Evidence Based
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11 Digestive Enzymes Supplement Benefits + Side Effects

Written by Anastasia Naoum, MS (Health Informatics) | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Anastasia Naoum, MS (Health Informatics) | Last updated:

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Digestive enzymes break down fats, proteins, and carbs so your body can absorb the nutrients. As supplements, they may improve digestion, gut health, pain, inflammation, and more. For optimal results, it’s essential to know which enzyme or combination to use for a particular condition. Read on to learn the benefits, side effects, and precautions of digestive enzymes supplements.

What Are Digestive Enzymes?

Digestive enzymes are a broad group of enzymes that break down large nutrients such as fats, proteins, and carbs into smaller ones your body can absorb easier. The body naturally produces most of these enzymes in the pancreas, while smaller amounts are made 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 depend on a complex set of factors. People use supplemental enzymes to improve digestion, relieve inflammation, gut infections, pain, and more.

Health Benefits

Please note: most health benefits are limited to specific combinations or individual enzymes, and they may not translate to digestive enzymes as a whole.

Effective:

1) 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 [5, 6, 7].

In multiple clinical trials with over 750 adults and children with EPI, prescription digestive enzymes (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 [8, 9, 10, 11, 12, 13].

Based on these results, the FDA has approved prescription pancreatic enzymes for the treatment of EPI. However, digestive enzyme supplements are much less potent than prescription products, and the FDA doesn’t assure their quality. They should never be used instead of prescription enzymes for a diagnosed condition.

Possibly Effective:

2) Indigestion

Specific enzymes can help with lactose intolerance, celiac disease, and other causes of indigestion [14, 15, 16, 7, 17].

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) [18, 19, 20, 21].

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 [14].

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 [22, 23].

Additionally, actinidin from kiwi enhanced the digestion of food proteins in rats (beef muscle protein, gelatin, soy protein isolate, and gluten) [15].

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 [16, 24].

3) Gut Inflammation

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 [25, 26, 27, 28, 29, 30, 31].

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 [25, 26, 27, 32, 33, 34, 29, 35].

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) [30].

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 [36]

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 [37, 38, 39, 40, 41, 42, 43].

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 [44, 31, 45, 46].

4) Microbial Infections

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 [47, 48, 49].

Some enzymes may help with dengue fever, a viral disease caused by mosquito bites. In clinical studies with more than 700 people with dengue fever, papaya extract increased red blood cells, blood platelets, and decreased hospital stay [50, 51, 52, 53, 54, 55, 56, 57, 58].

In 60 children with sepsis, trypsin, bromelain, and rutin reduced fever and improved the symptoms after 21 days, compared to placebo [59].

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 [60].

In animal and cell studies, trypsin, alpha-amylase, cellulase, pepsin, and papain destroyed biofilm colonies and blocked the growth of the following microbes [61, 62, 63, 38, 64, 37, 65, 66, 67, 68]:

  • Bacteria that cause food-borne illnesses, gut, and stomach infections
  • Staph bacteria (respiratory and skin infections)
  • Bacteria that cause burn wound infections
  • E. coli (UTIs)
  • 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 further investigate and confirm these effects.

5) Pain and Swelling

In several clinical trials with over 400 people who underwent surgery, enzymes supplementation (bromelain, chymotrypsin, pancreatin, papain, trypsin, serrapeptase) reduced pain and swelling and decreased the need for painkillers [69, 70, 71, 72, 73, 74, 75, 76, 77].

In 192 people with shingles (herpes zoster), digestive enzymes supplementation reduced pain as effectively as the drug acyclovir [78].

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 [79, 80, 81].

6) Joint Disorders

In multiple trials of more than 1,000 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 [82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 81, 95, 96].

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 [97, 98].

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) [99].

7) 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 [100, 101, 102, 103, 104, 51]:

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 [100, 101, 102].

However, in 68 diabetics, bromelain did not reduce risk factors for heart disease (high blood fats, high blood pressure) [105].

In animal and cell studies, bromelain, actinidin, and nattokinase reduced blood platelet clumping. Bromelain also increased the survival of heart cells and protected them from poor blood flow [106, 107, 108, 109, 110, 111, 112].

8) Chemotherapy Side Effects and Cancer Symptoms

Based on the preliminary evidence, digestive enzymes may help by reducing some of the side effects of cancer treatments, lowering inflammation, and improving digestion [113, 114, 115, 116, 117, 45, 118, 119 ].

In clinical studies with over 2,500 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 [116, 113, 114, 115].

However, these results shouldn’t be interpreted as supportive of the anticancer effects of digestive enzymes. None of them is approved for cancer prevention or treatment.

9) 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 [120, 121, 122, 77].

In clinical studies with more than 200 people with inflamed sinuses (sinusitis), bromelain and serrapeptase improved symptoms such as 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 [123, 124, 125, 126, 127].

In a trial of 130 people, proteases (papain, bromelain, trypsin, and chymotrypsin) lowered high TGF-beta levels, thus lowering inflammation [121].

In a 3-month study of 27 children with lung inflammation (bronchitis), digestive enzyme supplements improved their symptoms [128].

In mice and rats, chymotrypsin, trypsin, and serrapeptase reduced swelling and inflammation. These enzymes worked better than NSAIDs [129, 130, 131].

10) 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 [77, 122, 132, 133, 134, 135].

In 192 people with shingles (herpes zoster), digestive enzymes supplementation reduced skin wounds and redness as effectively as the typical drug acyclovir [78].

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 [132, 136, 137].

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 [77].

In rats and pigs, topical application of papain and bromelain removed dead cells and tissue (debris), accelerated wound closure and reduced inflammatory markers [138, 139, 140, 141, 142, 143, 144].

Insufficient Evidence:

No valid clinical evidence supports the use of digestive enzymes for any of the conditions in this section. Below is a summary of up-to-date animal studies, cell-based research, or low-quality clinical trials which should spark further investigation. However, you shouldn’t interpret them as supportive of any health benefit.

11) Developmental Disorders

In two 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) [36, 145].

However, in 43 children with autism, digestive enzymes did not improve behavior, gut symptoms, or sleep quality compared to placebo [146].

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

Animal and Cellular Research (Lacking Evidence)

No clinical evidence supports the use of digestive enzymes for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.

Alzheimer’s Disease

Amyloid-beta plaques contribute to the onset of Alzheimer’s disease [147].

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 [148, 149, 150, 151].

Diabetes

In more than 2,000 people, those with low amylase levels had increased rates 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 [152].

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 [153, 139, 154, 155, 156].

Effects on Weight Control

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 [157].

Type 2 diabetes and metabolic syndrome are commonly accompanied by obesity. Based on the previously mentioned studies, some digestive enzymes may help lower blood sugar levels, which might indirectly help with weight loss [153, 139, 154, 155, 156].

However, the available evidence is far from conclusive. At this point, digestive enzymes can’t be recommended as a complementary approach to weight loss.

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 some 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 are warranted.

Summary of Mechanisms

Overall, digestive enzymes improve digestion by [14, 18, 19, 8, 9, 10, 16]:

  • 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 [25, 26, 27, 28, 29, 30, 31, 39, 40, 45, 46, 37, 38, 43]:

  • 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 [47, 48, 51, 61, 62]:

  • 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 [82, 83, 134].

Side Effects & Precautions

This list does not cover all possible side effects. Contact your doctor or pharmacist if you notice any other side effects. In the US, you may report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada, you may report side effects to Health Canada at 1-866-234-2345.

Most digestive enzymes are non-toxic and safe to consume. Common side-effects are mild and include [158, 159, 160, 161, 11, 162, 163, 12]:

  • Diarrhea
  • Constipation
  • Nausea
  • Stomach pain
  • Gas
  • Headache
  • Fatigue
  • Skin rash
  • Blood sugar fluctuations

There is a case reported of gut inflammation following high-dose of pancreatic enzyme supplements [164].

Allergic Reactions

People who are allergic to pineapple should not take bromelain supplements [165, 166, 167, 168].

People who are allergic to papaya or latex, should not take papain supplements [169, 170].

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

Pregnancy/Fertility

Unripe or semi-ripe papayas can be dangerous for pregnant women, as it may stimulate contractions. Therefore, papain may be unsafe for pregnant women [171].

In male rats and mice, papaya extracts decreased sperm motility and reduced male fertility [172, 173, 174, 175].

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

Drug Interactions

Supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before supplementing and let them know about all drugs and supplements you are using or considering.

Blood Thinners

People should avoid taking bromelain, papain, nattokinase, and serrapeptase together with blood thinners, such as heparin, aspirin or warfarin at the same time because it can increase the risk of bleeding [176, 177, 51, 178, 179, 180].

Antibiotics

Bromelain may increase the absorption of :

  • Penicillin
  • Tetracyclines (antibiotics that fight bacterial infections)

Possibly, it may also decrease their side-effects [158, 181, 182, 183].

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 [184].

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 [185, 186, 187].

Digestive Enzyme Supplements & Dosage

Prescription Enzymes

Pancrelipase or pancreatin are combination pancreas enzymes containing lipases, amylases, and proteases derived from pork, beef, fungi or bacteria [188, 189, 190].

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 [191, 192].

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 [193, 193, 194].

Dietary Supplements

Digestive enzymes supplements have not been approved by the FDA for medical use. In general, regulatory bodies aren’t assuring the quality, safety, and efficacy of supplements. Speak with your doctor before supplementing.

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 (between meals) for a few weeks have been used [25, 29].

Bromelain is available as a tablet, capsule, cream, liquid extract, powder, and tincture and the recommended dosage is 750mg/day [158, 159, 105, 102, 195].

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 [20, 189, 19].

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 [196, 197].

Furthermore, digestive enzymes intake caused mouth ulcers and bleeding in a dog with pancreatic insufficiency (EPI) [198].

In healthy dogs, digestive enzymes supplementation did not increase fat, carbs or protein absorption [199].

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 Reviews and Experiences

The opinions expressed in this section are solely from the users who may or may not have a medical background. SelfDecode does not endorse any specific product, service, or treatment. Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice because of something you have read on SelfDecode.

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

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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