Title Herbal product comprising cinnamon and coffee for treating diabetes and reducing the risk of cardiovascular disease

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).

[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:

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.

[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

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 aromatlcum (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

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

(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 hypertensive 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,

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 (PO.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.

[0027] 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

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

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-I) in vitro and glycogen synthase kinase-3D (GSK-3 D) in vivo. The inhibition of PTP-I 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

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 ¹ A to V. 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 of Agricultural 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

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 manganese 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

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

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 (95TCL0.88-1.01). 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

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- 1 -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

complex, physiological mixture of various other effectors [ATP, ADP, AMP, P ₁ , fructose- 1- 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 PI3K-related kinases, as well as the lipid kinase activity of class Ia PBKs. The latter finding is of importance because it is now well established that activation of the class Ia PDKs is an integral component of the insulin signally network, and is necessary to elicit many of insulin's effects on glucose and lipid metabolism

[0056] 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. Theophylline acts as a smooth muscle relaxant that primarily affects bronchioles and acts as a chronotrope and inotrope. Paraxanthine increases lipolysis.

[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.