Bromelain

Bromelain is an extract derived from the stems of pineapples, although it exists in all parts of the fresh plant and fruit, which has many uses. The extract has a history of folk and modern medicinal use. As a supplement it is thought to have anti-inflammatory effects. Bromelain also contains chemicals that might interfere with the growth of tumor cells and slow blood clotting, but there is no peer-reviewed research showing any efficacy against tumours. As a culinary ingredient it is used primarily as a tenderizer.

The term "bromelain" may refer to either of two protease enzymes extracted from the plants of the family, Bromeliaceae, or it may refer to a combination of those enzymes along with other compounds produced in an extract.

The US National Institute of Health rates bromelain as only possibly effective against osteoarthritis, but only when taken in combination with trypsin and rutin (Phlogenzym). The same institute has stated that it is possibly ineffective for preventing post-exercise muscle tiredness. In addition, there is no evidence to rate the effectivity of the product for any other disorder.

Extract components
Bromelain extract is a mixture of protein-digesting enzymes—called proteolytic enzymes or proteases—and several other substances in smaller quantities. The proteolytic enzymes are referred to as sulfhydryl proteases, since a free sulfhydryl group of a cysteine side-chain is required for function. The two main enzymes are:


 * Stem bromelain -
 * Fruit bromelain -

The other substances typically include peroxidase, acid phosphatase, protease inhibitors, and calcium.

History
Pineapples have a long tradition as a medicinal plant among the natives of South and Central America. The first isolation of bromelain was recorded by the Venezuelan chemist Vicente Marcano in 1891 from the fruit of pineapple. In 1892, Chittenden, assisted by Joslin and Meara, investigated the matter fully (Trans. Conn. Acad. Arts Sci. 8, 281-308), and called it 'bromelin'. Later, the term 'bromelain' was introduced and originally the term was applied to any protease from any member of the plant family Bromeliaceae.

Bromelain was first introduced as a therapeutic supplement in 1957. First, research on bromelain was conducted in Hawaii, but more recently has been conducted in countries in Asia, Europe, and Latin America. Recently, researchers in Germany have taken a great interest in bromelain research. Currently, Bromelain is the thirteenth most widely used herbal medicine in Germany.

Potential medical uses
Available in some countries as a product under the name 'Ananase', bromelain began its reputation for various uses in folk medicine and continues to be explored as a potential healing agent in alternative medicine. First introduced in medical research in 1957, bromelain may work by blocking some proinflammatory metabolites when applied topically. Bromelain may be used after surgery to reduce swelling. Preliminary research indicates that bromelain may affect migration of neutrophils to sites of acute inflammation.

As a potential anti-inflammatory agent, it may be useful for treating arthritis, but has neither been confirmed in human studies for this use, nor is it approved with a health claim for such an effect by the Food and Drug Administration or European Food Safety Authority. The Natural Medicines Comprehensive Database suggests that bromelain, when used in conjunction with trypsin and rutin is as effective as some prescription analgesics in the management of osteoarthritis.

Bromelain has not been scientifically proven to be effective in any other diseases and it has not been licensed by the Food and Drug Administration for the treatment of any other disorder.

Systemic enzyme therapy (consisting of combinations of proteolytic enzymes such as bromelain, trypsin, chymotrypsin, and papain) has been investigated in Europe to evaluate the efficacy of proteolytic enzymes in the treatment of breast, colorectal, and plasmacytoma cancer patients. In mice with experimental colitis, 6 months of dietary bromelain from pineapple stem or from fresh juice decreased the severity of colonic inflammation and reduced the number of cancerous lesions in the colon.

Bromelain supplements may increase the risk associated with heart rate, blood clotting and bleeding post-surgery.

Meat tenderizing
Along with papain, bromelain is one of the most popular substances to use for meat tenderizing.

Today, about 90% of meat tenderizer is used in consumer households. Bromelain is sold in a powdered form, which is combined with a marinade, or directly sprinkled on the uncooked meat. The enzyme will penetrate the meat and, by a process called forking, cause the meat to become tender and palatable when cooked. If the enzyme is allowed to work for too long, however, the meat may become too "mushy" for the preferences of many consumers.

Cooked or canned pineapple does not have a tenderizing effect, as the enzymes are heat-labile and destroyed in the cooking process.

Some prepared meat products, such as meatballs and commercially available marinades, include pineapple and/or pineapple-derived ingredients.

Apart from the mushiness of meat that has been over-tenderized, the activity of bromelain and similarly proteolytic plant enzymes may be undesirable where it is inappropriate. In dishes that depend on their protein content for important attributes, uncooked pineapple or its juice may be a nuisance. For example, some dishes such as brawn and jelly rely on the setting of gelatin. They will not set if they contain raw pineapple or pineapple juice. Raw figs, papaya, and similarly proteolytic vegetable matter causes similar problems. To prevent the incompatibility with gelatin problem, the fresh fruit should be cooked, or at least parboiled, sufficiently to inactivate the enzymes before using in such dishes. In general, thorough heating to above about 65 degrees C will suffice. This problem does not affect dishes based on non-proteinaceaous gelling agents, such as agar, although such agents may be prevented from gelling by too much heating in acid recipes.

Pharmacodynamics
Bromelain increases blood fibrinolytic activity as well as inhibiting fibrinogen synthesis. It also directly degrades fibrin and fibrinogen. Kininogen and bradykinin serum and tissue levels are lowered by bromelain, and it also affects prostaglandin synthesis, which gives it its anti-inflammatory effects. Bromelain has been found to reduce the excretion of proinflammatory cytokines as well as chemokines in a study into its possible mechanism of action in ulcerative colitis, inflammatory bowel disease, and Crohn's disease.

Production
Bromelain is produced in Thailand, Taiwan, and other tropical parts of the world where pineapples are grown.

Bromelain is prepared from the stem part of the pineapple plant after harvesting the fruit for other commercial purposes. This stem part is peeled, crushed, and pressed to obtain the juice containing the soluble bromelain enzyme. Further processing includes purification and concentration of the enzyme. In India Bromelain is manufactured by Excellent Biotechnologies, Bangalore in large quantities.

Other plant proteases
Other plant proteases include papain (from the papaya), actinidin (from the kiwi fruit), and ficin (from the fig).

Temperature stability
At the optimum temperature, the enzyme acts the fastest, however (at least the fruit variant) is destroyed within few minutes. After an hour at 50 C, 83% of the enzyme remains, while at 40 C, practically 100% remains. As a result of this, the optimum temperature for maximum cumulated activity over time is 35 - 45 C. At room temperature, the enzyme can survive at least a week even under multiple freeze-thaw cycles.