Evidence Based

13 Digestive Enzyme Supplement Benefits + Side Effects

Written by Anastasia Naoum, MS (Health Informatics) | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology) | Written by Anastasia Naoum, MS (Health Informatics) | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Digestive enzymes break down fats, proteins, and carbs so your body can absorb the nutrients. And although some supplements may promise to be your gut genie in a bottle, they’re one you may need to keep revisiting until you address the underlying cause of your digestive issues. Digestive enzymes do have legitimate benefits if used appropriately. Learn more about how different enzymes work, what various supplements contain, and how to naturally boost your levels.

What Are Digestive Enzymes?

Digestive enzymes are a broad group of enzymes that break down large molecules such as fats, proteins, and carbs into smaller ones your body can absorb easier. You naturally produce most of these enzymes in the pancreas, while you also make smaller amounts in the stomach, small intestine, and mouth [1, 2, 3, 4].

The following enzymes help you soak up nutrients from specific foods [1, 2, 3, 4]:

  • Proteases break down proteins into amino acids
  • Lipases break down fats into fatty acids
  • Amylases break down carbs into simple sugars, such as glucose

Their main role is to aid your digestion and the amount and activity of these enzymes in your body depends on a complex set of factors. Since everyone experienced at least a minor issue with digestion in their life, the easiest option seems to be to just supplement with the lacking enzyme.

What’s more, research suggests that some digestive enzymes may help with various digestive disorders, weight loss, inflammation, cancer, gut infections, and even autism [4, 5, 6, 7]…

But is it that simple?

In most cases: no.

To Supplement or Not to Supplement

If you have low enzyme levels and suffer from indigestion, you are usually presented with two basic options: to take enzyme supplements or to work to change your diet and lifestyle to increase your enzyme production.

That said, it’s not that you have to strictly choose one or the other. Combining the two is also an option in certain situations. Digestive enzyme supplements may feel like a short-term life-saver for some. And oftentimes, they help lower indigestion symptoms. But they are usually no long-term solution [8].

Digestive enzymes do offer relief to people who chronically suffer from specific issues such as chronic pancreatitis (inflammation of the pancreas) and cystic fibrosis. In those cases, doctors prescribe potent FDA-approved digestive enzymes (pancrelipase) [9].

Another group of digestive enzymes are the more popular and diverse over-the-counter supplements. However, there’s little evidence that their use for some common gut problems will be beneficial.

What’s more, they come with a major drawback: they won’t do anything to restore your natural enzyme production. If you don’t have a serious problem with your pancreas, the chances are you probably don’t need them.

Ideally, you should work with a practitioner to uncover the underlying cause of your gut issues. This will help you create and follow a holistic program that will get you back on the right track.

For this reason, we included a brief section about ways to naturally increase your digestive enzymes with diet and lifestyle, after explaining the function and benefits of each enzyme type. We also explore all the research behind using digestive enzymes for less proven issues, such as IBS, IBD, and inflammation–with the above limitations in mind.

What Causes Low Digestive Enzymes?

Low levels of digestive enzymes show that the pancreas is not working properly and is struggling to produce important digestive compounds. In severe form, this condition is called exocrine pancreatic insufficiency (EPI). In this condition, cells of the pancreas that make digestive enzymes are destroyed over time [10, 11, 12].

However, EPI is not the only cause, although it’s the most serious one. Various conditions can decrease the production of digestive enzymes (to a smaller or greater extent) and/or damage the pancreas, including all the following:

  • Cystic fibrosis [13, 14].
  • Chronic pancreatitis [15, 16, 17, 10].
  • Pancreatic cancer and Zollinger–Ellison syndrome [18].
  • Diabetes, type 1, type 2, and diabetes in pregnancy (gestational diabetes) [19, 20,14, 16, 21, 22, 23, 24].
  • Obesity [25, 16].
  • High triglycerides (hypertriglyceridemia) [14].
  • Insulin resistance [26].
  • Metabolic syndrome [21, 16, 27].
  • Autism [28, 29]
  • Nonalcoholic fatty liver disease (NAFLD) [30].
  • Cancer radiotherapy and/or chemotherapy [31].
  • Leaky gut [32].
  • Celiac disease [11, 12].
  • Short bowel syndrome [33, 11].
  • Stomach ulcers [33, 11].
  • Autoimmune diseases (Crohn’s disease, multiple sclerosis, lupus) [11, 12, 34].
  • Genetic disorders (Lactose intolerance, Congenital sucrase-isomaltase deficiency, Pompe disease, lipase deficiency, Shwachman–Diamond syndrome)[35, 36, 37, 38, 39, 40, 41, 42, 10, 43, 11]

Digestive enzyme production also gradually declines with aging [44].

Types of Digestive Enzymes & How They Work

Fats: Lipases

Lipases are enzymes that break down fats. They are produced in the pancreas but can also be extracted from plants, animals, and fungi. These include [45, 46, 47]:

  • Plants: avocado, walnut, pinenut, coconut, lupin, lentils, chickpea, mungbean, oats, castor beans, and eggplant
  • Animals: cows, pigs
  • Fungi: Aspergillus oryzae, Rhizopus arrhizus.

Sugars: Amaylases

Amylases or amylolytic enzymes break down complex carbs into simple sugars. Digestion of carbs is very important since carbs are ultimately broken down to glucose—the main energy source that fuels our bodies [48, 49].

These enzymes broadly include amylases (alpha-amylase, beta-amylase, glucoamylase), as well as maltase-glucoamylase, sucrase-isomaltase, and lactase [50, 51, 52].


The body produces two types of amylase, the salivary and the pancreatic. Salivary amylase is produced by salivary glands and it starts digesting food as you chew it. Pancreatic amylase is produced by the pancreas and helps digest complex sugars in your gut [2].

Amylases can be found in and extracted from various sources, such as [53, 54, 55, 49, 56]:

  • Plants: Banana, mango, honey
  • Dairy products: milk, kefir
  • Bacteria: Bacillus, Pseudomonas, and Streptomyces
  • Fungi: Aspergillus, Penicillium

There are three main types of amylases, alpha-amylases, beta-amylases, and glucoamylases [51].


Maltase (alpha-glucosidase family) is an enzyme produced in the small intestine to break down maltose into glucose. Various malted products contain this sugar, while the enzyme that breaks it down is also found in plants, bacteria, and yeast [41, 57].


Sucrase-isomaltase (alpha-glucosidase family) breaks down table sugar (sucrose) into fructose and glucose. It can also improve immune function, help with bone and stomach cancer and reduce oxidative stress [58, 57].


Lactase (beta-galactosidase family) breaks down lactose, a sugar found in milk products, into glucose and galactose. People lacking this enzyme have lactose intolerance. The lactose added to supplements is produced by fungi, such as Aspergillus niger or yeast, such as Kluyveromyces lactis  [57, 37, 59].

Proteins: Proteases

Proteases or proteolytic enzymes are produced in the stomach and the pancreas to break down proteins to amino acids [60, 61].

Some proteases are essential to the human body and allow cells to properly divide and be eliminated once they are no longer needed. Proteases also support immune function, wound healing, blood clotting, and many other vital functions. For this reason, they play a crucial role in fighting infections, inflammation, cancer, heart diseases and other conditions [4, 62, 61].

Among different proteases, some are widely used in the pharmaceutical industry as drugs, while others can be monitored as diagnostic markers [63, 64].

Other proteases are available as dietary supplements and are extracted from various sources, including [65, 5, 66, 67, 68, 69, 70]:

  • Plants: pineapples, papayas, kiwis, soybeans, honey
  • Carnivorous plants: sundews, Venus flytrap, tropical, North American and Australian pitcher plants, corkscrew plants, and bladderworts
  • Animals: pigs, cows
  • Fungi: Aspergillus niger, Aspergillus oryzae.

An abundance of proteases exists, but some are more important for gut health than others. We cover the most important ones below.

Trypsin and Chymotrypsin

Trypsin and chymotrypsin are protease enzymes you make to break down proteins in the small intestine. Aside from pepsin secreted in the stomach, these two are the main protein-degrading enzymes you produce. In supplements, they are usually made from ox, pig or cow pancreas. Alternatively, they can also be extracted from fungi, plants, and bacteria [71, 72, 73].

Trypsin can fight bacteria by preventing the formation of biofilms. It also helps lower inflammation and reduce pain and swelling from joint and muscle injuries [74, 75, 76].

Chymotrypsin and trypsin supplements have been on the market since the 1960’s and have been tested in many clinical trials for combating inflammation and helping heal wounds [77, 78].

Aside from these proteases, which are naturally produced in your digestive system, many specific proteases are found in foods and can be formulated into more potent supplements.


Bromelain is extracted from the fruit or stem of pineapples (Ananas comosus). It is a mix of proteases that break down proteins into amino acids and other enzymes [5, 4].

The other enzymes in bromelain include phosphatase, glucosidase, peroxidase, cellulase. Interestingly, bromelain is also made up of some protease inhibitors that stop specific protein-digesting enzymes outside the gut from breaking down proteins you need. As a result,  blocking them may help fight off infections and inflammation [79, 80, 81].

Stem and fruit bromelain are prepared differently. Fruit bromelain is prepared by so-called ultrafiltration of cooled pineapple juice. Stem bromelain is made when pineapple stems are centrifuged, filtered, and freeze-dried [82, 82].

This is important because stem bromelain has a higher protease content compared to fruit bromelain [83].

Thanks to its wide-spectrum enzymes, bromelain can may help with digestion and weight loss, reduce pain, and provides benefits to you skin. It has also strong inflammation- and cancer-fighting properties and supports good heart health [5, 84, 85, 86].


Papain is a protease extracted from papaya (Carica papaya). If you like papayas, you can get enough of this enzyme by eating them raw. Alternatively, papain supplements are available as chewable tablets or as regular capsules [67, 87, 88, 89].

Papain has been used traditionally to decrease pain, inflammation and swelling. Studies show that it can improve digestion, reduce bloating, gas, diarrhea, and it might also help fight cancer and infections [90, 91, 92].


Few people have heard about actinidin, a protease found in green kiwifruits (Actinidia deliciosa). It enhances digestion and improves constipation and other  IBS symptoms. This enzyme can also be used as a meat tenderizer [93, 94, 95, 96, 97].

Serrapeptase & Nattokinase

Serrapeptase and nattokinase are not digestive enzymes, but they are proteases that affect inflammation and blood clotting. And although they don’t influence digestion, some supplement formulations combine them with typical digestive enzymes to achieve a wider spectrum of benefits.

Serrapeptase is extracted from the bacteria Serratia e15, found in silkworms. It acts to degrade harmful inflammatory proteins. For this reason, many people who struggle with chronic pain seek it as a natural alternative to strong pharmaceutical painkillers [98, 99].

Nattokinase is an enzyme found in nattō, a fermented soybean product. This protease breaks proteins that cause excessive blood clotting, making it a promising natural remedy for heart and circulatory issues. It is produced when the soybeans are cooked and later fermented by adding the bacteria Bacillus subtilis natto. To get its benefits, you can eat nattō or take it as a dietary supplement [68, 100, 101].

Combination Enzymes (PEPs & Dietary Supplements)

Digestive enzymes are often combined, both in clinical practice and in scientific research.

In fact, your body will always make and use various enzymes at the same time. It only makes sense to mimic an ideal natural balance with supplements rather than to use any enzyme in isolation. The only exceptions are specific genetic defects (e.g. lactose intolerance) or disorders (pancreatic insufficiency) [73].

One such combination enzyme is the prescription-grade pancrelipase. It contains lipase, amylase, and trypsin (protease). Another, called pancreatin, contains the same enzymes and both are extracted from the pancreas of animals (pigs or cows) [102, 103, 104, 73].

The only FDA-approved Pancreatic Enzyme Products (PEPs) marketed in the US are:

  • Creon
  • Zenpep
  • Pancreaze
  • Ultresa
  • Viokace
  • Pertzye

Some have enteric coating that helps enzymes survive the acidic environment of the stomach and delays their release until they reach the intestines. They are prescribed in cases of pancreatic insufficiency [102, 103, 104, 73].

Although these enzymes are typically extracted from animals, many other over-the-counter (OTC) digestive enzymes can be isolated from plants, bacteria (lipase) or fungi (protease and amylase) [105, 66].

OTC digestive enzymes are used as dietary supplements to support digestion, not to cure or treat any health problems. They are also not regulated by the FDA and their contents and ingredients can greatly vary. Numerous combinations exist, sometimes with added nutrients or probiotics.

Digestive Enzymes vs. Probiotics

As diverse a group as digestive enzymes are, perhaps only one other category is even larger and more diversified: probiotics. The “good enzymes” and the “good bacteria” get along very well in your gut. They have a very tight relationship.

Although one needs the other, each has a distinctive role. How exactly are digestive enzymes different from probiotic bacteria?

The most obvious difference is that digestive enzymes are proteins produced by your digestive organs that mostly act in the intestines, whereas probiotics are bacteria that tend to live in your colon. Digestive enzymes break down fats, proteins, and carbs into smaller nutrients you can absorb. Probiotics, in a nutshell, maintain your immune function, digest fibers, and also influence your mood through the gut-brain axis. [2, 106, 72, 107, 108, 109].

Now, here’s where the line gets blurry: many probiotic bacteria produce digestive enzymes. Various bacteria in your gut may produce proteases, lipases, and amylases. On the other hand, digestive enzymes enhance the activity of your good bacteria. For this reason, probiotics and digestive enzymes are a great match. They form a sort of unique gut mega-network [110, 111].

If something set your gut microbiome off, you need to up your intake of probiotic-rich fermented products (such as kefir or supplements) to re-establish your good bacteria. On the other hand, if your digestive enzymes are low, you need to work on supporting your pancreas and gut to rebalance your natural enzyme production (if possible).

If both are off, you’re probably in big trouble, as this can cause a host of gut and brain problems, including IBD, IBS, food sensitivities, leaky gut, leaky brain, and many more symptoms that most mainstream doctors won’t take seriously.

The only condition for which you may need to think twice about supplementing with both probiotics and digestive enzymes is SIBO. In this case, digestive enzymes will ease some symptoms and may help clear the overgrowth. But probiotics (and especially those with prebiotics) may even worsen both your gut symptoms and brain fog. This is because the probiotic bacteria from supplements may stay in your small intestine and cause further overgrowth [112, 113].

Probiotics Increase Digestive Enzyme Activity and Vice Versa

Several studies support the theory that digestive enzymes and probiotics act closely together as part of your gut’s mega-network.

In a 2-month study on 34 women, banana amylase reduced bloating and increased the good gut bacteria (bifidobacteria) [114].

In chickens, a probiotic increased the activity of proteases and amylases while enzymes (proteases or amylases and glucoamylases) increased the gut bacteria [115, 116].

In piglets, another probiotic (Bacillus amyloliquefaciens) enhanced the activity of chymotrypsin and amylases. In mice, pancrelipase supplementation increased the good gut bacteria, such as Lactobacillus reuteri [117, 118].

In a cell study, probiotics and digestive enzymes increased the good gut bacteria and prevented gut bacteria disturbances from antibiotics and chemotherapy [119].

Additional Synergies

Aside from the already mentioned synergies, the combination of digestive enzymes with probiotics may improve blood lipids. In mice, a diverse combination of both lowered LDL-cholesterol, and increased HDL-cholesterol (amylase, glucoamylase, lipase, bromelain, maltase, lactase, hemicellulose, xylanase, papain, and invertase)  [120].

Gastric Acid Support

Some digestive enzyme supplements also contain betaine hydrochloric acid or betaine HCl. It is used to increase gastric acid (HCl), especially if you are not producing enough. Betaine HCl is also sold as a standalone supplement. Betaine is a naturally occurring substance, found foods like beets, spinach, and whole wheat foods. Note that betaine (TMG) alone will not increase your stomach acid, as it does not contain HCl [121].

Clinical studies confirmed that betaine HCl can lower stomach pH levels, which may additionally support your digestion and help you soak up more nutrients. It also helps raise stomach acid levels if you’re taking acid-reducing drugs, like proton pump inhibitors (PPIs like Losec, Nexium, and Prevabid). However, you shouldn’t use Betaine HCl if you have normal gastric acid levels, as too much acid can damage the stomach lining and cause ulcers [121].

If you’re not sure whether your gastric levels are low, some practitioners recommend doing an “HCl challenge”. Buy a supplement with betaine HCl and take 1 capsule before a large meal. If you feel burning or warmth in your stomach, indigestion, or an “acidic” sensation, you are probably producing enough gastric acid already. In that case, you shouldn’t take betaine HCl. If you don’t feel different, you may be deficient. Practitioners recommend slowly increasing the dosage until you feel stomach warmth (but not to an unpleasant extent).

One study suggests that the betaine HCl challenge is tolerated well, but this approach mostly relies on clinical experience. If you’re not sure whether your stomach acid levels are low, it’s best to consult a practitioner [122].

Health Benefits

1) Digestion

Digestive enzymes help you soak up nutrients. Moreover, specific enzymes can help with lactose intolerance and celiac disease, and others with the exocrine pancreatic insufficiency (EPI) [123, 124, 125, 12, 126].

For example, in several clinical studies with over 100 adults and children with lactose intolerance, lactase supplementation increased lactose digestion and improved symptoms (cramping, nausea, pain, diarrhea, bloating, gas) [127, 59, 128, 129].

In an 11-week study on 51 people with indigestion, bromelain together with essential oils, baking soda, and sodium alginate, normalized bowel movements, gas, bloating, and overall digestion [123].

In clinical studies with over 80 people with increased protein intake, fungal proteases supplements (extracted from Aspergillus) increased protein absorption and improved the blood fat levels [130, 131].

Additionally, actinidin from kiwi enhanced the digestion of food proteins in rats (beef muscle protein, gelatin, soy protein isolate, and gluten) [124].

In cell studies, nattokinase and papain broke down parts of gliadin, a component of gluten, so these have the potential to help people with celiac disease [125, 132].

Pancreatic Insufficiency (EPI)

In exocrine pancreatic insufficiency (EPI), the pancreas is not working properly and is not producing sufficient digestive enzymes (proteases, amylases, lipases). Causes of EPI include pancreas inflammation (pancreatitis), pancreatic cancer, cystic fibrosis, or pancreatic surgery. Symptoms include maldigestion, stomach pain, gas, diarrhea, weight loss, and excess fat in stool [10, 11, 12].

Supplementation with digestive enzymes is recommended for EPI [12, 126].

In several clinical trials with over 750 adults and children with EPI, digestive enzymes supplements (pancrelipase, pancreatin) increased fat and protein absorption, decreased fat in the stool, reduced gas and stomach pain, and improved stool consistency and quality of life [133, 134, 135, 102, 103, 104, 136, 137, 138, 139, 140, 141, 142, 105, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153].

However, in 133 people with chronic pancreas inflammation (pancreatitis), digestive enzymes supplements did not reduce stomach pain [154, 155, 156, 157, 139].

2) IBS and IBD

Digestive enzymes may improve digestive problems related to IBS and IBD such as constipation, diarrhea, stomach pain, bloating and gas. They also might lower inflammatory markers and increase good gut bacteria [67, 158, 159, 8, 90, 114, 160].

In clinical studies with over 570 people with IBS, IBD, or chronic stomach inflammation (gastritis), digestive enzyme supplements improved symptoms such as heartburn, bloating, constipation, painful bowel movements, gas, stomach fullness, and stomach pain and reduced inflammation [67, 158, 159,95, 8, 161, 94, 95, 162, 163, 164, 165, 166, 90, 167].

The following enzymes were used:

  • Pancrelipase
  • Actinidin
  • Papain
  • Amylases
  • Lipases
  • Maltase

In a 60-day study on 34 women, banana amylase reduced bloating and increased the good gut bacteria (bifidobacteria) [114].

Additionally, papain and pepsin improved the quality of stools, decreased stomach pain and vomiting in  100 children with autism. Researchers pointed to a possible gut-brain connection [168]

Animal studies give us more clues about the possible benefits. In piglets and cell studies, bromelain, pepsin, alpha-amylase, and cellulase killed harmful bacteria that cause stomach and gut infections and possibly contribute to IBD [169, 170, 171, 172, 173, 174, 175].

In mice with IBD, bromelain decreased CD44 production, which lowered colon inflammation and reduced the incidence and the severity of ulcerative colitis. It also prevented gut spasms. In cell studies, it lowered inflammatory markers (IFN-γ, TNF-alpha, GM-CSF) involved in IBD [176, 160, 79, 177].

In pigs, actinidin increased the protein digestion and improved bowel movements [178].

3) Fighting Infections and SIBO

Digestive enzymes such as amylases and trypsin, and proteases such as nattokinase and serrapeptase. protect against infections. They prevent new biofilms from being formed and destroy existing colonies. Biofilms are a mass of hard-to-eliminate bacteria that stick to surfaces in the body and are hard to get rid of [76, 76, 179, 180].

Some enzymes may help with dengue fever, a viral disease caused by mosquito bite. In clinical studies with more than 700 people with dengue fever, papaya extract increased red blood cells, blood platelets, and decreased hospital stay [181, 182, 183, 184, 185, 186, 187, 188, 189].

In 60 children with sepsis, trypsin, bromelain, and rutin reduced fever and improved the symptoms after 21 days, compared to placebo [190].

Surprisingly, certain enzymes may improve vaginal health. In a 3-year study on 62 women with vaginal fungal infection (candidiasis), a supplement containing papain, bromelain and rutin improved the symptoms and decreased recurrence of the infection over the next 3 years [191].

In animal and cell studies, trypsin, alpha-amylase, cellulase, pepsin, papain, and serrapeptase destroyed biofilm colonies and blocked the growth of the following microbes [75, 192, 193, 170, 194, 169, 195, 196, 197, 198]:

  • Many bacteria that cause food-borne illnesses, gut, and stomach infections
  • Staph bacteria (respiratory and skin infections)
  • Bacteria that cause burn wound infections
  • E. coli (urine infection, IBD)
  • Salmonella
  • H. pylori (stomach ulcers)
  • Candida

Therefore, digestive enzymes may potentially help with SIBO, skin, urine, respiratory and gut infections. Clinical studies would need to investigate and confirm these effects, especially in people with SIBO.

4) Pain and Swelling

In several clinical trials with over 400 people who underwent surgery, digestive enzymes supplementation (bromelain, chymotrypsin, pancreatin,  papain, trypsin, serrapeptase) reduced pain and swelling after and decreased the need for painkillers [199, 200, 201, 202, 203, 204, 205, 200, 206, 207].

In 192 people with shingles (herpes zoster), digestive enzymes supplementation reduced pain as effectively as the drug acyclovir [208].

In clinical studies with over 100 people, digestive enzymes supplementation (trypsin, papain, lipase, chymotrypsin, bromelain, amylase) decreased muscle pain and soreness and prevented muscle damage after exercise compared to placebo [209, 210, 211].

5) Joint Disorders

Osteoarthritis (OA) is the most common long-term joint disorder, affecting over 30 million Americans. In osteoarthritis, the cartilage breaks down and the bones within the joint rub together, causing pain, swelling and problems moving the joint [212].

In several clinical studies with more than 1k people with knee or shoulder osteoarthritis, digestive enzyme supplements decreased joint pain, swelling, and stiffness, while enhancing the quality of life and improving knee or shoulder function [74, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 211, 225, 226].

The following were used:

  • Pancreatin
  • Trypsin and chymotrypsin
  • Papain
  • Lipase and amylase

In clinical studies with over 30 people with a ruptured or herniated discs, chymotrypsin and trypsin reduced the intake of painkillers and improved leg movement by decreasing swelling in the nerves compared to placebo [227, 228].

Although it helped in some of the studies, the evidence for bromelain is mixed. In a 16-week study on 30 people with knee osteoarthritis, bromelain did not improve the symptoms (knee pain, function, stiffness) [229].

6) Heart Health

Overall, some digestive enzymes may protect the heart by lowering blood fat levels and platelet clumping. Bromelain shows some promise alone, but it most likely only works well in combination with the protease nattokinase. Nattokinase is well-known for lowering excessive blood clotting, and the two are sometimes combined in supplements [230, 231, 86232, 233, 234, 235, 236, 68, 182]:

In clinical studies with over 120 people, bromelain normalized the number of blood platelets,  reduced blood platelet clumping and prevented excessive clotting, reducing the risk of heart disease [230, 231, 86].

However, in 68 diabetics, bromelain did not reduce risk factors for heart disease (high blood fats, high blood pressure) [237].

In animal and cell studies, bromelain, actinidin, and nattokinase reduced blood platelet clumping and blocked excessive blood clotting. Bromelain also increased the survival of heart cells and protected them from poor blood flow [232, 233, 234, 235, 238, 239, 240, 234, 241, 242, 85, 243, 244, 245].

In contrast, papain increased the production of red blood cells and blood platelets in mice. It may have benefits for people with low platelets and possibly in some with anemia [246].

7) Cancer

The anti-cancer potential of digestive enzymes relies on limited data that needs to be examined in clinical studies. Based on the evidence, digestive enzymes may help by reducing some of the side effects of cancer treatments, lowering inflammation, and improving digestion [247, 248, 62, 249, 250, 250, 251, 252, 253, 254255, 256, 79, 257, 258 ].

In clinical studies with over 2,5k people with cancer, digestive enzyme supplementation improved cancer-related gut disturbances, mental issues, breathing difficulties, headaches, pain, appetite, skin disorders, and infections. They also reduced the side effects of chemotherapy and radiotherapy [249, 247, 248, 62].

In mice with various types of cancer (leukemia, sarcoma, lung carcinoma, adenocarcinoma), bromelain reduced tumor formation and size, increased survival rates and prevented cancer growth. Bromelain also reduced inflammatory markers and blocked inflammatory pathways that promote cancer growth in cells [250, 255, 256, 79, 257, 258].

Both bromelain and papain prevented cancer growth and spread in cells, increasing the death of cancer cells [251, 252, 253, 254, 259, 260, 91, 261, 92, 262, 263, 264].

8) Inflammation

Overall, digestive enzymes may lower inflammatory substances and block inflammatory enzymes and pathways. They might also help break down dead cells and tissues, which helps drain harmful substances from the inflammatory site. They are often combined with non-digestive enzymes like serrapeptase to achieve these effects [265, 266, 267, 207].

In clinical studies with more than 200 people with inflamed sinuses (sinusitis), bromelain and serrapeptase improved symptoms such as a stuffed nose, sinus tenderness, pain, and runny nose. This combination worked faster and better than other alternative therapies. In mice, bromelain also improved allergic asthma [268, 269, 270, 271, 272].

In a clinical study on 130 people, proteases (papain, bromelain, trypsin, and chymotrypsin) lowered high TGF-beta levels, thus lowering inflammation [266].

In a 3-month clinical study on 27 children with lung inflammation (bronchitis), digestive enzyme supplements improved their symptoms [273].

In mice and rats, chymotrypsin, trypsin, and serrapeptase reduced swelling and decreased the inflammation. These enzymes worked better than NSAIDs [274, 64, 275].

Interestingly, papaya extract stimulated the immune system. It increased the production of antibodies (IgG and IgM) and decreased oxidative stress [276, 277,  278].

9) Wound Healing

Digestive enzymes (trypsin, chymotrypsin, papain, bromelain, in combination with serrapeptase) promote wound healing by breaking the fibrin barrier and improving blood flow in the wound area. They also remove dead cells and tissue and increase the production of collagen[207, 267, 279, 280, 78, 281].

In 192 people with shingles (herpes zoster), digestive enzymes supplementation reduced skin wounds and redness as effectively as the typical drug acyclovir [208].

In clinical studies with over 100 people with burns, chymotrypsin and trypsin lowered inflammatory cytokines (IL-1, IL-6), reduced oxidative stress and blocked tissue damage [279, 282, 283].

In a clinical study on 75 people after orthopedic surgery, trypsin, and chymotrypsin decreased the wound redness, tenderness, swelling and discharge more than bromelain or serrapeptase   [207].

In rats and pigs, topical application of papain and bromelain removed dead cells and tissue (debris), accelerated wound closure and reduced inflammatory markers [284, 285, 286, 287, 288, 289, 290].

10) Autism

In clinical studies with over 140 children and adults with autism, digestive enzymes (papain, pepsin, bromelain, lactase) improved the emotional status, general behavior, and gut symptoms (quality of stools, stomach pain, vomiting) [168, 291].

However, in 43 children with autism, digestive enzymes did not improve behavior, gut symptoms, or sleep quality compared to placebo [292].

It’s possible that they can positively affect the gut-brain connection, but more research is needed.

11) Alzheimer’s Disease

Amyloid-beta plaques contribute to the onset of Alzheimer’s disease [293].

In animal (rats, zebrafish) and cell studies, various digestive enzymes (trypsin, bromelain, nattokinase, serrapeptase, and alpha-chymotrypsin) increased the breakdown of amyloid-beta and decreased levels of acetylcholinesterase, whose over-activity can worsen cognition  [294, 295, 296, 297].

Based on these studies, the role of digestive enzymes for preventing cognitive decline and Alzheimer’s is still far from clear.

12) Diabetes

In more than 2k people, people with low amylase levels had increased risk of type 2 diabetes and metabolic syndrome. However, clinical studies have not examined the benefits of digestive enzymes for diabetes prevention. Only limited animal and cell-based studies point to papain’s potential [298].

In diabetic rats, papain lowered blood sugar levels, decreased triglycerides and cholesterol, and prevented pancreas and liver damage. In rat cells, papaya extract blocked key enzymes (α-amylase, α-glucosidase) linked to diabetes type 2 [299, 285, 300, 301, 302].

13) Weight Loss

While digestive enzymes are a popular part of weight-loss regimes, the studies to support this are almost non-existent. Only a couple of cell-based studies suggest that bromelain carries the potential to boost fat burning.

In one cell study, bromelain blocked fat formation by decreasing proteins and enzymes (PPARγ, adiponectin, fatty acid synthase (FAS), and others) that work to store more fats. It also increased fat breakdown and the death of fat cells [303].

Type 2 diabetes and metabolic syndrome are commonly accompanied by obesity. Based on the previously mentioned studies, some digestive enzymes may also help lower blood sugar levels enzymes linked to type 2 diabetes, which may indirectly help with weight loss [299, 285, 300, 301, 302].

Limitations and Caveats

Although there are sufficient clinical trials for some health benefits of digestive enzymes, most studies are decades old and the study population suffers from specific disorders. There is a lack of studies of digestive enzymes on healthy people.

Moreover, for many benefits, the evidence is based only on animal and cell studies or clinical studies with a very small number of participants.

Further studies on the health benefits and risks of digestive enzymes should be encouraged.

Summary of Mechanisms

Overall, digestive enzymes improve digestion by [123, 127, 59, 133, 134, 135, 125]:

  • Increasing the absorption of fats and proteins while breaking down complex carbs
  • Enhancing lactose digestion for people with lactose intolerance
  • Breaking down gliadin, a component of gluten, which helps people with celiac disease

They may help IBS and IBD by [67, 158, 159, 8, 90, 114, 160, 171, 172, 79, 177, 169, 170, 175]:

  • Improving symptoms of bloating, constipation, painful bowel movements, and flatulence
  • Lowering inflammatory markers (CD44, IFN-γ, TNF-alpha, GM-CSF) involved in IBD
  • Increasing the good gut bacteria (bifidobacteria)

In addition, digestive enzymes may help your body fight off infections by [76, 76, 179, 182, 75, 192]:

  • Blocking the growth of harmful gut bacteria that cause stomach and gut infections and helping to kill yeast and viruses
  • Blocking and destroying biofilms, a sticky mass of bacteria that resists common treatments

The ability of your natural digestive enzymes to combat infections and reduce a myriad of gut complaints explains their common use as supplements in functional medicine. Practitioners often prescribe them as part of protocols for SIBO, leaky gut, and Candida.

Additionally, some enzymes may also ease joint disorders, lower pain and inflammation, and improve heart health. Note that these benefits will depend on specific enzymes. For example, only bromelain aids weight loss and only amylase may help prevent diabetes [74, 213, 78].

Side Effects & Precautions

Most digestive enzymes (bromelain, papain, pancrelipase, pancreatin, actinidin, nattokinase)  are non-toxic and safe to consume. Common side-effects are mild and include [84, 304, 305, 252, 168, 306, 307, 308, 102, 103, 104, 104, 152]:

  • Diarrhea
  • Constipation
  • Nausea
  • Stomach pain
  • Gas
  • Headache
  • Fatigue
  • Skin rash
  • Increased or decreased blood sugar levels (for pancrelipase/pancreatin).

There is a case reported of gut inflammation following high-dose of pancreatic enzyme supplements [309].

Allergic Reactions

People who are allergic to pineapple should not take bromelain supplements [310, 311, 312, 313].

People who are allergic to papaya or latex, should not take papain supplements [314, 315].

If you’re allergic to any product from which an enzyme is produced, you should avoid it.


Unripe or semi-ripe papayas can be dangerous for pregnant women, as it may stimulate contractions. Therefore, papain may be unsafe for pregnant women [316].

In male rats and mice, papaya extracts decreased sperm motility and reduced male fertility [317, 318, 319, 320].

Many digestive enzyme supplements have not been thoroughly researched in terms of safety. Unless prescribed by your doctor, it’s best to about these supplements while pregnant or breastfeeding.

Drug Interactions

Blood Thinners

People should avoid taking bromelain, papain and nattokinase, serrapeptase together with blood thinners, such as heparin, aspirin or warfarin at the same time because it can increase the risk of bleeding [321, 322, 182, 323, 324, 98].
There is also a risk of clotting mechanical heart valves if nattokinase is substituted for warfarin [325].


Bromelain may increase the absorption of :

  • Penicillin
  • Tetracyclines (antibiotics that fight bacterial infections)

Possibly, it may also decrease their side-effects [84, 326, 327, 328].

Diabetes Drugs

Papain may reduce blood sugar levels, so it should not be taken together with diabetes drugs, as it might cause very low blood sugar levels [329].

Acarbose and miglitol are diabetes drugs, which lower blood sugar levels by blocking alpha-glucosidases.Therefore, alpha-amylases, maltase and pancreatin may reduce the efficiency of the drugs and cause high blood sugar levels [330, 331, 332].

Genetic Predispositions

Amylase & Carbs

Salivary amylase is produced by the AMY1A, while pancreatic amylase is produced by the AMY2A and AMY2B genes. People with a low number of AMY1A copies are less able to digest and use complex carbs (glucose malabsorption) and more likely to have a higher body mass index (BMI) and obesity [48, 333, 334, 335, 336, 337, 338, 335, 339].

On the contrary, people with a high number of AMY1A copies, can better digest starch (glucose tolerance), have more good gut bacteria, can lose weight easier and are less likely to develop diabetes type 2, metabolic syndrome, and insulin resistance [340298, 341, 342, 343].

Pancreas Insufficiency

Exocrine pancreatic insufficiency (EPI), a condition which causes low production of digestive enzymes, can also be caused by rare, genetic disorders. These include Shwachman–Diamond syndrome (mutations in the SBDS gene) and  Johanson-Blizzard syndrome (mutations in the UBR1 gene) [42, 43]

Lactose Intolerance

Lactase is an enzyme that breaks down lactose, a sugar found in milk products, into glucose and galactose and is coded in the LCT gene. Mutations in the LCT gene, such as LCT- 13910CC can lead to lactase deficiency and lactose intolerance. People with lactose intolerance who consume lactose-dairy products may experience stomach pain, bloating, gas, nausea, and diarrhea [35, 36].

Sucrose and Maltose Intolerance

Sucrase-isomaltase is coded in the SI gene, and variations in the SI gene, such as V577G and C1531W mutations lead to congenital sucrase-isomaltase deficiency. People with this rare disorder cannot break down the sugars sucrose and maltose. After consumption of sucrose and maltose, people will experience stomach cramps, bloating, excess gas, and diarrhea [38, 39].

Pompe Disease

Alpha-glucosidase is an enzyme encoded in the GAA gene. Mutations in the GAA gene can lead to a serious disorder called Pompe disease, or glycogen storage disease type 2. Pompe disease is caused by the buildup of a complex sugar (glycogen) in the body’s cells, which impairs the muscles and the organs function. People with Pompe disease suffer from respiratory failure, heart damage, and severe muscle weakness [40, 41].

Ways to Naturally Boost Digestive Enzymes

Herbal Bitters

Many bitter herbs can increase your production of digestive enzymes and help you overcome gut problems [344+, 345, 346, 347+].

Extracts of bitter herbs can be used in various ways: added to food, poured into drinks such as tea or alcoholic beverages, or taken alone in their pure form. Several herbs are traditionally combined into digestive elixirs, the most well-known ones being Swedish bitters and Iberogast. Bitters are typically used before a meal to stimulate digestive juices.

Enzyme-rich Foods

One option is to increase the consumption of food naturally rich in digestive enzymes such as [5, 4, 348, 53, 54, 55, 67, 45, 349, 350, 351]:

  • Pineapple (bromelain)
  • Kiwis (actinidin)
  • Papaya (papain)
  • Banana (amylases)
  • Mango (amylases)
  • Honey (amylases, proteases)
  • Avocado (lipase)
  • Walnuts (lipase)
  • Pinenuts (lipase)
  • Coconut (lipase)
  • Lentils (lipase)
  • Chickpeas (lipase)
  • Mungbean (lipase)
  • Oats (lipase)
  • Castor beans (lipase)
  • Eggplant (lipase)
  • Ginger (protease)
  • Kefir (lipase, protease, lactase)

Of course, don’t experiment with foods you know you don’t do well with.


A healthy gut microbiome is essential for proper digestive enzymes function. To increase your good gut bacteria, include more fermented foods in your diet. Alternatively, you can search for specific probiotic strains or their combination in supplement form.


In a study with over 400 people, moderately intense exercise increased amylase levels [352].

Weight Loss

In a study with 160 people, obese and overweight people had lower amylase, which increased with weight loss [25].

Stop Smoking

In 70 people, smokers had lower amylase levels compared to nonsmokers [353, 16].

Avoid Late-night Meals/Snacks

In 2.5k people, eating late in the evening was linked with low amylase levels [354].

Digestive Enzyme Supplements & Dosage

Prescription Enzymes

Pancrelipase or pancreatin are combination digestive enzyme supplements, containing lipases, amylases, and proteases derived from pork, beef, fungi or bacteria [105, 106, 66].

The recommended dosage for pancreatin/pancrelipase is 25,000–50,000 units of lipase per meal. To ensure that they are well mixed with the food in the stomach, pancreatin should be taken during or immediately after the meal [355, 146].

For people with cystic fibrosis, 500–3,000 lipase units/kg per meal is recommended. For children with cystic fibrosis, aged 4 or younger, 1,000 lipase units/kg per meal are recommended, whereas for older children 500 lipase units/kg per meal are suggested [356, 356, 144].

Dietary Supplements

Papain is available as fruit mash or as a powder which can be mixed with water or juice. In clinical studies, 20ml or 20g, once or twice a day for a few weeks have been used. You should take the supplement between meals [67,90].

Bromelain is available as a tablet, capsule, cream, liquid extract, powder, and tincture and the recommended dosage is 750mg/day. [84, 304, 237, 86, 5].

Lactase supplements are either added directly to the milk or are available as soft gel capsules, caplets, and chewable tablets. The most efficient dosage in clinical studies was 6000 IU of lactase  [128, 106, 59].

For dosage recommendations on separate digestive enzymes, you can read these articles:

Digestive Enzymes for Dogs

In dogs with pancreatic insufficiency (EPI), digestive enzymes supplementations improved and digestion and reduced fat in the stool, stomach pain and improved bowel movements. However, in severe cases, supplementation did not help [357, 358].

Furthermore, digestive enzymes intake caused mouth ulcers and bleeding in a dog with pancreatic insufficiency (EPI) [359].

In healthy dogs, digestive enzymes supplementation did not increase fat, carbs or protein absorption [360].

Overall, the evidence is lacking to support the use of digestive enzymes in healthy dogs. Avoid giving them to your dog unless explicitly prescribed by a qualified veterinarian.

User Experiences

Most users were happy with multi-ingredient digestive enzyme supplements. Users experienced some improvement in digestive issues, such as diarrhea, constipation, bloating and gas. However, some users also experienced side-effects, such as increased blood sugar levels, red eyes, frequent urination, and stomach pain.

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About the Author

Anastasia Naoum

MS (Health Informatics)
Anastasia holds an MSc in Health Informatics from the Sheffield University, an MSc in Health Economics from the Erasmus University of Rotterdam and a BSc in Economics from the University of Macedonia.
Anastasia grew up in a medical environment, as both her parents are doctors and developed from a young age a passion for medicine and health. She has worked in several institutions and associations which promoted healthy living and sustainable healthcare systems. Currently, she is leading a green life, sailing with her boyfriend across Europe, living in their sailboat with the help of solar and wind power, minimizing CO2 production.

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