ApplePhenon®

A Unique Nutraceutical with Multiple

Clinically-Validated Health Benefits

Table of Contents
Introduction………………………………………………………………………………………..2

Cardiovascular Health……………………………………………………………………………..5

Anti-Allergic Properties…………………………………………………………………….……..8

Anti-Obesity Effect of ApplePhenon…………………………………………………………….11

The Athlete’s Edge………………………………………………………………………………13

Other Potential Benefits Validated by Human Clinical Research……………………………….16

Summary…………………………………………………………………………………………18

References………………………………………………………………………………………..19

1
 Introduction

What is ApplePhenon?
ApplePhenon is an extract from whole, wild-harvested, unripe apples which is covered by three
US patents. ApplePhenon has an extremely high concentration of beneficial active components.
The primary active components in ApplePhenon are natural polyphenols. While polyphenols are
present in other vegetables, the polyphenols extracted from these unripe apples are unique and
exceptionally health-giving. The primary polyphenols in ApplePhenon are procyanidins. At
60% of the total polyphenol content, these procyanidins are predominantly “oligomeric
procyanidins” or “OPCs” (Figure 1). Scientists have found that OPC’s have less polymerization

Figure 1. Chemical composition of polyphenols in ApplePhenon.

than other procyanidins and are very active with a large variety of physiological activities.
OPC’s have also been found to be more bioavailable, meaning that they can be absorbed and
utilized more easily by the human body. The remaining 40% of polyphenols present in
ApplePhenon are mainly phenolic carboxylic acids and catechins. Together, these constituents
form a health supplement that has several clinical applications. ApplePhenon, when compared
with other nutraceuticals such as Pycnogenol®, grape seed extract, green tea extract and many
others, has consistently demonstrated superior qualities. Compared with grape seed and green tea
extracts, two common commercial sources of polyphenols in the market, the main components of
ApplePhenonTM are oligomeric procyanidins consisting of the molecules mainly from dim-mers
to 15-mers of catechins (Figure 2).

2
 Figure 2. Comparison of procyanidin profile of ApplePhenon and
green tea extract and grape seed extract.

“The Original Apple”

Botanists have determined that the very first apple species originated in Central Asia. This is the
species used in ApplePhenon and it is from this precise location that the apples used in
ApplePhenon are wild-harvested. ApplePhenon delivers a concentrated extract of “The Original
Apple” taken directly from its ancestral birthplace in “The Homeland of the Original Apple.”
While this is very interesting from the scientific standpoint, brands promoting ApplePhenon will
also find this of great value from a marketing perspective.

How is ApplePhenon Processed?

ApplePhenon is produced in a patented manner to ensure that the health-giving polyphenols are
perfectly preserved throughout the process and ultimately, delivered to the consumer. As
evidence of this special technique, it has been proven that ApplePhenon has up to ten times the
polyphenol content of other apple products. These polyphenols have a distinctive composition in
comparison with other polyphenol products and they are highly bioavailable; in all likelihood
these are two of the key factors that make ApplePhenon so valuable from a health perspective.

BGG uses a proprietary “mild extraction” process which is employed to protect these
polyphenols during the extraction process. This is a crucial factor in our patented technology:
ApplePhenon has very high anti-inflammatory and antioxidant properties which would certainly

3
be damaged or destroyed by harsh processing. It is full of polyphenols, procyanidins and
catechins which can also be adversely affected by inferior processing. BGG takes all the
necessary precautionary steps during every part of the process to preserve ApplePhenon’s fragile
nutrients and its anti-inflammatory and antioxidant activity. After our mild extraction process,
the polyphenols undergo an advanced purification process that is also designed to protect
ApplePhenon’s health-giving properties. And of course, during every step of handling and
packaging throughout the entire process, the same high level of care is given to ensure a top
quality ingredient that will make people healthier.

Overview of Existing Research

In total, ApplePhenon has been the subject of over $15 million in medical research studies. It is
a very impressive fact that there are currently over 100 positive studies related to ApplePhenon
covering a wide range of health benefits. Among these, several were conducted as state-of-the-
art, double-blind, placebo-controlled human clinical studies. These human clinical studies along
with their supporting pre-clinical trials have led to a wide range of clinically-validated
applications in humans. Published human clinical research has shown that the apple polyphenols
present in ApplePhenon have:

 Anti-Inflammatory Activity
 Cardiovascular Benefits and the Ability to Improve Blood Lipid Profiles
 Anti-Allergic Properties
 Potential Benefits for Diabetics
 Anti-Obesity Properties
 Joint Health and Mobility Benefits
 Anti-Viral and Anti-Bacterial Activity
 Potential Benefits for Athletes such as Increased Endurance
 In addition, a unique human clinical trial even found that ApplePhenon applied topically
has the potential to enhance hair growth

In support of the human clinical research listed above, extensive exploration in animal models
and in-vitro experiments have been done in each of these areas to further validate the research in
humans. We will examine each of these health applications in this paper.

Outside of the impressive list of health benefits demonstrated in human trials, additional animal
and in-vitro research has opened up new possibilities for the use of ApplePhenon to improve
health and even to extend life. The life extension potential of apple polyphenols is of particular
interest as it has been validated in five separate studies across four different species. Besides
being tested in a model organism used in life extension research, the species of roundworm
called Caenorhabditis elegans, apple polyphenols have also been tested in fruit flies, yeast, and
most notably in rodents. In all four organisms and across all five studies, apple polyphenols
consistently increased the lifespan of each species. Should this translate to similar benefits in
humans (as it very well may due to the variety of species, including rodents, in which apple

4
polyphenols have demonstrated the capacity to increase lifespan), the implications would be
momentous.

The area of research with the single highest number of positive studies on the apple polyphenols
present in ApplePhenon is in cancer prevention. Although human clinical research has yet to
commence in this realm, there are already 22 positive studies which clearly point to
ApplePhenon’s strong potential as a prophylactic treatment against cancer. As might be
expected, the literature shows that the polyphenols present in ApplePhenon have stronger cancer
preventative activity than polyphenols from other sources.

Finally, substantial pre-clinical research has been done on the ability of apple polyphenols to 1)
assist in digestion and elimination; 2) provide protection to organs such as the brain and liver; 3)
protect the lungs in smokers; and finally, 4) to promote dental health and cavity prevention.
(Please Note: While this review is principally dedicated to an examination of ApplePhenon’s
potential health benefits that have been validated in human clinical research, we briefly mention
these other potential benefits from pre-clinical research in order that the Reader may fully
understand the wide range of possible applications. For a complete list of over 100 abstracts
showing all of the benefits referenced throughout this review, please contact BGG at our North
American headquarters by e-mail at support@bggworld.com or by telephone at 949.748.7348.)

Cardiovascular Health
Cardiovascular Research in Humans
The first clinical trial we’ll discuss was done on 71 moderately obese men and women with a
body mass index ranging from 23 to 30. This study compared the effects of ApplePhenon with
an extract from hops to see which might have cardiovascular benefits. This study was a state-of-
the-art clinical trial—randomized, double blind and placebo controlled, and done by scientists
associated with one of Japan’s leading and most respected corporations. Subjects took either
600mg of ApplePhenon each day, 600mg of hops extract, or placebo for a 12-week period. The
results of this study showed that:

 ApplePhenon significantly decreased total cholesterol levels

 ApplePhenon also significantly decreased LDL (bad) cholesterol levels
 600 mg of ApplePhenon performed markedly better than 600 mg of hops extract
 The visceral fat area (abdominal fat) of the ApplePhenon treatment group improved as
compared with the control group
 The level of adiponectin also improved compared to the control group

5
  And of course, it’s important to point out that no adverse reactions were observed and no
clinical problems manifested as a result of this study (Nagasako-Akazome, et al, 2007)

While this study alone is clear evidence of ApplePhenon’s ability to demonstrably improve the
cardiovascular profile of people in just 12 weeks, there are two other excellent human studies in
this area. The next study we’ll discuss was interesting in that it tested both humans and mice and
found similar results in both species. This study touched on all three common areas of
cardiovascular research—in-vitro testing; an animal model; as well as a human clinical trial. The
results showed that both ApplePhenon as a whole as well as the procyanidin component of
ApplePhenon (which is approximately 60% of the total polyphenol content) inhibited pancreatic
lipase activity in-vitro. The more notable part of this study was a test of how ApplePhenon
would affect triglyceride absorption in mice and also in humans. Both species were given
ApplePhenon and at the same time, triglycerides were ingested. The people and the mice taking
ApplePhenon did not show an increase in plasma triglyceride levels, while the control groups
did. The conclusion was that ApplePhenon “…inhibited triglyceride absorption by inhibiting
pancreatic lipase activity in mice and humans” (Sugiyama, et al, 2007).

The third human study is very noteworthy in that it established a dose-dependent effect for
ApplePhenon in significantly improving blood lipid chemistry in subjects with slightly elevated
cholesterol levels in only 4 weeks. Results showed:

 Total cholesterol levels decreased significantly and dose-dependently versus control

 LDL cholesterol decreased significantly as well
 HDL (good) cholesterol increased significantly

This is a very substantial study in that the time frame was 1/3 of the time frame in the first
cholesterol study we cited above. In just four weeks ApplePhenon completely overhauled the
lipid profile of people with slightly high cholesterol levels. The fact that this study demonstrated
that ApplePhenon works dose-dependently clearly adds additional weight to these findings. And
fortunately, the human studies are corroborated by more than ten different pre-clinical trials
showing cardiovascular benefits from consumption of apple polyphenols.

Pre-Clinical Cardiovascular Research

There are far too many studies to delve into each in detail, so we’ll briefly summarize each study
and are happy to provide more information if requested:

1) Over 400 food extracts were tested for effects on oxidized LDL receptors. Of all of these
extracts only ApplePhenon and grape seed extract potently inhibited oxidized LDL
uptake in hamster cells (Nishizuka, et al, 2011)
2) Dose-dependence was validated in rats fed cholesterol with the control group having
significantly better blood lipid profiles (Osada, et al, 2006)
3) A rodent study showed that absorption of cholesterol oxidation products was reduced by
consumption of ApplePhenon (Ogino, et al, 2007)

6
 4) Cholesterol esterification was dose-dependently decreased by apple procyanidins (as
compared to wine polyphenols which did not show this activity) (Vidal et al, 2005)
5) The ratio of HDL to LDL cholesterol was positively impacted by apple polyphenols in
rodents (Lam, et al, 2008)
6) In an interesting rat study, ApplePhenon was responsible for relaxing the vascular walls
(Byun, et al, 2012)
7) A recent study showed again that apple polyphenols dose-dependently improved blood
lipid profiles in hyperlipidemic mice (Yao, et al, 2014)
8) Apple polyphenols inhibited pre-adipose tissues from becoming adipose tissues in mouse
cells (Shoji, et al, 2000).
9) Researchers using a mouse model concluded that apple polyphenols “…may play a role
in preventing atherosclerosis disease by decreasing uric acid level” (Auclair, et al, 2008)
10) ApplePhenon was responsible for a “potent vasorelaxation” in rat aorta cells (Matsui, et
al, 2009)
11) Finally, in a study last year, scientists found that apple polyphenols improved
cardiotoxicity and attributed this health benefit to its antioxidant activity (Vineetha, et al,
2014)

Research Related to Cardiovascular Health

The pre-clinical research on ApplePhenon’s potential cardiovascular benefits we discussed above
certainly adds a great level of credibility to the human research cited earlier. Additionally,
within the long list of other potential benefits of ApplePhenon, there are several related areas of
research that are strong indicators of its potential as a cardiovascular tonic which we’ll briefly
point out here:

 ApplePhenon has been shown to have anti-inflammatory properties. Systemic or “Silent”

Inflammation is a leading cause of cardiovascular disease along with several other life-
threatening maladies. ApplePhenon’s anti-inflammatory activity may have a preventative
effect against systemic inflammation.
 ApplePhenon has consistently proven its superior antioxidant activity to other
polyphenol-containing nutraceutical ingredients. This antioxidant action is a clear
pathway to decreasing oxidation of LDL cholesterol, which is considered by many
experts to be a key to combatting heart disease.
 Clinical research has shown potential for ApplePhenon in treating obesity, another
leading cause of heart disease. In addition, three separate rodent trials have all shown
great promise in this area.
 There have been two human clinical trials and a pre-clinical supporting study all showing
potential benefits of apple polyphenols for diabetics, another group highly prone to
cardiovascular issues.
 The correlation between dental and gum issues, silent inflammation and cardiovascular
health has been discussed by many scientists. It is interesting to note that ApplePhenon

7
 has demonstrated the ability to combat oral bacteria, plaque and gingivitis, which is
another potential indication of an additional benefit for cardiovascular health.
 Lastly, and perhaps most significantly, the ability of apple polyphenols to extend the
lifespan of four completely different organisms must be noted again. Cardiovascular
disease is the leading cause of death in humans and cancer is close behind at #2; this data,
coupled with the long list of medical research studies showing that apple polyphenols
may have very positive benefits in preventing each of these diseases, plays right along
with its ability to extend the lifespan of living things. While some of these experiments
were done on lower organisms such as yeast, flies and worms, there is a mammal study in
mice as well with very positive results. (Plus, we should point out that the worm study
was done on a worm considered a model organism in life extension research.)

To summarize, the cardiovascular benefits of ApplePhenon are quickly approaching critical

mass, and there is strong evidence that anyone concerned with boosting their heart health and
preventing the world’s leading cause of death should consume 600mg of ApplePhenon on a daily
basis.

Anti-Allergic Properties

Allergy Research in Humans

The first clinical trial we’ll discuss was done with 33 patients with persistent allergic rhinitis.
This study was a state-of-the-art clinical trial—randomized, double blind and placebo controlled,
and done by scientists associated with one of Japan’s leading and most respected corporations.
The aim of this study was to find a safe and natural alternative to anti-histamines and steroid
treatments which are the current commonly used treatments for people suffering from persistent
rhinitis. The problem with both of these drugs is that they have side effects. For anti-histamines,
side effects include nausea and vomiting, blurred vision, confusion, dry mouth, and even trouble
urinating. With steroid treatment, the potential side effects are much more serious; they include
high blood pressure and increased blood sugar levels, glaucoma and cataract, mood swings and
thinning bones. Additionally, patients sometimes experience weight gain and fluid retention as
well as thinning skin. Surely, a safe and natural alternative to these side-effect laden drugs
would be of great clinical interest. And fortunately, this study and the others we’ll examine
show that ApplePhenon may be exactly that: A safe and natural treatment for a variety of
allergic conditions. The study report pointed out:

“Polyphenols derived from apples [ApplePhenon was used] have been reported to
suppress histamine release from rat cells, reduce auricular allergy in mice, and alleviate

8
 skin inflammation in atopic patients. These effects suggest that apple polyphenols are
effective for the treatment of various allergic disorders” (Enomoto, et al, 2006).

ApplePhenon is easily diluted in water, so the patients were given a drink containing
ApplePhenon during this trial. The patients, with an age range of 15 to 65, all had suffered
persistent allergic rhinitis for a period of at least three years, and in each patient the rhinitis was
classified as moderate to severe. Patients were separated into three groups—the control group
took a placebo and the two other groups took ApplePhenon at two different dosage levels.
Results were very positive:

 Both the low-dose and high-dose treatment groups experienced significant improvements
in sneezing attacks
 In addition to improved sneezing attacks, the high-dose group also experienced reduced
nasal discharge
 The percentage of people who showed improvement in the swelling of the nasal turbinate
was higher in the treatment groups

The researchers summarized: “We conclude that apple polyphenols are effective in alleviating
the symptoms of persistent allergic rhinitis” (Enomoto, et al, 2006). Thus, they had proven their
original hypothesis that ApplePhenon may be a safe and natural alternative to commonly
prescribed drugs for allergies.

An earlier study on patients suffering from cedar pollinosis showed similar results. People living
in areas with many cedar trees such as parts of the United States, Mexico and Japan often suffer
from an allergic reaction to the pollen these trees release in spring. This is another form of
allergic rhinitis similar in many ways to hay fever. Patients in the treatment group in this double-
blind study took 500mg per day of ApplePhenon for 12 weeks. During the early period of pollen
dispersion as well as during the main period, sneezing scores decreased in patients taking
ApplePhenon (Kishi, et al, 2005).

Another clinical trial related to allergies was done on a different condition. This study examined
ApplePhenon’s effects on sufferers of atopic dermatitis, an itchy skin disorder that is often
chronic. After 8 weeks, the patients taking ApplePhenon once again had very positive results:

 Reduced inflammation
 Reduced itching
 Improved skin cracking
 Improved peripheral blood eosinophil counts
 Reduced sleep disturbance

The study concluded: “The results suggest that [ApplePhenon] has an anti-allergic effect and
that its use improved the symptoms of atopic dermatitis” (Kojima, et al, 2000).

9
 Pre-Clinical Research on Allergies
In addition to these excellent human clinical trials, there are several pre-clinical trials which
further validate ApplePhenon’s potential as an anti-allergy remedy. We will briefly summarize
this research below; however, anyone interested in more details about these studies should please
contact BGG North America.

1. Back in 2005, researchers discovered the mechanism of action for ApplePhenon’s anti-
allergic effects: ApplePhenon “reduced the degranulation of mast cells caused by cross-
linking of the high-affinity receptor for IgE (FcepsilonRI) with IgE and the antigen.” It
did this in a dose dependent manner (Tokura, et al, 2005).
2. An early in-vitro experiment showed that ApplePhenon could inhibit the release of
histamine in two different cell types (Kanda, 1998).
3. Applephenon was tested both in-vitro and in mice and showed anti-allergic properties in
both parts of this study. Once again, dose-dependence was noted (Nakano, et al, 2008).
4. ApplePhenon prevented the development of food allergies in mice (Akiyama, et al,
2005).

10
 5. ApplePhenon had a very positive effect on mice with allergies including reducing
swelling in a dose-dependent manner (Akiyama, et al, 2000).
6. In a very recent study apple polyphenols again demonstrated an anti-allergic effect
against food allergies in mice (Singh, et al, 2014).

Based on three very positive placebo-controlled human clinical trials and six supporting studies
in both rodent models and in test tubes, it is clear that ApplePhenon has a broad spectrum anti-
allergic effect and would be a logical clinical intervention to provide relief to allergy sufferers.
ApplePhenon’s anti-inflammatory properties probably play an important role in its anti-allergic
effect.

It is interesting to note how ApplePhenon positively affected very different types of allergic
conditions. For example, not only did it have excellent results with sufferers of very common
allergic conditions such as allergic rhinitis and pollinosis; it also was very effective for people
suffering from an allergic skin condition called atopic dermatitis.

Anti-Obesity Effect of ApplePhenon

ApplePhenon Decreases Abdominal Fat in Double-Blind

Human Clinical Trial
“Visceral fat” is abdominal fat. It is also known as organ fat as it concentrates around the vital
organs close to the abdominal cavity. Excess fat in this area has been targeted by researches as
the most detrimental to maintaining good health. Abdominal obesity, in particular, has been
closely associated with an increase in the risk of cardiovascular disease and heart attacks. In
addition to increased cardiovascular disease, visceral fat has been linked with diverse diseases
such as Type-2 diabetes, other metabolic and vascular diseases, and even Alzheimer’s (Razay, et
al, 2006).

Fortunately, ApplePhenon at a standard dose of 600mg per day has proven effective in
decreasing visceral fat within an eight to twelve week time frame. This was a state-of-the-art
human clinical trial—randomized, double-blind and placebo-controlled—and was carried out by
scientists associated with one of Japan’s leading and most respected corporations. In addition to
testing ApplePhenon’s effect on obesity, this study also tested for safety and found no
deleterious effects even with excessive intake of ApplePhenon.

The trial involved 94 volunteers who ranged from moderately underweight to moderately obese.
ApplePhenon was diluted in beverage form, and the treatment group consumed beverages with
600mg of ApplePhenon for 12 weeks while the placebo group consumed an equal amount of

11
beverage without ApplePhenon. Visceral fat was measured at baseline, at 8 weeks, and finally at
12 weeks. The results were extremely positive: After 8 weeks, subjects who started with normal
visceral fat levels had no significant changes. However, subjects who started the study with high
visceral fat levels had significant reductions at both 8 and 12 weeks. The statistical analysis
revealed that after 8 weeks, the reduction in fat was significant at P < 0.05. But after 12 weeks,
the reduction in fat was extremely significant at P < 0.01 (Akazome, et al, 2010). This may
indicate that the use of ApplePhenon over time has more pronounced effects for obesity, so the
logical conclusion would be to consume ApplePhenon for at least 12 weeks to reduce abdominal
fat levels. And while the study did not continue past the 12 week mark, it may prove wise to use
ApplePhenon on a continuous basis for people wishing to reduce abdominal fat levels and
maintain their lower fat levels ongoing.

Pre-Clinical Research on Obesity

In addition to this excellent human clinical trial, there are several pre-clinical trials which further
validate ApplePhenon’s potential in the battle against obesity. We will briefly summarize this
research below; however, anyone interested in more details about these studies should please
contact BGG North America.

12
 1. A recent study in rats fed them a high fat, high sugar diet and tested the effect of apple
polyphenols versus control. Among several blood marker improvements, the researchers
concluded that “Apple polyphenols protect against body weight gain and fat deposition
and improve glucose tolerance in rats.” This study pointed toward adipocyte gene
expression as the mechanism for apple polyphenols’ anti-obesity effect (Boque, et al,
2013).
2. Rats fed a high fat diet that was supplemented with ApplePhenon showed a decreased
level of adipose tissue over a nine-week study (Osada, et al, 2006).
3. ApplePhenon was fed to rats on either a high fat diet or normal diet against control.
Similar to the human clinical cited above, results showed that the rats fed ApplePhenon
had decreased abdominal fat. Additionally, ApplePhenon reduced weight and decreased
triglyceride levels (Ohta, et al, 2006).
4. Polyphenols from seven different sources were compared in a rodent trial. The animals
were fed a high fat and high sucrose diet. Apple polyphenols outperformed all other
polyphenols in obesity prevention. Results included lower weight, lower fat mass and
improved insulin resistance. Finally, out of all the different polyphenols tested, only
apple polyphenols prevented hyperglycemia and hyperleptinaemia (Boque, et al, 2013).
5. Finally, ApplePhenon was fed to rats along with triglycerides. The rats that were given
ApplePhenon excreted double the levels of triglycerides in their feces compared to the
control group (Sugiyama, et al, 2007). This study showed a possible mechanism for
ApplePhenon’s anti-obesity effect in that it prevents the absorption of fats such as
triglycerides.

Based on the very positive placebo-controlled human clinical trial showing that ApplePhenon
decreases visceral fat plus five supporting studies in rodent models, it is evident that
ApplePhenon has the capacity to treat obesity and decrease abdominal fat.

The Athlete’s Edge

ApplePhenon Increases Endurance and Prevents Physical

Fatigue in Double-Blind Human Clinical Study
One of the most limiting factors an athlete faces is fatigue. Of course, this is true during
competition for endurance athletes involved in distance running, swimming, biking and other
events requiring long-range stamina. But it’s also true for athletes involved in most other athletic
endeavors during training and in many cases, also during competition when having the edge in
endurance can mean the difference between victory and second-run. But it’s not just competitive
athletes who are concerned with endurance—middle-aged and elderly people, weekend warriors,
young mothers—practically everyone can all use extra stamina.

13
Fortunately, ApplePhenon has been tested in humans and proven capable of preventing fatigue
and increasing endurance. This was a randomized, double-blind and placebo-controlled study.
The subjects were separated into three separate groups. One group took 1200mg per day of
ApplePhenon. Another group took 1000mg per day of ascorbic acid (a form of Vitamin C).
Finally, the third group took a placebo. It’s interesting to note that this study only lasted eight
days, a relatively short period of time to see clear results from taking this type of natural
substance for endurance improvement.

The test for physical fatigue used was a bicycle ergometer. The subjects did a two hour long
fixed workload trial at the beginning of the study and again after eight days at the end of the
study. During the two hour workload, the subjects performed a maximum velocity test for ten
seconds after the first half hour and then again near the end of the two hour period. The results
showed that the subjects taking ApplePhenon performed better during the ten second maximum
velocity test than the subjects taking placebo or ascorbic acid. This points toward the use of
ApplePhenon for competitive athletes who want to be able to maintain endurance during long
events such as marathons and get that last surge of stamina in the final minutes; but it also shows
that ApplePhenon may be the perfect supplement for anyone who gets tired while working or
participating in sports.

Unpublished Human Clinical Research on Improving

Athletic Performance
Two very exciting human clinical trials are currently awaiting publication that pertain directly to
athletic performance. While we cannot reveal all the details of these studies pending publication,
we can give a brief summary of their exciting results:

 In a study done on college athletes, ApplePhenon was compared to placebo and CoQ10
over two weeks. Subjects were tested to see how many seconds they could hold a
weighted knee stretch as a measure of strength and endurance. Remarkably, after only
two weeks, the athletes taking ApplePhenon could hold the knee stretch four times longer
than those taking placebo. Compared to the CoQ10 athletes, the ApplePhenon athletes
could hold the knee stretch over twice as long (pending publication).

 The second study was similar to the first in that the subjects took either ApplePhenon,
CoQ10 or placebo. But it was different in two key ways: Firstly, this study was not done
on athletes; rather, it was done on random subjects aged 18 – 60. Secondly, the test was a
measure of bicycle pedal speed. This study lasted for only eight days. As one might
expect, results showed that the ApplePhenon group had significantly faster pedal speed
after supplementation than the placebo group or the CoQ10 group (pending publication).

14
 Pre-Clinical Research on Athletic Performance
In addition to these excellent human clinical trials, there are some pre-clinical trials which
further validate ApplePhenon’s potential for enhancing athletic performance. We will briefly
summarize this research below; however, anyone interested in more details about these studies
should please contact BGG North America.

1. A study with rats showed that ApplePhenon improves muscle function. It is interesting
to note that this study also tested the rats’ adipose (fat) tissue and found that the group
supplemented with ApplePhenon had significantly lower levels (Nakazato, et al, 2007).
2. A research group led by the same lead scientist, Dr. Nakazato, found that ApplePhenon
not only improves muscle function in rats, but it also prevents muscle injury as well
(Nakazato, et al, 2010).
3. In related research, scientists tested apple polyphenols’ capacity to protect the
mitochondria of the cell from damage. The mitochondria is the cell’s powerhouse—the
part of the cell responsible for energy production. The results were very positive; not only
did the apple polyphenols protect the mitochondria from damage in a dose-dependent
manner, but they also protected against oxidation and increased the cells’ viability
(Carrasco-Pozo, et al, 2010). This is relevant to our discussion here because, by
protecting the mitochondria from damage and oxidation, ApplePhenon is thereby
increasing energy and preventing fatigue (similar to what was found in the first human
clinical trial cited above).

A final note about a related human clinical trial—one of the most troubling consequences of
training for and participating in sports for many athletes is related to joint health. Joint injuries
and decreases in flexibility can inhibit training programs and prevent athletes competing at their
top performance levels or, in severe cases, competing at all. Apple peel powder rich in
polyphenols was tested in a recent clinical trial to see what effects it might have on joint health.
After twelve weeks, results showed improvement in range-of-motion and decreased pain. The
researchers found “multifaceted anti-inflammatory properties, improved joint function, improved
serum antioxidant protection status, and observed pain reduction” (Jensen, et al, 2014). This is
another strong benefit for athletes and active people—apple polyphenols can help keep your
joints flexible and pain-free.

Between the published and unpublished human clinical trials as well as the supporting pre-
clinical research, it is evident that ApplePhenon may be a huge edge for competitive athletes in
their quest for increasing strength and endurance. It would also benefit other people by simply
giving them more energy and power during the day. Coupled with the human clinical trial
showing potential for apple polyphenols in the area of joint health and mobility, it appears that
ApplePhenon is an ideal supplement for all active people desiring better performance.

15
16
 Other Potential Benefits Validated by
Human Clinical Research

There are emerging categories of potential benefits for ApplePhenon aside from the four we
delved into in detail above. In fact, there are four different benefits that have been validated in
human clinical research that we will present in this section. One of these benefits was mentioned
in the last section on athletic performance: Apple peel powder rich in polyphenols was shown to
have excellent benefits in the area of joint health. Subjects in the control group had reduced
pain, increased mobility, improved antioxidant status and increased anti-inflammatory activity
(Jensen, et al, 2014). Now let us briefly discuss the other three benefits.

Diabetes
Two clinical trials have pointed toward the ability of apple polyphenols to improve health issues
associated with diabetes. One of these studies validated the benefits in both humans and rodents.
Additionally, a separate in-vitro experiment has validated this research.

In February of 2015, a group of scientists tested an extract of unripe apples to see how it would
affect glucose metabolism. They found statistically significant results on two parameters related
to blood glucose levels and metabolism. They concluded that the results showed that unripe
apple extract “can be used as a health-promoting natural product for the reduction of postprandial
glycaemia and to improve the health of patients with diabetes (Makarova, et al, 2015).

The second human clinical study we’ll examine was done a year earlier. The researchers found
a similar result; however, they did their study in both humans and rats. In this case, apple
polyphenols substantially decreased intestinal glucose absorption in both people and rodents, and
there was a corresponding decrease in plasma insulin levels and blood glucose levels (Schulze, et
al, 2014).

The supporting in-vitro study tested polyphenols and polyphonic acid from both apples and
strawberries to examine their effect on glucose uptake and transport in human intestinal cells.
The strawberry extract was non-competitive with the apple extract. The apple extract was

17
successful in its activity on glucose uptake and transport (Manzano and Williamson, 2010),
which lends further support to the two human clinical trials cited above.

Thus, with two positive human clinical trials and a supporting in-vitro study, it appears that apple
polyphenols can be helpful for diabetic patients to maintain healthy blood glucose and plasma
insulin levels.

Anti-Viral and Anti-Bacterial Activity

Apple polyphenols have shown anti-viral and antibacterial activity in humans, mice and test
tubes:

 In a study on both humans and mice, apple procyanidins enhanced the response of Type I
IFN (this is a central pathway that provides critical protection from viral and bacterial
infections) (Snyder, et al 2014).
 In an in-vitro study, ApplePhenon binded with the deadly cholera toxin in vero cells
(Morinaga, et al, 2005).
 An earlier study showed that ApplePhenon inhibited the biological and enzymatic
activities of cholera toxin. The researchers concluded that ApplePhenon “can be used in
a precautionary and therapeutic manner in the treatment of cholera patients” (Saito,
2002).
 In mice, apple polyphenols protected against influenza virus. The researchers
hypothesized that the mechanism of action may be the alleviation of stress-induced
impairment of the immune function and the polyphenols’ antioxidant activity (He, et al,
2011).
 Another in-vitro study showed that apple procyanidins stimulate innate anti-viral
immunity in human cells infected with the dengue virus. The conclusion: “The capacity
of OPC’s to increase sensitivity to IFN-I could be applicable to many viral infections and
two separate anti-viral mechanisms suggest OPC’s may represent a novel, robust anti-
viral therapy (Kimmel, et al, 2011).

Novel Treatment for Hair Loss

Finally, in a very interesting double-blind human clinical trial on 43 volunteers, ApplePhenon
was shown capable of accelerating hair growth! The authors pointed out that the procyanidins in
ApplePhenon had already shown hair-growing activity in-vitro and in rodent research, so they
decided to test this functionality in humans. They had men with male pattern baldness apply a
solution of 0.7% ApplePhenon topically to their bald areas for twelve months. After six months,
they tested the group applying ApplePhenon and they showed a statistically significant increase
in the total number of hairs compared to the control group. (This result was extremely highly
significant: P < 0.001%.) They also noted that the ApplePhenon group showed an improvement

18
in hair density (Takahashi, et al, 2005). This is a very interesting way that men can combat male
pattern baldness—by applying a little ApplePhenon to their heads each night before bed.

Summary
We’ve examined a lot of different areas in which ApplePhenon can improve people’s health;
prevent diseases; give athletes better stamina; prevent allergies; prevent obesity; even grow hair
faster. This is an incredible substance, and that’s why BGG patented it in the USA—so that our
customers can market ApplePhenon with peace of mind that they have a unique, clinically
validated nutraceutical backed up by three active patents. The medical research is strong in areas
such as cardiovascular support and allergy relief. It is solid in areas such as enhancing athletic
performance and combatting obesity. And it is emerging in areas such as support for diabetics,
joint health, as an anti-viral and anti-bacterial, and as a way for balding men to accelerate hair
growth. Meanwhile, there are many potential health benefits successfully studied in animal
research that may one day be validated in humans as well. Exciting possibilities include
ApplePhenon’s cancer preventive properties (which have been confirmed in 22 different animal
trials and in-vitro experiments). And nothing is more exciting than the possibility that the
polyphenols in ApplePhenon have life extension properties as was witnessed in studies involving
four different organisms.

We encourage our Readers to investigate this research further. For anyone interested, BGG
North America has made available an extensive list of research abstracts featuring over 100
studies showing positive benefits associated with ApplePhenon. Please contact us at our North
American headquarters by e-mail at support@bggworld.com or by telephone at 949.748.7348 to
get your free copy today.

19
20
 References

Akazome, Y., Kametani, N., Kanda, T., Shimasaki, H., Kobayashi, S. (2010). “Evaluation of
Safety of Excessive Intake and Efficacy of Long-term Intake of Beverages Containing Apple
Polyphenols.” Journal of Oleo Science 2010:59, (6):321-3388

Akiymana, H., Sakushima, J., Taniuchi, S., Kanda, T., Yanagida, A., Kojima, T., Teshima, R.,
Kobayashi, Y., Goda, Y., Toyoda, M. (2000). “Antiallergic effect of apple polyphenols on the
allergic model mouse.” Biological and Pharmaceutical Bulletin 2000 Nov;23(11):1370-3.

Akiyama, H., Sato, Y., Watanabe, T., Nagaoka, M., Yoshioka, Y., Shoji, T., Kanda, T., Yamada,
K., Totsuka, M., Teshima, R., Sawada, J., Goda, Y., Maitani, T. (2005). “Dietary unripe apple
polyphenol inhibits the development of food allergies in murine models.” Febs Letters 2005
Aug 15;579(20):4485-91.

Ataka, S., Tanaka, M., Nozaki, S., Mizuma, H., Mizuno, K., Tahara, T., Sugino, T., Shirai, T.,
Kajimoto, Y., Kuratsune, H., Kajimoto, O., Watanabe, Y. (2007). “Effects of ApplePhenon and
ascorbic acid on physical fatigue.” Journal of Nutrition 2007 May;23(5):419-23.

Auclair, S., Silberberg, M., Gueux, E., Morand, C., Mazur, A., Milenkovic, D., Scalbert, A.
(2008). “Apple polyphenols and fibers attenuate atherosclerosis in apolipoprotein E-deficient
mice.” Journal of Agriculture and Food Chemistry 2008 Jul 23:56(14):5558-63.

Boque, N., Campion, J., de la Iglesia, R., de la Garza, A., Milagro, F., San Roman, B., Banuelos,
O., Martinez, J. (2013). “Screening of polyphenolic plant extracts for anti-obesity properties in
Wistar rats.” Journal of the Science of Food and Agriculture 2013 Mar 30;93(5):1226-32.

Boque, N., de la Iglesia, R., de la Garza, A., Miagro, F., Olivares, M., Banuelos, O., Soria, A.,
Rodriguez-Sanchez, S., Martinez, J., Campion, J. (2013). “Prevention of diet-induced obesity
by apple polyphenols in Wistar rats through regulation of adipocyte gene expression and DNA
methylation patterns.” Molecular Nutrition and Food Research 2013 Aug;57(8).

Byun, E., Korematsu, S., Ishikawa, T., Nishizuka, T., Ohshima, S., Kanda, T., Matsui, T.
(2012). “Apple procyanidins induce hyperpolarization of rat aorta endothelial cells via
activation of K+ channels.” Journal of Nutritional Biochemistry 23(2012) 278-286.

Carrasco-Pozo, C., Gotteland, M., Speisky, H. (2010). “Protection by apple peel polyphenols
against indomethacin-induced oxidative stress, mitochondrial damage and cytotoxicity.” Journal
of Pharmacy and Pharmacology 2010 Jul;62(7):943-50.

Enomoto, T., Nagasako-Akazome, Y., Kanda, T., Ikeda, M., Dake, Y. (2006). “Clinical effects
of apple polyphenols on persistent allergic rhinitis: A randomized double-blind placebo

21
controlled parallel arm study.” Journal of Investigative Allergology and Clinical Immunology
2006;16(5):283-9.

He, R., Wang, M., Wang, C., Chen B., Lu, C., Yao, X., Chen, J., Kurihara, H. (2011).
“Protective effect of apple polyphenols against stress-provoked influenza virus infection in
restraint mice.” Journal of Agriculture and Food Chemistry 2011 Apr 27;59(8):3730-7.

Jensen, G., Attridge, V., Benson, K., Beaman, J., Carter, S., Ager, D. (2014). “Consumption of
dried apple peel powder increases joint function and range of motion.” Journal of Medicinal
Food 2014 Nov;17(11):1204-13.

Kanda, T., Akiyama, H., Yanagida, A., Tanabe, M., Goda, Y., Toyoda, M., Teshima, R., Saito,
Y. (1998). “Inhibitory effects of apple polyphenol on induced histamine release from RBL-2H3
cells and rat mast cells.” Bioscience Biotechnology Biochemistry 1998 Jun;62(7):1284-9.

Kimmel, E., Jerome, M., Holderness, J., Snyder, D., Kemoli, S., Jutila, M., Hedges, J. (2011).
“Oligomeric procyanidins stimulate innate antiviral immunity in dengue virus infected human
PBMCs.” Antiviral Research 2011 Apr;90(1):80-6.

Kishi, K., Saito, M., Saito, T., Kumemura, M., Okamatsu, H., Okita, M., Takazawa, K. (2005).
“Clinical efficacy of apple polyphenol for treating cedar pollinosis.” Bioscience Biotechnology
Biochemistry 2005 Apr;69(4):829-32

Kojima, T., Akiyama, H., Sasai, M., Taniuchi, S., Goda, Y., Toyoda, M., Kobayashi, Y. (2000).
“Anti-allergic effect of apple polyphenol on patients with atopic dermatitis: A pilot study.”
Allergology International (200)49:69-73.

Lam, C., Zhang, Z., Yu, H., Tsang, S., Huang, Y. Chen Z. (2008). “Apple polyphenols inhibit
plasma CETP activity and reduce the ratio of non-HDL to HDL cholesterol.” Molecular
Nutrition and Food Research 2008 Aug:52(8):950-8.

Makarova, E., Gornas, P., Konrade, I., Tirzite, D., Cirule, H., Gulbe, A., Pugajeva, I., Seglina,
D., Dambrova, M. (2015). “Acute anti-hyperglycaemic effects of an unripe apple preparation
containing phlorizin in healthy volunteers: a preliminary study.” Journal of the Science of Food
and Agriculture 2015 Feb;95(3)560-8.

Manzano, S., Williamson, G. (2010). “Polyphenols and phenolic acids from strawberry and
apple decrease glucose uptake and transport by human intestinal Caco-2 cells.” Molecular
Nutrition and Food Research 2010 Dec;54(12):1773-80.

Matsui, T., Korematsu, S., Byun, E., Nishizuka, T., Ohshima, S., Kanda, T. (2009). “Apple
procyanidins induced vascular relaxation in isolated rat aorta through NO/cGMP pathway in
combination with hyperpolarization by multiple K+ channel activations.” Bioscience
Biotechnology and Biochemistry 2009 Oct; 73(10):2246-51.

22
Morinaga, N., Iwamaru, Y., Yahiro, K., Tagashira, M., Moss, J., Noda, M. (2005). “Differential
activities of plant polyphenols on the binding and internalization of cholera toxin in vero cells.”
Journal of Biological Chemistry 2005 Jun 17;280(24):23303-9.

Nagasako-Akazome, Y., Kanda, T., Ohtake, Y., Shimasaki, H., Kobayashi, T. (2007). “Apple
polyphenols influence cholesterol metabolism in healthy subjects with relatively high body mass
index.” Journal of Oleo Science 2007;56(8):417-28.

Nagasako-Akazome, Y., Kanda, T., Ikeda, M., Shimasaki, H. (2005). “Serum Cholesterol-
Lowering Effect of Apple Polyphenols in Healthy Subjects.” Journal of Oleo Science, Vol. 54,
No. 3, 143-151 (2005).

Nakano, N., Nishiyama, C., Tokura, T., Nagasako-Akazome, Y., Ohtake, Y., Okumura, K.,
Ogawa, H. (2008). “Procyanidin C1 from apple extracts inhibits Fc epsilon RI-mediated mast
cell activation.” International Archives of Allergy and Immunology 2008;147(3):213-21.

Nakazato, K., Song, H., Waga, T. (2007). “Dietary apple polyphenols enhance gastrocnemius
function in Wistar rats.” Medicine and Science in Sports and Exercise 2007 Jun;39(6):934-40.

Nakazato, K., Ochi., Waga, T. (2010). “Dietary apple polyphenols have preventive effects
against lengthening contraction-induced muscle injuries.” Molecular Nutrition and Food
Research 2010 Mar;54(3):364-72.

Nishizuka, T., Fujita, Y., Sato, Y., Nakano, A., Kakino, A., Ohshima, S., Kanda, T., Yoshimoto,
R., Sawamura, T. (2011). “Procyanidins are potent inhibitors of LOX-1: a new player in the
French Paradox.” Proceedings of the Japan Academy. Series B Physical and Biological
Sciences 2011:87(3):104-13

Ogino Y., Osada, K., Nakamura, S., Ohta, Y., Kanda, T. Sugano, M. (2007). “Absorption of
dietary cholesterol oxidation products and their downstream metabolic effects are reduced by
dietary apple polyphenols.” Lipids 2007 Mar 42(2):151-61.

Ohta, Y., Sami, M., Kanda, T., Saito, K., Osada, K., Kato, H. (2006). “Gene expression analysis
of the anti-obesity effect of apple polyphenols in rats fed a high fat diet or a normal diet.”
Journal of Oleo Science, Vol. 55, No. 6, 305-314.

Osada, K., Funayama, M., Fuchi, S., Sami., Ohta, Y., Kanda, T., Ikeda, M. (2006). “Effects of
dietary procyanidins and tea polyphenols on adipose tissue mass and fatty acid metabolism in
rats on a high fat diet.” Journal of Oleo Science, Vol. 55, No. 2, 79-89.

Osada, K., Suzuki, T., Kawakami, Y., Senda, M., Kasai, A., Sami, M., Ohta, Y., Kanda, T.,
Ikeda, M. (2006). “Dose-dependent hypocholesterolemic actions of dietary apple polyphenol in
rats fed cholesterol.” Lipids 2006 Feb 41(2):133-9.

Razay, G., Vreugdenhil, A., Wilcock, G. (2006). “Obesity, abdominal obesity and Alzheimer
disease.” Dementia and Geriatric Cognitive Disorders 22(2):173-176.

23
Saito, T., Miyake, M., Toba, M., Okamatsu, H., Shimizu, S., Noda, M. (2002). “Inhibition by
apple polyphenols of ADP-ribosyltransferase activity of cholera toxin and toxin-induced fluid
accumulation in mice.” Microbiological Immunology 2002;46(4):249-55.

Schulze, C., Bangert, A., Kottra, G., Geillinger, K., Schwanck, B., Vollert, H., Blaschek, W.,
Daniel, H. (2014). “Inhibition of the intestinal sodium-coupled glucose transporter 1 (SGLT1)
by extracts and polyphenols from apple reduces postprandial blood glucose levels in mice and
humans.” Molecular Nutrition and Food Research 2014 Sep;58(9):1795-808.

Shoji, Koborj, Shinmoto, Yanagida, Kanda, Tsushida. (2000). “Inhibitory effects of apple
polyphenols on differentiation of 3T3-L1 cells into adipocytes.” Food Science and Technology
Research 6(2),I 19-121, 2000.

Singh, A., Demont, A., Actis-Goretta, L., Holvoet, S., Leveques, A., Lepage, M., Nutten, S.,
Mercenier, A. (2014). “Identification of epicatechin as one of the key bioactive constituents of
polyphenol-enriched extracts that demonstrate an anti-allergic effect in a murine model of food
allergy.” British Journal of Nutrition 2014 Aug;112(3):358-368.

Snyder, D., Robison, A., Kernoli, S., Kimmel, E., Holderness, J., Jutila, M., Hedges, J. (2014).
“Oral delivery of oligomeric procyanidins in Apple Poly® enhances type I IFN responses in
vivo.” Journal of Leukocyte Biology 2014 Jan 13.

Sugiyama, H., Akazome, Y., Shoji, T., Yamaguchi, A., Yasue, M., Kanda, T., Ohtake, T.
(2007). “Oligomeric procyanidins in apple polyphenol are main active components for inhibition
of pancreatic lipase and triglyceride absorption.” Journal of Agriculture and Food Chemistry
2007 May 30;55(11):4604-9

Takahashi, T., Kamimura, A., Kaoura, M., Toyoda, M., Morohashi, M. (2005). “Investigation
of the topical application of procyanidin oligomers from apples to identify their potential use as a
hair-growing agent.” Journal of Cosmetic Dermatology 2005 Dec;4(4):245-9.

Tokura, T., Nakano, N., Ito, T., Matsuda, H., Nagasako-Akazome, Y., Kanda, T., Ikeda, M.,
Okumura, K., Ogawa, H., Nishiyama, C. (2005). “Inhibitory effect of polyphenol-enriched
apple extracts on mast cell degranulation in vitro targeting the binding between IgE and
FcepsilonRI.” Bioscience Biotechnology Biochemistry 2005 Oct;69(10):1974-7.

Vidal, R., Hernandez-Vallejo, S., Pauquai, T., Texier, O., Rousset, M., Chambaz, J., Demignot,
S., Lacorte, JM. (2005). “Apple procyanidins decrease cholesterol esterification and lipoprotein
secretion n Caco-2/TC7 enterocytes.” Journal of Lipid Research 2005 Feb:46(2):258-68.

Vineetha, V., Girija, S., Soumya, R., Raghu, K. (2014). “Polyphenol-rich apple peel extract
attenuates arsenic trioxide induced cardiotoxicity in H9c2 cells via its antioxidant activity.”
Food and Function 2014 Mar;5(3):502-511.

24
Yao, N., He, R., Zeng, X., Huang, X., Du, T., Cui, J., Hiroshi, K. (2012). “Hypotriglyceridemic
effects of apple polyphenols extract via up-regulation of lipoprotein lipase in triton WR-1339-
induced mice.” Chinese Journal of Integrative Medicine 2014 Jan:20(1):31-5.

25