It’s an antiviral drug that’s commonly used to treat patients with HIV/AIDS and hepatitis C. Protease inhibitors prevent viral replication by blocking protease so new HIV will not become a mature virus that can infect other cells (specifically called CD4 cells). Basically, these drugs are meant to reduce the amount of HIV in the body in order to slow down the progression of the virus.

To replicate itself, the HIV virus uses immune cells in the body, called CD4 cells, so it will spread. Protease enzymes allow for this replication, but HIV protease inhibitor drugs block the enzymes from allowing the virus to multiply. (15)

These types of drugs have well-known side effects and interact with other medications, so if you are living with HIV or hepatitis C, you want to consult with your health care provider before adding protease inhibitors to your treatment plan.

For people who aren’t infected with HIV or hepatitis C, they want to make sure they are producing enough protease. When your body is functioning properly, it will produce enough protease to break down the protein in your body. When the body doesn’t manufacture enough protease, however, it can lead to conditions affecting the metabolic, digestive, cardiovascular and immune systems.

What are the signs of protease deficiency? Someone who isn’t consuming or producing enough protease enzymes may experience the following symptoms of deficiency: (16)

  • excess gas
  • cramping
  • heartburn
  • indigestion
  • abdominal discomfort
  • diarrhea
  • constipation
  • joint stiffness
  • fatigue
  • premature skin wrinkles
  • gray hair


You are going to find protease enzymes in some fruits, vegetables and fermented foods, and you are not going to find them in processed, fried, baked, boiled or even canned foods. Cooking or processing foods, even fruits and vegetables, kills the enzymes. So you want to focus on eating fresh fruits, raw vegetables, and fermented foods like sauerkraut, kefir, yogurt and miso. Other enzyme-rich foods include sprouted nuts and seeds and uncooked or slightly cooked grain products, like wheat germ.

The top protease foods that you should add to your diet to improve your digestion, immune function and cardiovascular health (just to name a few benefits), include:

  1. Pineapple
  2. Payaya
  3. Ginger
  4. Kiwi
  5. Yogurt
  6. Cheese
  7. Kefir
  8. Miso soup
  9. Sauerkraut
  10. Tempeh

To boost your protease and other enzyme levels, the key is to increase your intake of raw and fermented foods. You’ll also want to chew your food thoroughly. When your food mixes with saliva and is broken down in your mouth, this begins the digestion process. The more you chew, the less work has to be done in your stomach and small intestine.

Protease benefits and foods - Dr. Axe


  • The first report on proteases was published in the Journal of Biological Chemistry in 1905. Since then, more than 350,000 scientific articles have been written on these enzymes.
  • More than 2 percent of our genes encode proteases.
  • The most abundant protease genes found in humans are metalloproteases, followed by serine, cysteine, threonine and aspartyl genes. (17)
  • The first FDA-approved protease drug was u-PA (urokinase), which was approved for clinical application in 1978 and is still used today for its ability to dissolve blood clots in blood vessels and intravenous catheters.
  • Protease accounts for about 60 percent of the total enzyme market in the world, making it the most important industrial enzyme of interest today. (18)

Risks and Side Effects

The side effects of protease supplements vary depending on the type of protease you are consuming, but generally they may include gastrointestinal issues like cramping and diarrhea, allergic reactions, and burning when protease enzymes are applied topically.

If you are taking proteases, be aware that they may interfere with blood-clotting and blood-thinning drugs. If you take these types of medications, consult with your health care provider before using any new dietary supplement.

Final Thoughts

  • The function of proteases is necessary for all living organisms.
  • Proteases enzymes allow for proteolysis, the process that breaks the long, chainlike molecules of proteins so that they can be digested.
  • Proteases are produced by the pancreas, and they are also found in some fruits, bacteria and other microbes. Three different types of proteases include pepsin, trypsin and chymotrypsin.
  • Bromelain is the type of protease that can be found in pineapple stems and papain is found in the latex of papaya. Proteases can also be found in fermented foods, such as miso, sauerkraut and tempeh.
  • The top protease benefits include its ability to allow for the digestion of proteins and the absorption of amino acids, boost immune function, promote cardiovascular health, accelerate tissue repair and possibly prevent colon cancer.

Read Next: Proteolytic Enzymes Reduce Inflammation and Boost Immunity

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