Papaya Enzyme: Uses And Health Advantages

  • Alice Cui MSci Applied Medical Sciences, UCL

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Introduction

Papain, the enzyme of papayas, has long been used across many different cultures as a multifaceted agent that has applications across healthcare. It belongs to a papain-like protease family and is revered for its ability to break down large proteins. Using papain in different contexts originated in South America to tenderise meat with its medicinal properties extensively explored since then. Recent research delves into its potential role in obesity, antibacterial properties, treatment of parasitic infections such as Strongyloidiasis, combating atherosclerosis, and countering oxidative stress. Additionally, it has been incorporated into wound cleansers, showing promise in speeding up the healing process. Most notable of all, papain has been investigated as an alternative treatment for cholangiocarcinoma, a challenging bile duct cancer. Amidst its health benefits, papain poses allergenic risks with studies revealing skin sensitization potential, emphasising the importance of understanding its allergic implications. Read on to find out more about papains’ uses across a variety of different areas as well as considerations regarding its allergenic properties. 

What is a papaya enzyme?

The enzyme of a papaya is commonly known as ‘papain’. Papain is part of a group of proteins called the papain-like protease family that can do a range of different things such as breaking down larger proteins and working on pairs of amino acids in protein peptidases. Proteins in this family can be found in all plants and mammals as well as eubacteria, yeast, and protozoa.1

Composition and key components

The precursor protein is like a building made up of 345 smaller parts known as amino acids. These 345 parts are structurally grouped in 3 sections with the whole structure being held together by special disulfide bridges. Papain’s active site has 2 important amino acids cysteine-25 and histidine-159 that work together for the enzyme to function.2

Forms and uses 

There are many uses of the papaya enzyme in a variety of areas.

In South America, papain has long been used to tenderise meat to be eaten as it breaks down the tough fibres.3 You can eat raw papaya to incorporate papain into your diet but you can also find it sold in capsules, topical creams, and chewable forms. The medicinal uses for papain are widespread with reviews on the major scientific findings revealing the antibacterial, antitumor, antiviral, hypoglycaemic, and anti-inflammatory properties of the enzyme.4 There is emerging research on the uses in the context of obesity and digestive health, treating strongyloidiasis and atherosclerosis as well as its antioxidant properties. It has been explored in using the enzyme to speed up the healing of wounds and even researched as a therapeutic target in bile duct cancer. Read on to explore the latest scientific research papers and the uses of the enzyme in healthcare. 

Uses of papaya enzyme in healthcare

Obesity

Recently, the use of papain to treat obesity has been studied by giving it to mice on high-fat diets and looking at the fat content in their cells. Papin reduced weight gain in the livers and fat tissues of the mice and also reduced cholesterol levels. As well as this, the study also identified a potential mechanism of action for why papain can be so beneficial for aiding digestion and reducing levels of obesity. They found that papain works by changing the levels of certain proteins related to fat and inflammation. It also works on a pathway that helps control your metabolism. This emerging research shows the potential for using papain to prevent and treat obesity and underscores the importance of the enzyme in digestion.5

Antibacterial properties

Another study from 2015 looked into how well papain could fight certain bacteria and fungi. They highlighted that while more research is needed, papain was effective in stopping the growth of various microorganisms and could be a good resource to use for killing germs.6 

There are also different types of bacteria that can populate drinks like citrus juices even after pasteurisation. A 2016 study looked at how papain can combat the population of bacteria in these types of drinks and saw that the enzyme effectively reduced the bacteria present. In bacteria-contaminated orange juice, papain successfully eliminated the bacteria showing the enzymes' antibacterial potential.7

Strongyloidiasis

This is a disease caused by the parasitic worm roundworms. There are over 40 different types of these parasites that can infect livestock, reptiles, and birds. Symptoms include abdominal pain, diarrhoea, and rashes and are typically treated with antiparasitic medications over the course of 14 days.8 in 2017 a study looked into the effectiveness of papain against fighting this parasite. They found that at high concentrations, the papaya sap could destroy some or all of the eggs and larvae of the parasite. This was even seen at lower concentrations showing that both the sap and purified papain could be useful in treating this type of human parasitic infection.9

Atherosclerosis 

Atherosclerosis is caused by a buildup of plaque in the lining of an artery and causes thickening or hardening of the artery wall. It can make it difficult for blood to flow through them and increase the risk of a heart attack.10 A 2018 study looked at how well papain could affect the early stages of this condition. They showed that papain could stop cell clusters from forming and prevent the activation of these cells that cause the thickening and hardening of the arteries. While they did show that this phenomenon could be influenced by other substances, however, the study suggests that papain could help to prevent the early stages of this condition by affecting the underlying cell processes.11

Anti-inflammatory benefits 

Many researchers believe that papain can exert anti-inflammatory properties. Previous research used animal models to examine this effect in Carica papaya seed extract. They found this extract to contain bioactive compounds such as alkaloids and polyphenols which can help to reduce pain and inflammation. The extract successfully reduced pain-related behaviours in rats and mice, underscoring its potential as an anti-inflammatory.12

Oxidative stress 

Oxidative stress can damage cells and tissues due to an imbalance between antioxidants and pro-oxidants leading to inflammation and chronic diseases. Antioxidants can help to manage these conditions. A recent review highlights how papaya extracts can counteract oxidative stress due to their antioxidant properties. It can neutralise harmful substances through different pathways that activate the body’s defence mechanisms. It can be used in medications and supplements to help manage conditions caused by oxidative stress and is continuously being researched as a potential treatment for chronic diseases.13

Wound healing properties 

Papain has also been incorporated into the formulation of wound cleanser to simplify the management of wounds by combining a cleanser and debridement into one formula. Animal studies have found that papain-based wound cleansers can help to speed up the healing process. It was also found to demonstrate antibacterial properties. While it appears to be effective, more research is needed to determine the safety of usage on humans before the product can be widely distributed.14

Cholangiocarcinoma 

Cholangiocarcinoma (CC) is a common and challenging type of bile duct cancer. Papain has been explored as an anticancer agent in human CC cell cultures. Researchers have studied how the extract influences cell growth, movement, invasion, and other characteristics of CC tumour cells. Papain has been found to reduce the proliferation, migration, and invasion of CC. It also affected signalling pathways linked to cancer and decreased levels of certain proteins involved in the pathways. This is an exciting result for papain as a much-needed alternative treatment to CC and underscores the extract as a potential therapeutic target.15

Papain as an allergen 

While allergies to papaya are less studied today, there is a wealth of research between 1970-1980 that identifies papain as a common allergen. In a study with 500 patients from an allergy clinic, 5 patients were found to be sensitive to papain.16 This may not seem like a huge number, but it is important for clinicians to know about reactions to less common allergens to allow for improved diagnosis and management of allergic conditions. 

Many beauty gurus endorse papaya enzyme as a “gentle exfoliant” due to its ability to break down large proteins. Although the enzyme has a wealth of health benefits in other areas, many scientists believe that it can irritate your skin. Research has confirmed papains’ ability to cause skin sensitisation using human skin cells in a lab. It was found to increase water loss through the skin, break down proteins in the skin, and cause blood vessels to widen. When applied to the skin, papain causes inflammation by triggering an immune response.17

Summary

In summary, papaya enzyme remains a highly versatile agent with a diverse range of applications. From its role in obesity management to exhibiting antibacterial anti-inflammatory benefits, the enzyme showcases significant potential. However, caution is warranted as papain can act as a rare allergen, eliciting sensitization reactions, particularly on the skin. Understanding the dual nature of papain, and balancing its therapeutic advantages with potential allergic responses is crucial for informed medical practices. Further research is essential to unravel additional dimensions of papain’s utility and to ensure safe usage across various healthcare applications.

References

  • Rawlings ND, Barrett AJ. [32] Families of cysteine peptidases. Methods in Enzymology, vol. 244, Elsevier; 1994, p. 461–86. https://doi.org/10.1016/0076-6879(94)44034-4.
  • UniProt n.d. https://www.uniprot.org/uniprotkb/P00784/entry (accessed December 1, 2023).
  • Maiti AK, Ahlawat SS, Sharma DP, Khanna N. APPLICATION OF NATURAL TENDERIZERS IN MEAT- A REVIEW. Agricultural Reviews n.d.;29:226–30.
  • Singh SP, Kumar S, Mathan SV, Tomar MS, Singh RK, Verma PK, et al. Therapeutic application of Carica papaya leaf extract in the management of human diseases. Daru 2020;28:735–44. https://doi.org/10.1007/s40199-020-00348-7.
  • Kang Y-M, Kang H-A, Cominguez DC, Kim S-H, An H-J. Papain Ameliorates Lipid Accumulation and Inflammation in High-Fat Diet-Induced Obesity Mice and 3T3-L1 Adipocytes via AMPK Activation. Int J Mol Sci 2021;22:9885. https://doi.org/10.3390/ijms22189885.
  • Mota VDS, Turrini RNT, Poveda VDB. Antimicrobial activity of Eucalyptus globulus oil, xylitol and papain: a pilot study. Rev Esc Enferm USP 2015;49:0216–20. https://doi.org/10.1590/S0080-623420150000200005.
  • Dos Anjos MM, Da Silva AA, De Pascoli IC, Mikcha JMG, Machinski M, Peralta RM, et al. Antibacterial activity of papain and bromelain on Alicyclobacillus spp. International Journal of Food Microbiology 2016;216:121–6. https://doi.org/10.1016/j.ijfoodmicro.2015.10.007.
  • Strongyloidiasis: Causes, Symptoms, Prevention & Treatment. Cleveland Clinic n.d. https://my.clevelandclinic.org/health/diseases/14074-strongyloidiasis (accessed December 1, 2023).
  • Moraes D, Levenhagen MA, Costa-Cruz JM, da Costa AP, Rodrigues RM. In vitro efficacy of latex and purified papain from Carica papaya against Strongyloides venezuelensis eggs and larvae. Rev Inst Med Trop Sao Paulo 2017;59:e7. https://doi.org/10.1590/S1678-9946201759007.
  • Atherosclerosis n.d. https://www.hopkinsmedicine.org/health/conditions-and-diseases/atherosclerosis (accessed December 1, 2023).
  • Fei X, Yuan W, Zhao Y, Wang H, Bai S, Huang Q. Papain Ameliorates the MPAs Formation-Mediated Activation of Monocytes by Inhibiting Cox-2 Expression via Regulating the MAPKs and PI3K/Akt Signal Pathway. Biomed Res Int 2018;2018:3632084. https://doi.org/10.1155/2018/3632084.
  • Ahmed MZ, Kamble S. Antinociceptive Action of the Seeds of Carica Papaya Linn Extrcted in Aqueous Medium in Mice. Biomedical and Pharmacology Journal 2018;11:197–201. https://doi.org/10.13005/bpj/1363.
  • Kong YR, Jong YX, Balakrishnan M, Bok ZK, Weng JKK, Tay KC, et al. Beneficial Role of Carica papaya Extracts and Phytochemicals on Oxidative Stress and Related Diseases: A Mini Review. Biology 2021;10:287. https://doi.org/10.3390/biology10040287.
  • Ajlia SASH, Majid FAA, Suvik A, Effendy MAW, Serati Nou H. Efficacy of Papain-based Wound Cleanser in Promoting Wound Regeneration. Pakistan J of Biological Sciences 2010;13:596–603. https://doi.org/10.3923/pjbs.2010.596.603.
  • Müller A, Barat S, Chen X, Bui KC, Bozko P, Malek NP, et al. Comparative study of antitumor effects of bromelain and papain in human cholangiocarcinoma cell lines. International Journal of Oncology 2016;48:2025–34. https://doi.org/10.3892/ijo.2016.3411.
  • Mansfield LE, Ting S, Haverly RW, Yoo TJ. The incidence and clinical implications of hypersensitivity to papain in an allergic population, confirmed by blinded oral challenge. Ann Allergy 1985;55:541–3.
  • Stremnitzer C, Manzano-Szalai K, Willensdorfer A, Starkl P, Pieper M, König P, et al. Papain Degrades Tight Junction Proteins of Human Keratinocytes In Vitro and Sensitizes C57BL/6 Mice via the Skin Independent of its Enzymatic Activity or TLR4 Activation. J Invest Dermatol 2015;135:1790–800. https://doi.org/10.1038/jid.2015.58.

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Jessica Nicholson

Master of Neuroscience – MSc, University of Sussex

I have a BSc in Psychology with Neuroscience as well as an MSc in Neuroscience. I am passionate about bridging the gap between healthcare, science and the wider community. I have worked for the NHS as a youth research advisor and I also enjoy volunteering/support work with local charities that support the disabled community.

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