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Enzyme Market Review
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Enzyme Market Review
November 2012
D
ietary supplement market analysts continue to forecast the
growth of the digestive supplement category. The latest statistics
from the National Institutes of Health state that as many as
70 million people suffer from digestive disorders. Approximately
20% of Americans suffer with symptoms of gastroesophageal
reflux disease (GERD) at least once a week. Incidence rates for
GERD have risen throughout the world including Belgium (28%),
Germany (14%), Mexico (35%), Malaysia (38%), Norway (31%)
and Turkey (20-23%).1 Likewise, the incidence of functional
dyspepsia (non-ulcer indigestion) affects a large portion of the
world’s population: Argentina (43%), Germany (20%), Malaysia
(30%), Sweden (25%), Turkey (28%) and the United States
(up to 12%). Another common digestive complaint is functional
constipation, with high incidence rates throughout the world:
Australia (30%), Canada (16%), Colombia (27%), Mexico (19%),
Netherlands (22%), Turkey (24%) and the United States
(18-27%). Digestive issues affect the lives of millions
of people globally.1
Once considered a normal consequence of aging, digestive
discomfort is now viewed as amendable by consumers. Probiotic
products have led the way in educating consumers that this
discomfort can be altered. Part of the benefit of these microorganisms is their ability to produce enzymes that may augment
the digestive system. Digestive enzyme supplements and probiotic supplements are complementary products that may and often
do work together to support optimal digestive health. In recent
years, there has been growing international interest in combining
the benefits of probiotics and digestive enzymes. Supplemental
enzymes have a long history of use for digestive support.
In addition to digestive supplements, different enzymes have
applications in a variety of nutritional products. One exciting
innovation is in the production of oligosaccharides from ingested
starch. Transglucosidase and levansucrase build non-digestible
fibers when consumed with a meal. This enzymatic action has
many nutritional benefits, including decreasing the caloric
availability and glycemic index from dietary carbohydrates as
well as acting as a prebiotic fiber to support the growth of
probiotics. Other enzymes act as antioxidants or offer systemic
benefits. Enzyme supplementation is a robust market with
excellent opportunities for expansion.
Enzyme Supplement History
While the recognized use of enzymes as feed additives,
dietary supplements and therapeutic agents is relatively new,
consumption of enzymes predates written history. Through trial
and error, our ancestors discovered the digestive benefits of
enzymes. Meats were hung and allowed to age to produce a
tender, more flavorful and nutritious steak. Other foods were
allowed or even specifically treated to induce the digestive
benefits of fermentation. Enzymes, either inherent in the food
or introduced by microbes, essentially predigested the foods and
contributed to the health of individuals long before anyone knew
what an enzyme was or did.
The enzyme industry as it exists today began in the late
19th century. By 1894, Dr. Jokichi Takamine had been granted
U.S. Patent No. 525,823, “Process of making diastatic enzyme,”
which detailed the process and extraction of amylases from
koji. His patented product, Taka-diastase, was marketed by
Parke, Davis & Company as a digestive aid beginning at the turn
of the century and is still marketed throughout the world.
By the 1920s, doctors were observing significant changes in
patients’ health and some theorized that the growth of the canning
industry and pasteurization was the cause. Dr. Edward Howell
recognized these processes altered the intake of digestive
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food enzymes. By 1932, Dr. Howell had formed National Enzyme
Company to provide supplemental enzymes to replace those
destroyed in cooking, canning and food processing.
Research soon began on the benefits of adding enzymes to
animal feeds to increase growth and health. At the same time,
the food processing industry had begun selectively applying
enzymes to produce improved food products. These applications
produced a large body of research that included the investigation
of the safety and toxicity of various enzyme ferments. Today,
the use of enzymes in foods, animal feeds and dietary
supplements is common.
The Role of Enzymes
Enzymes are proteins that function as catalysts to initiate and
regulate the biochemical processes that are necessary for life. The
human body produces thousands of different enzymes to build,
repair and maintain itself. In your body, as you read this report
there are thousands of enzymes directing the processes of each
of the billions of cells that make up your body. They are even directly
involved in allowing you to see, read and understand the words
on this page.
Enzymes are such a critical part of a healthy functioning
body that many genetic disorders are the result of inefficient,
deficient or absence of one or more enzymes. Other dysfunctions
may occur when enzyme systems become imbalanced. The
benefits of many vitamins and minerals are due to their ability
to affect the activity of various enzymes. These nutrients often
act as cofactors and coenzymes that activate or increase the
functionality of enzymes. Enzymes are vital for our daily
health and wellness.
Enzymes exhibit substrate specificity, meaning they will
only catalyze a reaction with a specific compound or group
of compounds. For example, proteases will only catalyze the
breakdown of proteins and will not react with carbohydrates or
fats. The ability of an enzyme to interact with its substrate
is attributed to the conformational structure of the enzyme’s
active site. Simply stated, the active site of a protease will “fit”
with the shape of proteins where it does not “fit” with a
carbohydrate or fat.
“Enzyme activity expression can be profoundly impacted by
factors such as pH and temperature,” explains James McNeal,
Laboratory Manager, SORA Labs. These factors may denature
or alter the structure of the enzyme protein and reduce their
activity. Some enzymes exhibit broad ranges of efficacious pH
or temperature while others are very specific. McNeal elaborated
that “many fungally-derived enzymes display an impressive
active range of pH and temperature, which makes them suitable
for a variety of applications, both in vivo and in industrial/
production settings.”
Every function of living cells requires enzymes. Their
roles in human physiology include: 1) building required
materials, 2) carrying compounds through cell membranes,
3) detoxifying harmful chemicals, 4) neutralizing free radicals and
5) breaking down the foods we eat for use throughout the body.
Enzyme Supplements
Enzyme supplements fall into two broad categories: digestive
and systemic. Digestive enzymes are taken with meals and are
designed to support digestion. Systemic enzymes are taken on an
empty stomach and are intended for action beyond the gastrointestinal (GI) tract. See table 1 for a list of enzymes commonly seen
in supplements. The vast majority of these enzymes have been
used in both supplements and foods prior to the passage of the
Dietary Supplement Health & Education Act (DSHEA) in 1994.
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TABLE 1. Common Enzymes found in U.S. Dietary Supplements
ENZYME
DIGESTIVE
SYSTEMIC
COMMON SOURCE ORGANISMS
COMMON ACTIVITY UNITS
CARBOHYDRASES
alpha-Amylase
X
Aspergillus oryzae, A. niger, Bacillus subtilis, B. amyloliquefaciens
DU, SKB
Glucoamylase
(aka amyloglucosidase)
X
Aspergillus niger, A. oryzae, Rhizopus oryzae
Diastase
X
Aspergillus oryzae
DP, MaltU
Invertase
X
Saccharomyces cerevisiae
INVU, SU
Lactase
X
Aspergillus oryzae
ALU, LacU
alpha-Galactosidase
X
Aspergillus niger
GalU
Cellulase
X
Aspergillus niger, Trichoderma longibrachiatum
CU
Hemicellulase
X
Aspergillus niger, Trichoderma longibrachiatum
HCU
AGU
Pectinases
X
Aspergillus niger
beta-Glucanase
X
Trichoderma longibrachiatum
endoPG, AJDU
BGU
Xylanase
X
Trichoderma longibrachiatum
XU
PROTEASES
Bromelain
X
X
Ananas comosus
PU, GDU, MCU
Papain
X
X
Carica papaya
PU, GDU, MCU
Protease
X
X
Aspergillus oryza, A. niger, A. melleu, Bacillus subtilis, B. licheniformis
HUT, SAP, AP, PC
Peptidase
X
X
Aspergillus niger
HUT, SAP, AP
Chymotrypsin
X
X
bovine pancreas
USP
Trypsin
X
X
porcine pancreas
USP
Pepsin
X
X
porcine stomach
USP
LIPASES
Lipase
X
Aspergillus niger, Candida rugosa, Rhizopus oryzae
LU, FIP
Pancreatin
X
porcine pancreas
USP
Pancrealipase
X
porcine pancreas
USP
CatU, Baker U
OTHER ENZYMES
X
Aspergillus niger
Lactoferrin
X
bovine liver
Lactoperoxidase
X
bovine milk
Lysozyme
X
hen egg
X
bovine liver, Cucumis melo
Catalase
Super Oxide Dismutase (SOD)
X
X
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McCord-Fridovitch (MFU)
4
10-15%
HCI—secreted in stomach; activates pepsin,
denatures proteins
PEPSIN—secreted in stomach, activated by
gastric acid
polypeptides
SMALL INTESTINE
STOMACH
of protein digestion begins in the stomach
AMINOPEPTIDASES—secreted by
pancreas into the small intestine;
include trypsin, chymotrypsin, elastase
& carboxypeptidase
oligopeptides & free amino acids
AMINOPEPTIDASES—secreted by the
intestinal brush border membrane
tri-, dipeptides & free amino acids
Figure 2. Healthy Fat Digestion
LINGUAL LIPASE—secreted in the mouth;
begins fat digestion in the mouth & continues
action in the stomach
GASTRIC LIPASE—secreted in the stomach
20%
SMALL INTESTINE
STOMACH
MOUTH
amount digested by
lingual & gastric lipases
before entering duodenum
BILE SALTS—produced by the gall bladder;
effectively emulsifying dietary fats for
improved enzymatic access
PANCREATIC LIPASES—includes lipases
and esterases; complete the process
of fat digestion
monoacylglyceride & 2 free
fatty acids
Figure 3. Healthy Carbohydrate Digestion
SALIVARY AMYLASE—secreted in the mouth;
begins starch digestion & continues action in
the stomach until inactivated by gastric acidity
30-40%
amount starch digestion completed
by salivary amylase
SMALL INTESTINE
This product category includes the bulk of the enzyme
supplements on the U.S. market today. Like many probiotics,
they support improved nutrient availability and may help
prevent occasional gastric distress.
Anthony Collier, president and CEO, National Enzyme
Company, explains, “Raw foods are rich in enzymes and can
play a pivotal role in human digestion. By contrast, the typical
American diet consists of highly processed enzyme-deficient
cooked foods, rich in artificial ingredients and other chemicals.”
Digestive supplements replace food enzymes lost in cooking
and processing. These supplements may also compensate for
digestive enzyme deficiencies or counter food intolerances.
Our ability to digest the foods we eat may be negatively
influenced by many factors including diet, stress, illness,
medication and age.
According to Dr. Edward Howell, the upper portion of the
human stomach functions as a food-enzyme stomach. “When
raw food with its enzymes is eaten, it goes into this peristalsisfree food-enzyme section of our stomach where these food
enzymes digest the food.” Dr. Howell explained “digestion
continues in the food-enzyme section of the stomach for
one-half to one hour” or until the rising acidity inactivates the
food enzymes.2 It is in this same section of the stomach that
many supplemental digestive enzymes are most effective.
“Dr. Howell did extensive research to validate his theories,”
says Collier. “He was 100-percent a German scientist and this
motivated him to access all related research, a monumental
task in the days before the internet. One fact that Howell
discovered was the enlarged size of the human pancreas in
populations consuming enzyme-deficient processed foods.
This was key evidence supporting his Food Enzyme Concept.”
Figure 1. Healthy Protein Digestion
MOUTH
Digestive Enzyme Supplements
PANCREATIC AMYLASE—secreted by the
pancreas; continues starch digestion
maltose, trisaccharides,
oligosaccharides & -limit dextrins
DISACCHARIDASES—produced by the brush
border membrane; include lactase, sucrase &
glucoamylase; complete digestion of complex
carbohydrates & sugars
simple sugars: fructose, glucose
& galactose
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To further explore Dr. Howell’s theory, National Enzyme
Company conducted a pilot study to explore whether taking
digestive enzyme supplements with a “modern cooked meal”
could mitigate or decrease various markers of inflammation,
including a reduction in leukocytosis.
Numerous markers of inflammation were explored in the
randomized, double blind, placebo-controlled pilot clinical study
with 10 healthy volunteers. Blood was drawn immediately prior
to and 45 minutes after eating the meal. On average, all
measurable markers of inflammation were reduced as a
result of taking digestive enzymes during the meal.
NEC’s Chief Medical Consultant, Paul Nemiroff, M.D., Ph.D.,
FACS, states, “The potential health implications of this are
tremendous. Less inflammatory response in the body may be a
key factor in mitigating certain ailments. A large full scale study
is currently underway that NEC is sponsoring and utilizing a
contract research organization that will use the highest standards
of clinical research and what is considered the ‘The Gold Standard’
of research often employed by pharmaceutical companies. This
study examines the effects of digestive enzymes on various
parameters of inflammation.”
Digestion & Indigestion
The human body produces at least 22 different enzymes to
break down proteins, fats and carbohydrates to provide energy
and building blocks.
Protein comprises as much as 20-percent of the average
American diet. Digestion of protein begins in the stomach when
pepsin is activated in the low pH environment created by the
secretion of HCL by cells of the gastric mucosa. In addition to
activating pepsin, the acid also helps denature the proteins
allowing improved enzyme accessibility to peptide bonds.
Studies indicate that 10 to 15 percent of dietary protein digestion
is initiated in the stomach. In the small intestine, the pancreatic
proteases (trypsin, chymotrypsin, elastase, and carboxypeptidase)
continue the digestion of proteins, creating oligopeptides and
free amino acids. Aminopeptidases produced by the intestinal
brush-border membrane further hydrolyze the oligopeptides to
produce tripeptides, dipeptides and free amino acids.3
Supplementation of proteases ensures complete digestion
of proteins. Incomplete protein digestion is linked to the
occurrence of food allergies. A rising concern in the Western
world, food allergies currently affect as much as 4 percent
of the population. Research by Untersmayr et al, reports the
negative impact decreased gastric HCL and the resultant lack
of pepsin activity on protein digestion and an increased risk
of sensitization to food allergens.4 A supplemental source of
proteases that is able to work in the altered pH environment
may counter the lack of pepsin activity, enhancing protein
digestion and limiting allergic responses. Fungal proteases
offer an excellent pH profile for activity under these conditions.
Gluten intolerance is also a growing concern throughout
the world. Gluten is a generic term referring to a group of
complex gluconated peptides commonly found in wheat,
barley and rye. Rich in proline, glutens are highly resistant to
digestion by the proteases of the human digestive tract. In
sufficient concentration they may elicit an immune response
in sensitive individuals that often includes extreme gastric
discomfort. While abstaining from foods containing gluten
is the only way to eliminate these problems, researchers are
actively pursuing a solution utilizing supplemental proteases
to digest the offending peptides.5 Bromelain, papain and the
fungal enzyme dipeptidyl peptidase IV (DPPiv) have all been
shown to hydrolyze these peptides. These proteases may
provide digestive benefits for unavoidable low levels
of gluten consumption.6
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Fats are an important part of a healthy diet and currently make
up 30 to 40 percent of the typical Western diet. Digestion of fats
begins with the production of lingual lipase in the mouth and
continues in the stomach with the secretion of gastric lipase,
together digesting as much as 20 percent of dietary fats. In the
intestine, the fats are emulsified with bile allowing pancreatic
lipases improved access for hydrolysis. The digestive end product of
each triglyceride is two free fatty acids and a monoacylglyceride.3
While often vilified as a primary cause of obesity, the
consumption of adequate levels of fat is a critical part of
human metabolism. The proper digestion of dietary fats
delivers essential fatty acids (EFAs) and structural building
blocks for cell membranes, myelin sheaths and other tissues
as well as providing an energy source. Healthy fat digestion
is also vital for the absorption of fat soluble vitamins and
other nutrients. Insufficient production of lipase by the body
can lead to rapid loose stools and the loss of key nutrients.
Supplemental lipase can increase fat digestion and improve
nutrient assimilation.
Danielle Harrison, Scientific and Regulatory Affairs
Manager, at National Enzyme Company, reports in vitro
studies have shown blends of fungal lipases effectively
increase the availability of EFAs from dietary oils. She said,
“We conducted the analysis on many different oils and the
blend consistently increased the level of essential fatty acids
released from the test oils.”
Dietary carbohydrates including simple sugars, disaccharides and
complex carbohydrates make up as much as 50 percent of the
American diet. Carbohydrate digestion begins in the mouth with
salivary amylase, which continues until inactivated by stomach acid.
Salivary amylase digests as much as 30 to 40 percent of complex
carbohydrates such as starch. Once the food passes to the small
intestine, pancreatic amylase takes over the digestion of complex
carbohydrates. It is also in the small intestine that the brush border
membrane disaccharidases are produced. These enzymes include
lactase, sucrase and glucoamylase. The systematic action of these
enzymes produces the simple sugars fructose, glucose and galactose.3
Lactase deficiency is the most widely occurring enzyme
deficiency in the world, affecting nearly 70 percent of the
world’s adult population. Low secretion of the enzyme
causes individuals to suffer gastric discomfort including
bloating, flatulence, diarrhea and abdominal pain. These
symptoms often cause individuals to drastically reduce their
consumption of dairy products. often with the unfortunate
consequence of reduced calcium intake. Research indicates
individuals who avoid dairy foods due to perceived dairy
intolerance have a higher risk for osteoporosis.7 Lactase
supplements have been shown to reduce gastric discomfort
when taken with dairy foods.
The secretion of digestive enzymes decreases with age, contributing to increased gastric discomfort, decreased food consumption
and/or variety. It can also contribute to potential nutritional deficiencies in elderly individuals. One interesting study reported on the
benefit of supplemental lipase in these individuals. The scientists
found when fungal lipase was given with a meal, the rate of gastric
emptying was accelerated. A slow rate of gastric emptying signals
greater satiation and may be a contributing factor in geriatric
malnutrition. The accelerated gastric emptying with supplemental
lipase resulted in decreased satiation, which in turn may prompt
elderly individuals to increase consumption levels.8
Systemic Enzyme Supplements
Many of the enzymes used for systemic applications are the
same enzymes that support digestion when taken with meals.
However, when taken between meals on an empty stomach they
provide systemic support beyond the GI tract.
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“Systemic enzyme products are intended to nutritionally
support the healthy functions of various systems of the body,” says
Richard Mihalik, Director of Innovation and Product Development
for National Enzyme Company. “A few examples include enzyme
products for systemic antioxidant support, products to support
joint health, products to support muscle health and products to
support a healthy glucose metabolism.”
Sources of Enzyme Supplements
Digestive enzyme supplements are designed to support
healthy digestion and optimal nutrient absorption. The enzymes
in these products may be of animal, plant or microbial origin, and
some supplements combine enzymes from different sources. The
majority of digestive enzyme supplements in the U.S. market are
derived from microbial fermentation. These enzymes offer several
advantages including:
1) Broad pH range
a) Effective in the upper stomach earlier
in the digestive process
b) Many exhibit activity in the intestinal environment
as well
2) Availability of diverse range of enzymatic activities
3) No requirement for enteric coating
4) Vegetarian
a) No ethical concerns
b) No meat contamination or BSE issues
Another group of vegetarian enzymes are those derived from
various plants including bromelain (from pineapple) and papain
(from papaya). Both are extracts that include multiple enzymes,
but are standardized for their proteolytic enzymes. While both
have some benefit in support of protein digestion, they are most
commonly used in systemic products to support the immune and
musculoskeletal systems. Superoxide dismutase (SOD) extracted
from melon is a potent systemic antioxidant.
Most animal enzymes are derived from the stomach
and pancreatic tissues of cattle and swine. The mammalian
enzymes used in digestive products include pepsin, pancreatin,
pancrelipase, trypsin and chymotrypsin. Systemic enzymes
derived from animals include the pancreatic proteases trypsin
and chymotrypsin as well as lysozyme from egg white,
lactoperoxidase from cow’s milk and SOD from cow’s liver.
Markets of Opportunity for Enzyme-Based Products
Supplemental enzyme products have traditionally been
marketed to support digestion and improve nutrient availability.
Lactase based products for dairy intolerance as well as broadspectrum digestive aids are foundation products on many retailers’
shelves. The rising awareness of gluten intolerance has prompted
the development of enzyme products targeting this concern. Still
other products are formulated specifically for older adults whose
secretion of digestive enzymes may be reduced due to aging.
Product development research continues to seek enzymes that offer
nutritional benefit to consumers. Various enzyme supplements may
also offer immune support; muscle, joint and soft tissue support;
and metabolic support.
Beyond the general retail channel, today’s nutritional supplement
market offers some unique opportunities for enzyme-based products.
Sports
This product category has seen tremendous growth in the
United States as well as in foreign markets including Brazil and
many European nations. Patrick Kuruk, Strategic Account
Representative, National Enzyme Company, says blends of
proteases, such as NEC’s BioCore® EDGE, increase the bioavailability
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of free amino acids including the BCAA leucine. With 23 years of
experience in sports nutrition and a master’s of science in
exercise physiology, Kuruk knows the importance of proper
nutrition for athletes. He explains that “adding EDGE to a sports
nutrition protein product can indirectly increase protein
synthesis and muscle growth in the recovering athlete.” Blends
of carbohydrases may also offer important energy support for
the training athlete. Both amino acid availability and energy
availability can have a stimulatory effect on muscle
development and recovery.
Systemic proteases may also specifically benefit training
athletes. Studies indicate these types of products may attenuate
the pain and inflammation associated with intensive exercise.
Collier explains that “systemic proteases can significantly reduce
recovery time. One of our patents relates to the ability of such
blends to reduce TNF-alpha.” Proteolytic enzymes are often
combined with antioxidant ingredients such as super oxide
dismutase, quercetin, resveratrol or grape seed extract to
combat increased levels of oxidative damage that occur along
with intensive exercise. Studies support the use of these
products to reduce the occurrence of delayed onset muscle
soreness (DOMS).9
Immune support is also of vital concern to athletes. Studies
have shown the intensive training by high level athletes has a
negative impact on the immune system. Intense exercise induces
significant changes in the body including elevated stress
hormones, pro-inflammatory cytokines and reactive oxygen
species. Other facets of the immune system, i.e. natural killer (NK)
cells activity, T-lymphocyte and upper airway neutrophil function,
are suppressed during recovery from endurance type exercise. This
suppression can last for up to 72 hours during which time athletes
are at increased risk for contracting infection.10 Nutritional support
can play a pivotal role in helping maintain wellness. Certain
systemic enzymes may also support athletes during this critical
time. Mihalik highlights the benefits of lactoferrin and lysozyme
for this application.
Health Care Providers
The Nutrition Business Journal is predicting growth potential
in this market, stating it will be “one of the most vibrant and
fastest-growing sales channels in the nutrition industry for the
next 10 years.” This growth is attributed in part to the expanding
knowledge and use of nutritional supplements. Once largely
limited to pioneering chiropractors and other alternative medicine
providers, in-office supplement sales are becoming more widely
embraced across the medical professions.
Opportunities for enzyme supplements in these markets
abound. Products designed for oral health may be sold through
dental offices while both digestive products and systemic
products may be useful supplements in general practices. Still
other enzyme products may be specifically designed to address
the unique digestive needs of a given population. For instance,
many children diagnosed with autistic spectrum disorder deal
with digestive issues. Several companies have developed
targeted digestive products to address this specialized need.
As noted previously, gluten intolerance is a growing concern in
the United States and this market channel offers a unique
opportunity for products designed to reduce gluten’s negative GI
impact. Certain supplemental proteolytic enzymes have limited
action against these peptides and can be beneficial in reducing
gastric discomfort. Further, research supports the removal the
carbohydrate portion of the compound for improved
detoxification of gluten.11 Mihalik defines a well-formulated
product for gluten sensitivity as including enzymes “that work on
both the carbohydrate portions of the molecules as well as the
variety of protein bonds present in the complex protein structures
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to achieve the most complete degradation possible. Every enzyme
extract available from different suppliers has a little different
activity and side activity profile that a formulator needs to be
aware of to make the best formulation possible.”
There is tremendous opportunity for enzyme-based products in
the supplement market. The growing incidence of digestive
disorders indicates that our modern lifestyle is detrimental to
gastrointestinal health and general wellness. Collier emphasizes
that “taking digestive enzymes with each meal supports maximum
nutrient availability from the foods we eat as well as reducing
inflammation. These supplements are beneficial for all age groups.”
In addition to digestive enzyme supplements there are also
expanding opportunities for systemic enzyme products as well as
other enzyme products. Enzymes offer a unique activity profile
•
that can enhance many different formulations.
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References
1.
Guarner et al. Map of Digestive Disorders & Diseases. April 2008.
http://www.worldgastroenterology.org/assets/downloads/pdf/wdhd/2008/events/
map_of_digestive_disorders_2008.pdf
2. Howell. Enzyme Nutrition: The Food Enzyme Concept. (Avery: 1985) pp 9-10.
3. Goodman. Insights into digestion and absorption of major nutrients in humans. Adv
Physiol Edu. 2010 Jun; 34(2): 44-53.
4. Untersmayr & Jensen-Jerolim. The role of protein digestibility and antacids on food allergy
Outcomes. J Allergy Clin Immunol. 2008 June ; 121(6): 1301–1310.
5. Shan et al. Identification and Analysis of Multivalent Proteolytically Resistant Peptides from
Gluten: Implications for Celiac Sprue. J Proteome Res. 2005 ; 4(5): 1732–1741.
6. Ehren et al. A Food-Grade Enzyme Preparation with Modest Gluten Detoxification
Properties. PLoS One. 2009; 4(7): e6313.
7. Jackson & Savaiano. Lactose Maldigestion, Calcium Intake and Osteoporosis in African-,
Asian-, and Hispanic-Americans. J Am Coll Nutr. 2001; 20(2): 198S-207S.
8. Nakae et al. Effects of aging and gastric lipolysis on gastric emptying of lipid in liquid meal.
J Gastroenterol. 1999 Aug; 34(4): 445-559.
9. Udani et al. BounceBack capsules for reduction of DOMS after eccentric exercise: a
randomized, double-blind, placebo-controlled, crossover pilot study. J Int Soc Sports Nutr.
2009 Jun; 6:14.
10. Gleeson. Immune function in sport and exercise. J Appl Physiol. 2007; 103: 693-699.
11. Phelan et al. Coeliac disease: the abolition of gliadin toxicity by enzymes from Aspergillus
niger. Clin Sci Mol Med. 1977 Ju; 53(1): 35-43.
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