EP1888173A2 - Novel use of (-)-epigallocatechin gallate - Google Patents
Novel use of (-)-epigallocatechin gallateInfo
- Publication number
- EP1888173A2 EP1888173A2 EP06743119A EP06743119A EP1888173A2 EP 1888173 A2 EP1888173 A2 EP 1888173A2 EP 06743119 A EP06743119 A EP 06743119A EP 06743119 A EP06743119 A EP 06743119A EP 1888173 A2 EP1888173 A2 EP 1888173A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- humans
- body weight
- epigallocatechin gallate
- group
- mammal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Definitions
- the present invention refers to the use of (-)-epigallocatechin gallate (EGCG), preferably in combination with a sympathomimeticum, - for increasing/stimulating the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, especially during post prandial conditions;
- EGCG epigallocatechin gallate
- mammals selected from the group consisting of hu- mans, cats, dogs and horses, preferably in humans;
- the preferred sympathomimeticum is caffeine.
- the invention further refers to the corre- sponding methods. Uses
- a first object of the present invention is the use of EGCG for increasing the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, prefera- bly in humans.
- EGCG has especially an influence on the prandial and post-prandial fat oxidation.
- the EGCG may be administered in the form of (fortified) food or (fortified) feed, dietary supplements, beverages, tablets, granules, capsules, pastes, food additives, feed additives, or effervescent formulations. If it is administered in the form of a beverage, it shows its positive influence on the fat oxidation faster than if it is administered in the form of a capsule. In a preferred embodiment of the present invention EGCG is therefore administered in such a way that it is present or moreover that its concentration is at a high level during the intake of food/feed/beverages, especially during the fat intake, of the mammal. That means that EGCG is preferably administered before or simultaneously with the food/feed/beverages.
- the EGCG is part of the food/feed.
- Examples are cereal bars containing EGCG.
- EGCG is used in combination with a sympathomimeticum.
- Espe- cially preferred is also the use of compositions such as dietary supplements consisting essentially of EGCG and caffeine.
- the energy expenditure is not changed by the increased fat oxidation induced by the use of EGCG.
- a second object of the present invention is the use of EGCG for supporting the metaboli- zation of fat in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans.
- EGCG is therefore administered in such a way that it is present or moreover that its concentration is at a high level during the intake of food/feed/beverages, especially during the fat intake, of the mammal selected from the group consisting of humans, cats, dogs and horses, preferably of the humans. That means that EGCG is preferably administered before or simultaneously with the food/feed/beverages.
- the EGCG is part of the food/feed. Examples are cereal bars containing EGCG.
- a third object of the present invention is the use of EGCG for reducing the weight of mammals selected from the group consisting of humans, cats, dogs and horses, preferably the weight of humans.
- EGCG is used in combination with a sympathomimeticum.
- a forth object of the present invention is the use of EGCG for reducing the fat mass in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans.
- EGCG is used in combination with a sympathomimeticum.
- the visceral and/or the subcutaneous fat is reduced by the use of EGCG, preferably in combination with a sympathomimeticum.
- the visceral fat layer is considered an important element in the development of the metabolic syndrome.
- a fifth object of the present invention is the use of EGCG, preferably in combination with a sympathomimeticum, for increasing the endurance in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans. Therefore, the present invention is also directed to sport beverages containing EGCG, preferably highly purified EGCG as defined below, more preferably in combination with caffeine.
- a sixth object of the present invention is the use of EGCG for reducing the carbohydrate oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans.
- EGCG is used in combination with a sympathomimeticum.
- a seventh object of the present invention is the use of EGCG for reducing the respiratory quotient in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans.
- EGCG is used in combination with a sympathomimeticum.
- Respiratory quotient CRO Animal cells obtain energy in the form of ATP by oxidizing food molecules through the process of respiration. Carbohydrates and fatty acids are the most important fuels for generating ATP in animal cells. - A -
- the respiratory quotient measures the ratio of the volume of carbon dioxide (V(Co 2 )) produced by an organism to the volume of oxygen consumed (V(O 2 )).
- the volumes of O 2 and CO 2 are measured by indirect calorimetry
- An eighth object of the present invention is the use of EGCG for improving the flow mediated dilation, thereby contributing to the beneficial effects on coronary health, in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans.
- EGCG acutely increases the flow mediated dilation thereby improving the endothelial function.
- EGCG elicits this effect when present in plasma.
- Endothelial function is regarded as an important element in the development of the metabolic syndrome. Thus, EGCG prevents the development of the metabolic syndrome.
- the used EGCG has a purity of at least 80%, preferably of at least 85%, more preferably of at least 90%, even more preferably of at least 92%, most preferably of at least 94%.
- an aqueous green tea extract containing EGCG in an amount of at least 80% (preferred of at least 85%, more preferred of at least 90%, even more preferred of at least 92%, most preferred of at least 94%), based on the total amount of the extract, as e.g. and preferably obtained by any of the processes described in US 6,383,392, EP 1 103 550, US 10/246 112 and EP 1 077 21 1.
- the total amount of other polyphenols and catechins such as gallocatechin gallate, catechin gallate, epicatechin gallate, epigallocatechin, gallocatechin and epicate- chin is low, preferably it is ⁇ 5 weight-%, based on the total weight of the green tea extract. More preferably the amount of gallocatechin gallate is ⁇ 2.5 weight-%, and/or the amount of epicatechin gallate is ⁇ 5 weight-% (preferably ⁇ 3 weight-%), and/or the amount of caffeine is ⁇ 2.5 weight-%, preferably ⁇ 0.1 weight-%, and/or the amount of gallic acid is ⁇ 0.1 weight-%, based on the total weight of the green tea extract.
- a sympathomimeticum is a substance that stimulates the sympathetic nervous system.
- a preferred example of such a substance is caffeine. Therefore the present invention refers to the use of a combination of EGCG and caffeine for the uses as given above. If caffeine is used in combination with EGCG the daily dosage of caffeine varies preferably from 2.5 mg per kg body weight to 7.5 mg per kg body weight.
- sympathomimetica that may be used in combination with EGCG are theophylline, theobromine or extracts of xanthine containing plants such as cacao plants, coffee plants, barley and ginger.
- the sympathetic nervous system is also stimulated by physical activity such as sport, so that sport can also be seen as sympathomimeticum. Therefore, the present invention relates also to the use of EGCG as given above, preferably of highly purified EGCG as defined above, in combination with physical activity.
- Preferred subjects for the uses/methods of the present invention are humans.
- the daily dosage of EGCG varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
- the daily dosage of EGCG varies from 10 to 1500 mg, preferably from 150 to 600 mg, more preferably from 300 to 600 mg, most preferably it is 300 mg.
- a ninth object of the present invention is a method for increasing the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of EGCG, preferably in combination with an effective dose of a sympathomimeticum, to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of (-)- epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
- a tenth object of the present invention is a method for supporting the metabolization of fat in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of EGCG, preferably in combination with an effective dose of a sympathomimeticum, to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of (-)- epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
- An eleventh object of the present invention is a method for reducing the fat mass in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of EGCG, preferably in combination with a sympathomimeticum, to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of EGCG varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
- a twelfth object of the present invention is a method for reducing the weight of mammals selected from the group consisting of humans, cats, dogs and horses, preferably for reducing the weight of humans, said method comprising the step of administering an effective dose of EGCG, preferably in combination with a sympathomimeticum, to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of EGCG varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
- a thirteenth object of the present invention is a method for increasing the endurance in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of EGCG, preferably in combination with a sympathomimeticum, to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of EGCG varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
- a forteenth object of the present invention is a method for reducing the carbohydrate oxi- dation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of EGCG, preferably in combination with a sympathomimeticum, to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of EGCG varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
- the methods further comprise the step of the mammals selected from the group consisting of humans, cats, dogs and horses performing physical activity, preferably the methods further comprise the step of the humans performing physical activity.
- a fifteenth object of the present invention is a method for reducing the respiratory quotient in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of (-)- epigallocatechin gallate, preferably in combination with a sympathomimeticum, to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of (-)-epigallo- catechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
- a sixteenth object of the present invention is a method for improving the flow mediated dilation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, thereby contributing to a beneficial effect on the coronary health, said method comprising the step of administering an effective dose of (-)-epigallocatechin gallate to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of (-)-epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
- the mammals are humans with a body mass index above 25.
- the body mass index is the number obtained by dividing the body weight in kilogramm of a human by the square of its height in meters.
- the EGCG has a purity of at least 80%, preferably of at least 85%, more preferably of at least 90%, even more preferably of at least 92%, most preferably of at least 94%.
- an EGCG obtained by any of the processes described in US 6,383,392, EP 1 103 550, US 10/246 112 and EP 1 077 211.
- the EGCG may be administered in the form of (fortified) food or (fortified) feed, dietary supplements, beverages, food additives, or feed additives.
- Non-limiting examples of food are dairy products such as yoghurts, cereal bars and bakery items such as cakes and cookies; but EGCG may also be added to any other food/feed a mammal selected from the group consisting of humans, cats, dogs and horses regularly eats. Food may also be in liquid form such as soups and dairy products (muesli drinks).
- Non-limiting examples of beverages for humans are non-alcoholic drinks such as soft drinks, sport drinks, fruit juices, lemonades, near-water drinks (i.e. low calorie drinks based on water), teas and milk based drinks.
- Preferred forms of dietary supplements are tablets, pills, granules, dragees, capsules, and effervescent formulations.
- EGCG is administered in the form of a beverage, it shows its positive influence on the fat oxidation and the endurance faster than if it is administered in the form of a capsule.
- EGCG is therefore administered in such a way that it is present or moreover that its concentration is at a high level during the intake of food/feed/beverages, especially during the fat intake, of the mammal selected from the group consisting of humans, cats, dogs and horses, preferably of the human, and during the activity for which endurance is needed, respectively. That means that EGCG is preferably administered before or simultaneously with the food/feed/beverages.
- the (composition/dietary supplement containing) EGCG is incorporated by the mammal selected from the group consisting of humans, cats, dogs and horses, preferably of the human, at least half an hour before the intake of food, feed or beverages, preferably at a point in time between 0.5 and 1.5 hours before the intake of food, feed or beverages. If EGCG is administered in form of fortified food, feed or beverages it is simultaneously incorporated by the mammal selected from the group consisting of humans, cats, dogs and horses, preferably of the human, with such fortified food, feed or beverage.
- EGCG is used in combination with a sympathomimeticum.
- the present invention is also directed to the use of (-)-epigallocatechin gallate, preferably in combination with a sympathomimeticum, for the manufacture of a composition - for increasing the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans;*
- composition is administered in such a way that (-)-epigallocatechin gallate is present in the body during the intake of food/feed/beverages of the mammal, preferably that it is present in a high concentration in the body during the intake of food/feed/beverages of the mammal selected from the group consisting of humans, cats, dogs and horses, preferably of the human.
- composition is administered in such a way that (-)-epigallocatechin gallate is present, preferably in high concentration, in the body when the mammal selected from the group consisting of humans, cats, dogs and horses, preferably when the human, is performing the activity for which endurance is needed.
- the dietary supplement is incorporated by said mammal at least half an hour before the intake of food, feed or beverages, even more pre- ferred at a point in time between half an hour and one and a half hour before the intake of food, feed or beverages.
- the EGCG has a purity of at least 80%, preferably of at least 85%, more preferably of at least 90%, even more preferably of at least 92%, most preferably of at least 94%.
- an aqueous green tea extract containing EGCG in an amount of at least 80% (preferred of at least 85%, more preferred of at least 90%, even more preferred of at least 92%, most preferred of at least 94%), based on the total amount of the extract, as e.g. and preferably obtained by any of the processes described in US 6,383,392, EP 1 103 550, US 10/246 112 and EP 1 077 211.
- the total amount of other polyphenols and catechins such as gallocatechin gallate, catechin gallate, epicatechin gallate, epigallocatechin, gallocatechin and epicatechin is low, preferably it is ⁇ 5 weight-%, based on the total weight of the green tea extract. More preferably the amount of gallocatechin gallate is ⁇ 2.5 weight-%, and/or the amount of epicatechin gallate is ⁇ 5 weight-% (preferably ⁇ 3 weight-%), and/or the amount of caffeine is ⁇ 2.5 weight-%, preferably ⁇ 0.1 weight-%, and/or the amount of gallic acid is ⁇ 0.1 weight-%, based on the total weight of the green tea extract.
- the dietary supplement preferably additionally contains a sympathomimeticum such as caffeine. Therefore the present invention refers to the use of a combination of EGCG and caffeine for the uses as given above. If caffeine is used in combination with EGCG the daily dosage of caffeine varies preferably from 2.5 mg per kg body weight to 7.5 mg per kg body weight.
- the sympathetic nervous system is also stimulated by physical activity such as sport, so that sport can also be seen as sympathomimeticum. Therefore, the present invention relates also to the use of EGCG as given above, preferably of highly purified EGCG as defined above, in combination with physical activity.
- Preferred subjects for the uses/methods of the present invention are humans.
- the daily dosage of EGCG varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most pref- erably from 4.0 to 4.5 mg per kg body weight per day.
- the daily dosage of EGCG varies from 10 to 1500 mg, preferably from 150 to 600 mg, more preferably from 300 to 600 mg, most preferably it is 300 mg.
- the dietary supplement containing (-)-epigallocatechin gallate may be incorporated by the mammal simultaneously with the food, feed or beverage, respectively.
- further objects of the present invention are: 0 Use of a dietary supplement containing (-)-epigallocatechin gallate for increasing the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal simultaneously with the regular intake of food, feed or beverages containing said fat whose oxidation is increased.
- a dietary supplement containing (— )-epigallocatechin gallate for reducing the weight of a mammal selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal simultaneously with the intake of food, feed or beverages.
- a dietary supplement containing (-)-epigallocatechin gallate for reducing the fat mass in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal simultaneously with the intake of food, feed or beverages.
- a dietary supplement containing (-)-epigallocatechin gallate for reducing the carbohydrate oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal simultane- ously with the regular intake of food, feed or beverages containing said carbohydrate whose oxidation is reduced.
- the food, feed or beverage itself may be fortified with (-)-epigallocatechin gallate.
- (-)-epigallocatechin gallate is incorporated by said mammal simultaneously with the intake of food, feed and beverages, respectively.
- the food, feed or beverage is fortified with EGCG in such an amount so that the daily dosage of EGCG varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
- the food, feed or beverage is fortified with EGCG in such an amount so that the daily dosage of EGCG varies from 10 to 1500 mg, preferably from 150 to 600 mg, more preferably from 300 to 600 mg, most preferably it is 300 mg.
- Experiment D 150 mg EGCG + 100 mg caffeine, one capsule, twice per day per os for two days;
- Experiment E placebo, one capsule, twice per day per os for two days; two capsules, prior basal and one capsule prior to post-prandial measurement.
- the study supplements were taken orally twice daily, 1.0 hours before breakfast and dinner, respectively for which specific nutritional guidelines had to be followed.
- variable was treatment (EGCG, caffeine, placebo). Pairwise comparison across treatments was per- formed by using t-test with bonferroni's correction. A p- value smaller than 0.05 was considered significant. Values are given as mean ⁇ SD. Graphical displays were generated. If a numeric and/or statistical analysis was not possible a descriptive analysis was done.
- the "*" indicates a statistical significance between treatment and placebo, whereas "p” represents the probability that an observed difference between the intervention and control groups is due to chance alone if the null hypothesis is true.
- a p- value of 0.05 or less rejects the null hypothesis "at the 5% level", i.e. the statistical assumptions used imply that only 5% of the time the supposed statistical process would pro- prise a finding this extreme that the null hypothesis is true.
- 5% and 10% are common significance levels to which p-values are compared.
- Fig. 1 shows the difference in the respiratory quotient of the groups A to D in comparison to group E.
- the respiratory quotient was assessed by indirect calorimetry using a Deltatrac.
- group A, C and D the respiratory quotient was reduced in comparison to group E during basal conditions.
- these differences were still existing or even increased.
- the respiratory quotient was also different between group B and group E.
- Fig. 2 shows the difference in the lipid oxidation rate of the groups A to D in comparison to group E.
- the lipid oxidation rate was assessed by indirect calorimetry using a Deltatrac.
- group A, B, C and D the lipid oxidation rate was increased in comparison to group E during basal conditions. During post prandial conditions these differences were more pronounced.
- Statistical significance was observed for group C and D during basal conditions and for group D at post prandial conditions.
- Fig. 3 shows the difference in the carbohydrate oxidation rate of the groups A to D in comparison to group E.
- the carbohydrate oxidation rate was assessed by indirect calorimetry using a Deltatrac.
- group A, B, C and D the carbohydrate oxidation rate was reduced in comparison to group E during basal conditions. During post prandial conditions these differences were more pronounced. Statistical significance was observed for group D during prandial conditions.
- Fig. 4 shows the increase in the lipid oxidation rate of the groups A to D relative to group E between basal and post prandial conditions.
- the lipid oxidation rate was assessed by indirect calorimetry using a Deltatrac. There was an increase in lipid oxidation rate from basal to post prandial conditions in group A, B, and C, whereas it was highest in group A. No change was observed for group D.
- Fig. 5 shows the lipid oxidation rate of the groups A, C, D and E during maximum post prandial stimulation due to the test meal.
- the lipid oxidation rate was assessed by indirect calorimetry using a Deltatrac. Lipid oxidation rate increased in group A, C, D, and E, whereas the lipid oxidation rate of group A, C and D were higher compared to group E,
- Fig. 6 shows the synergism between groups A and C on fat oxidation during maximum post prandial stimulation.
- the lipid oxidation rate was assessed by indirect calorimetry using a Deltatrac.
- Group D has higher lipid oxidation than the sum of group A and group C, suggesting a synergism.
- FIG. 8 TEAVIGOTM improves flow mediated dilation
- Fig. 8 shows the difference in flow mediated dilation (FMD) of the groups A and E in comparison to baseline for acute (2 hours), and chronic (2 weeks) treatment.
- FMD flow mediated dilation
- Fig. 9 shows the difference in EGCG plasma levels the groups A and E in comparison to baseline for acute (2 hours), and chronic (2 weeks) treatment.
- EGCG in plasma was determined by High Performance Liquid Chromatography-Mass Spectrometry.
- group A EGCG levels were increased after acute administration.
- group E after acute administration.
- group E after chronic treatment.
- the plasma EGCG level returned to baseline after chronic treatment. This is due to assessing the EGCG level 14 hours after the last administration. Therefore, EGCG does not accumulate in plasma.
- Fig. 10 shows the lipid oxidation rate of the groups A to E.
- the lipid oxidation rate was assessed by indirect calorimetry using a Deltatrac. In all groups the lipid oxidation rate is higher during basal conditions compared to post prandial conditions. Between groups, lipid oxidation rate in group E is lowest under the respective condition. Statistical significance was observed for group C and D during basal conditions and for group D at post prandial conditions.
- Fig. 11 shows the carbohydrate oxidation rate of the groups A to E.
- the carbohydrate oxidation rate was assessed by indirect calorimetry using a Deltatrac. In all groups the carbo- hydrate oxidation rate is higher during post prandial conditions compared to basal conditions. Between groups, carbohydrate oxidation rate in group E is highest under the respective condition. Statistical significance was observed for group D during post prandial.
Abstract
The present invention refers to the use of (-) -epigallocatechin gallate, preferably in combination with a sympathomimeticum, preferably caffeine, <and otherwise improving fat metabolism and carbohydrate metabolism, thereby improving a number of pathophysiological conditions>.
Description
Novel use of (-Vepigallocatechin gallate
The present invention refers to the use of (-)-epigallocatechin gallate (EGCG), preferably in combination with a sympathomimeticum, - for increasing/stimulating the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, especially during post prandial conditions;
- for supporting the metabolization of fat in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans; - for reducing the weight of mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans;
- for reducing the fat mass in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans;
- for increasing the endurance in mammals selected from the group consisting of hu- mans, cats, dogs and horses, preferably in humans;
- for reducing the carbohydrate oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans;
- for reducing the respiratory quotient in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans; and - for improving the flow mediated dilation, thereby contributing to the beneficial effects on coronary health, in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans.
The preferred sympathomimeticum is caffeine. The invention further refers to the corre- sponding methods.
Uses
A first object of the present invention is the use of EGCG for increasing the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, prefera- bly in humans. The fat oxidation encompasses the pre-prandial, prandial and post-prandial fat oxidation, i.e. the fat (= lipid) oxidation before, during and after the meals taken by the mammals selected from the group consisting of humans, cats, dogs and horses, preferably by the humans. EGCG has especially an influence on the prandial and post-prandial fat oxidation. The EGCG may be administered in the form of (fortified) food or (fortified) feed, dietary supplements, beverages, tablets, granules, capsules, pastes, food additives, feed additives, or effervescent formulations. If it is administered in the form of a beverage, it shows its positive influence on the fat oxidation faster than if it is administered in the form of a capsule. In a preferred embodiment of the present invention EGCG is therefore administered in such a way that it is present or moreover that its concentration is at a high level during the intake of food/feed/beverages, especially during the fat intake, of the mammal. That means that EGCG is preferably administered before or simultaneously with the food/feed/beverages. In a preferred embodiment of the invention the EGCG is part of the food/feed. Examples are cereal bars containing EGCG. In a preferred embodiment of the present invention EGCG is used in combination with a sympathomimeticum. Espe- cially preferred is also the use of compositions such as dietary supplements consisting essentially of EGCG and caffeine. Advantageously the energy expenditure is not changed by the increased fat oxidation induced by the use of EGCG.
A second object of the present invention is the use of EGCG for supporting the metaboli- zation of fat in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans. In a preferred embodiment of this object of the present invention EGCG is therefore administered in such a way that it is present or moreover that its concentration is at a high level during the intake of food/feed/beverages, especially during the fat intake, of the mammal selected from the group consisting of humans, cats, dogs and horses, preferably of the humans. That means that EGCG is preferably administered before or simultaneously with the food/feed/beverages. In a preferred embodiment of the invention the EGCG is part of the food/feed. Examples are cereal bars containing EGCG.
A third object of the present invention is the use of EGCG for reducing the weight of mammals selected from the group consisting of humans, cats, dogs and horses, preferably the weight of humans. In a preferred embodiment of this object EGCG is used in combination with a sympathomimeticum.
A forth object of the present invention is the use of EGCG for reducing the fat mass in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans. In a preferred embodiment of this object EGCG is used in combination with a sympathomimeticum. Especially the visceral and/or the subcutaneous fat is reduced by the use of EGCG, preferably in combination with a sympathomimeticum. The visceral fat layer is considered an important element in the development of the metabolic syndrome.
A fifth object of the present invention is the use of EGCG, preferably in combination with a sympathomimeticum, for increasing the endurance in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans. Therefore, the present invention is also directed to sport beverages containing EGCG, preferably highly purified EGCG as defined below, more preferably in combination with caffeine.
A sixth object of the present invention is the use of EGCG for reducing the carbohydrate oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans. In a preferred embodiment of this object EGCG is used in combination with a sympathomimeticum.
A seventh object of the present invention is the use of EGCG for reducing the respiratory quotient in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans. In a preferred embodiment of this object EGCG is used in combination with a sympathomimeticum.
Respiratory quotient CRO) Animal cells obtain energy in the form of ATP by oxidizing food molecules through the process of respiration. Carbohydrates and fatty acids are the most important fuels for generating ATP in animal cells.
- A -
The respiratory quotient (RQ) measures the ratio of the volume of carbon dioxide (V(Co2)) produced by an organism to the volume of oxygen consumed (V(O2)).
RQ=V(CO2)/V(O2)
The volumes of O2 and CO2 are measured by indirect calorimetry
The RQ depends on which fuel source is being metabolized: C6Hi2O6 + 6 O2 -» 6 CO2+ 6 H2ORQ = 6/6 = 1.0 (carbohydrate) C18H34O2 + 25.5 O2 -» 18 CO2 + 17 H2O RQ = 18/25.5 = 0.7 (fat)
An eighth object of the present invention is the use of EGCG for improving the flow mediated dilation, thereby contributing to the beneficial effects on coronary health, in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans. EGCG acutely increases the flow mediated dilation thereby improving the endothelial function. EGCG elicits this effect when present in plasma. Endothelial function is regarded as an important element in the development of the metabolic syndrome. Thus, EGCG prevents the development of the metabolic syndrome.
In preferred embodiments of the present invention the used EGCG has a purity of at least 80%, preferably of at least 85%, more preferably of at least 90%, even more preferably of at least 92%, most preferably of at least 94%. Especially preferred is also an aqueous green tea extract containing EGCG in an amount of at least 80% (preferred of at least 85%, more preferred of at least 90%, even more preferred of at least 92%, most preferred of at least 94%), based on the total amount of the extract, as e.g. and preferably obtained by any of the processes described in US 6,383,392, EP 1 103 550, US 10/246 112 and EP 1 077 21 1. Preferably the total amount of other polyphenols and catechins such as gallocatechin gallate, catechin gallate, epicatechin gallate, epigallocatechin, gallocatechin and epicate- chin is low, preferably it is < 5 weight-%, based on the total weight of the green tea extract. More preferably the amount of gallocatechin gallate is < 2.5 weight-%, and/or the amount of epicatechin gallate is ≤ 5 weight-% (preferably < 3 weight-%), and/or the amount of caffeine is < 2.5 weight-%, preferably < 0.1 weight-%, and/or the amount of gallic acid is < 0.1 weight-%, based on the total weight of the green tea extract.
A sympathomimeticum is a substance that stimulates the sympathetic nervous system. A preferred example of such a substance is caffeine. Therefore the present invention refers to the use of a combination of EGCG and caffeine for the uses as given above. If caffeine is used in combination with EGCG the daily dosage of caffeine varies preferably from 2.5 mg per kg body weight to 7.5 mg per kg body weight.
Other examples of sympathomimetica that may be used in combination with EGCG are theophylline, theobromine or extracts of xanthine containing plants such as cacao plants, coffee plants, barley and ginger.
The sympathetic nervous system is also stimulated by physical activity such as sport, so that sport can also be seen as sympathomimeticum. Therefore, the present invention relates also to the use of EGCG as given above, preferably of highly purified EGCG as defined above, in combination with physical activity.
Preferred subjects for the uses/methods of the present invention are humans.
In preferred embodiments of the uses as given above the daily dosage of EGCG varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
Thus, for humans with a weight of 70 kg, the daily dosage of EGCG varies from 10 to 1500 mg, preferably from 150 to 600 mg, more preferably from 300 to 600 mg, most preferably it is 300 mg.
Methods
A ninth object of the present invention is a method for increasing the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of EGCG, preferably in combination with an effective dose of a sympathomimeticum, to a mammal
selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of (-)- epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
A tenth object of the present invention is a method for supporting the metabolization of fat in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of EGCG, preferably in combination with an effective dose of a sympathomimeticum, to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of (-)- epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
An eleventh object of the present invention is a method for reducing the fat mass in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of EGCG, preferably in combination with a sympathomimeticum, to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of EGCG varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
A twelfth object of the present invention is a method for reducing the weight of mammals selected from the group consisting of humans, cats, dogs and horses, preferably for reducing the weight of humans, said method comprising the step of administering an effective dose of EGCG, preferably in combination with a sympathomimeticum, to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of EGCG varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per
day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
A thirteenth object of the present invention is a method for increasing the endurance in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of EGCG, preferably in combination with a sympathomimeticum, to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of EGCG varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
A forteenth object of the present invention is a method for reducing the carbohydrate oxi- dation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of EGCG, preferably in combination with a sympathomimeticum, to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of EGCG varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
In preferred embodiments of the methods as given above, the methods further comprise the step of the mammals selected from the group consisting of humans, cats, dogs and horses performing physical activity, preferably the methods further comprise the step of the humans performing physical activity.
A fifteenth object of the present invention is a method for reducing the respiratory quotient in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of (-)- epigallocatechin gallate, preferably in combination with a sympathomimeticum, to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of (-)-epigallo-
catechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
A sixteenth object of the present invention is a method for improving the flow mediated dilation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, thereby contributing to a beneficial effect on the coronary health, said method comprising the step of administering an effective dose of (-)-epigallocatechin gallate to a mammal selected from the group consisting of humans, cats, dogs and horses, preferably to a human, which is in need thereof, characterized in that the effective dose of (-)-epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
In further preferred embodiments of the methods as given above the mammals are humans with a body mass index above 25. The body mass index is the number obtained by dividing the body weight in kilogramm of a human by the square of its height in meters.
In especially preferred embodiments of the methods as given above the EGCG has a purity of at least 80%, preferably of at least 85%, more preferably of at least 90%, even more preferably of at least 92%, most preferably of at least 94%. Especially preferred is an EGCG obtained by any of the processes described in US 6,383,392, EP 1 103 550, US 10/246 112 and EP 1 077 211.
As already stated above the EGCG may be administered in the form of (fortified) food or (fortified) feed, dietary supplements, beverages, food additives, or feed additives.
Non-limiting examples of food, especially for humans, are dairy products such as yoghurts, cereal bars and bakery items such as cakes and cookies; but EGCG may also be added to any other food/feed a mammal selected from the group consisting of humans, cats, dogs and horses regularly eats. Food may also be in liquid form such as soups and dairy products (muesli drinks).
Non-limiting examples of beverages for humans are non-alcoholic drinks such as soft drinks, sport drinks, fruit juices, lemonades, near-water drinks (i.e. low calorie drinks based on water), teas and milk based drinks.
Preferred forms of dietary supplements are tablets, pills, granules, dragees, capsules, and effervescent formulations.
If EGCG is administered in the form of a beverage, it shows its positive influence on the fat oxidation and the endurance faster than if it is administered in the form of a capsule. In a preferred embodiment of the present invention EGCG is therefore administered in such a way that it is present or moreover that its concentration is at a high level during the intake of food/feed/beverages, especially during the fat intake, of the mammal selected from the group consisting of humans, cats, dogs and horses, preferably of the human, and during the activity for which endurance is needed, respectively. That means that EGCG is preferably administered before or simultaneously with the food/feed/beverages. In an especially preferred embodiment of the present invention the (composition/dietary supplement containing) EGCG is incorporated by the mammal selected from the group consisting of humans, cats, dogs and horses, preferably of the human, at least half an hour before the intake of food, feed or beverages, preferably at a point in time between 0.5 and 1.5 hours before the intake of food, feed or beverages. If EGCG is administered in form of fortified food, feed or beverages it is simultaneously incorporated by the mammal selected from the group consisting of humans, cats, dogs and horses, preferably of the human, with such fortified food, feed or beverage.
In a preferred embodiment of the present invention EGCG is used in combination with a sympathomimeticum.
The present invention is also directed to the use of (-)-epigallocatechin gallate, preferably in combination with a sympathomimeticum, for the manufacture of a composition - for increasing the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans;*
- for supporting the metabolization of fat in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans;4
- for reducing the weight of mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans;
- for reducing the fat mass in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans; - for increasing the endurance in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans;*
- for reducing the carbohydrate oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans;
- for reducing the respiratory quotient in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans;
- for improving the flow mediated dilation, thereby for contributing to the beneficial effects on coronary heart, in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans.
♦ In preferred embodiments of the present invention the composition is administered in such a way that (-)-epigallocatechin gallate is present in the body during the intake of food/feed/beverages of the mammal, preferably that it is present in a high concentration in the body during the intake of food/feed/beverages of the mammal selected from the group consisting of humans, cats, dogs and horses, preferably of the human.
• In preferred embodiments of the present invention the composition is administered in such a way that (-)-epigallocatechin gallate is present, preferably in high concentration, in the body when the mammal selected from the group consisting of humans, cats, dogs and horses, preferably when the human, is performing the activity for which endurance is needed.
The preferences mentioned above for (-)-epigallocatechin gallate, the sympathomimeti- cum, the mammals, the form in which the composition is administered, and the daily dosage of (-)-epigallocatechin gallate also apply here.
Also objects of the present invention are the methods according to claims 26 to 38.
Further objects of the present invention are:
* Use of a dietary supplement containing (-)-epigallocatechin gallate for increasing the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal before the regular intake of food, feed or beverages containing said fat whose oxidation is increased.
* Use of a dietary supplement containing (-)-epigallocatechin gallate for reducing the weight of a mammal selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal before the intake of food, feed or beverages.
* Use of a dietary supplement containing (-)-epigallocatechin gallate for reducing the fat mass in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal before the intake of food, feed or beverages.
* Use of a dietary supplement containing (-)-epigallocatechin gallate for reducing the carbohydrate oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal before the regular intake of food, feed or beverages containing said carbohydrate whose oxidation is reduced.
In preferred embodiments of these uses (*) the dietary supplement is incorporated by said mammal at least half an hour before the intake of food, feed or beverages, even more pre- ferred at a point in time between half an hour and one and a half hour before the intake of food, feed or beverages.
In preferred embodiments of these uses the EGCG has a purity of at least 80%, preferably of at least 85%, more preferably of at least 90%, even more preferably of at least 92%, most preferably of at least 94%. Especially preferred is also an aqueous green tea extract containing EGCG in an amount of at least 80% (preferred of at least 85%, more preferred of at least 90%, even more preferred of at least 92%, most preferred of at least 94%), based on the total amount of the extract, as e.g. and preferably obtained by any of the processes described in US 6,383,392, EP 1 103 550, US 10/246 112 and EP 1 077 211. Preferably
the total amount of other polyphenols and catechins such as gallocatechin gallate, catechin gallate, epicatechin gallate, epigallocatechin, gallocatechin and epicatechin is low, preferably it is < 5 weight-%, based on the total weight of the green tea extract. More preferably the amount of gallocatechin gallate is < 2.5 weight-%, and/or the amount of epicatechin gallate is < 5 weight-% (preferably < 3 weight-%), and/or the amount of caffeine is < 2.5 weight-%, preferably < 0.1 weight-%, and/or the amount of gallic acid is < 0.1 weight-%, based on the total weight of the green tea extract.
The dietary supplement preferably additionally contains a sympathomimeticum such as caffeine. Therefore the present invention refers to the use of a combination of EGCG and caffeine for the uses as given above. If caffeine is used in combination with EGCG the daily dosage of caffeine varies preferably from 2.5 mg per kg body weight to 7.5 mg per kg body weight.
The sympathetic nervous system is also stimulated by physical activity such as sport, so that sport can also be seen as sympathomimeticum. Therefore, the present invention relates also to the use of EGCG as given above, preferably of highly purified EGCG as defined above, in combination with physical activity.
Preferred subjects for the uses/methods of the present invention are humans.
In preferred embodiments of the uses as given above the daily dosage of EGCG varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most pref- erably from 4.0 to 4.5 mg per kg body weight per day.
Thus, for humans with a weight of 70 kg, the daily dosage of EGCG varies from 10 to 1500 mg, preferably from 150 to 600 mg, more preferably from 300 to 600 mg, most preferably it is 300 mg.
Alternatively the dietary supplement containing (-)-epigallocatechin gallate may be incorporated by the mammal simultaneously with the food, feed or beverage, respectively. Thus, further objects of the present invention are:
0 Use of a dietary supplement containing (-)-epigallocatechin gallate for increasing the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal simultaneously with the regular intake of food, feed or beverages containing said fat whose oxidation is increased.
0 Use of a dietary supplement containing (— )-epigallocatechin gallate for reducing the weight of a mammal selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal simultaneously with the intake of food, feed or beverages.
0 Use of a dietary supplement containing (-)-epigallocatechin gallate for reducing the fat mass in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal simultaneously with the intake of food, feed or beverages.
0 Use of a dietary supplement containing (-)-epigallocatechin gallate for reducing the carbohydrate oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal simultane- ously with the regular intake of food, feed or beverages containing said carbohydrate whose oxidation is reduced.
Here the same preferences as cited above apply.
In further embodiments of the present invention the food, feed or beverage itself may be fortified with (-)-epigallocatechin gallate. The advantage thereof is that the (-)- epigallocatechin gallate is incorporated by said mammal simultaneously with the intake of food, feed and beverages, respectively. Thus, further objects of the present invention are:
0 Use of a food, feed or beverage fortified with (-)-epigallocatechin gallate for increasing the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses.
0 Use of a a food, feed or beverage fortified with (-)-epigallocatechin gallate for reducing the weight of a mammal selected from the group consisting of humans, cats, dogs and horses.
0 Use of a food, feed or beverage fortified with (-)-epigallocatechin gallate for reducing the fat mass in mammals selected from the group consisting of humans, cats, dogs and horses.
0 Use of a food, feed or beverage fortified with (-)-epigallocatechin gallate for reducing the carbohydrate oxidation in mammals selected from the group consisting of humans, cats, dogs and horses.
In preferred embodiments of the uses as given above the food, feed or beverage is fortified with EGCG in such an amount so that the daily dosage of EGCG varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
Thus, for humans with a weight of 70 kg, the food, feed or beverage is fortified with EGCG in such an amount so that the daily dosage of EGCG varies from 10 to 1500 mg, preferably from 150 to 600 mg, more preferably from 300 to 600 mg, most preferably it is 300 mg.
The invention is illustrated further by the following examples.
Examples
The following abbreviations were used: os = oral supplementation
Example 1: Study
Study design double blind, randomized, placebo-controlled, cross over study, single center
Study population and planned sample size
12 healthy male volunteers (age 18-40, Body Mass Index 27 - 35), each volunteer underwent five experiments (A to E).
Study supplement
Hard-gelatin capsules with 300 mg EGCG, hard-gelatin capsules with 150 mg EGCG, hard-gelatin capsules with 100 mg caffeine, hard-gelatin capsules with 150 mg EGCG + 100 mg caffeine or hard-gelatin capsules with with placebo, twice a day.
Dosage regime
Experiment A
150 mg EGCG, one capsule, twice per day per os for two days;
300 mg EGCG, two capsules, prior basal and 150 mg EGCG, one capsule, prior to post- prandial measurement.
Experiment B
300 mg EGCG, one capsule, twice per day per os for two days;
600 mg EGCG, two capsules, prior basal and 300 mg EGCG, one capsule, prior to post- prandial measurement
Experiment C
100 mg caffeine, one capsule, twice per day per os for two days;
200 mg caffeine, two capsules, prior basal and 100 mg caffeine, one capsule, prior to postprandial measurement.
Experiment D 150 mg EGCG + 100 mg caffeine, one capsule, twice per day per os for two days;
300 mg EGCG + 200 mg caffeine, two capsules, prior basal and 150 mg EGCG + 100 mg caffeine, one capsule, post-prandial measurement.
Experiment E placebo, one capsule, twice per day per os for two days; two capsules, prior basal and one capsule prior to post-prandial measurement.
The study supplements were taken orally twice daily, 1.0 hours before breakfast and dinner, respectively for which specific nutritional guidelines had to be followed.
Duration of treatment
The supplementation lasted 3 days for each experiment, each supplementation was separated by > 1 week.
Parameters
> Fat oxidation, glucose oxidation, and thermogenesis by indirect calorimetry protein oxidation by urinary N-excretion
> EGCG and caffeine profile
> Vital signs (BP, HR) > Clinical chemistry
> Blood glucose and insulin level
> Adverse event reporting
Study procedures The recruitment and screening of volunteers (Visit 0) involved two stages:
1. The study procedures were explained. Screening consent was obtained. Medical history, general health, body composition, physical activity and food intake was assessed.
2. Determination of eligibility/inclusion: Eligibility was determined once all results including clinical laboratory were available. Volunteers signed the informed consent for the study and were randomly assigned to the five experiments (A, B, C, D, and E).
The volunteers were instructed to maintain their normal dietary habits. There was no excess physical activity 24 hours prior to the study.
The study procedures were performed at the different visits Vl - V5. Volunteers were then given their capsules and the respective instructions. Twice daily, over 3 days, volunteers received one capsule containing either 150 mg EGCG (group A), 300 mg EGCG (group B), 100 mg caffeine (group C), 150 mg EGCG + 100 mg caffeine (group D), or placebo (group E). All capsules had identical appearance. During this period, subjects drank no caffeine containing beverages.
At day 2, volunteers spent the night at the hospital. At day 3, 1.0 hours prior to basal measurements, volunteers received the daily dose of supplementation. 1.0 hours before the study meal volunteers received half of the daily dose of supplementation.
For completion of all tests and measurements at the different clinical visits a period of 7 days was not exceeded.
Statistical considerations
The main parameter (fat oxidation) was tested with analysis of variance: variable was treatment (EGCG, caffeine, placebo). Pairwise comparison across treatments was per- formed by using t-test with bonferroni's correction. A p- value smaller than 0.05 was considered significant. Values are given as mean ± SD. Graphical displays were generated. If a numeric and/or statistical analysis was not possible a descriptive analysis was done.
In the following figures the "*" indicates a statistical significance between treatment and placebo, whereas "p" represents the probability that an observed difference between the intervention and control groups is due to chance alone if the null hypothesis is true. A p- value of 0.05 or less rejects the null hypothesis "at the 5% level", i.e. the statistical assumptions used imply that only 5% of the time the supposed statistical process would pro-
duce a finding this extreme that the null hypothesis is true. 5% and 10% are common significance levels to which p-values are compared.
In all figures the following correlation applies:
0 group A; H] group B; Hffl group C; § group D; Lj group E.
Figure 1: Respiratory Quotient (RQ) X = delta in Respiratory Quotient; yl = basal, y2 = post prandial
Fig. 1 shows the difference in the respiratory quotient of the groups A to D in comparison to group E. The respiratory quotient was assessed by indirect calorimetry using a Deltatrac. In group A, C and D the respiratory quotient was reduced in comparison to group E during basal conditions. During post prandial conditions these differences were still existing or even increased. Furthermore, during post prandial conditions the respiratory quotient was also different between group B and group E.
Figure 2: Lipid oxidation (Lox) rate X = delta lipid oxidation g/4h; yl = basal, y2 = post prandial
Fig. 2 shows the difference in the lipid oxidation rate of the groups A to D in comparison to group E. The lipid oxidation rate was assessed by indirect calorimetry using a Deltatrac. In group A, B, C and D the lipid oxidation rate was increased in comparison to group E during basal conditions. During post prandial conditions these differences were more pronounced. Statistical significance was observed for group C and D during basal conditions and for group D at post prandial conditions.
Figure 3: Carbohydrate oxidation rate (Cox) X = delta carbohydrate oxidation g/4h; yl = basal, y2 = post prandial
Fig. 3 shows the difference in the carbohydrate oxidation rate of the groups A to D in comparison to group E. The carbohydrate oxidation rate was assessed by indirect calorimetry using a Deltatrac. In group A, B, C and D the carbohydrate oxidation rate was reduced in
comparison to group E during basal conditions. During post prandial conditions these differences were more pronounced. Statistical significance was observed for group D during prandial conditions.
Figure 4: Increase in postprandial lipid oxidation rate, relative to basal
X = delta between basal and post prandial lipid oxidation g/4h; yl = basal, y2 = post prandial
Fig. 4 shows the increase in the lipid oxidation rate of the groups A to D relative to group E between basal and post prandial conditions. The lipid oxidation rate was assessed by indirect calorimetry using a Deltatrac. There was an increase in lipid oxidation rate from basal to post prandial conditions in group A, B, and C, whereas it was highest in group A. No change was observed for group D.
Figure 5: Lipid oxidation rate during maximum post prandial stimulation
X = g/h; y = maximum post prandial stimulation (80 Min after the meal)
Fig. 5 shows the lipid oxidation rate of the groups A, C, D and E during maximum post prandial stimulation due to the test meal. The lipid oxidation rate was assessed by indirect calorimetry using a Deltatrac. Lipid oxidation rate increased in group A, C, D, and E, whereas the lipid oxidation rate of group A, C and D were higher compared to group E,
Figure 6: Synergism between EGCG and Caffeine on fat oxidation
X = Difference in fat oxidation vs. Placebo at maximal stimulation g/h; y = maximum post prandial stimulation (80 minutes after the meal)
Fig. 6 shows the synergism between groups A and C on fat oxidation during maximum post prandial stimulation. The lipid oxidation rate was assessed by indirect calorimetry using a Deltatrac. Group D has higher lipid oxidation than the sum of group A and group C, suggesting a synergism.
Figure 7: Changes in Energy Expenditure (EE) vs. placebo X = delta EE kJ/min; yl = basal, y2 = post prandial
Fig. 7 shows the difference in energy expenditure of the groups A to D in comparison to group E. Energy expenditure was assessed by indirect calorimetry using a Deltatrac. In groups A, B, and C energy expenditure was hardly changed, but there was a trend of slight reduction, whereas in group D it was unchanged in comparison to group E during basal conditions. During post prandial conditions these differences were blurred. Except for group C which showed increased energy expenditure during post prandial conditions.
Figure 8: TEAVIGO™ improves flow mediated dilation
X = Changes in FMD vs. baseline (%); yl = acute, y2 = chronic
Fig. 8 shows the difference in flow mediated dilation (FMD) of the groups A and E in comparison to baseline for acute (2 hours), and chronic (2 weeks) treatment. Flow mediated dilation was assessed by using ultrasound. In groups A, and E, flow mediated dilation was acutely increased compared to baseline. For chronic conditions the increases for both groups were blunted.
Figure 9: Plasma levels after TEAVIGO™ supplementation
X = Changes in plasma EGCG vs. baseline (%), baseline (%); yl = acute, y2 = chronic
Fig. 9 shows the difference in EGCG plasma levels the groups A and E in comparison to baseline for acute (2 hours), and chronic (2 weeks) treatment. EGCG in plasma was determined by High Performance Liquid Chromatography-Mass Spectrometry. In group A, EGCG levels were increased after acute administration. There was no change in group E after acute administration. The same is seen for group E after chronic treatment. The plasma EGCG level returned to baseline after chronic treatment. This is due to assessing the EGCG level 14 hours after the last administration. Therefore, EGCG does not accumulate in plasma.
Figure 10: Lipid oxidation rate X = lipid oxidation g/4h; yl = basal, y2 = post prandial
Fig. 10 shows the lipid oxidation rate of the groups A to E. The lipid oxidation rate was assessed by indirect calorimetry using a Deltatrac. In all groups the lipid oxidation rate is higher during basal conditions compared to post prandial conditions. Between groups, lipid
oxidation rate in group E is lowest under the respective condition. Statistical significance was observed for group C and D during basal conditions and for group D at post prandial conditions.
Figure 11: Carbohydrate oxidation rate
X = carbohydrate oxidation g/4h; yl = basal, y2 = post prandial
Fig. 11 shows the carbohydrate oxidation rate of the groups A to E. The carbohydrate oxidation rate was assessed by indirect calorimetry using a Deltatrac. In all groups the carbo- hydrate oxidation rate is higher during post prandial conditions compared to basal conditions. Between groups, carbohydrate oxidation rate in group E is highest under the respective condition. Statistical significance was observed for group D during post prandial.
Claims
1. Use of a dietary supplement containing (-)-epigallocatechin gallate for increasing the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal before the regular intake of food, feed or beverages containing said fat whose oxidation is increased.
2. Use of a dietary supplement containing (-)-epigallocatechin gallate for reducing the weight of a mammal selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal before the intake of food, feed or beverages.
3. Use of a dietary supplement containing (-)-epigallocatechin gallate for reducing the fat mass in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal before the intake of food, feed or beverages.
4. Use of a dietary supplement containing (-)-epigallocatechin gallate for reducing the carbohydrate oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal before the regular intake of food, feed or beverages containing said carbohydrate whose oxidation is reduced.
5. The use according to any one of claims 1 to 4, wherein the dietary supplement is incor- porated by said mammal at least half an hour before the intake of food, feed or beverages.
6. The use according to any one of claims 1 to 4, wherein the dietary supplement is incorporated by said mammal at a point in time between half an hour and one and a half hour before the intake of food, feed or beverages.
7. Use of a dietary supplement containing (-)-epigallocatechin gallate for increasing the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal simultaneously with the regular intake of food, feed or beverages containing said fat whose oxidation is increased.
8. Use of a dietary supplement containing (-)-epigallocatechin gallate for reducing the weight of a mammal selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal simultaneously with the intake of food, feed or beverages.
9. Use of a dietary supplement containing (-)-epigallocatechin gallate for reducing the fat mass in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal simultaneously with the intake of food, feed or beverages.
10. Use of a dietary supplement containing (-)-epigallocatechin gallate for reducing the carbohydrate oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, whereby the dietary supplement is incorporated by said mammal simultaneously with the regular intake of food, feed or beverages containing said carbohydrate whose oxidation is reduced.
1 1. Use of a food, feed or beverage fortified with (-)-epigallocatechin gallate for increasing the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses.
12. Use of a food, feed or beverage fortified with (-)-epigallocatechin gallate for reducing the weight of a mammal selected from the group consisting of humans, cats, dogs and horses.
13. Use of a food, feed or beverage fortified with (-)-epigallocatechin gallate for reducing the fat mass in mammals selected from the group consisting of humans, cats, dogs and horses.
14. Use of a food, feed or beverage fortified with (-)-epigallocatechin gallate for reducing the carbohydrate oxidation in mammals selected from the group consisting of humans, cats, dogs and horses.
15. Use of (-)-epigallocatechin gallate, preferably in combination with a sympathomimeti- cum, (for the manufacture of a composition) for reducing the respiratory quotient in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans.
16. Use of (-)-epigallocatechin gallate (for the manufacture of a composition) for improving the flow mediated dilation, thereby contributing to the beneficial effects on coronary heart, in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans.
17. Use of (-)-epigallocatechin gallate, preferably in combination with a sympathomimeti- cum, (for the manufacture of a composition) for supporting the metabolization of fat in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, wherein the (-)-epigallocatechin gallate is administered in such a way that it is present in the body during the intake of food/feed/beverages of the mammal selected from the group consisting of humans, cats, dogs and horses, preferably of the human, preferably that it is present in a high concentration in the body during the intake of food/feed/beverages of the mammal selected from the group consisting of humans, cats, dogs and horses, preferably of the human.
18. Use of (-)-epigallocatechin gallate, preferably in combination with a sympathomimeti- cum, (for the manufacture of a composition) for increasing the endurance in mammals selected from the group consisting of humans, cats, dogs and horses, preferably for increas- ing the endurance in humans.
19. The use according to claim 18, wherein the (-)-epigallocatechin gallate is administered in such a way that it is present, preferably in high concentration, in the body when the mammal selected from the group consisting of humans, cats, dogs and horses, preferably when the human, is performing the activity for which endurance is needed.
20. Use of (-)-epigallocatechin gallate, preferably in combination with a sympathomimeti- cum, for the manufacture of a composition for supporting the metabolization of fat in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, wherein the composition is administered in such a way that (-)- epigallocatechin gallate is present in the body during the intake of food/feed/beverages of said mammal, preferably that it is present in a high concentration in the body during the intake of food/feed/beverages of said mammal.
21. The use according to any of claims 1 to 20, wherein the daily dosage of (-)- epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight, preferably from 2.0 to 9 mg per kg body weight, more preferably from 4.0 to 9.0 mg per kg body weight, most preferably from 4.0 to 4.5 mg per kg body weight.
22. The use according to any of the claims 1 to 21, wherein the (-)-epigallocatechin gallate has a purity of at least 80%, preferably of at least 85%, more preferably of at least 90%.
23. The use according to any of the claims 15, 17, 18 and 20, wherein the sympathomi- meticum is caffeine.
24. The use according to any of the claims 15 to 23, wherein the (-)-epigallocatechin gallate is in a form selected from the group consisting of (fortified) food or (fortified) feed, dietary supplements, beverages, tablets, granules, capsules, pastes, food additives, feed ad- ditives, and effervescent formulations.
25. The use according to any of the claims 1 to 24, wherein the daily dosage of (-)- epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight, preferably from 2.0 to 9 mg per kg body weight, more preferably from 4.0 to 9.0 mg per kg body weight, most preferably from 4.0 to 4.5 mg per kg body weight.
26. A method for increasing the fat oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of (-)-epigallocatechin gallate, preferably in com- bination with an effective dose of a sympathomimeticum, to said mammal which is in need thereof before the intake of food, feed or beverage, containing said fat whose oxidation is increased, by said mammal, characterized in that the effective dose of (-)-epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
27. A method for supporting the metabolization of fat in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of (-)-epigallocatechin gallate, preferably in combination with an effective dose of a sympathomimeticum, to said mammal which is in need thereof before the intake of food, feed or beverage by said mammal, characterized in that the effective dose of (-)-epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
28. The method according to claim 26 or 27, wherein the (-)-epigallocatechin gallate is administered in such a way that it is present in a high concentration in the body during the intake of food/feed/beverages of said mammal.
29. A method for reducing the fat mass in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of (-)-epigallocatechin gallate, preferably in combination with a sympathomimeticum, to said mammal which is in need thereof before the intake of food, feed or beverage by said mammal, characterized in that the effective dose of (— )- epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
30. A method for reducing the weight of mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of (-)-epigallocatechin gallate, preferably in combination with a sympathomimeticum, to said mammal which is in need thereof before the intake of food, feed or beverage by said mammal, characterized in that the effective dose of (-)- epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
31. A method for reducing the carbohydrate oxidation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of (-)-epigallocatechin gallate, preferably in combination with a sympathomimeticum, to said mammal which is in need thereof before the intake of food, feed or beverage, containing said carbohydrate whose oxidation is reduced, by said mammal, characterized in that the effective dose of (-)-epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
32. The method according to any of the claims 26 to 31, further comprising the step of said mammal performing physical activity.
33. A method for increasing the endurance in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of (-)-epigallocatechin gallate, preferably in combination with a sympathomimeticum, to said mammal which is in need thereof, characterized in that the effective dose of (-)-epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
34. The method according to claim 33, wherein the (-)-epigallocatechin gallate is adminis- tered in such a way that it is present, preferably in a high concentration, in the body when said mammal is performing the activity for which endurance is needed.
35. A method for reducing the respiratory quotient in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, said method comprising the step of administering an effective dose of (-)-epigallocatechin gallate, preferably in combination with a sympathomimeticum, to said mammal which is in need thereof, characterized in that the effective dose of (-)-epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
36. A method for improving the flow mediated dilation in mammals selected from the group consisting of humans, cats, dogs and horses, preferably in humans, thereby contributing to a beneficial effect on the coronary health, said method comprising the step of administering an effective dose of (-)-epigallocatechin gallate to said mammal which is in need thereof, characterized in that the effective dose of (-)-epigallocatechin gallate varies from 0.14 to 25 mg per kg body weight per day, preferably from 2.0 to 9 mg per kg body weight per day, more preferably from 4.0 to 9.0 mg per kg body weight per day, most preferably from 4.0 to 4.5 mg per kg body weight per day.
37. The method according to any of the claims 26 to 36, wherein the mammals are humans with a body mass index above 25.
38. The method according to any of the claims 26 to 37, wherein the (-)-epigallocatechin gallate has a purity of at least 80%, preferably of at least 85%, more preferably of at least 90%.
39. Sport beverages containing (-)-epigallocatechin gallate, preferably (-)-epigallocatechin gallate with a purity of at least 80%.
Priority Applications (1)
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EP06743119A EP1888173A2 (en) | 2005-06-07 | 2006-06-07 | Novel use of (-)-epigallocatechin gallate |
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EP05012235 | 2005-06-07 | ||
EP05025412 | 2005-11-22 | ||
PCT/EP2006/005410 WO2006131326A2 (en) | 2005-06-07 | 2006-06-07 | Novel use of (-)-epigallocatechin gallate |
EP06743119A EP1888173A2 (en) | 2005-06-07 | 2006-06-07 | Novel use of (-)-epigallocatechin gallate |
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JP (1) | JP2008545766A (en) |
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EP1961310A1 (en) * | 2007-02-01 | 2008-08-27 | DSMIP Assets B.V. | Novel use of (-) -epigallocatechin gallate |
EP1969954A1 (en) * | 2007-02-01 | 2008-09-17 | DSMIP Assets B.V. | Sauce containing (-)-epigallocatechin gallate |
EP2022344A1 (en) * | 2007-08-02 | 2009-02-11 | Nestec S.A. | Reduction of fatigue as a result of exercise |
WO2009046964A1 (en) * | 2007-10-10 | 2009-04-16 | Dsm Ip Assets B.V. | Feed composition for companion animals |
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EP1767097A3 (en) * | 1999-08-16 | 2007-04-04 | DSMIP Assets B.V. | Green tea extracts |
JP3756438B2 (en) * | 2001-03-02 | 2006-03-15 | 花王株式会社 | Container drink |
JP3756510B2 (en) * | 2001-03-02 | 2006-03-15 | 花王株式会社 | Containerized beverage for burning body fat. |
JP4324335B2 (en) * | 2001-09-07 | 2009-09-02 | 花王株式会社 | Catechin-containing beverage |
EP1536698A1 (en) * | 2002-08-23 | 2005-06-08 | DSM IP Assets B.V. | Novel nutraceutical compositions comprising biotin |
CN100361599C (en) * | 2002-10-23 | 2008-01-16 | 克尔塞根控股有限公司 | Antioxidative compositions |
JP4494033B2 (en) * | 2003-02-10 | 2010-06-30 | 株式会社 伊藤園 | Serum cholesterol lowering agent, food and drink, and method for producing the same |
US20060121158A1 (en) * | 2003-06-04 | 2006-06-08 | Mario Ferruzzi | Weight management beverage |
US20050008712A1 (en) * | 2003-07-08 | 2005-01-13 | Debasis Bagchi | Compositions incorporating high-caffeine green tea extract and related methods for promoting healthy body weight |
EP1643863A2 (en) * | 2003-07-10 | 2006-04-12 | Carl A. Forest | Foods, beverages, condiments, spices and salad dressings with specialized supplements |
EP1662906A1 (en) * | 2003-09-23 | 2006-06-07 | DSM IP Assets B.V. | Compositions for the treatment and prevention of diabetes mellitus |
WO2005115425A1 (en) * | 2004-05-28 | 2005-12-08 | Suntory Limited | Composition comprising fermented tea extract as the main component and having effect of incrasing adiponectin |
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- 2006-06-07 EP EP06743119A patent/EP1888173A2/en not_active Withdrawn
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