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Bromelain - The Wonder Supplement by Tony Isaacs
I first experienced bromelain several
years ago when I was bitten by a brown recluse spider on the front
of my upper left leg – in three places no less. This was
the second time I had been bitten – the first time I was bitten
resulted in the loss of a chunk of flesh and, much worse, being
crippled for several months thanks to the treating physician botching
the treatment and thrusting his deadening needle into my bursal
sac. Since I did not want to repeat that ugly memory and
I had was in my first few years of studying natural health, I
decided to try to handle it myself.
One of the people I consulted for
help was an old naturopathic healer who claimed to have been a
doctor in Russia before immigrating to the United States many
decades ago. He suggested that, among other things,
I made sure that I used bromelain , which he called a wonder supplement.
And so, armed with garlic (which
I took internally and used externally), some hydrogen peroxide,
over-the-counter ointments, a vial of homeopathic ledum pallustre,
raw garlic, whatever else I could round up, and bromelain, I began
to treat the spider bites. For a couple of days it was touch
and go it seemed, as the bites continue to redden and swell and
the radiating areas of red and pink grew until it encompassed
an area about 6 inches by 12 inches. But then the tide turned
and the bites began to get better. Within a little over
a week, they were mostly healed and within two weeks there was
virtually no sign of the bites.
After the success against the spider
bite, I decided to take a closer look at bromelain. What
I found amazed me – bromelain truly is a wonder supplement!. Just
take a look at a partial list Bromelain’s proven powers to see
what I mean:
Bromelain:
*Helps bruises and injuries heal an
average of three times faster and helps athletes regain peak form
much more quickly.
*Is a strong binder and increases the absorption
of supplements and medicines up to three times or more of the
amount that the body would normally absorb.
*Helps heal or lessen,
Angina
Arthritis
Athletic and Musculoskeletal Injuries
Bacteria Infections
Bronchitis
Cancer and Tumors
Cellulitis
Cutaneous Staphlococcus Infection
Debridement of Burns
Dysmenorrhea
Edema
Inflammation
Maldisgestion
Pancreatic Insufficiency and Steatorrhea
Platelet Aggregations
Pneumonia
Rectal abscesses
Sinusitis
Surgical Truama
Thrombophlebitis
Since I have always been one to take
a healthy amount of vitamins, minerals and other healthy supplements,
I was extremely interested to see if Bromelain would help with
the absorption. All I had to do was take a look at the bright
fluorescent colored urine to know that much of what I take is
passing through the body without being absorbed. So, I started
taking a couple of 500 mg capsules of Bromelain daily. Lo
and behold, the color of my urine was much lighter. And
I felt more energetic too. I have no doubt it was the bromelain,
a favorite supplement which I continue to take daily.
For an even better idea of what bromelain
does and how it does it, I would like to share the following study
with you. Although a bit technical, it should give you an
even better idea of how amazing bromelain is and the accuracy
of what I have reported:
Bromelain: A Literature Review and
Discussion of its Therapeutic Applications
Gregory
S. Kelly, N.D.
Abstract
First introduced
as a therapeutic compound in 1957, bromelain's actions include:
(1) inhibition of platelet aggregation; (2) fibrinolytic activity;
(3) anti-inflammatory action; (4) anti-tumor action; (5) modulation
of cytokines and immunity; (6) skin debridement properties; (7)
enhanced absorption of other drugs; (8) mucolytic properties;
(9) digestive assistance; (10) enhanced wound healing; and (11)
cardiovascular and circulatory improvement. Bromelain is well
absorbed orally and available evidence indicates that it's therapeutic
effects are enhanced with higher doses. Although all of its mechanisms
of action are still not completely resolved, it has been demonstrated
to be a safe and effective supplement. (Alt Med Rev 1996;1(4):243-257)
Description
Pineapple has
been used as a medicinal plant in several native cultures and
bromelain has been known chemically since 1876. In 1957, bromelain
was introduced as a therapeutic compound when Heinicke found it
in high concentrations in pineapple stems.
Bromelain is
a general name for a family of sulfhydryl proteolytic enzymes
obtained from Ananas comosus, the pineapple plant. It is usually
distinguished as either fruit bromelain or stem bromelain depending
on its source, with all commercially available bromelain being
derived from the stem.1 The term bromelain will be
used to refer to stem bromelain in the remainder of this article.
Bromelain's
primary component is a sulfhydryl proteolytic fraction. Bromelain
also contains a peroxidase, acid phosphatase, several protease
inhibitors, and organically bound calcium. When the proteolytic
fraction of bromelain is purified and extracted, the result is
a potent proteolytic enzyme in vitro; however, this component
has been shown to be physiologically inactive in vivo for many
of the conditions where bromelain has a beneficial effect.2
It appears that a great deal of the physiological activity of
bromelain is not accounted for in its proteolytic fraction and
it is likely that the beneficial effects of bromelain are due
to multiple factors, not to one single factor that can be isolated.
To date, eight
basic proteolytically active components have been detected in
the stem. The two main components have been labeled F4 and F5.
The proteinase considered to be the most active fraction has been
designated as F9, which comprises about 2% of the total proteins.
It is estimated that 50% of the proteins in F4 and F5 are glycosylated,
whereas F9 was found to be unglycosylated. The optimal pH for
the F4 and F5 fractions is between 4.0 and 4.5 and for F9 close
to a neutral pH.3 The entire extract of bromelain has
been shown to exhibit its activity over a pH range of 4.5 to 9.8.4
Since bromelain
is derived from a natural source, different sources can exhibit
variability in their physiological activity, even when their proteolytic
activity is the same. Bromelain is not heat stable so it's physiological
activity can be further reduced by improper processing or storage
conditions.
Absorption
and Availability
Bromelain is
absorbed intact through the gastrointestinal tract of animals,
with up to 40% of the high molecular weight substances detected
in the blood after oral administration. The highest concentration
of bromelain is found in the blood 1 hour after administration;
however, its proteolytic activity is rapidly deactivated,5
probably by the normal plasma protease controls and serum alpha2-macroglobulin.
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.
Platelet
Aggregation, Fibrinolysis and Anti-Inflammatory Activity
The first conclusive
evidence that bromelain prevents aggregation of blood platelets
was reported in 1972. Bromelain was administered orally to 20
volunteers with a history of heart attack or stroke, or with high
platelet aggregation values. Bromelain decreased aggregation of
blood platelets in 17 of the subjects and normalized values in
8 of the 9 subjects who previously had high aggregation values.6
In vitro studies have demonstrated that bromelain inhibits platelet
aggregation stimulated by ADP
or epinephrine, as well as by prostaglandin precursors, in a dose-dependent
manner.7
Bromelain is
an effective fibrinolytic agent in vitro and in vivo; however,
its effect is more evident in purified fibrinogen solutions than
in plasma. This is probably due to the antiproteases present in
plasma. A dose-dependent reduction of serum fibrinogen level is
seen in rats following administration of bromelain, and at the
highest concentrations of bromelain, both prothrombin time (PT)
and activated partial thromboplastin time (APTT) are markedly
prolonged.89 Bromelain's fibrinolytic activity has
been attributed to the enhanced conversion of plasminogen to plasmin,
which limits the spread of the coagulation process by degrading
fibrin.
Bromelain seems
to have both direct as well as indirect actions involving other
enzyme systems in exerting its anti-inflammatory effect. Both
etodolac and bromelain inhibit the inflammatory pain in rats in
a dose-dependent manner.10 Bromelain was the most potent
of nine anti-inflammatory substances tested on experimentally-induced
edemas in rats;11 while prednisone and bromelain have
been shown to be comparable in their ability to reduce inflammation
in rats.12 Treatment with bromelain and emorfazone
has been shown to decrease significantly the heat-evoked immunoreactive
substance P release and subsequent edema in a rat model.13
Mechanism
of Action
Surface contact,
by collagen or platelets, activates the kinin system and the clotting
cascade by stimulating the conversion of Hageman factor to an
active protease (factor XIIa). Factor XIIa then activates the
kinin system by converting plasma prekallikrein into kallikrein,
and continues the intrinsic path of the clotting cascade by converting
factor XI to its active form. Kallikrein, in an autocatalytic
loop, accelerates the activation of Hageman factor, which continues
to potently activate both the kinin system and the clotting cascade.
In addition, Kallikrein cleaves (HMWK) to produce bradykinin,
a potent stimulator of both increased vascular permeability and
pain. The activation of the clotting cascade will culminate in
the conversion of fibrinogen to fibrin (see Figure 1). Fibrin
then forms a protective matrix around the injured area. This matrix
inhibits tissue drainage, promotes edema and blocks circulation
of blood flow.
In order to
determine the effects of bromelain on the plasma kallikrein system,
bradykinin levels and plasma exudation at the inflammatory site
were examined in rats. Bromelain (5 and 7.5 mg/kg) caused a dose-dependent
decrease of bradykinin levels at the inflammatory site and a parallel
decrease of the prekallikrein levels in sera. Plasma exudation
was also reduced dose dependently. Bradykinin-degrading activity
in sera was elevated after treatment with bromelain, although
it was unchanged in the pouch fluid.14 The levels of
high molecular weight (HMW) kininogen and pre-kallikrein in rat
plasma were markedly reduced after single injection of bromelain
(10 mg/kg, i.v.) and gradually recovered over a 72 hour period.
The level of low molecular weight (LMW) kininogen was not changed
during this period.15
Bromelain-treated
rats also show a reduction in Factor X and prothrombin, both of
which are needed for the activation of fibrinogen to fibrin through
the common pathway of the intrinsic and extrinsic cascade.16
This 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.
These actions result in significant reduction in pain and edema,
as well as enhanced circulation to the injured site.
After the formation
of a clot, vessel repair begins with the conversion of plasminogen
to plasmin, which then acts to degrade fibrin into smaller components
which can be removed by monocytes and macrophages. In rats, bromelain
has been shown to stimulate the conversion of plasminogen to plasmin,
resulting in increased fibrinolysis. This minimizes venous stasis,
facilitates drainage, increases permeability and restores the
tissue's biological continuity.16
The therapeutic
effect of bromelain may also be due to its ability to selectively
modulate the biosynthesis of thromboxanes and prostacyclins; two
groups of prostaglandins with opposite actions which ultimately
influence activation of cyclic-3,5-adenosine (cAMP), an important
cell-growth modulating compound.
The binding
of epinephrine, collagen, or thrombin to platelets activates the
enzymes phospholipase C and phospholipase A2 which release arachidonic
acid from membrane phospholipids (phosphatidylcholine and phosphatidylinositol).
Table 1 lists the inflammatory actions of arachidonic acid metabolites.
Plasminogen,
which is activated to plasmin by the oral administration of bromelain,
has been shown to inhibit the release of arachidonic acid from
cell membranes, resulting in decreased platelet aggregation and
modulation of the series 2 prostaglandins.17 It is
also hypothesized that bromelain therapy leads to a relative increase
of the endogenous prostaglandins, PGI2
and PGE2 over thromboxane
A2.18
Non-steroidal
anti-inflammatory drugs inhibit cyclooxygenase, which is required
for the synthesis of series 2 prostaglandins, resulting in a decrease
in both pro and anti-inflammatory prostaglandins. Rather than
blocking the arachidonic acid cascade at the enzyme cyclooxygenase,
like NSAIDs, bromelain may selectively decrease thromboxane generation
and change the ratio of thromboxane/prostacyclin (PGI2)
in favor of prostacyclin (see Figure 2). Bromelain, similar to
NSAIDs, has been shown to inhibit PGE2,
however, its action is significantly weaker.16 Table
2 lists bromelain's impact on selected mediators of inflammation.
Antitumor
The first documented
use of oral bromelain on cancer patients was in 1972. Twelve patients
with ovarian and breast tumors were given 600 mg of bromelain
daily for from 6 months to several years, with reported resolution
of some of the cancerous masses and a decrease in metastasis.19
Bromelain in doses of over 1000 mg daily has been combined with
chemotherapeutic agents such as 5-FU and vincristine, and has
been reported to result in tumor regression.19,20
Bromelain has
also decreased lung metastasis of Lewis lung cancer cells implanted
in mice in a dose-dependent manner. This antimetastatic potential
was demonstrated by both the active and inactive bromelain, with
or without proteolytic and anticoagulant properties.21,22
Cytokine
Induction
The successful
initiation of an immune response depends on T cells and macrophages,
along with the polypeptide factors they produce, called cytokines,
which play a key role in communication during normal immunological
response as well as infectious, inflammatory, and neoplastic disease
states. Table 3 lists cytokines and their activities.
Bromelain, papain,
and amylase have all been demonstrated to induce cytokine production
in human peripheral blood mononuclear cells. Treatment leads to
the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta
(IL-1 beta), and interleukin-6 (IL-6) in a time and dose-dependent
manner. Interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma),
which had no effect alone, synergistically increased TNF-alpha
production when applied together with the enzymes.23,24
The tryptic but not the autolytic fractions of papain and bromelain
have a higher (10- to 40-fold) inducing capacity for TNF production
than the untreated enzyme.25 Trypsin alone had only
a small inducing effect.
The ability
to induce cytokine production may explain the antitumor effects
observed after oral administration of polyenzyme preparations.
Immunity
Bromelain has
been shown to remove T-cell CD44 molecules from lymphocytes and
to affect T-cell activation. The highly purified bromelain protease
F9 was tested on the adhesion of peripheral blood lymphocytes
(PBL) to human umbilical vein endothelial cells (HUVEC). Both
bromelain and protease F9 reduced the _expression of CD44, but
F9 was about 10 times more active than bromelain; having about
97% inhibition of CD44 _expression. The results indicate that
F9 selectively decreases the CD44 mediated binding of PBL to HUVEC.26
Debridement
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.
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.27
Topical bromelain
has achieved complete debridement on experimental burns in rats
in an average of 1.9 days as compared to collagenase, which required
an average of 10.6 days for similar results.28
Topical bromelain
separates eschar at the interface with living tissue. It is hypothesized
that bromelain activates collagenase in living tissue which then
attacks the denatured collagen in the eschar. This produces a
demarcation between living and dead tissue. With very little scraping,
using a tongue depressor, all of the eschar can be removed and
a bed suitable for grafting results. By using bromelain, grafting
can occur as soon as 24 hours after the accident. Utilizing bromelain
cream in the treatment of burns usually results in minimal or
no scar tissue formation.
The applicability
of topical bromelain in frostbite eschar removal was extrapolated
and investigated. In the initial trial, no debridement other than
that of the superficial layers of the eschar was noted. Although
third degree burn injuries debrided to a graftable bed after two
topical applications of bromelain, frostbite injuries remained
unaffected.29
Potentiation of Antibiotics
Antibiotic potentiation
is one of the primary uses of bromelain in several foreign countries.
Bromelain can modify the permeability of organs and tissues to
different drugs. It prolongs sleeping time in mice administered
pentobarbital30 and increases spinal levels of penicillin
and gentamycin in rats. In humans, bromelain has been documented
to increase blood and urine levels of antibiotics16 and results
in higher blood and tissue levels of tetracycline and amoxycillin
when they are administered concurrently with bromelain.31
Treatment of
18 women with 80 mg of bromelain concurrently with amoxycillin
or tetracyclin resulted in increased serum levels and concentrations
of both antibiotics in uterus, ovarian tubes, and ovaries as compared
with controls. This effect was not generated by indomethacin,
an anti-inflammatory drug which acts as a cyclooxygenase inhibitor,
which indicates that bromelain has some undetermined activity
that enhances absorption and tissue distribution of antibiotics.32
A three-fold increase in the level of tetracycline in serum after
oral ingestion of 540 mg of enterically-coated bromelain has also
been demonstrated in a double blind test.33
Combined bromelain
and antibiotic therapy was instituted for 53 hospitalized patients
with the following conditions; pneumonia, bronchitis, cutaneous
staphylococcus infection, thrombophlebitis, cellulitis, pyelonephritis
and perirectal and rectal abscesses. Twenty three of the patients
had been on antibiotic therapy without success. Bromelain was
administered four times a day along with the following antibiotics
either alone or in combination; penicillin, chloramphenicol, erythromycin
or novobiacin. A control group of 56 patients was treated with
antibiotics alone. Of the 23 patients who had been unsuccessfully
treated with antibiotics, 22 responded favorably to the combined
treatment. In every disease state studied there was a significant
reduction in morbidity when the combination of bromelain and antibiotics
was used as opposed to antibiotics alone. Another group of 106
cases was treated with bromelain alone, with results comparable
to those obtained with antibiotic treatment.34
Forty eight
patients with acute sinusitis were placed on standard therapy,
which included antihistamines and analgesic agents, along with
antibiotics if indicated. Twenty three of the patients received
bromelain four times daily, while the remaining 25 received a
placebo. Of the patients receiving bromelain, 83% had complete
resolution of nasal mucosal inflammation compared with only 52%
in the placebo group. Improvement in breathing occurred in 78%
of those receiving bromelain as compared to 68% in those receiving
placebo. In the patients not receiving antibiotic treatment, 85%
of patients receiving bromelain had complete resolution of inflammation
of the nasal mucosa and complete resolution of breathing difficulties.
Only 40% of the placebo group had a similar outcome with respect
to inflammation, while 53% reported resolution of breathing difficulty.35
The potentiation
of antibiotics and other medicines by bromelain may be due to
enhanced absorption, as well as increased permeability of the
diseased tissue which enhances the access of the antibiotic to
the site of the infection. It is also thought that the use of
bromelain may provide a similar access to specific and non-specific
components of the immune system, therefore, enhancing the body's
utilization of its own healing resources.
Mucolytic
Properties
The topical
use of the enzymes, bromelain or papain, to remove excessive cervical
mucus was demonstrated in 1954. Observations following its use
demonstrated that pseudo and actual space-occupying lesions could
be more positively identified, and inflammatory changes of the
canal and its glands could be visualized with greater accuracy.36
Effects of bromelain
on rabbit sputum consistency were investigated in vitro and in
vivo. Of the enzymes tested, bromelain exerted the most potent
lowering effect on sputum viscosity and also showed a tendency
to increase the sputum volume.37
In a clinical
study of 124 patients hospitalized with chronic bronchitis, pneumonia
or bronchopneumonia, bronchiectasis, or pulmonary abscess, those
receiving bromelain orally showed a decrease in the volume and
purulence of the sputum.17 These results support the effectiveness
of bromelain in decreasing the viscosity of sputum so that it
can be more easily cleared from the respiratory tract.
Digestive
Aid
Bromelain has
been used successfully as a digestive enzyme following pancreatectomy,
in cases of exocrine pancreas insufficiency and in other intestinal
disorders.38 Because of its wide pH range, bromelain
has activity in the stomach as well as the small intestine. It
has also been shown to be an adequate replacement for pepsin and
trypsin in cases of deficiency. The combination of ox bile, pancreatin
and bromelain is effective in lowering stool fat excretion in
patients with pancreatic steatorrhoea. In addition, this combination
resulted in a gain in weight in most cases as well as an enhanced
subjective feeling of well being. Symptomatic improvement was
also noted in relation to pain, flatulence and stool frequency.39
Bromelain has
been reported to heal gastric ulcers in experimental animals.40
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% and glucosamine by 30 -90%. Increased uptake of
these substances may allow the gastric mucosa to heal more rapidly
under the influence of bromelain.41
In a study designed
to examine the effect of bromelain on enterotoxin receptor activity
in porcine small intestine, orally administered bromelain inhibited
enterotoxin attachment to pig small intestine in a dose-dependent
manner. Attachment was negligible after treatment. Serum biochemical
analysis and histopathological examination of treated piglets
showed no adverse effects with the bromelain treatment. Administration
of bromelain may therefore be useful for preventing enterotoxin-induced
diarrhea.42
Surgical
Procedures and Musculoskeletal Injuries
Bromelain also
has therapeutic effects in the treatment of inflammation and soft
tissue injuries. An early clinical trial on bromelain was conducted
on 74 boxers with bruises on the face and haematomas of the orbits,
lips, ears, chest and arms. Bromelain was given four times a day
for 4 days or until all signs of bruising had disappeared. A control
group of 72 boxers were given a placebo. In 58 of the boxers taking
bromelain, all signs of bruising cleared completely in four days,
with the remaining 16 requiring 8-10 days for complete clearance.
In the control group, only 10 had complete clearance within four
days, with the remainder requiring seven to fourteen days for
resolution.43
The edema-reducing
property of bromelain was investigated in traumatically-induced
hindleg edema in rats. After enteral application of bromelain
a significant reduction of the edema could be observed, however,
parenteral application only resulted in a minimal therapeutic
effect. Although enterally-applied enzymes are thought to be degraded
in the gut, the better results were obtained after oral administration
of bromelain, supporting the observation that bromelain can be
absorbed by the gut without losing its biological properties.11
Fifty-five pre-surgical
patients were divided into two groups. Group one, consisting of
22 patients, took bromelain four times a day for 48-72 hours prior
to surgery and continued for 72 hours after surgery. Group two,
consisting of 33 patients, took bromelain starting on the day
of surgery, with the first dose administered one hour prior to
surgery. Fifty percent of group one and 42.4% of group two had
complete disappearance of pain and inflammation within 72 hours.
Pain and inflammation persisted past 72 hours in only one member
of the group supplemented with bromelain for three days prior
to surgery, as opposed to five members of the group that started
supplementation one hour prior to surgery. In a separate study,
supplementation of bromelain starting 48-72 hours prior to surgery
reduced the average number of days for complete disappearance
of pain from 3.5 to 1.5, and disappearance of inflammation from
6.9 to 2.0 days, as compared with controls receiving no bromelain.44
Sixteen patients
undergoing oral surgery were given bromelain four times a day
starting 72 hours prior to surgery. At 24 hours after surgery,
75% of these patients were evaluated as having mild or no inflammation,
in contrast to only 19% of a group receiving a placebo. Twenty-four
hours after surgery, pain was either absent or mild in 38% of
bromelain-treated patients, as opposed to 13% receiving placebo.
After 72 hours, this increased to 75% of those in the bromelain
group, as compared to only 38% in the placebo group.45
In an observation
study involving 59 patients with blunt injuries to the musculoskeletal
system, the efficacy and tolerability of high-dose bromelain,
in addition to the usual therapeutic measures, was investigated.
Treatment with bromelain resulted in a clear reduction in all
four parameters tested; swelling, pain at rest and during movement,
and tenderness.46
Cardiovascular and Circulatory Applications
Research has
indicated that bromelain prevents aggregation of human blood platelets
in vivo and in vitro, prevents or minimizes the severity of angina
pectoris and transcient ischemic attacks (TIA), is useful in the
prevention and treatment of thrombosis and thrombophlebitis, may
break down cholesterol plaques, and exerts a potent fibrinolytic
activity. If administered for prolonged time periods, bromelain
also exerts an anti-hypertensive effect in experimental animals.2,47
Administration
of 400-1000
mg/day of bromelain to 14 patients with angina pectoris resulted
in the disappearance of symptoms in all patients within 4 to 90
days.48 Similar results have been observed in patients
taking between 500-700 mg/day of bromelain. After discontinuing
bromelain, angina attacks reappear after a variable period of
time, often triggered by stressful experiences.2
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 also been reported.49
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.40
The ability
of bromelain to influence these conditions may be due to its ability
to breakdown fibrinous plaques. Bromelain has been shown to dissolve
arteriosclerotic plaque in rabbit aorta in vivo and in vitro.2
It is likely that bromelain also increases vessel wall permeability
to oxygen and nutrients while increasing blood fluidity, both
of which aid in these conditions.
Toxicity,
Side Effects and Allergic Reactions
Bromelain is
considered to have very low toxicity, with an LD50 greater than
10g/kg. Toxicity tests on dogs, with increasing levels of bromelain
up to 750 mg/kg administered daily, showed no toxic effects after
six months. Dosages of1.5 g/kg/day administered to rats show no
carcinogenic or teratogenic effects. 51
In human clinical
tests, side effects have not been observed. Bromelain supplementation
up to 460 mg has been shown to have no effect on heart rate or
blood pressure; however, increasing doses up to 1840 mg have been
shown to increase the heart rate proportionately. In some cases
an increase of up to 80% of the baseline has been reported, which
may be a result of bromelain's influence on IL-1 and TNF production.
Maximum effects were seen at 2 hours but some residual effect
remained at 24 hours. At doses above 700 mg, palpitations and
subjective discomfort have been reported. Blood pressure changes
have not been demonstrated in humans at any dosage level.52
The allergenic
potential of proteolytic enzymes should not be underestimated,
for they cause, in particular, IgE-mediated respiratory allergies
of both the immediate type and the late-phase of immediate type
with predominantly respiratory symptoms. Allergy to bromelain
has been reported in workers of a blood-grouping laboratory, and
investigation indicates that (1) bromelain is a strong sensitizer,
(2) sensitization usually occurs due to inhalation and not to
ingestion, (3) bromelain allergy is occupationally acquired, and
adequate precautions are necessary.53 The risk of sensitization
to enzymes due to inhalation as a result of occupational exposure
is very high (up to 50%).54
Bromelain has
been shown to cross-react with the sera in about 28% of persons
with IgE allergic response to honeybee venom.55 Bromelain,
along with horseradish peroxidase and ascorbate oxidase are recognized
by the IgE of sera from patients who are hypersensitive to olive
tree pollen.56
Bromelain and
papain, due to their use as a meat tenderizer and to clarify beer,
are considered as potential ingestive allergens and may represent
an unrecognized cause of an allergic reaction following a meal.
As with other food substances, a small segment of the population,
particularly those with a sensitivity to pineapple, may be sensitive
to oral supplementation with bromelain. As contact allergens,
the enzymes play a minor role; however, it is thought that skin
testing with isolated proteases like bromelain may induce systemic
reactions in susceptible individuals, even at very high dilution.53,57
Indications for the Use of Bromelain
There are several
compelling reasons for supplementation with oral bromelain.
1. It inhibits
blood platelet aggregation, favorably modulates prostaglandin
formation and minimizes risk of coronary atherosclerotic disease.
2. It continues
to provide a desired physiological action for as long as it is
administered, with no evidence indicating that a tolerance develops.
3. It is considered
to be non-toxic and lacking in side effects, so it can be used
without concern in doses from 200 to 2000 mg for prolonged periods
of time.
4. It is a protein and seems to be as easily
metabolized as other dietary proteins.
5. It is well
absorbed and seems to have greater therapeutic impact when administered
orally as opposed to intravenously
6. While effective
for inflammation and injury, it is even more effective if administered
prior to a traumatic event, i.e. surgery or athletic competition.
7. It seems
to enhance the absorption of and improve the action of other substances
when they are administered in combination.
8. Because of
its impact on the cytokine system, particularly IL-1 and TNF,
which stimulate fever and acute phase response, and its demonstrated
ability to increase the heart rate, bromelain may assist in generating
an acute-stage healing response.
Dosage
and Prescription Instructions
Available research
does not demonstrate an enhanced efficacy of bromelain when it
is administered between meals. It is generally recommended that
bromelain be taken away from food unless it is being used as a
digestive aid, because it is believed that otherwise, it will
tend to act as a digestive enzyme and its therapeutic benefit
may be diminished. While this may in fact be the case, the clinical
studies conducted on bromelain have not followed this protocol.
Bromelain has
shown therapeutic benefits in doses as small as 160 mg/day; however,
it is thought that, for most conditions, best results occur starting
at a dose of
750-1000 mg/day. Most research on bromelain has been
done utilizing divided doses, usually four per day, and findings
indicate that results are dose-dependent. See Table 5 for a summary
of prescription instructions.
Conclusion
Bromelain has
been used for a variety of clinical applications for more than
35 years. Although its mechanisms of action has not been completed
resolved, bromelain has demonstrated a beneficial effect on the
kinin system, the coagulation cascade, the cytokine system, and
prostaglandin synthesis. Bromelain is believed to enhance the
absorption of flavonoids and has been shown to increase absorption
of glucosamine, so bromelain supplemention should be considered
when these nutrients are given. It may also enhance absorption
and utilization of many other substances; however, to date research
in this area has focused primarily on antibiotics. Bromelain has
been shown to exert a beneficial effect at doses as low as 160
mg/day, however, there is a general consensus among researchers
that the best results occur when bromelain is given in doses above
500 mg per day and that results improve in a dose-dependent manner
with higher levels of bromelain supplementation. Bromelain has
been demonstrated to be well absorbed after an oral dose and has
been shown to be safe at high doses for prolonged periods of time.
For the conditions discussed in this review, bromelain has shown
itself to be an effective supplement.
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DISCLAIMER:
The information contained in this publication is for educational
purposes only. It is not intended to diagnose illness nor prescribe
treatment. Rather, this material is designed to be used in cooperation
with your nutritionally-oriented health professional to deal with
your personal health problems. Should you use this information
on your own, you are prescribing for yourself, which is your constitutional
right, but neither the author nor publisher assume responsibility.
Tony M. Isaacs is the author of “Cancer’s Natural
Enemy”, “Collected Remedies”, and numerous health
articles and is a regular contributor to this newsletter.
