FROM:
Alternative Medicine Review 1998 (Aug); 3 (4): 302–330 ~ FULL TEXT
Description and Constituents
Bromelain is a general name for
a family of sulfhydryl-containing, proteolytic enzymes obtained from Ananas
comosus, the pineapple plant. Bromelain's primary component is a sulfhydryl
proteolytic fraction. Bromelain also contains a peroxidase, acid phosphatase,
several protease inhibitors, and organically-bound calcium. It appears
a great deal of the physiological activity of bromelain cannot be accounted
for by its proteolytic fraction and that the beneficial effects of bromelain
are due to multiple factors, not to one single, isolated factor.
A variety of designations have been
used to indicate the activity of bromelain, with published research varying
in the designation utilized. Rorer units (r.u.), gelatin dissolving units
(g.d.u.), and milk clotting units (m.c.u.) are the most commonly used measures
of activity. One gram of bromelain standardized to 2000 m.c.u would be
approximately equal to 1 gram with 1200 g.d.u. of activity or 8 grams with
100,000 r.u. of activity.
Pharmacokinetics Bromelain is absorbed
intact through the gastrointestinal tract of animals, with up to 40 percent
of the high molecular weight substances detected in the blood after oral
administration. The highest concentration of bromelain is found in the
blood one hour after administration; however, its proteolytic activity
is rapidly deactivated. [1
]
Mechanisms of Action
Bromelain's anti-inflammatory activity
appears to be due to a variety of physiological actions. Evidence indicates
that bromelain's action is in part a result of inhibiting the generation
of bradykinin at the inflammatory site via depletion of the plasma kallikrein
system, as well as limiting the formation of fibrin by reduction of clotting
cascade intermediates. [2-4] Bromelain has
also been shown to stimulate the conversion of plasminogen to plasmin,
resulting in increased fibrinolysis. [4]
Bromelain might be capable of selectively
modulating the biosynthesis of thromboxanes and prostacyclins, two groups
of prostaglandins with opposite actions which ultimately influence activation
of cyclic-3,5-adenosine, an important cell-growth modulating compound.
It is hypothesized that bromelain therapy leads to a relative increase
of the endogenous prostaglandins, PGI2 and PGE2 over thromboxane A2. [5]
Bromelain has been shown to decrease
aggregation of blood platelets. [6] It is
an effective fibrinolytic agent in vitro and in vivo; however, its effect
is more evident in purified fibrinogen solutions than in plasma. [7]
Clinical Indications
Antitumor: Several studies,
both animal and human, indicate bromelain might have some antimetastatic
ability. [8-10] In doses of over 1000 mg daily,
bromelain has been combined with chemotherapeutic agents such as 5-FU and
vincristine, resulting in tumor regression. [8, 11]
Immune Modulation: Bromelain
can induce cytokine production in human peripheral blood mononuclear cells.
Treatment leads to the production of tumor necrosis factor-alpha, interleukin-1-beta,
and interleukin-6 in a time- and dose-dependent manner. [12,13]
Bromelain has also been shown to remove T-cell CD44 molecules from lymphocytes
and to affect T-cell activation. [14]
Debridement of Wounds: Bromelain
applied topically as a cream (35% bromelain in a lipid base) can be beneficial
in the elimination of burn debris and in acceleration of healing. [15]
A non-proteolytic component of bromelain is responsible for this effect.
This component, referred to as escharase, has no hydrolytic enzyme activity
against normal protein substrates or various glycosaminoglycan substrates,
and its activity varies greatly from preparation to preparation. [16]
Potentiation of Antibiotics:
Antibiotic potentiation is one of the primary uses of bromelain in several
foreign countries. In humans, some undetermined activity of bromelain has
been documented to increase blood and urine levels of antibiotics. [17-19]
Combined bromelain and antibiotic
therapy has been shown to be more effective than antibiotics alone in a
variety of conditions including pneumonia, bronchitis, cutaneous staphylococcus
infection, thrombophlebitis, cellulitis, pyelonephritis, perirectal and
rectal abscesses, [20] and sinusitis. [21]
Mucolytic: In a clinical
study of 124 patients hospitalized with chronic bronchitis, pneumonia,
bronchopneumonia, bronchiectasis, or pulmonary abscess, those receiving
bromelain orally showed a decrease in the volume and purulence of the sputum. [22]
Digestive Aid: Bromelain
has been used successfully as a digestive enzyme following pancreatectomy,
in cases of exocrine pancreas insufficiency, and in other intestinal disorders. [23]
The combination of ox bile, pancreatin, and bromelain is effective in lowering
stool fat excretion in patients with pancreatic steatorrhoea and resulting
in a symptomatic improvement in pain, flatulence and stool frequency. [24]
Bromelain has been reported to heal
gastric ulcers in experimental animals. [25]
In an extensive study of the effect of bromelain on the gastric mucosa,
it was found that bromelain increased the uptake of radioactive sulfur
by 50 percent and glucosamine by 30-90 percent. Increased uptake of these
substances may allow the gastric mucosa to heal more rapidly. [26]
Surgical Procedures and Musculoskeletal
Injuries: Bromelain's most common application is in the treatment of
inflammation and soft tissue injuries. It has been shown to speed healing
from bruises and hematomas. [27] Treatment
with bromelain following blunt injuries to the musculoskeletal system results
in a clear reduction in swelling, pain at rest and during movement, and
tenderness. [28] Administration of bromelain
pre-surgically can reduce the average number of days for complete disappearance
of pain and inflammation. [29, 30]
Cardiovascular and Circulatory
Applications: Research has indicated that bromelain prevents or minimizes
the severity of angina pectoris. [31, 32] A
drastic reduction in the incidence of coronary infarct after administration
of potassium and magnesium orotate along with 120-400 mg of bromelain per
day has been reported. [33] In a study involving
73 patients with acute thrombophlebitis, bromelain, in addition to analgesics,
was shown to decrease all symptoms of inflammation; including, pain, edema,
tenderness, skin temperature, and disability. [34]
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