Note: Descriptions are shown in the official language in which they were submitted.
CA 02596200 2007-08-07
Title
HERBAL PRODUCT COMPRISIONG CINNAMON AND COFFEE
Field of the Invention
[0001] This invention relates to a new herbal product and in particular, to a
new herbal
product comprising cinnamon (Cinnamomi cassiae: Cinnamonum verum) and coffee.
Each of
these ingredients is known to demonstrate therapeutic effects but the
combination of the two
ingredients demonstrates significant synergism and improved therapeutic
effects.
Background of the Invention
[0002] Diabetes, hyperlipidemis and obesity, besides being detrimental to
health by
themselves, are all recognized risk factors for cardiovascular disease (CVD),
which is still the
number one killer in North America. Obesity is reaching epidemic proportions
in N. America
and Type 2 diabetes, with its close links to obesity, has become a major cause
for concern. High
blood cholesterol levels have persisted as a key factor in the development of
atherosclerosis and
CVD, and high triglycerides have also been recognized as an important risk
factor, especially for
women. The incidence of metabolic syndrome (also known as insulin resistance
syndrome, or
syndrome X), which presents as a cluster of characteristics and symptoms,
including obesity,
increased waist circumference, borderline high blood glucose and blood
pressure levels, and
abnormal blood lipid levels, has been increasing sharply since it was first
recognised as a
common precursor to both CVD and diabetes.
[0003] While modern pharmaceutical drugs exist for the treatment of
hyperlipidemia,
diabetes, and CVD, the side effects associated with many of these drugs may
have severely
detrimental health effects which preclude their use, or these side effects may
simply reduces
patient compliance. As a result, a majority of the population has been looking
elsewhere for the
treatment of these diseases and conditions, and complementary therapies have
become a popular
alternative to the pharmaceutical model for treatment.
[0004] A herbal product which is a likely candidate as a treatment option is
cinnamon
(Cinnamomi cassiae; Cinnamomum verum).
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[0005] Cinnamon has been widely used for centuries, and is a traditional folk
herb for
diabetes mellitus in Russia, China and Korea. It is also thought to possess
anti-fever and
antibiotic properties, as well as being as mild analgesic and sedative. Recent
research has
focused on its ability to lower blood glucose levels. In recent animal
studies, its blood-glucose-
lowering ability was dose-dependent, with higher doses lowering glucose levels
more than lower
doses. Insulin levels increased, as did HDL cholesterol levels (the so-called
"good" cholesterol).
Total and LDL cholesterol levels and triglyceride levels, on the other hand,
were reduced with
cinnamon supplementation. An additional benefit of cinnamon supplementation
may be its
antioxidant capacity, due to its phenolic acids and flavonoids. This
antioxidant capacity may not
only slow the progression of Type 2 diabetes complications, by quenching the
excessive oxygen
free radical damage seen in diabetes, it may also protect LDL cholesterol from
oxidation,
reducing the likelihood of it being scavenged and incorporated into blood
vessel wall plaque, the
latter being a major part of atherosclerosis, hypertension and CVD.
[0006] Coffee is thought to have acute and long-term effects on health and its
consumption is
thought to be protective against the development of type 2 diabetes. Coffee is
consumed by
about 50% of the population North America and is the second most valuable
commodity in the
world. Various preliminary studies have indicated that coffee has protective
effects on diseases
ranging from type 2 diabetes to Parkinson's disease. Also, some studies have
indicated that
coffee may have a beneficial effect on abnormal liver chemistry, cirrhosis and
heptatocellular
carcinoma.
[0007] In a study done at the University of Washington School of Public Health
and
Community Medicine in Seattle Washington USA and reported at Acta Obstet
Gynecol Scand.
2007;86(2):161-6,. investigators Adeney, Williams, Schiff and Sorensen
examined the
relationship between coffee consumption and the risk of gestational diabetes
mellitus (GDM).
They reported that women who reported moderate pre-pregnancy caffeinated
coffee intake had a
significantly reduced risk of GDM compared with non-consumers. No risk
reduction was
reported with decaffeinated coffee intake.
[0008] Accordingly, the present inventors have combined these two basic
ingredients into a
single therapeutic formulation which demonstrates synergistic results. The
inventors have found
that the new therapeutic formulation has resulted in the following:
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1. Reduction in blood glucose levels and increased glucose tolerance in
diabetics and people
with metabolic syndrome.
2. Reduction in total and LDL cholesterol and triglycerides, and increase in
HDL cholesterol in
people with dyslipidemia, including people with metabolic syndrome.
3. Reduction in obesity.
4. Improved antioxidant capacity, with the potential to protect diabetics
against free radical
damage, and to reduce oxidized LDL cholesterol levels.
[0008] Thus, this new therapeutic formulation may be used to treat diabetes
and CVD, and
also in the precursor syndrome, where almost all of the characteristics of
this syndrome - high
total and LDL cholesterol, high triglyceride, low HDL cholesterol, borderline
high blood glucose
levels, obesity and high waist circumference - may be improved. Even
borderline high blood
pressure, which is normally affected by the degree of obesity, may be reduced.
In effect, this
therapeutic formulation will reduce the incidence of metabolic syndrome,
which, in turn, would
reduce the incidence of diabetes, CVD and obesity. This is the first herbal
combination with the
potential to have more significant effects than pharmaceutical drugs on this
triumvirate of
conditions which continues to have a major impact on the health of North
Americans.
Summary of the Invention
[0009] To this end, in one of its aspects, the present invention provides a
novel therapeutic
formulation which comprises cinnamon and coffee.
[0010] A further object of the present invention is to provide a new
therapeutic formulation
which comprises cinnamon and coffee in a ratio of about 500 milligrams of raw
cinnamon to
about 8000 milligrams of raw cinnamon per 250 millilitres of coffee.
[0011] A still further object of the present invention is to provide a new
therapeutic
formulation which comprises cinnamon and coffee in a ratio of about 200
milligrams of
cinnamon extract to about 800 milligrams of cinnamon extract per 250
millilitres of coffee.
[0012] A still further object of the invention is to provide a new therapeutic
product which
provides between about 2000 milligrams to about 8000 milligrams of raw
cinnamon per day
divided and mixed in 3 cups of coffee assuming that each cup is 250
millilitres.
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[0013] A yet still further object of the invention is to provide a new
therapeutic product
which provides between about 200 milligrams of cinnamon extract to about 800
milligrams of
cinnamon extract divided into 3 cups of coffee, each coffee cup being about
250 millilitres.
[0014] A still yet further object of the present invention is to provide a new
therapeutic
product which contains between about 3000 milligrams to about 6000 milligrams
of cinnamon
powder mixed in a standard cup of coffee.
Detailed Description of the Invention
[0015] The two active ingredients of the new therapeutic formulation are
cinnamon and
coffee.
[0016] In recent years numerous laboratory and clinical studies have been
conducted on
cinnamon by biological scientists, pharmacologists and pharmacists at
prestigious research
centres like Department of Pharmacy at the Kings College of London, University
of California,
Santa Barbara, Iowa State University and the U.S. Department of Agriculture.
All of these
studies show findings that confirm the therapeutic properties of cinnamon
claimed by the
traditional medicine and some of the research actually is considered to be
break through in the
field of natural health products. At USDA, scientists have been able to
identify the particular
molecule in cinnamon that mimics insulin and is responsible for its
hypoglycaemic properties.
[0017] The new therapeutic formulation contains cinnamon and coffee at a ratio
of between
133 milligrams of cinnamon extract to about 266milligrams of cinnamon extract
per 250
millilitre cup of coffee, which is the most synergistic combination of the two
ingredients for the
management of blood sugar levels of type 2 diabetes patients as well as for
normalizing the lipid
profiles.
[0018] The dietary habits of the developed countries such as Canada and United
States have
recently been criticized for causing an increase in the incidence of several
types of lifestyle-
related diseases such as diabetes, obesity and cardiovascular diseases.
Diabetes, a disorder of
carbohydrate, fat and protein metabolism attributed to diminished production
of insulin or
mounting resistance to its action, is the most common metabolic disease
presently. It is a major
cause of disability and hospitalization resulting in a significant financial
burden on the health
care system (Rathi et al. 2002 and Virdi et al. 2003), and is estimated to
cost Canadians up to $9
billion annually (Public Health Agency of Canada, 2005). It also has a
significant impact on the
health, quality of life and life expectancy of patients. Diabetes is a potent
risk factor for
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cardiovascular disease as it not only affecting glucose metabolism but also
influences lipid
metabolism (Jayasooriya et al. 2000). Diabetes is divided into two major
categories: type 1
diabetes, previously known as insulin dependent diabetes mellitus (IDDM), and
type 2 diabetes,
previously known as non-insulin dependent diabetes mellitus (NIDDM). Although
the
recommended treatments for these two categories are usually somewhat
different, insulin for
IDDM and lifestyle management for NIDDM, the overall result is improving
glucose
homeostasis. Lifestyle management such as changes in diet and an exercise
regimen continues
to be essential and effective but it may be insufficient or difficult for
patient compliance
rendering conventional drug therapies useful (Dey et al. 2002). The problems
with the use of
insulin or any other antidiabetic drugs are the presence of adverse effects
such as hypoglycemia
at higher doses, liver problems, lactic acidosis and diarrhea (Virdi et al.
2003). In recent years,
there has been a growing interest in herbal medicines specifically herbal
extracts as a popular
alternative in healthcare due to people's perception of it being a`natural'
product and therefore a
minimal chance of having any side effects. The current popularity is also due
to the many
botanicals reported for the management of diabetes in other alternative
systems of medicine such
as Ayurveda and Traditional Chinese Medicine, the interest in these herbal
plants has been
piqued.
[0019] The following is a brief description of the two ingredients and their
therapeutic
properties.
[0020] Cinnamomum aromaticum (sp. Cassia) is from the family Lauraceae. It is
a medium-
sized evergreen tree native to China and Vietnam. It contains volatile oils
composed of
cinnamaldehyde, phenolic compounds, flavonoid derivates, methylhydroxychalcone
polymer,
mucilage, calcium oxalate, resins, sugars, and coumarins. Cassia, the species
name for
Cinnamomum aromaticum comes from the Greek work "kassia" meaning "to strip off
the bark".
Cinnamon bark has been used medicinally in China since 2700 B.C.E and is said
to supplement
vital energy and blood, tone the kidney and spleen and acts as an antioxidant
(Blumenthal et al.
1998). Cinnamomum aromaticum has also been used in Korea, China and Russia as
a traditional
folk herb with hypoglycemic properties for the treatment of diabetes mellitus
(Kim et al. 2005).
[0021] The increasing prevalence of diabetes and cardiovascular disease is
evident
worldwide with an estimated 1700 new cases diagnosed daily (Jarvill-Taylor et
al. 2001).
Additionally, several million people worldwide are suffering from `pre-
diabetes' caused by high
CA 02596200 2007-08-07
glucose levels with a resistance to insulin (Khan et al. 2003). The primary
function of insulin is
to maintain low blood glucose, lipid and cholesterol levels to maintain a
sense of well-being.
Environmental factors such as diet, exercise, and stress also attribute to
decreasing insulin
sensitivity and increasing glucose and low-density lipoprotein (LDL)
cholesterol levels,
increasing the risk of cardiovascular diseases, obesity, dyslipidemias,
diabetes mellitus and
premature aging. The increase in disease is partly due to the augmented intake
of calories and
refined carbohydrates, lesser consumption of fibers and a more sedentary
lifestyle. Controlling
dietary intake and exercise could prevent disease but the majority of
individuals require an extra
aid to maintain normal health (Talpur et al., 2005). There is a growing
interest in herbal
remedies due to the side effects associated with therapeutic hypoglycemic
agents and insulin
(Kim et al. 2005). Botanical products with a long history of safety are widely
used to lower
glucose, lipid and cholesterol levels and for the prevention and treatment of
diabetes.
[0022] Cinnamomum aromaticum has been used as a hypoglycemic agent in ancient
medicines (Kim et al. 2005). The modern therapeutic properties of cinnamon are
supportable
based on thousands of years of use in well established systems of traditional
medicines, as well
as some modern clinical studies (Blumenthal et al. 1998). A number of well
proven in vivo
animal studies on Cinnamomum aromaticum demonstrate that activation of the
insulin receptor
increases autophosphorylation resulting in an increase in glucose uptake and
glycogen synthesis.
However, there is a limited amount of published data on the effects of
cinnamon consumption on
blood glucose in humans. In vivo, in vitro and human studies have established
that cinnamon
extract regulates insulin activity and reduces serum glucose and cholesterol
levels (Khan et al.
2003 and Kim et al. 2005).
[0023] In a study by Khan et al. in 2003, 60 men and women with type 2
diabetes ingested
daily doses of cinnamon or placebo capsules for 40 days followed by a 20-day
washout period.
Cinnamon capsules contained 1, 3 or 6 g of Cinnamomum aromaticum. After 20
days, only the
6 g cinnamon group showed significantly lower glucose levels. However, after
40 days, serum
glucose (18-29%), triglycerides (23-30%) and total cholesterol (12-26%)
concentrations were
significantly lower in all cinnamon groups. Total cholesterol was lower in all
groups at 40 days
but low-density lipoprotein (LDL) concentrations were only significantly lower
in the 3 g and 6
g cinnamon groups (10% and 24%, respectively). For the 1 g cinnamon group, LDL
concentrations continued to decline during the washout period and were
significant at 60 days
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(P<0.05). The decreased concentration of glucose was maintained by the 1 g
cinnamon group
while triglyceride and total cholesterol levels were maintained in all
cinnamon groups throughout
the 20-day washout period.
[0024] Vanschoonbeek et al. 2006 performed a 6 week standardized placebo-
controlled
study to investigate the proposed benefits of Cinnamomum cassia on 25
postmenopausal women
diagnosed with type 2 diabetes. Patients were divided into two groups and
supplemented with
1.5 g/day of Cinnamomum or placebo to assess the effects on glucose tolerance
and whole-body
insulin sensitivity. At 0, 2 and 6 weeks oral glucose tolerance tests and
blood lipid profiles were
performed resulting in no time x treatment interaction observed for fasting
glucose, insulin
concentration, insulin resistance, (oral glucose) insulin sensitivity or
fasting blood lipid
concentrations. This study shows cinnamon supplementation does not have a
health benefit in
patients with type 2 diabetes contradicting the results found by Khan et al.
2003. Differences
between the two studies could be attributed to the selection of patients and
the combination of
medications taken. In the current study, only postmenopausal female patients
were included and
continued using commonly prescribed combinations of oral blood glucose-
lowering agents,
which was not a factor in the study by Khan et al. 2003, explaining the low
baseline values found
in the patients used in the current study. Although the authors concluded
cinnamon
supplementation in combination with oral blood glucose-lowering agents may not
be beneficial
to overweight, postmenopausal women, this is a small concentrated study not
factoring in the use
of other medications and patient characteristics.
[0025] In a study by Talpur et al. in 2005, Zucker fatty rats (ZFRs) and
spontaneously hyper-
tensive rats (SHRs) were fed water or essential oils in acute or chronic doses
to assess the effect
of essential oil combinations on insulin sensitivity. The essential oil
treatment consisted of 8
essential oils including cinnamon. Insulin sensitivity was determined by
systolic blood pressure
(SBP) and a glucose tolerance test. In the acute study, ZFRs and SHRs with
essential oil
treatments showed significant decreases in SBP at 4, 10 and 20 hours and at 4
hours,
respectively. However, SBP levels were equal to the control group at 30 hours
in ZFRs and at
10, 20 and 30 hours in SHRs. In the chronic study, ZFRs and SHRs consuming the
essential oils
showed significantly lower SBP at 8, 17 and 25 days in comparison to the
control group.
Decreases in SBP levels ranged from 11 to 20 mmHg. During the oral glucose
test, ZFRs
consuming the essential oil combination showed consistently lower levels of
circulating insulin,
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however these results were not significant. SHRs did not produce any effect on
insulin levels
and were equal to the controls, paralleling previous studies where effects
were only produced
when rats were challenged in stress-free environments (Verspohl et al. 2005).
The decreases in
SBP and circulating glucose levels, produced by both species of rats, enhance
insulin sensitivity
and parallels the idea that fluctuating SBP is the most sensitive index of
insulin sensitivity.
Cinnamon has been shown to have insulin-like actions and affect insulin
signalling (Broadhurst
et al. 2000), and as an ingredient in the essential oil combination it may
have a role in the
reduction of SBP.
[0026] In another study, Kim et al. 2006, administered db/db mice Cinnamomum
cassia
dosages of 50, 100, 150 or 200 mg/kg for 6 weeks to determine its effect on
blood glucose. The
control group showed high blood glucose levels at 2, 4, and 6 weeks. The
cinnamon extract-
treated group showed significantly lower blood glucose levels at each time
period (P<0.05, <0.01
and <0.001). Significant decreases in triglyceride and total cholesterol
levels were noted in the
cinnamon extract group. Similar to Khan et al. 2003 these results parallel the
hypoglycemic
effects in the cinnamon extract-treated group as reduced levels are maintained
for a long period
of time.
[00271 In a similar study by Verspohl et al. in 2005, blood glucose and plasma
insulin levels
were evaluated in Wistar rats given extracts of Cinnamomum bark, cassia or
zeylanicum. During
the glucose tolerance test, plasma insulin levels increased significantly
after the administration of
Cinnamomum extracts with cassia showing the most pronounced effect. The saline
placebo
group showed no effect on plasma insulin. In all extract-treated groups, blood
glucose levels did
not decrease unless the rat was challenged by a glucose tolerance test in a
stress-free
environment. Cinnamomum cassia produced a direct insulin stimulatory effect
showing superior
effects compared to zeylanicum.
[0028] The increase in fructose consumption has risen worldwide in the past
two decades as
a significant proportion of energy intake in the diet. Qin et al. 2004 fed 18
male Wistar rats a
high-fructose diet and 6 a control diet for 3 weeks to determine the effects
of glucose utilization
and insulin sensitivity. 12 of the rats consuming a high-fructose diet had
Cinnamomum cassia
extracts (300 mg/kg/day) added to their diet. During the euglycemic clamp
procedure to
measure glucose infusion rates (GIR), the 6 rats consuming only a high-
fructose diet showed
significant decreases (p<0.0001) in glucose infusion rates while cinnamon
treated rats produced
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significant increases, similar to the controls. The consumption of a high-
fructose diet, an
environmental factor contributing to diabetes, is common in the western
society; the addition of
Cinnamomum cassia extract to the diet shows a preventative effect, through an
increase in
glucose utilization and insulin sensitivity.
[0029] In another study, the effect of cinnamon extract on insulin action was
evaluated in
Wister rats. Qin et al. 2003 randomly assigned 18 rats into three groups:
saline, 30mg/kg and
300mg/kg cinnamon extract. Cinnamon treatment for 3 weeks did not have an
effect on plasma
free fatty acids and fasting blood glucose concentrations. Although these
levels were not
affected in the cinnamon treated group, a difference was prevalent in glucose
uptake compared to
the placebo group. A dose-dependent manner was noticed with glucose
utilization as 300mg/kg
enhanced glucose utilization to a greater degree than the 30mg/kg or control
groups.
[0030] Methylhydroxychalcone polymer (MHCP), a bioactive compound of cinnamon
extract, is hypothesized to trigger an insulin-like response. In a study by
Jarvill-Taylor et al.
2001, 3T3-L1 adipocytes were assessed with MHCP to determine its function as
an insulin
mimetic. Within the first 10 minutes of incubation, the insulin treated
adipocytes showed a 2.5
fold increase in glucose transport while the MHCP treated group did not show
any increase.
However, gradually over the one-hour period, glucose uptake increased in the
MHCP treated
group and at 60 minutes, a significant increase was noted. As noted in other
studies, the effect of
cinnamon did not diminish immediately after stopping treatment. As MHCP is
administered, the
kinase receptor is activated resulting in phosphorylation of the insulin
receptor, a similar effect is
seen throughout the insulin signaling pathway.
[0031] A similar study by Broadhurst et al. in 2000 reported an increase in
insulin action
demonstrated by cinnamon extract in vitro. Rat epididymal adipocytes were
given either insulin
or cinnamon extract after incubation to determine glucose metabolism. At all
dilutions (1:2,
1:10, 1:50) cells exposed to cinnamon extract showed a significant increase in
insulin-dependent
activity and the effect was maintained at the high dilution (1:50). As
adipocytes were treated
with cinnamon extract the insulin receptor kinase became activated, a
necessary requirement to
increase insulin sensitivity. The activation of kinase mimics insulin activity
in adipocytes.
Afterwards, active cinnamon extract was incubated with soluble
polyvinylpyrrolidone (PVP) to
determine if activity was associated with tannins or polyphenols. Cinnamon
readily bound to
PVP giving it a polyphenolic characterization. With an increase in glucose
metabolism, 98% of
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activity is attributed to PVP indicating the use of phenolics to destroy free
radicals that inhibit
the activation of insulin-receptor kinase. Cinnamon extract mimics the same
mechanism as
insulin in adipocytes, increasing insulin sensitivity and glucose metabolism.
[0032] Cinnamomum aromaticum (cinnamon) has convincingly been shown to prevent
and
control elevated glucose and blood lipid concentrations in both in vitro and
in vivo studies and
can be maintained for a long period after use. The insulin kinase receptor is
activated with
cinnamon extract demonstrating insulin-mimetic activity. Elevated glucose and
blood lipid
concentrations increase the incidence of diabetes and/or cardiovascular
health. The use of
cinnamon extract can prevent these diseases by regulating the insulin receptor
to increase
glucose uptake and metabolism.
[0033] To date there have been no formal pharmacokinetic studies done on this
plant in
animals or humans. The only information derived from literature was a study
conducted by
Khan et al. in 2003 that found Cinnamomum aromaticum (extract) has a prolonged
effect on the
human body for 20 days during the washout period. Several animal studies have
also shown
prolonged effects after consumption of cinnamon extract.
[0034] The exact mechanism of action of Cinnamomum aromaticum (extract) is
thought to
be that it acts as an insulin-mimetic by activating the kinase receptor and
increasing insulin
sensitivity. The interaction within the intracellular kinase domain triggers
an insulin-like
response and stimulates glucose oxidation. Cinnamon also regulates enzymes
inside the insulin
receptor kinase domain and inhibits both phosphotyrosine-specific protein
phosphatase (PTP-1)
in vitro and glycogen synthase kinase-3 ^(GSK-3 ^) in vivo. The inhibition of
PTP-1 keeps the
insulin receptor in an activated state and inhibition of GSK-3 ^ stimulates
glycogen production.
Cinnamon acts independently from insulin but similar levels of activity were
observed proposing
that it may activate the same cascade as the insulin signaling pathways
(Jarvill-Taylor et al.
2001).
[0035] Cinnamon significantly helps people with type 2 diabetes improve their
ability to
respond to insulin, thus normalizing their blood sugar levels. Both test tube
and animal studies
have shown that compounds in cinnamon not only stimulate insulin receptors,
but also inhibit an
enzyme that inactivates them, thus significantly increasing cells' ability to
use glucose. Studies
to confirm cinnamon's beneficial actions in humans are currently underway with
the most recent
report coming from researchers from the US Agricultural Research Service, who
have shown
CA 02596200 2007-08-07
that less than half a teaspoon per day of cinnamon reduces blood sugar levels
in persons with
type 2 diabetes. Their study included 60 Pakistani volunteers with type 2
diabetes who were not
taking insulin. Subjects were divided into six groups. For 40 days, groups 1,
2 and 3 were given
1, 3, or 6 grams per day of cinnamon while groups 4, 5 and 6 received placebo
capsules. Even
the lowest amount of cinnamon, 1 gram per day (approximately'/4 to %2
teaspoon), produced an
approximately 20% drop in blood sugar; cholesterol and triglycerides were
lowered as well.
When daily cinnamon was stopped, blood sugar levels began to increase.
[0036] Test tube, animal and human studies have all recently investigated
cinnamon's ability
to improve insulin activity, and thus our cells' ability to absorb and use
glucose from the blood.
[0037] Ongoing in vitro or test tube research conducted by Richard Anderson
and his
colleagues at the USDA Human Nutrition Research Center is providing new
understanding of
the mechanisms through which cinnamon enhances insulin activity. In their
latest paper,
published in the Journal ofAgricultural and Food Chemistry, Anderson et al.
characterize the
insulin-enhancing complexes in cinnamon-a collection of catechin/epicatechin
oligomers that
increase the body's insulin-dependent ability to use glucose roughly 20-fold..
Some scientists
had been concerned about potentially toxic effects of regularly consuming
cinnamon. This new
research shows that the potentially toxic compounds in cinnamon bark are found
primarily in the
lipid (fat) soluble fractions and are present only at very low levels in water
soluble cinnamon
extracts, which are the ones with the insulin-enhancing compounds.
[0038] A recent animal study demonstrating cinnamon's beneficial effects on
insulin activity
appeared in the December 2003 issue of Diabetes Research and Clinical
Practice. In this study,
when rats were given a daily dose of cinnamon (300 mg per kilogram of body
weight) for a 3
week period, their skeletal muscle was able to absorb 17% more blood sugar per
minute
compared to that of control rats, which had not received cinnamon, an increase
researchers
attributed to cinnamon's enhancement of the muscle cells' insulin-signaling
pathway. In humans
with type 2 diabetes, consuming as little as 1 gram of cinnamon per day was
found to reduce
blood sugar, triglycerides, LDL (bad) cholesterol, and total cholesterol, in a
study published in
the December 2003 issue of Diabetes Care. The placebo-controlled study
evaluated 60 people
with type 2 diabetes (30 men and 30 women ranging in age from 44 to 58 years)
who were
divided into 6 groups. Groups 1, 2, and 3 were given 1, 3, or 6 grams of
cinnamon daily, while
groups 4, 5, and 6 received 1, 3 or 6 grams of placebo. After 40 days, all
three levels of
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cinnamon reduced blood sugar levels by 18-29%, triglycerides 23-30%, LDL
cholesterol 7-27%,
and total cholesterol 12-26%, while no significant changes were seen in those
groups receiving
placebo. The researchers' conclusion: including cinnamon in the diet of people
with type 2
diabetes will reduce risk factors associated with diabetes and cardiovascular
diseases.(January
28, 2004)
[0039] The latest research on cinnamon shows that by enhancing insulin
signaling, cinnamon
can prevent insulin resistance even in animals fed a high-fructose diet! A
study published in the
February 2004 issue of Hormone Metabolism Research showed that when rats fed a
high-
fructose diet were also given cinnamon extract, their ability to respond to
and utilize glucose
(blood sugar) was improved so much that it was the same as that of rats on a
normal (control)
diet. Cinnamon is so powerful an antioxidant that, when compared to six other
antioxidant spices
(anise, ginger, licorice, mint, nutmeg and vanilla) and the chemical food
preservatives (BHA
(butylated hydroxyanisole), BHT (butylated hydroxytoluene), and propyl
gallate), cinnamon
prevented oxidation more effectively than all the other spices (except mint)
and the chemical
antioxidants. (May 6, 2004).
[0040] In addition to its unique essential oils, cinnamon is an excellent
source of the trace
mineral man ag nese and a very good source of dietary fiber, iron and calcium.
The combination
of calcium and fiber in cinnamon is important and can be helpful for the
prevention of several
different conditions. Both calcium and fiber can bind to bile salts and help
remove them from the
body. By removing bile, fiber helps to prevent the damage that certain bile
salts can cause to
colon cells, thereby reducing the risk of colon cancer. In addition, when bile
is removed by fiber,
the body must break down cholesterol in order to make new bile. This process
can help to lower
high cholesterol levels, which can be helpful in preventing atherosclerosis
and heart disease.
[0041] Cinnamaldehyde (also called cinnamic aldehyde) has been well-researched
for its
effects on blood platelets. Platelets are constituents of blood that are meant
to clump together
under emergency circumstances (like physical injury) as a way to stop
bleeding, but under
normal circumstances, they can make blood flow inadequate if they clump
together too much.
The cinnaldehyde in cinnamon helps prevent unwanted clumping of blood
platelets. (The way it
accomplishes this health-protective act is by inhibiting the release of an
inflammatory fatty acid
called arachidonic acid from platelet membranes and reducing the formation of
an inflammatory
messaging molecule called thromboxane A2.) Cinnamon's ability to lower the
release of
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arachidonic acid from cell membranes also puts it in the category of an "anti-
inflammatory" food
that can be helpful in lessening inflammation.
[0042] Cinnamon's essential oils also qualify it as an "anti-microbial" food,
and cinnamon
has been studied for its ability to help stop the growth of bacteria as well
as fungi, including the
commonly problematic yeast Candida. In laboratory tests, growth of yeasts that
were resistant to
the commonly used anti-fungal medication fluconazole was often (though not
always) stopped by
cinnamon extracts.
[0043] Cinnamon's antimicrobial properties are so effective that recent
research
demonstrates this spice can be used as an alternative to traditional food
preservatives. In a study,
published in the August 2003 issue of the International Journal of Food
Microbiology, the
addition of just a few drops of cinnamon essential oil to 100 ml
(approximately 3 ounces) of
carrot broth, which was then refrigerated, inhibited the growth of the food
borne pathogenic
Bacillus cereus for at least 60 days. When the broth was refrigerated without
the addition of
cinnamon oil, the pathogenic B. cereus flourished despite the cold
temperature. In addition,
researchers noted that the addition of cinnamon not only acted as an effective
preservative but
improved the flavor of the broth.(October 1, 2003).
[0044] In addition to the active components in its essential oils and its
nutrient composition,
cinnamon has also been valued in energy-based medical systems, such as
Traditional Chinese
Medicine, for its warming qualities. In these traditions, cinnamon has been
used to provide relief
when faced with the onset of a cold or flu, especially when mixed in a tea
with some fresh
ginger.
[0045] As stated before, coffee is thought to have acute and long-term effects
on health and its
consumption is thought to be protective against the development of type 2
diabetes. Coffee is
consumed by about 50% of the population North America and is the second most
valuable
commodity in the world. Various preliminary studies have indictaed that coffee
has protective
effects on diseases ranging from type 2 diabetes to Parkinson's disease. Also,
some studies have
indicated that coffee may have a beneficial effect on abnormal liver
chemistry, cirrhosis and
heptatocellular carcinoma.
[0046] In a study done at the University of Washington School of Public Health
and Community
Medicine in Seattle Washington USA and reported at Acta Obstet Gynecol Scand.
2007;86(2):161-6,. investigators Adeney, Williams, Schiff and Sorensen
examined the
13
CA 02596200 2007-08-07
relationship between coffee consumption and the risk of gestational diabetes
mellitus (GDM).
They reported that women who reported moderate pre-pregnancy caffeinated
coffee intake had a
significantly reduced risk of GDM compared with non-consumers. No risk
reduction was
reported with decaffeinated coffee intake.
[0047] It has been found from many studies that coffee has a protective effect
on type 2 diabetes.
This association was first published in a cohort of 117,111 Dutch men and
women 30 to 60 years
of age. In this study, the relative risk of type 2 diabetes was 0.50
(95%CI:0.35-0.72) when
comparing > 7 cups/d versus < 2 cups/d. Several other studies are consistent
with this first
observation. Only two studies have shown null results: a prosective,
population-based study of
diabetes among Pima Indians and a longitudinal study in Finland. However, the
study among
Pima Indians had very few heavy coffee drinkers. In a recent systemic review
in which nine
prospective studies were evaluated, the overall relative risk for the
comparison of the highest
category of coffee consumption (> 6-9 cups per day depending on the study)
compared with the
lowest category (0-< 2 cups per day) was 0.65 (95%CI:0.54-0.78). A similar
comparison
between the second-highest category (4-6 cups per day) and the lowest category
yielded an
overall relative risk of 0.72 (05%CI:0.62-0.83). Only when the third-highest
category (1-4 cups
per day) was compared with the lowest category did the relative risk become
null: 0.94
(95TCI:0.88-1.01). Similarly, cross-sectional studies have shown identical
consistent protective
effects in different populations.
[0048] The mechanisms for the protective effect of coffee on type 2 diabetes
is still not clear.
Because decaffeinated coffee is also associated with decreased risk of type 2
diabetes, it has been
proposed that substances other than caffeine are responsible for this
protective effect. Coffee is
rich in chlorogenic acid, a known antioxidant that can inhibit the glucose-6-
phosphatase system
and decrease intestinal absorption of glucose. Furthermore, chlorogenic acid
derivatives called
quinidines are also associated with an increase in insulin sensitivity.
Consistent with this
hypothesis, epidemiologic studies show improvement in glucose metabolism with
long-term
coffee intake.
[0049] Paradoxically, caffeine impaired insulin sensitivity acutely in short-
term controlled trials,
suggesting that caffeine does not directly account for the protection by
coffee. Magnesium has
also been proposed as another potential substance involved in the protective
effect of coffee on
the risk of type 2 diabetes. However, adjusting for magnesium intake in
observational studies
14
CA 02596200 2007-08-07
did not attenuate the association between coffee and type 2 diabetes. It has
also been proposed
that the thermogenic effect of coffee could be related to its protective
effect. Caffeine increases
the resting metabolic rate, and the protective effect of coffee on type 2
diabetes was observed
only among people who had lost weight in one prospective study.
[0050] Epidemiologic studies consistently show a strong protective effect of
coffee on type 2
diabetes. Intake of more than 4 cups per day is required to achieve these
results.
[0051] Other studies have shown that the administration of caffeine found in
coffee results in a
significant decrease in insulin-mediated glucose uptake in resting human.
Carbohydrate storage
is also significantly reduced after caffeine ingestion. It is thought
therefore that caffeine
ingestion in the form of coffee plays a role in the development of insulin
resistance which is
beneficial for certain individuals such as those at risk for the development
of type 2 diabetes.
[0052] Other studies have corroborated that caffeine represented by a moderate
consumption of
coffee decreases insulin sensitivity to the level of glucose-lowering agents
such as metformin
and thiazolidinedione derivatives.
[0053] It is thought that these results are caused by the presence of caffeine
in the coffee.
Caffeine is a natural plant alkaloid, found in numerous plant species.
Caffeine is a central
nervous system and metabolic stimulant, that is commonly used recreationally
and medically to
reduce physical fatigue and promote mental alertness. Caffeine stimulates the
central nervous
system and the spinal cord, resulting in increased alertness and wakefulness
[0054] Caffeine has also been shown to inhibit skeletal muscle glycogen
phosphorylase [GPa
and GPb]. The inhibition is competitive with glucose-l-phosphate and
reversible by AMP.
Caffeine acts with glucose in a synergistic, competitive, and nonexclusive
manner to inhibit both
liver and muscle GPa and GPb. The binding of one ligand facilitates the
binding of the other,
and the inhibition caused by the binding of both is not only greater than that
caused by either
ligand alone, but also greater than if the interaction were additive.
Recently, it has been shown
that the inhibitory effects of caffeine and the synergism with glucose is
preserved even within a
CA 02596200 2007-08-07
complex, physiological mixture of various other effectors [ATP, ADP, AMP, P;,
fructose-l-
phosphate, G6P and UDP-glucose].
[0055] There is evidence from studies that caffeine has inhibitory effects on
phosphoinositide
[PI] metabolism. Recently, caffeine has demonstrated to inhibit the protein
kinase activity of
P13K-related kinases, as well as the lipid kinase activity of class la PI3Ks.
The latter finding is
of importance because it is now well established that activation of the class
la PI3Ks is an
integral component of the insulin signally network, and is necessary to elicit
many of insulin's
effects on glucose and lipid metabolism
100561 Caffeine readily crosses the blood brain barrier. Once in the brain,
the principal mode of
action of caffeine is as an adenosine receptor antagonist. Adenosine
antagonism was clearly
demonstrated for CNS-related functions in vivo, in studies examining the
stimulatory effects of
methylxanthines on mice behavior and locomotor activity. Methylxanthine-
induced antagonism
of various physiological actions of adenosine was demonstrated in several
peripheral tissues,
including smooth and striated muscle, adipocytes, heart, platelets, adrenals,
and pancreas. The
IC50 value for adenosine antagonism was demonstrated to be 10 uM. The
reduction in adenosine
activity results in increased activity of dopamine, which accounts for the
stimulatory effects of
caffeine. Caffeine produces positive effects by aiding concentration,
alleviating fatigue and
increasing wakefulness as a result antagonist action on adenosine receptors,
the mechanism
underlying the psychomotor effects of caffeine.
[0057] The metabolites of caffeine also contribute to its effects. Theobromine
is a vasodilator
that increases oxygen and nutrient flow to the brain and muscles.
Theophyllline acts as a smooth
muscle relaxant that primarily affects bronchioles and acts as a chronotrope
and inotrope.
Paraxanthine increases lipolysis.
16
CA 02596200 2007-08-07
[0058] The present inventors have shown that the new therapeutic formulation
comprising
cinnamon and coffee demonstrates synergist activity and inter alia:
(a) healthy glucose level for people with type 2 diabetes;
(b) optimum level of cholesterol and triglycertides for people of all ages and
thus
reduces the risk of cardiovascular disease.
[0059] The new therapeutic formulation has also been proven as a powerful
antioxidant and
effective in helping to prevent cancer, heart disease, and stroke.
[0060] Another major benefit of the new therapeutic formulation is that it can
prevent insulin
resistance, a major and common complication that develops in people with type
II diabetes in
later years.
[0061] The two main ingredients of the new therapeutic formulation come from
cinnamon
and coffee. Both the ingredients have been successfully used as effective
remedies for many
medical conditions in Indian, Chinese and South American Traditional Medicine.
[0062] The product may be prepared by mixing cinnamon and coffee together and
then
making a beverage therefrom or by making coffee as a beverage and then adding
cinnamon to
the beverage form of coffee.
[0063] The coffee may be made and ground from standard coffee beans in any
form desired
by the user. Cinnamon may be admixed as cinnamon extract or cinnamon powder.
If cinnamon
extract is used, the ratio should be between 200 milligrams and 800 milligrams
per day. If raw
cinnamon is used, the ratio should be between 2000 milligrams of raw cinnamon
and 8000
milligrams of raw cinnamon per day.
[0064] If the cinnamon were added to a standard cup of coffee assuming that
the cup is 250
millilitres, the minimum dosage per cup would be 50 milligrams of cinnamon
extract to 800
milligrams of cinnamon extract or 500 milligrams of raw cinnamon to about 8000
milligrams of
raw cinnamon per 250 millilitres cup.
[0065] Flavouring agents made be added to either mask the flavour of the
cinnamon or to
enhance it. This is up to the individual taste of the consumer.
[0066] Although the disclosure describes a preferred embodiment, the invention
is not so
limited. For a definition of the invention, reference is made to the claims.
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