Why Proteolytic Enzymes Should be In Your Formulary

Why Proteolytic Enzymes Should be In Your Formulary

Proteolytic enzymes can be commonly overlooked when prescribing nutrients, yet their value is enormous.  First reported by P. A. Levene in his studies on “The Cleavage Products of Proteases” in the first issue of The Journal of Biological Chemistry published October 1, 1905, and used successfully in Germany in the 1960s, it was discovered that the recognized benefits included: reducing inflammation, decreasing pain from osteoarthritis, treating viral infections, and helping patients suffering from autoimmune diseases. 

What we now know is they affect even more processes in our bodies.


They are often called proteases, peptidases, or proteinases and are produced in the digestive tract. There are the major enzymes: exopeptidases that work at the protein ends, and endopeptidases that have a catalytic mechanism and work at a variety of target sites.  They are also present in archaea, bacteria, algae, plants, viruses, and some animals.  Usually, the digestive enzymes we get in a product such as trypsin and chymotrypsin are sourced from porcine or bovine sources, while others like papain and bromelain are sourced from fruits.

The ability of proteolytic enzymes to exert influence over a wide variety of physiological and biochemical processes occurs when they break down the long chains of proteins into peptides and then amino acids in our foods. 

If our bodies do not manufacture these enzymes in sufficient quantity, we can take them by supplementation or increasing the food source.  Some of the most common proteases include cymotrypsin, pepsin, trypsin, papain, bromelian, and serrapeptase.  Great food sources include pineapple and papaya, and good backup choices are kimchi, asparagus, ginger, kiwi, and sauerkraut.

Enzymes are very efficient, so ingesting them with a meal will trigger the breakdown of the protein in the food very quickly. In order to benefit in many other ways other than as a digestive aid, it is important to take them on an empty stomach 45-60 minutes before eating, or 2 hours after a meal.  This also allows better absorption to act as an anti-inflammatory product in the bloodstream.


Dosage will range from two a day, up to 15 a day for chronic conditions.  For acute conditions, 30 per day in divided doses is commonly prescribed for up to 6 weeks.  Should the patient experience diarrhea or excessive gas, the dosage should then be decreased.

Smaller doses taken more frequently and for an extended period of time are now commonly used for IBD, IBS, constipation, diarrhea, hypochlorrhydria, enzyme/pancreatic insufficiency, and joint inflammation.


Supplements containing proteolytic enzymes have led to a significant improvement in constipation, bloating, gas, and abdominal pain. (Onken, et al.) Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro. Clin Immunol. 2008;126(3):345-352. doi:10.1016/j.clim.2007.11.002 Long used for GI health, there are also promising studies demonstrating that bromelain may be beneficial in preventing colon cancer. (Ehteda, et al.)


Including foods high in proteolytic enzymes in the cancer fight may prove very beneficial, because the fiber present in these foods binds to the cancer-causing toxins that cause free radical damage in the colon.  Decreasing the inflammation in the colon may also help those with ulcerative colitis, Crohn’s, and celiac disease.

Fighting infection is another promising benefit, especially in light of our current pandemic.  Proteolytic enzymes increase the potency of natural killer cells. Proteolytic enzymes are also capable of the degradation of pathogens that can inhibit the normal functioning of the immune system. 

Evidence suggests that papain and trypsin help in breaking the existing pathogenic immune complexes and prevent their formation, thereby helping in an increased lymphatic drainage.  Possibly this is an immune system booster a lot of us need.

According to a published study by Gioia, et al., “As for common viral infections, the crucial event for the viral life cycle is the entry of genetic material inside the host cell, realized by the spike protein of the virus through its binding to host receptors and its activation by host proteases; this is followed by translation of the viral RNA into a polyprotein, exploiting the host cell machinery. The production of individual mature viral proteins is pivotal for replication and release of new virions.

Several proteolytic enzymes either of the host and of the virus act in a concerted fashion to regulate and coordinate specific steps of the viral replication and assembly, such as (i) the entry of the virus, (ii) the maturation of the polyprotein, and (iii) the assembly of the secreted virions for further diffusion. Therefore, proteases involved in these three steps are important targets, envisioning that molecules which interfere with their activity are promising therapeutic compounds.” (Gioia et al)

A review of 10 studies found that the proteolytic enzyme bromelain was effective at reducing symptoms of pain, swelling, and joint stiffness in those with osteoarthritis. (Brien et al)

In our office, proteolytic enzymes are used quite frequently for acute injuries such as sprain/strains or fractures, thus seeing a reduction in healing time that is significant.   For over-exertion and muscle soreness, bromelain and serrapeptase are the best-used proteases.

Post-surgical treatments also include proteolytic enzymes to speed up the recovery time. Studies have demonstrated reduced swelling, pain intensity, and bruising.  (Al-Khateeb et al). As reported in Sports, Medicine, And Health: Proceedings Of The XXIV World Congress Of Sports Medicine, Amsterdam, 27 May – 1 June 1990 [International Congress Series No. 921], enzyme therapy given before and after surgery lessens swelling, inflammation, and pain. It may also prevent scarring. In some cases, less pain medication is needed.  Animal studies have shown that both papain and bromelain speed wound healing and accelerate new tissue growth when applied directly to the skin. (Rosenberg, et al).  Taking the powdered form, mixing it in a coconut oil base, and directly packing it into a wound, is an easy treatment for wound care.

Another great use of proteolytic enzymes is for sinusitis.  Most of our combo products include bromelain, along with natural antihistamines, to reduce the inflammation on the nasal turbinates associated with a sinus infection.

Lastly, elevations of my patient lab markers, such as CRP and ESR have also been reduced and normalized within 30-90 days utilizing proteolytic enzymes, so consider their usage for abnormal inflammatory markers seen on blood labs.


Proteolytic enzyme supplements are typically safe.  Occasional side effects of gas, bloating and vomiting may occur at very high dosages.  Some patients may be allergic to certain proteolytic enzymes, the most common being the bromelain in pineapple.  (Matsumura, Y.)  Also, use caution in patients who have liver disease and those on blood-thinning medications, including low-dose aspirin therapy.  The serrapeptase enzyme may be difficult for the liver to break down. Since thinning of the blood is a common side effect, it may warrant a change in or avoidance of blood-thinning medications, in some cases. Lastly, be aware of the potential of pancrelipase if prescribed to your patients to cause a folic acid deficiency in long-term usage. (Krishnamurty, et al.)

Remember to put proteolytic enzymes on your shelf, in your online dispensary, and in your patients’ hands. The safety and efficacy allow these products to be used for most of your patient populations for a variety of conditions.   They are a simple yet effective treatment, improving patient outcomes in a relatively short period of time.


Yasuhiro Matsumura, “Role of Allergen Source-Derived Proteases in Sensitization via Airway Epithelial Cells”, Journal of Allergy, vol. 2012, Article ID 903659, 11 pages, 2012. https://doi.org/10.1155/2012/903659

Krishnamurty DM, Rabiee A, Jagannath SB, Andersen DK. Delayed release pancrelipase for treatment of pancreatic exocrine insufficiency associated with chronic pancreatitis. Ther Clin Risk Manag. 2009;5(3):507-520. doi:10.2147/tcrm.s319

Braun JM, Schneider B, Beuth HJ. Therapeutic use, efficiency and safety of the proteolytic pineapple enzyme Bromelain-POS in children with acute sinusitis in Germany. In Vivo. 2005 Mar-Apr;19(2):417-21. PMID: 15796206.

Gioia M, Ciaccio C, Calligari P, De Simone G, Sbardella D, Tundo G, Fasciglione GF, Di Masi A, Di Pierro D, Bocedi A, Ascenzi P, Coletta M. Role of proteolytic enzymes in the COVID-19 infection and promising therapeutic approaches. Biochem Pharmacol. 2020 Dec;182:114225. doi:

Levene, P. A. (1905) J. Biol. Chem. 1 45–58

Mótyán JA, Tóth F, Tőzsér J. Research applications of proteolytic enzymes in molecular biology. Biomolecules. 2013;3(4):923-942. Published 2013 Nov 8. doi:10.3390/biom3040923

Onken JE, Greer PK, Calingaert B, et al. Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro. Clin Immunol. 2008;126:345-52.

Amini A, Ehteda A, Masoumi Moghaddam S, Akhter J, Pillai K, Morris DL. Cytotoxic effects of bromelain in human gastrointestinal carcinoma cell lines (MKN45, KATO-III, HT29-5F12, and HT29-5M21). Onco Targets Ther. 2013;6:403-409. Published 2013 Apr 16. doi:10.2147/OTT.S43072

Brien S, Lewith G, Walker A, Hicks SM, Middleton D. Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies. Evid Based Complement Alternat Med. 2004;1(3):251-257. doi:10.1093/ecam/neh035

Udani JK, Singh BB, Singh VJ, Sandoval E. BounceBack capsules for reduction of DOMS after eccentric exercise: a randomized, double-blind, placebo-controlled, crossover pilot study. J Int Soc Sports Nutr. 2009;6:14. Published 2009 Jun 5. doi:10.1186/1550-2783-6-14

Al-Khateeb TH, Nusair Y. Effect of the proteolytic enzyme serrapeptase on swelling, pain and trismus after surgical extraction of mandibular third molars. Int J Oral Maxillofac Surg. 2008 Mar;37(3):264-8. doi: 10.1016/j.ijom.2007.11.011. Epub 2008 Feb 12. PMID: 18272344. Rosenberg L, Krieger Y, Silberstein E, Arnon O, Sinelnikov IA, Bogdanov-Berezovsky A, Singer AJ. Selectivity of a bromelain based enzymatic debridement agent: a porcine study. Burns. 2012 Nov;38(7):1035-40. doi: 10.1016/j.burns.2012.02.011. Epu

About Author


Dr. Cindy M. Howard has been in private practice since 1999. She is board certified in Internal Disorders and Nutrition and hold a fellowship in Medical Acupuncture. She is the past president of the ACA Council on Diagnosis and Internal Disorders and serves currently as the Northern Illinois Delegate for the American Chiropractic Association. She serves on the medical advisory board for The Functional Medicine University and Integrative Therapeutics. Dr. Howard is the Director of Functional Nutrition for Neurosport Elite which focuses on sports performance for serious to elite athletes. She also teaches for the diplomate program and is an Executive Board member and Instructor for POWERPlay in Sports. She is the team Chiropractic Physician for DREAMZ Elite competitive cheer.

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