What percentage of the enzymes are destroyed by cooking your food?

9/9/15
Diplomat, American Academy of Pain Management (AAPM)
Member, Society for Integrative Oncology (SIO)
`
Legislative Board Member of the Arizona Association of Naturopathic Physicians
Previous Member, Board of Directors of The Naturopathic Academy of Therapeutic
Injections (NATI)
Member, Board of Directors of The Naturopathic Physicians Board of Aesthetic Medicine
(NPBAM)
Adjunct Faculty, Arizona State University
Previous Member, The Consortium to Advance Integrative Healing and Wellness at
Arizona State University
Member, American Association of Naturopathic Physicians (AANP)
Member, Arizona Naturopathic Medical Association (AZNMA)
What percentage of the enzymes are destroyed by cooking your
food? 100%, 25%, or 75%
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Lecturer and Researcher:
World Nutrition, Inc.
Heel, Inc – MediNatura, Inc.
BioGenesis, Inc.
Olympian Labs
Pharmax/Seroyal Inc,
Senergy, Inc.
SCENAR, USA
Spectracell Laboratories
Enzymes are proteins that speed up chemical
reactions
Established between 50,000 and 70,000 different
enzymes in the body that regulate metabolic functions
Most people think about digestive enzymes but less
than 99.999% have to do with digestion
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https://www.youtube.com/watch?v=ok9esggzN18
Metabolic enzymes – run our bodies (each tissue and
organ has its specific enzymes)
Food enzymes – from raw foods
Digestive enzymes – digest our foods
Source: Pearson Education, Inc. 2006
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Without enzymes we would be nothing more than a set of lifeless
chemical substances made up of proteins, vitamins, minerals and
water
ENZYMES are the workers
The enzyme complex may harbor a protein carrier inhabited by a
vital energy factor
“The proteins in enzymes serve merely as carriers of enzyme activity
factors. …they are protein carriers charged with vital energy factors,
just as your car battery consists of metal plates charged with
electrical energy”
A radiated or cooked potato won’t sprout
Heat over 118 kills enzymes
Cooking temperatures destroy 100% of the enzymes in food
Source: Smith AL (Ed) (1997). Oxford dictionary of biochemistry and molecular biology. Oxford [Oxfordshire]: Oxford
University Press.
Source: Koshland DE (February 1958).
"Application of a Theory of Enzyme Specificity to Protein Synthesis". Proc. Natl.
Acad. Sci. U.S.A. 44 (2): 98–104.
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Source: Sauke, David J.; Metzler, David E.; Metzler, Carol M. (2001). Biochemistry: the
chemical reactions of living cells (2nd ed.). San Diego: Harcourt/Academic Press.
Original theory
Newer evidence is showing that at least amylin
(peptide hormone released from the endocrine
pancreas decreases in middle age but then increases
as we age
This may explain some of the anorexia of aging and
delayed gastric emptying
Abstract
The secretory response of the exocrine pancreas to an intravenous
bolus of secretin (1.0 U/kg) was studied in healthy men and women
below and above 45 years of age. We studied the secretory pattern,
i.e., electrolyte and enzyme secretion in 8 sequential, 10-min
collections and cumulative values for each parameter. Within the
male group, no significant changes were observed, except for higher
amylase and lipase secretions in the older subjects. On the other
hand, females over 45 yr old had secretory patterns that showed a
decline of flow and of bicarbonate concentration and output. No
significant secretory differences were observed in the groups of
younger males and females. When the over-45 groups of men and
women were compared, the women exhibited a significant decrease
in bicarbonate concentration and output. Moreover, this group of
women had a cumulative 80-min output of bicarbonate and lipase
significantly below these parameters in the men. Possible
mechanisms are discussed.
Source: Tiscornia OM1, Cresta MA, de Lehmann ES, Celener D, Dreiling DA. Int J Pancreatol. 1986 Jul;1(2):95-118.
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Share many of the same enzymes such as protease,
papain, bromelain but do not function similarly
Digestive enzymes taken with a meal and speed up
the breakdown of food
Proteolytic enzymes taken between meals enter the
bloodstream and aid metabolic functions
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Proteases – digest protein
Amylases – digest carbohydrates
Lipases – digest fat
Maltase – reduces maltose to dextrose
Digestive enzymes not only help promote optimal digestion,
they may also help avert inflammation, speed post-surgical
recovery time, and serve as a useful adjuvant cancer therapy.
Source: Modified from
Gitler (1964).
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Secretion Approximate Normal
Daily Value (mL)
Average
Concentration of
some Electrolytes (Na+, K+, Cl-,
HCO3-) (meq/L)
Other Ingredients
Saliva
1000-1500
10, 26, 10, 8
Amylase, SCN-,
somatostatin, EGF, NGF
Gastric Juice Bile
1500
150, 15, 130, ---
H+, pepsin
Bile 1000
146, 5, 110, 46
Bile acids, cholesterol,
phospholipids Fe, Zn, Cu,
Mn
Pancreatic Juice and
Enzymes
1500
157, 7, 50, 110
Digestive
Intestinal Juices
4000
140, 6, 100, 17
Digestive Enzymes, IgA
Total
~9000 (all but 100-200 mL
reabsorbed)
Source: Modified from Wilson and Green (1988).
Well documented in pancreatic insufficiency
MOST FAMILIAR PANCREATIC ENZYMES:
Protease
Pancrelipase
Pancreatic amylase (to treat pancreatic insufficiency)
DIGESTIVE AID For Healthy Subjects as well
Digestive enzyme (lipase, protease and amylase) before and
after a fatty meal reported sig less gas, bloating and fullness
than controls with a pharmaceutical enzyme
Suarez F, Levitt MD, Adshead J, Barkin JS. Pancreatic supplements reduce symptomatic response of healthy subjects
to a high fat meal. Dig Dis Sci. 1999;44(7):1317-1321.
Plant based are more active over a broader pH range
Touted to survive a pH of 2 or 3
This may allow the enzymes to get past the acidic environment
of stomach and protect them to reach small intestine
Animal derived function in a narrower pH range
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Vast majority of metabolic enzymes – regulate liver function and the
immune system are proteases
Proteolytic is a term used for hydrolytic enzymes that facilitate a
chemical breakdown of proteins
Occur naturally in all organisms
Constitute 1-5% of human genetic content
Hooper NM. (2002). Proteases in Biology and Medicine. London: Portland Press. ISBN 1-85578-147-6.
6 classes of enzymes
Type used for purposes discussed here are serene proteases except
bromelian and papain which are cysteine proteases (responsible in
humans for cell aging, cell death and immune responses
Chapman HA, Riese RJ, Shi GP (1997). "Emerging roles for cysteine proteases in human biology." Annu. Rev. Physiol
22
Proteolytic enzymes such as trypsin and chymotrypsin (pancreas of cattle or
pigs) have been used as therapeutic agents in humans and animals for over
100 years (Morris, 1891).
Historically proteolytic enzymes have been used therapeutically in 4 areas:
(1) as oral agents for some gastrointestinal disorders, (2) as local agents to
debride or solubilize collections of proteinaceous materials that either foster
or cause disease, (3) as anti-inflammatory agents, and (4) as thrombolytic
agents (Sherry and Fletcher, 1960).
Mammalian trypsins and chymotrypsins have been used with good results
for wound healing (Spittler and Parmenter, 1954) and as an antiinflammatory agent (Martin et al., 1955) in veterinary medicine (Lecht and
Stephenson, 1968) and human medicine (Leipner and Saller, 2000). The
medical application of trypsin I and other cold-adapted serine proteases
from the Atlantic cod includes the use of the native trypsin I for
inflammation, fungal diseases, acne, wound healing, and other
dermatologic indications (psoriasis, and eczema), as well as for general and
dental hygiene (Bjarnason, 2000).
Convert food we eat into
chemical structures
Convert prepared food into
new muscle, flesh, bone,
nerves and glands
Working with the liver they
store excess food for future
energy and building needs
Support elimination organs
such as lungs, kidneys, liver,
skin and colon
Blood coagulation
Iron bound in the red blood
cells
Provide oxidation
Convert protein into fat or
sugar/carbs into fat
Convert fats to carbs for
energy
THOUSANDS OF METABOLIC
TASKS
Help build phosphorus into
bone
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1. Broken down by stomach acid
Enteric coated or specialized delivery
systems
Non-animal derived enzymes. Fungal
and plant-based enzymes survive
stomach acid. Oral supplementation
with non-animal derived enzymes, such
as microbial or fungal enzymes
Those manufactured by a fermentation
process of Aspergillus, for example-possess unusually high stability and
activity throughout a wide range of pH
conditions (from a pH of 2-10
Brad Rachman, "Unique Features and Application of Non-Animal
Derived Enzymes." Clinical Nutrition Insights. 510 8/97 Vol. 5, No. 10.
2. Too large to pass through the
walls of the small intestine
Definitive answer as to how they
accomplish this is unknown
Proteolytic enzymes may increase the
permeability of the mucosal
epithelium and, hence, facilitate their
own absorption by a mechanism of
self-enhanced paracellular diffusion
KOLAC C., STREICHHAN P., LEHR C.-M. "Oral bioavailability of
proteolytic enzymes." European journal of pharmaceutics and
biopharmaceutics. 1996, vol. 42, no4, pp. 222-232 (68 ref.)
Reactivated past the acidic stomach
acid
Found in the blood stream
Laura P. Hale. "Proteolytic activity and immunogenicity of oral
bromelain within the gastrointestinal tract of mice." International
Immunopharmacology. Volume 4, Issue 2, February 2004, Pages
255--264.
25
Abstract
The oral bioavailability of proteolytic enzymes such as e.g. trypsin, chymotrypsin, papain and
bromelain has been discussed since their introduction as anti-inflammatory, anti-edematose
and immunostimulating agents. The controversy about oral enzyme absorption has not yet
been solved, because in the blood proteolytic enzymes bind to antiproteinases and therefore
are difficult to quantify with immunological, enzymic and radiochemical methods. Therefore,
the amounts of enzymes absorbed in vivo tend to be underestimated (immunological, enzymic
methods) or overestimated (radiochemical methods). Quantification as an objective parameter,
however, is pivotal for any bioavailability study. Regardless of these analytical difficulties it is
presently accepted that proteolytic enzymes when orally administered to man can be detected
in the blood plasma, at least to some extent, in their intact, biologically active form. What,
however, is still unknown, is the mechanism by which the large molecules cross the intestinal
barrier. Using Caco-2 monolayers as a model, some progress was made to better understand
this phenomenon. The proteolytic enzymes trypsin, chymotrypsin, papain and bromelain
decreased the transepithelial electrical resistance and simultaneously increased the transport of
fluorescent marker substances, which normally are not transported across the Caco-2
monolayer. Mucin, albumin and fetal calf serum influence differently the behavior of these
enzymes thus indicating different mechanisms of action for the enzymes. The results suggest
that proteolytic enzymes are able to increase the permeability of the mucosal epithelium and,
hence, facilitate their own absorption by a mechanism of self-enhanced paracellular diffusion.
KOLAC C., STREICHHAN P., LEHR C.-M. "Oral bioavailability of proteolytic enzymes." European journal of pharmaceutics and
biopharmaceutics. 1996, vol. 42, no4, pp. 222-232 (68 ref.) http://cat.inist.fr/?aModele=afficheN&cpsidt=3191444
Abstract
A sensitive sandwich enzyme immunoassay (e.i.a.) for serrapeptase (TSP),
an orally available anti-inflammatory proteinase, was established using
affinity-purified anti-TSP rabbit IgG and its Fab' fragment conjugated with
horseradish peroxidase as the first and the second antibodies respectively.
TSP in the plasma was determined by the e.i.a. after its oral administration
(100 mg/kg) to rats. The peak concentration was observed between 30 min
and 2 h after administration. TSP in the plasma samples was trapped on a
microtitre plate coated with the affinity-purified anti-TSP rabbit IgG, and
the hydrolysis of a synthetic fluorogenic substrate, butoxycarbonylGlu(benzyloxy)-Ala-Arg-4-methylcoumaryl-7-amide, by the trapped TSP was
fluorometrically measured (proteinase assay). The values obtained by the
e.i.a. and those obtained by the proteinase assay correlated well for various
plasma samples. These results indicate that orally administered TSP was
absorbed from the intestinal tract and transferred into the circulation in an
enzymically active form.
Moriya N1, Nakata M, Nakamura M, Takaoka M, Iwasa S, Kato K, Kakinuma A Biotechnol Appl Biochem. 1994 Aug;20 ( Pt 1):
101-8.
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Abstract
These results provided the first evidence that nattokinase can be measured
directly in the blood of humans. The results further suggest that a larger,
more extensive, pharmacokinetic study of nattokinase is warranted.
Additionally, looking for intact enzyme and bioactive nattokinase peptides
should be a consideration for future studies investigating the
pharmacokinetic profile of nattokinase.
Ero MP1, Ng CM, Mihailovski T, Harvey NR, Lewis BH. Altern Ther Health Med. 2013 May-Jun;19(3):16-9.
For the assimilation of nutrients by the body, the bulk of the
foodstuffs mist first undergo mastication and digestion. In this
process, polymeric substances, such as starches, proteins, and
triglycerides, are broken down into their “building blocks” of
monomeric sugars, amino acids, fatty acids, etc. With the
exception of most vitamins and inorganic substituents, this
digestive breakdown process is necessary for absorption into
the body.
During digestion/hydrolysis of the polymeric nutrients
(especially proteins), the vitamins and trace elements
associated with them are released, allowing their more efficient
absorption.
Bromelain is a general name for a family of sulfhydryl-containing
proteolytic enzymes obtained from Ananas comosus, the pineapple
fruit and stem.
Although bromelain’s primary constituent is a sulfhydryl proteolytic
fraction, it also contains escharase (a non-proteolytic component in
bromelain thought to be important in the action of topical
bromelain), peroxidase, acid phosphatase, several protease
inhibitors, and organically-bound calcium.
The beneficial effects of bromelain are due to multiple constituents
apart from its proteolytic fraction.
http://www.ncbi.nlm.nih.gov/pubmed/?term=bromelain+inflammation
http://www.altmedrev.com/publications/15/4/361.pdf
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Bromelain, is absorbed unchanged from the intestine of
animals at a rate of 40%; in animal experiments it was found to
have primarily anti-edema, anti-inflammatory, and
coagulation-inhibiting effects. These effects are due to an
enhancement of the serum fibrinolytic activity and inhibition of
the fibrinogen synthesis, as well as a direct degradation of
fibrin and fibrinogen. Bromelain lowers kininogen and
bradykinin serum and tissue levels and has an influence on
prostaglandin synthesis, thus acting anti-inflammatory. In in
vitro and in animal studies, experimentally induced tumours
could be inhibited by bromelain. Although many studies do not
give extensive statistical data, the effects of bromelain in
animal studies seem to be dose-dependent. Further
investigations have to be carried out.
Lotz-Winter H. Planta Med. 1990;56(3):249-253.
After a short description of the uses of pineapple as folk medicine by
the natives of the tropics, the more important new pharmaceutical
applications of bromelain, reported between 1975 and 1978, are
presented. Although the exact chemical structure of all active
components of bromelain is not fully determined, this substance has
shown distinct pharmacological promise.
Its properties include: (1) interference with growth of malignant
cells; (2) inhibition of platelet aggregation; (3) fibrinolytic activity;
(4) anti-inflammatory action; (5) skin debridement properties. These
biological functions of bromelain, a non-toxic compound, have
therapeutic values in modulating: (a) tumor growth; (b) blood
coagulation; (c) inflammatory changes; (d) debridement of third
degree burns; (e) enhancement of absorption of drugs. The
mechanism of action of bromelain affecting these varied biological
effects relates in part to its modulation of the arachidonate cascade.
Taussig SJ, Batkin S. J Ethnopharmacol.1988;22(2):191-203.
Abstract
Bromelain (Br), an extract from pineapple stem with cysteine protease
activity, exerts anti-inflammatory effects in a number of inflammatory
models. We have previously shown that Br treatment decreased activated
CD4(+) T cells and has a therapeutic role in an ovalbumin-induced murine
model of allergic airway disease. The current study was designed to
determine the effect of Br on CD4(+) T cell activation, specifically the
expression of CD25 in vitro. CD25 is up regulated upon T cell activation,
found as a soluble fraction (sCD25) and is a therapeutic target in
inflammation, autoimmunity and allergy. Br treatment of anti-CD3
stimulated CD4(+) T cells reduced CD25 expression in a dose and time
dependent manner. This reduction of CD25 was dependent on the
proteolytic action of Br as the addition of E64 (a cysteine protease inhibitor)
abrogated this response. The concentration of sCD25 was increased in
supernatants of Br treated activated CD4(+) T cells as compared to control
cells, suggesting that Br proteolytically cleaved cell-surface CD25. This novel
mechanism of action identifies how Br may exert its therapeutic benefits in
inflammatory conditions.
Kim JY1, Gum SN, Paik JK, Lim HH, Kim KC, Ogasawara K, Inoue K, Park S, Jang Y, Lee JH. Hypertens Res. 2008 Aug;31(8):
1583-8. doi: 10.1291/hypres.31.1583. Int Immunopharmacol. 2009 Mar;9(3):340-6. doi: 10.1016/j.intimp.2008.12.012. Epub
2009 Jan 20.
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Abstract
CONCLUSION:
Bromelain, acting through its barrier, anti-inflammatory,
antioxidant, and proteolytic effects and without increasing
bleeding tendency or having any adverse effects on wound
healing, may be a suitable agent for intra-abdominal adhesion
prevention.
Sahbaz A1, Aynioglu O2, Isik H3, Ozmen U4, Cengil O5, Gun BD6, Gungorduk K7. Int J Surg. 2015 Jan 6;14C:7-11. doi:
10.1016/j.ijsu.2014.12.024. [Epub ahead of print]
Abstract
BACKGROUND:
Bromelain, a mixture of proteolytic enzymes typically derived from pineapple stem,
decreases production of proinflammatory cytokines and leukocyte homing to sites of
inflammation. We previously showed that short-term oral treatment with bromelain
purified from pineapple stem decreased the severity of colonic inflammation in
C57BL/6 Il10(-/-) mice with chronic colitis. Since fresh pineapple fruit contains
similar bromelain enzymes but at different proportions, this study aimed to
determine whether long-term dietary supplementation with pineapple (supplied as
juice) could decrease colon inflammation and neoplasia in Il10(-/-) mice with
chronic colitis as compared with bromelain derived from stem.
CONCLUSIONS:
These results demonstrate that long-term dietary supplementation with fresh or
unpasteurized frozen pineapple juice with proteolytically active bromelain enzymes
is safe and decreases inflammation severity and the incidence and multiplicity of
inflammation-associated colonic neoplasia in this commonly used murine model of
inflammatory bowel disease.
Hale LP1, Chichlowski M, Trinh CT, Greer PK. Inflamm Bowel Dis. 2010 Dec;16(12):2012-21. doi: 10.1002/ibd.21320.
Abstract
Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have
therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory
bowel disease. The purpose of this work was to understand potential mechanisms for this antiinflammatory activity. Exposure to bromelain in vitro has been shown to remove a number of
cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and
CD128b/CXCR2 that serve as receptors for the neutrophil chemoattractant IL-8 and its murine
homologues. We hypothesized that specific proteolytic removal of CD128 molecules by
bromelain would inhibit neutrophil migration to IL-8 and thus decrease acute responses to
inflammatory stimuli. Using an in vitro chemotaxis assay, we demonstrated a 40% reduction in
migration of bromelain- vs. sham-treated human neutrophils in response to rhIL-8. Migration to
the bacterial peptide analog fMLP was unaffected, indicating that bromelain does not induce a
global defect in leukocyte migration. In vivo bromelain treatment generated a 50-85%
reduction in neutrophil migration in 3 different murine models of leukocyte migration into the
inflamed peritoneal cavity. Intravital microscopy demonstrated that although in vivo bromelain
treatment transiently decreased leukocyte rolling, its primary long-term effect was abrogation
of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in
adhesion were correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin
molecules that mediate rolling following in vivo bromelain treatment and minimal reexpression of CD128 over the time period studied. Taken together, these studies demonstrate
that bromelain can effectively decrease neutrophil migration to sites of acute inflammation and
support the specific removal of the CD128 chemokine receptor as a potential mechanism of
action.
Fitzhugh DJ1, Shan S, Dewhirst MW, Hale LP. Clin Immunol. 2008 Jul;128(1):66-74. doi: 10.1016/j.clim.2008.02.015. Epub
2008 May 14.
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Fitzhugh DJ1, Shan S, Dewhirst MW, Hale LP. "Bromelain treatment decreases
neutrophil migration to sites of inflammation." Clin Immunol. 2008 Jul;128(1):
66-74. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2516972/
Cirelli MG. "Treatment of inflammation and edema with bromelain." Delaware
Med J 1962;34:159--67. http://www.ncbi.nlm.nih.gov/pubmed/13879585
Akhtar NM1, Naseer R, Farooqi AZ, Aziz W, Nazir M. "Oral enzyme combination
versus diclofenac in the treatment of osteoarthritis of the knee--a double-blind
prospective randomized study." Clin Rheumatol. 2004 Oct;23(5):410-5. http://
www.ncbi.nlm.nih.gov/pubmed/15278753
Heinicke R, van der Wal L, Yokoyama M. "Effect of bromelain (Ananase) on
human platelet aggregation." Experientia 1972;28:844--5. http://
www.ncbi.nlm.nih.gov/pubmed/4658882
Juhasz B, Thirunavukkarasu M, Pant R, Zhan L, Penumathsa SV, et al.
"Bromelain induces cardioprotection against ischemia-reperfusion injury
through Akt/FOXO pathway in rat myocardium." Am J Physiol Heart Circ
Physiol. 2008 Mar;294(3):H1365-70. http://www.ncbi.nlm.nih.gov/pmc/
articles/PMC2581828/
37
Bromelain treatment alters leukocyte expression of cell surface
molecules involved in cellular adhesion and activation.
Hale LP, Greer PK, Sempowski GD. Clin Immunol. 2002;104(2): 183-190
Bromelain – inhibits platelet aggregation and interferes with
the growth of malignant cells
Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application: an update. J
Ethnopharmacol. 1988;22(2):191-203
Abstract
In vitro treatment of human peripheral blood mononuclear cells (PBMNC) with
proteolytic enzymes (bromelain, papain) and amylase leads to the production of
large amounts of tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1 β), and
interleukin-6 (IL-6) in a time and dose dependent manner. Increased TNF-α and IL-6
production was already found after 4-6 hours of incubation, and plateau levels were
reached after 12-16 hours. Plateau levels up to 1500 pg TNF-α/ml/10(6) PBMNC,
13000 pg IL-1 β/ml/10(6) PBMNC, and 23000 pg IL-6/ml/10(6) PBMNC were
observed. Control cultures contained below 35 pg/ml/10(6) PBMNC of TNF-α, IL-1
β or IL-6. In contrast to TNF-α which was undetectable after more than 24 hours,
peak levels of IL-1 β and IL-6 were still present at 24 hours. After incubation of the
enzyme solution for some hours at 56 degrees C the cytokine inducing capacity
disappeared. Neutralization experiments with inactivating antibodies,
radioimmunoassay, and western blotting after electrophoretic separation showed
that the TNF-like activity found in the lytic assay was due to TNF-α. Interferon-α
(IFN-α) and Interferon-ϒ (IFN-ϒ), which had no effect alone, synergistically
increased TNF-α production when applied together with the enzymes. A commercial
mixture of these enzymes (Wobenzym), which was also investigated, showed a
similar concentration and time dependence, as well as synergism with the
interferons. A synergistic effect on TNF-α production was also found with the
enzymes and phorbol ester (PMA).
Desser L1, Rehberger A, Paukovits W. Cancer Biother. 1994 Fall;9(3):253-63.
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Papain is a cysteine hydrolase that is stable and active under a wide range
of conditions. It is very stable even at elevated temperatures (Cohen et al.
1986). The latex of Carica papaya is a rich source of four cysteine
endopeptidases including papain, chymopapain, glycyl endopeptidase, and
caricain.. Papain is a minor constituent, but has been more widely studied
because it is more easily purified (Azarkan 2003).
Carico papaya
Papaya fruit contains several enzymes including
Papain
Cymopapain A
Cymopapain B
Papaya peptidase A
http://www.worthington-biochem.com/pap/default.html
Abstract
The influence of domestic papain to the course of experimental
inflammation due to formalin, dextrane, histamine, serotonin
and infectious arthritis has been studied. The domestic papain
in doses of 0.325 and 0.75 mg/kg possesses strongly marked
anti-inflammatory activity and this ability is no less than that of
butadion and indomethacin.
Rakhimov MR. "Anti-inflammatory activity of domestic papain]." Eksp Klin Farmakol. 2001 Jul-Aug;64(4):48-9.
http://www.ncbi.nlm.nih.gov/pubmed/11589110
Papain
Increases the release of ROS (reactive oxygen species) by
polymorphonuclear cells.
Natural Medicines Comprehensive Database. http://www.naturaldatabase.com. Updated January 22, 2014. Accessed
January 22, 2014.
41
Abstract
Cysteine proteases have traditionally been viewed as lysosomal
mediators of terminal protein degradation. However, recent findings
refute this limited view and suggest a more expanded role for
cysteine proteases in human biology. Several newly discovered
members of this enzyme class are regulated proteases with limited
tissue expression, which implies specific roles in cellular physiology.
These roles appear to include apoptosis, MHC class II immune
responses, prohormone processing, and extracellular matrix
remodeling important to bone development. The ability of
macrophages and other cells to mobilize elastolytic cysteine
proteases to their surfaces under specialized conditions may also lead
to accelerated collagen and elastin degradation at sites of
inflammation in diseases such as atherosclerosis and emphysema.
The development of inhibitors of specific cysteine proteases promises
to provide new drugs for modifying immunity, osteoporosis, and
chronic inflammation.
Chapman HA1, Riese RJ, Shi GP. Annu Rev Physiol. 1997;59:63-88.
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Papain
Increases the release of ROS (reactive oxygen species) by
polymorphonuclear cells (Therapeutic Research N
Natural Medicines Comprehensive Database. http://
www.naturaldatabase.com. Updated January 22, 2014.
Accessed January 22, 2014.
Natto is made from fermented soybeans with a beneficial
bacteria (Bacillus subtilis natto)
Contains no Soy
Fujita M., Nomura K., Hong K., Ito Y., Asada A. and Nishimuro S. "Purification and Characterization of a Strong Fibrinolytic
Enzyme (Nattokinase) in the Vegetable Cheese Natto, a Popular Soybean Fermented Food in Japan." Biochemical and
Biophysical Research Communications, Vol. 197, Issue 3, 30 December 1993, pp. 1340-1347.
80 + studies on inflammatory disorders
http://www.ncbi.nlm.nih.gov/pubmed/?term=nattokinase
44
Studies have also shown that nattokinase works as an ACE
inhibitor to help lower blood pressure. In fact, a 2008 study
conducted over eight weeks, found that nattokinase was able to
moderately lower both systolic and diastolic blood pressure in
hypertensive human subjects.
Kim JY, Gum SN, Paik JK, et al. "Effects of nattokinase on blood pressure: a randomized, controlled trial."
Hypertens Res. 2008;31(8):1583-1588. http://www.ncbi.nlm.nih.gov/pubmed/18971533
2009 study out of Taiwan found that nattokinase has the ability
to dissolve amyloid fibrils, which means it may help prevent
Alzheimer's disease.
Murakami K1, Yamanaka N, Ohnishi K, Fukayama M, Yoshino M. "Inhibition of angiotensin I converting enzyme by
subtilisin NAT (nattokinase) in natto, a Japanese traditional fermented food." Food Funct. 2012 Jun;3(6):674-8.
45
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Abstract
BACKGROUND:
Bromelain, a mixture of proteolytic enzymes typically derived from pineapple stem,
decreases production of proinflammatory cytokines and leukocyte homing to sites of
inflammation. We previously showed that short-term oral treatment with bromelain
purified from pineapple stem decreased the severity of colonic inflammation in
C57BL/6 Il10(-/-) mice with chronic colitis. Since fresh pineapple fruit contains
similar bromelain enzymes but at different proportions, this study aimed to
determine whether long-term dietary supplementation with pineapple (supplied as
juice) could decrease colon inflammation and neoplasia in Il10(-/-) mice with
chronic colitis as compared with bromelain derived from stem.
CONCLUSIONS:
These results demonstrate that long-term dietary supplementation with fresh or
unpasteurized frozen pineapple juice with proteolytically active bromelain enzymes
is safe and decreases inflammation severity and the incidence and multiplicity of
inflammation-associated colonic neoplasia in this commonly used murine model of
inflammatory bowel disease.
Hale LP1, Chichlowski M, Trinh CT, Greer PK. Inflamm Bowel Dis. 2010 Dec;16(12):2012-21. doi: 10.1002/ibd.21320.
Produced by fungus Aspergillus melleus
Anti-inflammatory
Anti-viral properties
Mucolytic
Respiratory
Fossati A. "Anti-inflammatory effects of seaprose-S on various inflammation models." Drugs Exp Clin Res. 1999;25(6):263-70.
http://www.ncbi.nlm.nih.gov/pubmed/10713864
Moretti M, Bertoli E, Bulgarelli S, Testoni C, et al. "Effects of seaprose on sputum biochemical components in chronic bronchitic patients: a double-blind
study vs placebo." Int J Clin Pharmacol Res. 1993;13(5):275-80. http://www.ncbi.nlm.nih.gov/pubmed/8200722?dopt=Abstract
Braga PC, Rampoldi C et al "In vitro rheological assessment of mucolytic activity induced by seaprose." Pharmacol Res 1990;22(5):611-617. http://
www.ncbi.nlm.nih.gov/pubmed/2277801
DVT and Thrombophlebitis
Bracale G, Selvetella L. "Clinical study of the efficacy of and tolerance to seaprose S in inflammatory venous disease. Controlled study
versus serratio-peptidase." Minerva Cardioangiol. 1996 Oct;44(10):515-24. http://www.ncbi.nlm.nih.gov/pubmed/9091835
47
Abstract
This study was designed to compare the efficacy and safety of seaprose S and serratiopeptidase in the treatment of venous inflammatory disease. Forty patients entered the study
(11 males, 29 females), mean age 54.3 years (range 30-77), mean weight 74.8 kg (range
51-96), with superficial thrombophlebitis. The trial was conducted following a controlled,
between patients, randomized experimental design. Seaprose S was administered as 30 mg
tablets at a daily dosage of 90 mg (one tab t.i.d.), and serratio-peptidase as 5 mg tablets, at a
dose of 30 mg per day (two tabs t.i.d.), both orally, for 14 days. Twenty patients received
seaprose S and 20 serratio-peptidase. The findings indicate that seaprose S was more effective
and better tolerated than serratio-peptidase. Although the group of patients assigned to
seaprose S had considerably more severe initial symptoms, by the end of treatment
spontaneous pain was reduced 68.7% from the baseline mean score (from 3.2 to 1.0), as
compared with a 63.3% reduction in the serratio-peptidase group (from 3.0 to 1.1). Pain on
pressure was reduced 61.1% with seaprose S (from 3.6 to 1.4), compared to 57.6% with the
reference treatment (from 3.3 to 1.4). Edema was reduced respectively 75% (from 1.6 to 0.4)
and 56.2% (from 1.6 to 0.7); erythema diminished 72.4% (from 2.9 to 0.8) and 58.3% (from
2.4 to 1.0); nighttime cramps were 61.1% less (from 1.8 to 0.7) compared with 52.9% (from
1.7 to 0.8); hemorrhagic suffusion was 53.3% less (from 1.5 to 0.7) compared with 41.7%
(from 1.2 to 0.7); cutaneous dystrophy was reduced by 11.1% (from 1.8 to 1.6) and 7.7%
(from 1.3 to 1.2). At the end of the treatment with seaprose S efficacy was assessed as good or
excellent in 85% of the cases, compared with 65% for serratio-peptidase. Seaprose S caused no
adverse reactions. During serratio-peptidase treatment one patient reported diarrhea, requiring
temporary dosage reduction and specific treatment. It can thus be confirmed that seaprose S
was effective and well tolerated in patients with inflammatory venous diseases.
Bracale G1, Selvetella L. Minerva Cardioangiol. 1996 Oct;44(10):515-24.
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The aim of this study was to investigate the ability of serrapeptase to reduce
postoperative swelling, pain and trismus after third molar surgery. Twentyfour healthy individuals with symmetrically impacted mandibular third
molars underwent surgical removal in a prospective, intra-individual,
randomized, double-blind, cross-over study. Teeth were removed in 2
sessions by the same surgeon. At each session, one third molar was removed
under local anaesthesia via a buccal osteotomy. All patients received a
combination of either serrapeptase 5mg or placebo tablets and 1000 mg
paracetamol tablets at either the 1st or 2nd operation in accordance with
the randomization plan. Cheek thickness, pain and interincisal distance
were measured preoperatively, and on the 1st, 2nd, 3rd and 7th
postoperative days. Cheek thickness and maximum interincisal distance
were measured using calipers. Pain intensity was assessed clinically using a
numeric scale. There was a significant reduction in the extent of cheek
swelling and pain intensity in the serrapeptase group at the 2nd, 3rd and
7th postoperative days (P<0.05), but no significant difference in mean
maximal interincisal distance was found between the 2 groups (P>0.05).
Al-Khateeb TH, Nusair Y. Int J Oral Maxillofac Surg. 2008; 37:264-268.
Celiac sprue is an inflammatory disease of the small intestine caused by
dietary gluten and treated by adherence to a life-long gluten-free diet. The
recent identification of immunodominant gluten peptides, the discovery of
their cogent properties, and the elucidation of the mechanisms by which
they engender immunopathology in genetically susceptible individuals have
advanced our understanding of the molecular pathogenesis of this complex
disease, enabling the rational design of new therapeutic strategies. The most
clinically advanced of these is oral enzyme therapy, in which enzymes
capable of proteolyzing gluten (i.e., glutenases) are delivered to the
alimentary tract of a celiac sprue patient to detoxify ingested gluten in situ.
In this chapter, we discuss the key challenges for discovery and preclinical
development of oral enzyme therapies for celiac sprue. Methods for lead
identification, assay development, gram-scale production and formulation,
and lead optimization for next-generation proteases are described and
critically assessed.
Methods Enzymol. 2012;502:241-71. doi: 10.1016/B978-0-12-416039-2.00013-6.
Strong evidence indicates that enzymotherapy ameliorates the disturbed
composition and properties of blood and vessel walls, acts preventively as
well as therapeutically in thromboses, thromboflebitides and consequences
of venous insufficiency; it seems be prospective in afflictions of arterial bed,
including vasculitides and glomerulonephritides, also. The key feature of
enzymotherapy is the immunomodulatory activity. There exists a strong
evidence for the favourable modulation of pathogenic autoantibodies,
inhibition of the neogenesis of immune complexes and cleavage of their
deposits, normalization of the T cell system, network of cytokines, adhesion
molecules and inflammatory cascades. Besides the direct peptidolytic and
proteolytic effects of hydrolases, the indirect effects realized in the course of
interaction between the resorbed enzymes and their natural "partners"—
anti-proteases (mainly alfa-2-macroglobulin)—have become a topic of
intensive research. The author feels, that systemic enzyme therapy should
become a regular component of the treatment of immunopathologic
processes in general and of angiologic diseases specifically.
Bratisl Lek Listy. 1995 Oct;96(10):566-9.http://www.ncbi.nlm.nih.gov/pubmed/8620329
51
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To evaluate the effectiveness of systemic enzyme therapy for the control of
edema in patients who undergo bimaxillary orthognathic. Thirty patients
were included in this double-blinded, randomized, control trial. Before
surgery, each patient was allotted a code (study or control group). Nine
anthropometric points were selected. Thickness of the soft tissue at each of
these points was measured using an ultrasound device. These
measurements were performed on the day before surgery and 1, 5, and 15
days after surgery. The study group was given a twice-daily dose of systemic
enzyme therapy from the first postoperative day for 5 days; the control
group was given placebo. The percentage of difference in the thickness of
the soft tissue was calculated at each of the 9 points on postoperative days
1, 5, and 15. These data were analyzed and compared using the MannWhitney test. The statistical evaluation showed a significant difference in
soft tissue thickness between the 2 groups, especially on days 5 and 15, at
most assessed points. The results of this study suggest that systemic enzyme
therapy significantly decreases postoperative edema in orthognathic
surgery, precluding long-term corticosteroid use.
J Oral Maxillofac Surg. 2013 Jul;71(7):1261-7. doi: 10.1016/j.joms.2013.01.008. Epub 2013 Apr 6.
A new anti-infective strategy to reduce adhesion-mediated virulence in Staphylococcus aureus affecting
surface proteins.
Our results suggest that SPEP could be developed as a potential anti-infective agent
capable to hinder the entry of S. aureus into human tissues, and also impair the ability of this pathogen to
form biofilm on prostheses, catheters and medical devices. Artini M, Scoarughi GL, Papa R, Cellini A, Carpentieri A, Pucci P, Amoresano
A, Gazzola S, Cocconcelli PS, Selan L. Int J Immunopathol Pharmacol. 2011 Jul-Sep;24(3):661-72.
Comparison of the action of different proteases on virulence properties related to the staphylococcal surface.
That proteases, in particular the metalloprotease serratiopeptidase, can interfere with adhesion and invasion
of eukaryotic cells and biofilm formation in staphylococci and their use could represent a viable treatment
for the development of novel combination therapies. Artini M, Papa R, Scoarughi GL, Galano E, Barbato G, Pucci P, Selan L. J Appl
Microbiol. 2013 Jan;114(1):266-77. doi: 10.1111/jam.12038. Epub 2012 Nov 19. Protease treatment affects both invasion ability and biofilm formation in Listeria
monocytogenes.
Protease treatment affects both invasion ability and biofilm formation in Listeria monocytogenes.
These cell-surface proteins are known to function as ligands in the interaction between these bacteria and
their host cells, and our data suggest that treatment with this natural enzyme may provide a useful tool in
the prevention of the initial adhesion of L. monocytogenes to the human gut. Longhi C, Scoarughi GL, Poggiali F, Cellini A,
Carpentieri A, Seganti L, Pucci P, Amoresano A, Cocconcelli PS, Artini M, Costerton JW, Selan L. Microb Pathog. 2008 Jul;45(1):45-52. doi: 10.1016/j.micpath.
2008.01.007. Epub 2008 Mar 25.
The effect of proteolytic enzyme serratiopeptidase in the treatment of experimental implant-related infection.
The antibiofilm property of the enzyme may enhance antibiotic efficacy in the treatment of staphylococcal
infections. Mecikoglu M, Saygi B, Yildirim Y, Karadag-Saygi E, Ramadan SS, Esemenli T. J Bone Joint Surg Am. 2006 Jun;88(6):1208-14.
Proteolytic enzymes: a new treatment strategy for prosthetic infections?
Serratiopeptidase greatly enhances the activity of ofloxacin on sessile cultures and can inhibit biofilm
formation. Selan L, Berlutti F, Passariello C, di-Ballanti MR, Thaller MC. Antimicrob Agents Chemother. 1993 Dec;37(12):2618-21.
We evaluated an anti-inflammatory enzyme drug Danzen
(Serrapeptase: Takeda Chemical Industries, Ltd.) on 70 patients
complaining of breast engorgement. These patients were randomly
divided into 2 groups, a treatment group and a placebo group. A
single observer, unaware of the group the patients were in, assessed
the severity of each of the symptoms and signs of breast
engorgement before treatment was commenced, and daily for 3 days,
during which therapy was administered. Danzen was noted to be
superior to placebo for improvement of breast pain, breast swelling
and induration and while 85.7% of the patients receiving Danzen
had "Moderate to Marked" improvement, only 60.0% of the patients
receiving placebo had a similar degree of improvement. "Marked"
improvement was found in 22.9% of the treatment group and 2.9%
of the placebo group. These differences were statistically significant
(P less than 0.05). No adverse reactions were reported with the use
of Danzen. Danzen is a safe and effective method for the treatment
of breast engorgement.
Kee, W.H., Tan, S.L., Lee, V., and Salmon, Y.M. Singapore Med J. 1989; 30:48–54.
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Abstract
OBJECTIVES:
This study was planned to assess the response of serratiopeptidase in patients with carpal tunnel
syndrome (CTS).
METHODS:
Twenty patients with CTS were evaluated clinically. After baseline electrophysiological studies, these
patients were given serratiopeptidase 10 mg twice daily with initial short course of nimesulide.
Clinical and electrophysiological reassessment was done after 6 weeks.
RESULTS:
Mean age was 43.9 years with male to female ratio of 1:2.33. Sixty five percent cases showed
significant clinical improvement which was supported by significant improvement in
electrophysiological parameters. Recurrence was reported in four cases. No significant side effect was
observed.
CONCLUSIONS:
Serratiopeptidase therapy may proved to be a useful alternative mode of conservative treatment.
Larger study may be further helpful to establish the role of serratiopeptidase in CTS.
Panagariya, A. and Sharma, A.K. A preliminary trial of serratiopeptidase in patients with carpal tunnel syndrome. J Assoc Physicians India. 1999; 47: 1170–1172
The aim of this study was to compare the efficacy and safety of an oral enzyme-rutosid
combination (ERC) containing rutosid and the enzymes bromelain and trypsin, with that
of diclofenac in patients with osteoarthritis (OA) of the knee. A total of 103 patients
presenting with painful episodes of OA of the knee were treated for 6 weeks in two study
centers in a randomized, double-blind, parallel group trial. Altogether, 52 patients were
treated in the ERC group and 51 patients were treated in the diclofenac group. Primary
efficacy criteria were Lequesne's Algofunctional Index (LFI) and a 'complaint index',
including pain at rest, pain on motion and restricted function. The efficacy criteria were
analyzed by applying the Wilcoxon-Mann-Whitney test that provides the Mann-Whitney
estimator (MW) as a measure of relevance. Non-inferiority was considered to be proven if
the lower bound of the 97.5% one-sided confidence interval (CI-LB) was higher than MW
= 0.36 (benchmark of not yet relevant inferiority). Both treatments resulted in clear
improvements. Within the 6-week observation period, the mean value of the LFI
decreased from 13.0 to 9.4 in the ERC group and from 12.5 to 9.4 in the diclofenac
group. Non-inferiority of ERC was demonstrated by both primary criteria, LFI (MW =
0.5305; CI-LB = 0.4171) and complaint index (MW = 0.5434; CI-LB = 0.4296).
Considerable improvements were also seen in secondary efficacy criteria, with a slight
tendency towards superiority of ERC. The global judgment of efficacy by physician
resulted in at least good ratings for 51.4% of the ERC patients, and for 37.2% of the
diclofenac patients. In the majority of patients tolerability was judged in both drug groups
as very good or good. The current study indicates that ERC can be considered as an
effective and safe alternative to NSAIDs such as diclofenac in the treatment of painful
episodes of OA of the knee. Placebo-controlled studies are now needed to confirm these
results.
Akhtar NM, Naseer R, Farooqi AZ, et al. Clin Rheumatol. 2004;23:410-415.
The objective of this study was to establish the non-inferiority of an oral
enzyme therapy (Phlogenzym® -(PE)) as compared to the non-steroidal
anti-inflammatory drug (NSAID) diclofenac (DC) in patients with
osteoarthritis (OA) of the hip.
Reference: Klein G, Kullich W, Schnitker J, et al. Clin Exp Rheumatol.
2006;24:25-30.. 19
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Proteolytic properties
Reference: Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application: an update. J
Ethnopharmacol. 1988;22(2):191-203.
Effect on blood coagulation and prostaglandin levels Reference: Maurer HR. Bromelain: biochemistry, pharmacology and medical
use. Cell Mol Life Sci. 2001;58(9):1234-1245.
In vitro treatment of human peripheral blood mononuclear cells with
bromelain, papain, and amylase resulted in the production of large amounts
of TNF-a, IL-1b, and IL-6. Interferon-a and interferon-g, which had no effect
alone, synergistically increased TNF-a production when applied together
with the enzymes. (reword from Mayo) Reference: Desser L, Rehberger A, Paukovits W. Proteolytic enzymes and
amylase induce cytokine production in human peripheral blood mononuclear
cells in vitro. Cancer Biother. 1994;9(3): 253-263.
20 Healthy Men 18-29 y.o Protease supplements quickened the recovery of contractile capabilities Attenuated increases in pain after downhill running
Reference: Miller PC, Bailey SP, Barnes ME, Derr SJ, Hall EE. The effects
of protease supplementation on skeletal muscle function and DOMS
following downhill running. J Sports Sci. 2004;22(4): 365-372. Reduction in pain and swelling and hastening of healing from injuries Reference: Deitrick RE. Oral proteolytic enzymes in the treatment of
athletic injuries: a double-blind study. Pa Med. 1965;68(10):35-37.
50 participants with soft-tissue ankle injuries
No significant difference in swelling, bruising and function in groups
given oral proteolytic enzymes vs. enteric coated lactose tablets. Reference: Craig RP. The quantitative evaluation of the use of oral
proteolytic enzymes in the treatment of sprained ankles. Injury. 1975;
6(4):313-316. 20
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During the surgical extraction of 102 impacted lower wisdom
teeth the following factors were studied: the amount of trauma
applied during tooth removal; the duration of the operation;
post-operative swelling; post-operative trismus; sex differences;
the relationship between swelling and trismus; the pattern of
development and subsidence of swelling and trismus. This
study was combined with a clinical 'double-blind' trial of the
drug Chymoral.
Cameron IW. Br J Oral Surg. 1980;19:112-124.
Oral enzymes are known as therapy of herpes zoster for more than 30 years.
Nevertheless, today's standard treatment of herpes zoster in immunocompetent
patients is oral acyclovir. Other therapies are no longer customary because of their
insufficient efficacy and frequent side effects. The positive results obtained in earlier
studies with an orally administered enzyme combination preparation has led to the
assumption that this might definitely represent an alternative therapy. The purpose
of this study was to determine whether the enzyme combination differs from
acyclovir with regard to efficacy and tolerance in the treatment of acute herpes
zoster. In this double-blind, controlled, multicenter trial, immunocompetent patients
with herpes zoster were randomly assigned to receive one of the two test drugs for 7
days. The parameters of pain and skin lesions were measured over 14-21 days.
Forty-four patients were enrolled in the enzyme therapy (ET) group and 46 in the
acyclovir thérapie (AT) group. Following entry into the study, patients demonstrated
no significant differences with respect to anamnestic or clinical data. Significant
differences regarding the statistically evaluated parameters of efficacy were not seen
either. Paracetamol use and total pain over 14 days also failed to reveal any notable
differences between the two groups. Side effects were observed in four patients of
the ET group and in three of the AT group. Results suggest that the therapy of
herpes zoster with an orally applied enzyme combination preparation is a valid and
even cheaper alternative to therapy with acyclovir.
Kleine MW, Stauder GM, Beese EW. The intestinal absorption of orally administered hydrolytic enzymes and their effects in the
treatment of acute herpes zoster as compared with those of oral acyclovir therapy. Phytomedicine. 1995;2(1):7-15.
Combinations may work better than single enzymes
Combinations of hydrolytic enzymes have been used for the
treatment of a variety of diseases for many years, including the
treatment of inflammation, traumatological events, surgical
interventions, autoimmune and immune complex diseases,
rheumatological diseases, viral infections, and malignant
tumors
Stauder G. "Pharmacological effects of oral enzyme combinations." Cas Lek Cesk. 1995 Oct 4;134(19):620-4.
http://www.ncbi.nlm.nih.gov/pubmed/7585874
Lotz-Winter H. On the pharmacology of bromelain: an update with special regard to animal studies on dose-dependent effects.
Planta Med. 1990;56(3):249-253.
Ito C, Yamaguchi K, Shibutani Y, et al. Anti-inflammatory actions of proteases, bromelain, trypsin and their mixed preparation
Nihon Yakurigaku Zasshi. 1979;75(3):227-237.
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Flavonoids belong to a group of natural substances occurring normally
in the diet that exhibit a variety of beneficial effects on health. The antiinflammatory properties of flavonoids have been studied recently, in
order to establish and characterize their potential utility as therapeutic
agents in the treatment of inflammatory diseases. Several mechanisms
of action have been proposed to explain in vivo flavonoid antiinflammatory actions, such as antioxidant activity, inhibition of
eicosanoid generating enzymes or the modulation of the production of
proinflammatory molecules. Recent studies have also shown that some
flavonoids are modulators of proinflammatory gene expression, thus
leading to the attenuation of the inflammatory response. However,
much work remains to be done in order to achieve definitive conclusions
about their potential usefulness. This review summarizes the known
mechanisms involved in the anti-inflammatory activity of flavonoids and
the implications of these effects on the protection against cancer and
cardiovascular disease.
The aim of this review, a summary of the putative biological actions of
flavonoids, was to obtain a further understanding of the reported
beneficial health effects of these substances. Flavonoids occur naturally
in fruit, vegetables, and beverages such as tea and wine. Research in the
field of flavonoids has increased since the discovery of the French
paradox, i.e., the low cardiovascular mortality rate observed in
Mediterranean populations in association with red wine consumption
and a high saturated fat intake. Several other potential beneficial
properties of flavonoids have since been ascertained. We review the
different groups of known flavonoids, the probable mechanisms by
which they act, and the potential clinical applications of these
fascinating natural substances. Reference: Robert J Nijveldt, Els van Nood, Danny EC van Hoorn, Petra
G Boelens, Klaske van Norren, and Paul AM van Leeuwen
Chronic inflammation is being shown to be increasingly involved in the onset
and development of several pathological disturbances such as
arteriosclerosis, obesity, diabetes, neurodegenerative diseases and even
cancer. Treatment for chronic inflammatory disorders has not been solved,
and there is an urgent need to find new and safe anti-inflammatory
compounds. Flavonoids belong to a group of natural substances occurring
normally in the diet that exhibit a variety of beneficial effects on health. The
anti-inflammatory properties of flavonoids have been studied recently, in
order to establish and characterize their potential utility as therapeutic
agents in the treatment of inflammatory diseases. Several mechanisms of
action have been proposed to explain in vivo flavonoid anti-inflammatory
actions, such as antioxidant activity, inhibition of eicosanoid generating
enzymes or the modulation of the production of pro-inflammatory
molecules. Recent studies have also shown that some flavonoids are
modulators of pro-inflammatory gene expression, thus leading to the
attenuation of the inflammatory response. However, much work remains to
be done in order to achieve definitive conclusions about their potential
usefulness. This review summarizes the known mechanisms involved in the
anti-inflammatory activity of flavonoids and the implications of these effects
on the protection against cancer and cardiovascular disease.
Reference: García-Lafuente A, Guillamón E, Villares A, Rostagna MA,
Martínez JA. Inflamm Res. 2009;58:537-552.
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The present study evaluated the anti-hyperglycemic and lipidlowering properties of Emblica officinalis Gaertn. fruit in normal and
diabetic human volunteers. The results indicated a significant
decrease (P < 0.05) in fasting and 2-h post-prandial blood glucose
levels on the 21st day in both normal and diabetic subjects receiving
1, 2 or 3 g E. officinalis powder per day as compared with their
baseline values. Significant (P < 0.05) decreases were also observed
in total cholesterol and triglycerides in both normal and diabetic
volunteers on day 21 that were given either 2 or 3 g E. officinalis
powder per day. However, diabetic volunteers receiving only 3 g E.
officinalis powder exhibited a significant (P < 0.05) decrease in total
lipids on day 21. Both normal and diabetic volunteers receiving 2 or
3 g E. officinalis powder significantly (P < 0.05) improved highdensity lipoprotein-cholesterol and lowered low-density lipoproteincholesterol levels.
Reference: Akhtar MS1, Ramzan A, Ali A, Ahmad M. (2011). Int J Food Sci Nutr. 2011 Sep;
62(6):609-16. doi: 10.3109/09637486.2011.560565. Epub 2011 Apr 18.
Emblica officinalis Gaertn. or Phyllanthus emblica Linn, commonly known as Indian
gooseberry or Amla, is perhaps the most important medicinal plant in the Indian
traditional system of medicine, the Ayurveda. Several parts of the plant are used to
treat a variety of diseases, but the most important is the fruit. Many ailments are
treated by the fruit which is used either alone or in combination with other plants.
These include common cold and fever; as a diuretic, laxative, liver tonic, refrigerant,
stomachic, restorative, alterative, antipyretic, anti-inflammatory, hair tonic; to prevent
peptic ulcer and dyspepsia, and as a digestive. E. officinalis possesses antipyretic,
analgesic, antitussive, antiatherogenic, adaptogenic, cardioprotective,
gastroprotective, antianemic, antihypercholesterolemic, wound healing, antidiarrheal,
antiatherosclerotic, hepatoprotective, nephroprotective, and neuroprotective
properties as demonstrated in numerous preclinical studies. Furthermore,
experimental studies have reported that E. officinalis and some of its phytochemicals
also exhibit anticarcinogenic properties. E. officinalis is also reported to possess
radiomodulatory, chemomodulatory, chemopreventive, free radical scavenging,
antioxidant, anti-inflammatory, antimutagenic and immunomodulatory activities.
These properties are efficacious in the treatment and prevention of cancer. This review
summarizes the results related to these properties and also emphasizes the aspects
that warrant future research establishing its activity and utility as a cancer preventive
and therapeutic drug in humans.
Reference: Prasan R Bhandari, Mohammad Ameeruddin Kamdod. Department of Pharmacology,
SDM College of Medical Sciences and Hospital, Sattur, Dharwad, Karnataka, India
Medicinal plants are nature's gift to human beings to promote a disease free
healthy life. Many medicinal plants are present in a group of herbal
preparations of the Indian traditional health care system (Ayurveda) named
Rasayana proposed for their interesting antioxidant activities.
Phyllanthusemblica Linn. (syn. Emblica officinalis), commonly known as
Indian gooseberry or amla, family Euphorbiaceae, is an important herbal
drug used in unani (Graceo - arab) and ayurvedic systems of medicine. The
plant is used both as a medicine and as a tonic to build up lost vitality and
vigor.Phyllanthus emblica is highly nutritious and could be an important
dietary source of vitamin C, amino acids, and minerals. The plant also
contains phenolic compounds, tannins, phyllembelic acid, phyllembelin,
rutin, curcum-inoids, and emblicol. All parts of the plant are used for
medicinal purposes, especially the fruit, which has been used in Ayurveda as
a potent rasayana and in traditional medicine for the treatment of diarrhea,
jaundice, and inflammation. Various plant parts show antidiabetic,
hypolipidemic, antibacterial, antioxidant, antiulcerogenic, hepatoprotective,
gastroprotective, and chemopreventive properties. Here we discuss its
historical, etymological, morphological and pharmacological aspects.
Reference: Krishnaveni M, Mirunalini S. J Basic Clin Physiol Pharmacol.
2010;21:93-105.
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Rutin, also known as violaguercitrin, is a bioflavonoid and has a wide range
of biological activity. However, the effect of this compound on arteries is not
elucidated. Therefore, the objective of this study was to investigate the
mechanism underling the induction of vasodilation in pulmonary artery (PA)
by the natural product, rutin. Firstly, the isometric tension of the artery rings
was studied in vitro with force-electricity transducers. In PA endotheliumintact (EI) rings, rutin elicited concentration-dependent relaxation after the
PA rings were pre-contracted by phenylephrine (PE), but induced mesenteric
artery (MA) vasoconstriction. Inhibited the endothelial nitric oxide synthase
(eNOS) by NG-Nitro-L-arginine Methyl Ester (L-NAME) or removed the PA
endothelium would decrease the relaxation effect of rutin. The NO
production was increased in rutin-treated bovine pulmonary artery
endothelial cells (BPAECs) detected by fluorescent probe 4-amino-5methylamino-2',7'-difluorofluorescein diacetate (DAF-FM), which verify the
functional study results. Moreover, western blot analysis revealed that rutin
increased the phosphorylation of eNOS at Ser 1177, but decreased the
phosphorylation of eNOS at Thr 495, and did not affect the overall
expression of eNOS. These results suggested that rutin-induced relaxation
of PAs share NO-eNOS activation pathways, including phosphorylation of
Ser 1177, and dephosphorylation at Thr 495. Rutin also has specific action
because it exerts a vasodilator influence on the PAs but not MAs.
Reference: Li Q, Niu S, Wang R, Li Y, Zhang R, Zhu D. Int Angiol. 2012;31:557-564.
Abstract
Systemic enzyme therapy was recently subjected to experimental investigations and
to rigorous clinical studies in cancer patients. The designs of the relevant clinical
cohort studies followed the guidelines of Good Epidemiological Practice and
represent level IIB in evidence-based medicine (EBM). Scientifically sound
experimental in vitro and in vivo investigations are far advanced and document
promising immunological, anti-inflammatory, anti-infectious, and antitumor/
antimetastatic activities of proteolytic enzyme mixtures (containing trypsin,
chymotrypsin, and papain) or bromelain. EBM level II clinical studies, which are
accepted by the European Union to show safety and efficacy of medical treatments,
were performed to evaluate the benefit of complementary systemic enzyme therapy
in cancer patients suffering from breast and colorectal cancers and plasmacytoma.
These studies demonstrated that systemic enzyme therapy significantly decreased
tumor-induced and therapy-induced side effects and complaints such as nausea,
gastrointestinal complaints, fatigue, weight loss, and restlessness and obviously
stabilized the quality of life. For plasmacytoma patients, complementary systemic
enzyme therapy was shown to increase the response rates, the duration of
remissions, and the overall survival times. These promising data resulted in an
"orphan drug status" designation for a systemic enzyme product, which should
motivate further studies on this complementary treatment.
Beuth J1. Integr Cancer Ther. 2008 Dec;7(4):311-6. doi: 10.1177/1534735408327251.
ASK FOR A CERTIFICATE OF ANALYSIS
FCC – Food Chemical Codex - national standard for evaluation of enzymes accepted standard of the
FDA
Look at Activity – ex. HUT for protease (not just measured in mg weight) activity level and potency
200,000 HUT means the enzymes work 200,000 times – vs mg of mineral or vitamin
Should include 3 basics:
a. Amylase to digest starch (carbs)
b. More than 1 protease for more complete breakdown of proteins and utilization of different
biological pathways
200,000 HUT of protease optimal
Vegetarian source for tolerance of stomach acid
Non- enzyme ingredients included that increase efficacy and provide complementary benefits
c. Lipase to break down fats
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Case History:
Chief Complaint: Joint Pain and fatigue
HPI: 63 Year Old Female with joint pain for past 5 years. No resolve with
NSAIDs.
Also noted: HTN, OA, Orthostatic Hypotension
11/2010 hs CRP 4.5 Pain level 8 Mobility – decreased by 70%
3/2010 hs CRP 1.23 Pain level 2 Mobility – decreased by 10%
6/2015 hs CRP 0.6 Pain level 0 Mobility – no restriction
Blood pressure stabilized to WNL in 4 mos. of implementation
Case History:
Chief Complaint: Swelling of hands and pain in joints - mostly upper
extremities
HPI: 68 Year Old Male . CMO of major local hospital complaining of joint pain
not resolved with multiple medication trials.
Also noted: Hyperlipidemia, OA, Metabolic Syndrome
1/2014 hsCRP 6.5 Pain level 6 Mobility- decreased by 40%
3/2014 hsCRP 0.3 Pain level 1-2 Mobility – no restrictions
LDL decreased by 60%
Weight loss of 35 pounds in 8 mos. Of implementation
Low risk
Quality is important
Various contaminants including lead and arsenic are found in
some OTC poor quality supplements.
Interactions not well understood but not reported to cause
significant concern.
Children with cystic fibrosis – rare but severe fibrosing
colonopathy.
FitzSimmons SC, Burkhart GA, Borowitz D, et al. High-dose pancreatic-enzyme supplements and fibrosing colonopathy in
children with cystic fibrosis. N Engl J Med. 1997;336(18): 1283-1289.
Oral bromelain – may cause gastrointestinal tract disturbances or diarrhea
Papain – excessive dosages can cause esophageal perforation
Gastritis – start lower doses of proteases for 3-6 weeks then to
recommended dosage
Raw papain or papaya latex can be an irritant and vesicant
Immunoglobulin E – mediated allergic reactions to bromelain may occur
and can include a cross-allergencity between wheat flour and bromelain
Topical – trypsin may cause localized pain and transient burning
Therapeutic Research Faculty. Natural Medicines Comprehensive Database. http://www.naturaldatabase.com. Updated
January 22, 2014. Accessed January 22, 2014.
Oral chymotrypsin – rare anaphylaxis
Pregnant and lactating women advise to consult doctors before ingestion
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How do Systemic Enzymes and Digestive Enzymes Differ?
USE OF ENZYME SUPPLEMEMENTS IS INCREASING IN THE
U.S.
Emerging clinical data seem to support many of the purported
benefits
However, as with many dietary supplements, some of the
existing research is generally challenged by methodological
weaknesses, small sample sizes, heterogeneity of product, and
lack of uniform outcome measures
Well-designed studies are needed to further characterize the
role of enzyme supplements.
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