Bromelain

Bromelain is a mixture of so-called proteolytic enzymes, i.e. protein-degrading enzymes, derived from the pineapple (fruit of the pineapple tree, family Bromeliaceae). So far, a total of eight proteolytic components have been identified in bromelain, but other types of enzymes, glycoproteins, carbohydrates and other substances are also present. (1)

Bromelain can be extracted directly from fruit, but bromelain from the stem of the pineapple tree is mainly used for the production of dietary supplements, as it is normally a waste product and yet the concentration of bromelain is very high. However, the enzyme composition of the fruit and the stem is slightly different – bromelain from the stem contains more proteases. (2)

History

The pineapple is a traditional plant of tropical and subtropical regions, grown mainly in the Philippines, Hawaii, Thailand, Indonesia, Malaysia, Kenya, India, China and other countries. Its healing properties were known especially in the traditional medicine of Central and South America – the local people used pineapple compresses for wounds and other skin problems and drank the juice for digestive problems. Bromelain itself was first isolated from pineapple juice in 1891 and has been used as a dietary supplement since 1957.

Healing effects

Although bromelain is primarily a mixture of proteolytic enzymes, its positive effects on the human body are mediated by pathways other than protein degradation. For example, it has quite significant epigenetic effects – it affects the activity of a number of genes involved in cell signalling (i.e. processes that influence cell behaviour) and the production of microRNAs, which are short stretches of RNA that carry no genetic information but can completely stop the process of protein production by individual genes. However, it can also affect fat metabolism, disorders of which can contribute to many problems, including cancer (4).

Anti-inflammatory action

Bromelain is one of the most powerful natural anti-inflammatory agents, affecting most of the mechanisms involved in the development of inflammatory processes. Of particular importance is its ability to suppress the production of the COX-2 enzyme, which is essential for the reaction that produces prostaglandin E2 from arachidonic acid – a substance that directly causes inflammation and is involved in the development of many inflammation-related problems, including, for example, cancer. Bromelain also regulates the production of cytokines, which are other substances involved in inflammation – interestingly, in this respect, it acts in two ways: on the one hand, it promotes the production of substances that activate the immune system and allow a rapid response to cellular stress, and on the other hand, it suppresses the production of cytokines when immune cells are already activated and inflammation is already underway. At the same time, it regulates the penetration of immune cells into damaged tissues, another important mechanism of inflammation, and also affects the production of transforming growth factor TGF-beta, one of the main regulators of inflammation in patients with rheumatoid arthritis. (5-8)

Immunity and antimicrobial action

Bromelain is also one of the agents that effectively stimulate immunity. For example, in addition to regulating cytokine production, it activates a whole spectrum of immune cells, such as macrophages, NK cells and T-lymphocytes (9, 10).

Bromelain also acts directly on some microbes. It is relatively effective in infectious intestinal diseases causing diarrhoea, such as those caused by Escherichia coli or Vibrio cholera. It influences their signalling pathways and, in the case of E. coli, it can also affect specific receptors on the intestinal mucosa, thereby preventing the microbes from attaching to it. However, it also helps to alleviate, for example, yeast infections, and it also works against some parasites in the digestive tract – especially nematodes (9, 14).

The combination of bromelain and curcumin is even effective in boosting immunity to fight COVID-19, and the same goes for the combination of bromelain with acetylcysteine. (38, 39)

Moreover, bromelain can be very effective in the treatment of antibiotics – it increases their bioavailability (for example, by increasing the concentration of the drug in the blood) and reduces their side effects. Thus, in a number of diseases, such as cystitis, bronchitis and pneumonia, the combination of antibiotics with bromelain has been shown to be more effective than antibiotics alone (9, 14).

Autoimmune diseases

In autoimmune diseases, the anti-inflammatory action of bromelain plays an important role, especially its ability to regulate the production of TNF-alpha, one of the most potent cytokines promoting inflammation. TNF-alpha plays a key role in autoimmune diseases, particularly those affecting the gut. In particular, bromelain can effectively reduce the intensity of symptoms in people suffering from autoimmune bowel diseases (e.g. Crohn’s disease or ulcerative colitis), and it is also very effective in rheumatoid arthritis, where it reduces swelling and pain in addition to inflammation (9, 11, 12).

Research also suggests the possible effectiveness of bromelain in scleroderma, a disease that initially affects the skin but gradually affects connective tissues and internal organs (37).

Tumour diseases

The anti-cancer effects of bromelain have been the subject of a number of studies. It turns out that it can be very effective in the fight against cancer because it acts against it through several mechanisms:

One of them is the regulation of cell growth and death. The cell cycle is controlled by two pathways in the body. The first is the control of proliferation, i.e. cell division, because cancer cells are characterised by their ability to divide very rapidly and unregulated. The second is apoptosis, or cell death, in which the damaged cell, which could become the germ of a tumour, kills itself – this ability is also impaired in cancer. Bromelain can selectively promote apoptosis of cancer cells. In fact, it increases the activity of the p53 gene, which is sometimes referred to as the “cancer cop”. This leads to the production of the Bax protein, which contributes to the disruption of the mitochondrial membrane of cancer cells. At the same time, it reduces the activity of substances that enhance the survival of cancer cells (5, 15, 16).

An interesting part of bromelain’s antitumor action is the suppression of platelet activation. Cancer cells have a number of strategies that increase their chances of survival, one of which is platelet activation. These then cluster around the emerging tumour, making it impossible for immune cells to recognise and destroy it (5, 17).

In order to grow, a tumour needs nourishment, so new blood vessels are created to carry nutrients and oxygen to all its cells. It’s a process called angioneogenesis. And bromelain is one of the substances that can effectively inhibit angioneogenesis. (18, 19)

Another important way in which bromelain helps cancer is by limiting metastasis. It limits the activation of nuclear factor NF-kB, which is essential for the functioning of proteins that are found on the surface of cancer cells and allow them to attach to different tissues in the body. (20)

The anticancer activity of bromelain is exerted in a large number of tumour types, it is particularly effective in colon tumours (especially those with mutations in the KRAS gene), breast, lung, stomach, skin, pancreas and also in leukaemia. (1, 4, 5, 36)

Diseases of the heart and blood vessels

The effect of bromelain on the suppression of platelet aggregation is not only applicable in the prevention and treatment of cancer, but also in cardiovascular diseases. It (and its ability to regulate fibrinogen levels in the blood) prevents blood clots. It also helps to lower blood pressure, reduce the amount of atherosclerotic deposits in the blood vessels and reduce the intensity of symptoms of coronary heart disease, formerly known as angina pectoris – typical attacks of this disease disappeared completely in one study while taking bromelain and did not reappear until two months after its discontinuation (5, 21, 22).

Another study described the effectiveness of bromelain in acute thrombophlebitis (inflammatory vein disease accompanied by clot formation), where pain, inflammation and swelling were relieved, and it is also suitable for varicose veins (23, 25).

Arthrosis

Although bromelain cannot affect the actual causes of arthrosis, its ability to reduce inflammation, swelling and pain – in this respect, it works comparably to drugs from the group of non-steroidal antirheumatic drugs – is significantly applied in the most common joint disease. In one study on this topic, for example, volunteers with knee arthritis experienced an 80% reduction in these symptoms after three weeks of use. The dosage ranged from 160 to 1890 mg/day in the different studies, with a therapeutic effect already observed at the lowest dosage. More significant effects were found at doses as low as 540 mg (26).

Injuries and post-operative conditions

The ability of bromelain to suppress platelet clumping may also be applicable in the treatment of wounds. For example, in one study conducted as early as 1960, it was administered to boxers who had numerous bruises on their faces and arms after a fight – after only four days, the bruises virtually disappeared (27).

Bromelain can also effectively relieve post-traumatic swelling, it is used to treat acute sports injuries (specifically muscle and tendon injuries) and the cream containing it also supports the treatment of burns. After surgical procedures, bromelain significantly reduces the healing time, but its use in the 2 weeks prior to surgery is not recommended due to the increased risk of bleeding (1, 28-30, 63).

In conjunction with special exercises, it has also proved useful for carpal tunnel syndrome (31).

Sinusitis

Research also suggests that bromelain may be very useful for people suffering from chronic sinusitis. A dose of 500 mg twice daily for 30 days significantly reduced mucus production in their sinuses (32).

Asthma and allergies

Bromelain can reduce allergic sensitization and symptom intensity after exposure to an allergen. This, together with its anti-inflammatory action, is beneficial in asthma as well as in other types of allergies (33).

Weight Loss

Bromelain may also be useful in weight reduction. It promotes fat burning, suppresses the formation and differentiation of fat cells, which helps to reduce fat storage, and also promotes fat cell apoptosis (34).

Peyronie’s disease

Bromelain also brings hope to men suffering from Peyronie’s disease. This is a curvature of the penis that occurs mostly in older men and completely prevents them from sexual activity. Increased levels of collagen and plaque in the blood, due to poor functioning of digestive enzymes, is thought to be one of the causes of its occurrence. Bromelain helps to break down collagen from the blood. (37)

Digestive disorders

Since bromelain contains a mixture of proteolytic enzymes, it can greatly promote protein digestion and is often used for other digestive disorders. For example, it can effectively relieve constipation and also counteract stomach ulcers. (35, 37)

Use and contraindications

Bromelain is well absorbed (usually about 40% of the amount consumed is absorbed into the blood) and is safe to take. In animal experiments, it has not shown toxicity or other major adverse effects even at daily doses above 750 mg per kilogram of weight. Only minor effects, mainly in the form of indigestion, have been reported. However, some persons may be allergic to bromelain (42, 43, 45).

For indigestion, a dosage of 250 mg/day is recommended, for most other problems it is around 500 mg/day, and after surgery and for cancer, doses of up to 1000 mg/day are usually recommended. 2000 mg is considered the maximum safe dose for humans (46).

Due to its effect on platelets, bromelain helps to reduce blood clotting and should therefore not be taken with drugs that also reduce clotting – these include Warfarin, but also Aspirin. Bromelain also increases the effectiveness of some antibiotics (such as tetracycline or amoxicillin) and sedative drugs – benzodiazepines (anti-anxiety drugs), barbiturates, tricyclic antidepressants, sleeping pills, as well as some herbs (such as valerian) and alcohol (42).

Suitable combinations

The combination of bromelain with quercetin is very effective. Not only are they mutually supportive in their effects (especially in terms of anti-inflammatory and anti-tumour activity), but bromelain also significantly increases the bioavailability of quercetin. The same applies to the combination of bromelain and curcumin (40, 41).

Arthritis: bromelain + trypsin + rutin (44), bromelain + curcumin

Cancer: bromelain + curcumin, bromelain + quercetin

Heart and blood vessels: bromelain + quercetin

Immunity: bromelain + curcumin, bromelain + acetylcysteine