Bromelain is another available supplement

http://store.yahoo.com/iherb/bromelain.html

Very interesting - the profile of this compound is consistent with
that of other herbs/natural substances believed to have anti-cancer
effects. What do I mean by that? Well, in general such substances
are ANTI INFLAMMATORY and BLOOD THINNERS. There is some strange
relationship between blood coagulation and metastasis, see
experimentalandunconventional post #91, "natural" blood thinners may
help slow metastasis, but this is really unknown. The "Anti
Inflammatory" part seems to be roughly related to COX-2 and/or
Prostaglandin inhibitors. So every time I see an herb touted as "anti
inflammatory", I start to look for evidence it has been studied for
anti cancer effect as well....

There were a couple of abstracts regarding Bromelain and cancer
published in the last year - looks like research is mainly European
(Germany). The volume of abstracts on Bromelain/cancer is not as
great as some other things...but I still believe this one may be
promising (because of its similar profile to better researched
herbs). The first abstract below is quite interesting, says
"Especially promising are reports on animal experiments claiming an
antimetastatic efficacy and inhibition of metastasis-associated
platelet aggregation as well as inhibition of growth and invasiveness
of tumor cells".

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See the following site for more info
http://www.healthwell.com/healthnotes/Supp/Bromelain.cfm


What does it do? Bromelain is one of a group of proteolytic enzymes
(enzymes capable of digesting protein). It is widely believed that
most orally ingested enzymes are destroyed by the digestive juices
prior to being absorbed. However, there is evidence that significant
amounts of bromelain can be absorbed intact.1 Proteolytic enzymes
other than bromelain are often used with people who suffer from
malabsorption. Although bromelain in combination with other enzymes
and ox bile has been reported to help digest food,2 it is generally
not used for this purpose. However, bromelain does contribute to the
digestion of protein, and may therefore be used as a digestive aid.
Although many doctors assume that other proteolytic enzymes, such as
those found in pancreatin, are more effective than bromelain in
helping digestion and absorption, almost no research compares the
relative effects of these enzymes.

Bromelain is an anti-inflammatory agent and for this reason is
helpful in healing minor injuries, particularly sprains and strains,
muscle injuries, and the pain, swelling, and tenderness that
accompany sports injuries.3 4 5 Topically applied bromelain in the
form of a cream may be beneficial for cleaning debris from burns6 and
frostbite,7 possibly enhancing the rate of healing.8 This use of
bromelain should be supervised by a doctor.

Also as a result of its anti-inflammatory effect, bromelain has been
found to dramatically reduce postoperative swelling in controlled
human research.9 Double-blind research has found bromelain effective
in reducing swelling, bruising,10 and pain, for women having minor
surgery in conjunction with giving birth (episiotomy).11

The anti-inflammatory effect of bromelain is the probable reason this
enzyme has been found effective for people suffering from
sinusitis.12 Some of the evidence supporting bromelain in the
treatment of sinusitis comes from double-blind research.13

Bromelain, in combination with trypsin (another enzyme) may enhance
the effect of antibiotics in people with a urinary tract infection.
In a double-blind study, 100% of people who received
bromelain/trypsin in combination with antibiotics had a resolution of
their infection, compared to only 46% of those who received
antibiotics alone.14

Again, probably due to its anti-inflammatory action, bromelain was
reported to help patients with rheumatoid arthritis in preliminary
research.15 In that trial, in which bromelain was given for varying
(3-week to 13-month) periods, 73% had good to excellent results.

Bromelain is a natural blood thinner because it prevents excessive
blood platelet stickiness.16 This may explain, in part, the positive
reports in a few clinical trials of bromelain to decrease symptoms of
angina and thrombophlebitis.17 18 In addition, bromelain reduces the
thickness of mucus, which may benefit patients with asthma or chronic
bronchitis.19

Preliminary evidence in both animals and people suggests that
bromelain may possess antitumor activity, though the true importance
of this effect is poorly understood.20

Bromelain can induce beneficial changes in white blood cells with
possible effects on immune function.21 22 However, whether these
effects would help people with immune system problems remains unclear.

Where is it found? Bromelain is found mostly in the stems of
pineapples and is available as a dietary supplement.

How much is usually taken? Assessing the right amount of bromelain to
take is complicated. Most bromelain research was conducted years ago,
when amounts used were listed in units of activity that no longer
exist. These old units do not precisely convert to new ones. Today,
bromelain is measured in MCUs (milk clotting units) or GDUs (gelatin
dissolving units). One GDU equals approximately 1.5 MCU. Strong
products contain at least 2,000 MCU (1,200–1,333 GDU) per gram (1,000
mg). A supplement containing 500 mg labeled "2,000 MCU per gram"
would have 1,000 MCU of activity. Some doctors recommend as much as
3,000 MCU taken three times per day for several days, followed by
2,000 MCU three times per day.23 Much of the research uses smaller
amounts, more like the equivalent of approximately 500 MCU taken four
times per day. However, most of the bromelain used in the studies was
enteric-coated in order to prevent it from being destroyed by gastric
juice. It is likely, therefore, that currently available bromelain
preparations (which typically are not enteric-coated) are of lower
potency than the bromelain used in most studies.

Are there any side effects or interactions? Bromelain is generally
safe and free of side effects when taken in moderate amounts.
However, one preliminary report indicates increased heart rate with
the use of bromelain.24 In addition, some people are allergic to
bromelain. Because bromelain acts as a blood thinner and little is
known about how bromelain interacts with blood-thinning drugs, people
should avoid combining such drugs with bromelain in order to reduce
the theoretical risk of excessive bleeding.

**********************************************************************
Cell Mol Life Sci 2001 Aug;58(9):1234-45

Bromelain: biochemistry, pharmacology and medical use.

Maurer HR.

Department of Biochemistry, Molecular Biology and Biotechnology,
Institute of Pharmacy, Freie Universitat Berlin, Germany.
hrmaurer@...

Bromelain is a crude extract from the pineapple that contains, among
other components, various closely related proteinases, demonstrating,
in vitro and in vivo, antiedematous, antiinflammatory, antithrombotic
and fibrinolytic activities. The active factors involved are
biochemically characterized only in part. Due to its efficacy after
oral administration, its safety and lack of undesired side effects,
bromelain has earned growing acceptance and compliance among patients
as a phytotherapeutical drug. A wide range of therapeutic benefits
has been claimed for bromelain, such as reversible inhibition of
platelet aggregation, angina pectoris, bronchitis, sinusitis,
surgical traumas, thrombophlebitis, pyelonephritis and enhanced
absorption of drugs, particularly of antibiotics. Biochemical
experiments indicate that these pharmacological properties depend on
the proteolytic activity only partly, suggesting the presence of
nonprotein factors in bromelain. Recent results from preclinical and
pharmacological studies recommend bromelain as an orally given drug
for complementary tumor therapy: bromelain acts as an immunomodulator
by raising the impaired immunocytotoxicity of monocytes against tumor
cells from patients and by inducing the production of distinct
cytokines such as tumor necrosis factor-a, interleukin (Il)-1beta, Il-
6, and Il-8. In a recent clinical study with mammary tumor patients,
these findings could be partially confirmed. Especially promising are
reports on animal experiments claiming an antimetastatic efficacy and
inhibition of metastasis-associated platelet aggregation as well as
inhibition of growth and invasiveness of tumor cells. Apparently, the
antiinvasive activity does not depend on the proteolytic activity.
This is also true for bromelain effects on the modulation of immune
functions, its potential to eliminate burn debris and to accelerate
wound healing. Whether bromelain will gain wide acceptance as a drug
that inhibits platelet aggregation, is antimetastatic and facilitates
skin debridement, among other indications, will be determined by
further clinical trials. The claim that bromelain cannot be effective
after oral administration is definitely refuted at this time.

Publication Types:
Review
Review, Academic

PMID: 11577981
*********************************************************************
Cancer Chemother Pharmacol 2001 Jul;47 Suppl:S10-5 Related Articles,
Books, LinkOut


Oral therapy with proteolytic enzymes decreases excessive TGF-beta
levels in human blood.

Desser L, Holomanova D, Zavadova E, Pavelka K, Mohr T, Herbacek I.

Institute of Cancer Research, University of Vienna, Austria.
ldesser@...

Therapy with oral proteolytic enzymes (OET) with combination drug
products containing papain, bromelain, trypsin, and chymotrypsin has
been shown to be beneficial in clinical settings such as radiotherapy-
induced fibrosis, bleomycin pneumotoxicity and immunosuppression in
cancer, all of which are nowadays known to be accompanied by
excessive transforming growth factor-beta (TGF-beta) production. It
has been demonstrated that proteolytic enzymes reduce TGF-beta levels
in serum by converting the protease inhibitor alpha2 macroglobulin
(alpha2M) from the "slow" form into the "fast" form, whereby the
"fast" form binds and inactivates TGF-beta irreversibly. In this
study we have investigated the effect of OET on the concentration of
TGF-beta1 in serum of patients with rheumatoid arthritis (RA) (n =
38), osteomyelofibrosis (OMF) (n = 7) and herpes zoster (HZ) (n = 7).
Seventy-eight healthy volunteers served as controls. TGF-beta1 levels
in serum were assessed by enzyme-linked immunosorbent assay (ELISA).
We have demonstrated that in healthy volunteers and in patients there
exists a correlation between active and latent TGF-beta1 in serum
(r=0.8021; P<0.0001). Treatment with OET had no significant effect on
TGF-beta1 concentration in healthy volunteers or patients with a
normal level of TGF-beta1. In patients with elevated TGF-beta1
concentration (> 50 ng/ml serum), OET reduced TGF-beta1 in RA (P <
0.005), in OMF (P < 0.05) and in HZ (P < 0.05). Conclusion: These
results support the concept that OET is beneficial in diseases
characterized in part by TGF-beta1 overproduction.

PMID: 11561866
*********************************************************************
Pathobiology 1996;64(6):339-46

Selective modulation of cell adhesion molecules on lymphocytes by
bromelain protease 5.

Kleef R, Delohery TM, Bovbjerg DH.

Memorial Sloan-Kettering Cancer Center, New York, N.Y. 10021, USA.

Human peripheral blood mononuclear cells from healthy donors were
treated ex vivo with the proteolytic enzyme bromelain and studied by
flow cytometry. Bromelain-treated lymphocytes exhibited 60-90%
reduced cell surface staining for CD44 and CD62-L molecules. While
the staining for molecules CD16, CD56 and CD49d was unaffected, a
moderate increase (10-40%) in expression of the beta(2)-integrins
CD11a-c was seen. This selective modulation of cell adhesion
molecules (CAM) was seen on T cells and NK cells, as well. The
selective modulation of CAM may help explain some of the clinical
effects observed after bromelain treatment in patients suffering from
chronic inflammatory disease, HIV and cancer.

PMID: 9159029
*********************************************************************
Oncol Rep 1999 Nov-Dec;6(6):1191-9

Effects of oral bromelain administration on the impaired
immunocytotoxicity of mononuclear cells from mammary tumor patients.

Eckert K, Grabowska E, Stange R, Schneider U, Eschmann K, Maurer HR.

Institut fur Pharmazie der Freien Universitat Berlin, Berlin, Germany.

The protease bromelain from pineapple was suggested for adjuvant
therapy of malignant diseases. We studied immunological effects of an
orally applied bromelain drug on 16 breast cancer patients in
comparison with healthy donors. Bromelain was applied for 10 days
with a daily dose of 3000 F.I.P. units and the immunocytotoxicity of
blood monocytes and lymphocytes against the leukemic K562 and MDA-MB-
231 mammary carcinoma target cells was determined in vitro. In
addition, the expression of the cell surface markers CD44, CD16,
CD11a and CD62L on lymphocytes and the secretion of IL-2 and IL-1beta
from monocytes was measured. Patients leukocytes expressed lower
bMAK-, MAK-, NK- and LAK-cell activities, compared with those from
healthy donors. Orally applied bromelain increased the reduced bMAK-
and MAK-cell activity of patients monocytes about 2-fold. When the
patients were classified on the basis of bromelain effects on the
monocytic cytotoxicity into bromelain responders and nonresponders,
about 40% of the patients responded to bromelain with an increase of
cytotoxicity from 7.8% to 54% (bMAK-cell activity) and from 16% to
47% (MAK-cell activity). Bromelain was less effective on the higher
cytotoxicity of monocytes from healthy donors, but stimulated the
secretion of IL-1beta from monocytes. In contrast, patient monocytes
secreted no detectable IL-1beta, before, during and after bromelain
treatment. Bromelain had no effects on the impaired patients NK- and
LAK-cell activity, but reduced the LAK-cell activity of healthy
donors. No IL-2 was found in the supernatants of untreated and
treated lymphocytes from healthy donors. Bromelain reduced the
expression of CD44, but weakly increased CD11a and CD62L expression
on patient lymphocytes, whereas CD16 remained unchanged. In vitro
bromelain application to lymphocytes had similar effects, with
greater reduction rates of CD44 and CD16 expression. As to
coagulation parameters in plasma of healthy donors, the activated
partial thromboplastin time was increased from 38 to 46 sec, leaving
prothrombin time and plasminogen unchanged. These data suggest, that
orally applied bromelain stimulates the deficient monocytic
cytotoxicity of mammary tumor patients, which may partially explain
its proposed antitumor activity.

Publication Types:
Clinical Trial

PMID: 10523679