METHODS FOR IMPROVING EXERCISE PERFORMANCE AND ENDURANCE THEREOF

Abstract

Provided are methods for improving exercise performance and endurance of a mammal, comprising administering to the mammal in need thereof a composition comprising dihydroberberine (DHB), or an analog or derivative thereof, and a physiologically acceptable carrier. DHB in the composition can serve as an antioxidant to defend red blood cells against oxidative stress damage, by scavenging reactive oxygen species generated during to increase the deformability and the survival of red blood cells.

Claims

1. A method for improving exercise performance and endurance of a mammal, comprising administering to the mammal in need thereof a composition which comprises a physiologically effective amount of dihydroberberine, or an analog or derivative thereof, and a physiologically acceptable carrier.

2. The method of claim 1, wherein the composition is administered orally.

3. The method of claim 1, wherein the composition is administrated in a form selected from the group consisting of aqueous solutions, aqueous suspensions, capsules, drops, granules, liquids, powders, syrups, tablets, functionalized foods, beverages, and sublingual articles.

4. The method of claim 1, wherein the composition is an ingestible composition.

5. The method of claim 4, wherein the ingestible composition is selected from the group consisting of a bioceutical composition, a dietary supplement, a medicated feed, a nutraceutical composition, and a pharmaceutical composition.

6. The method of claim 1, wherein the mammal is a human.

7. The method of claim 1, wherein the composition is administered at least once per day for a period of one to twelve weeks.

8. The method of claim 7, wherein the period is between four and twelve weeks.

9. The method of claim 1, wherein the composition is administrated to the mammal so that the daily intake of dihydroberberine is in an amount ranging from 1 mg/kg/day to 200 mg/kg/day.

10. The method of claim 9, wherein the amount ranges from 1 to 100 mg/kg/day.

11. The method of claim 5, wherein the composition is the dietary supplement.

12. The method of claim 11, wherein the composition further comprises a flavor-containing solid.

13. The method of claim 12, wherein the flavor-containing solid is cocoa.

14. The method of claim 11, wherein the dietary supplement is administered to the mammal prior to a first exercise period.

15. The method of claim 1, wherein dihydroberberine improves exercise performance and endurance and/or reduces muscle fatigue by carrying and releasing oxygen of red blood cells.

16. The method of claim 1, wherein the exercise performance and endurance are assessed based on at least one of the following: a running distance, running time, highest running speed, a change in the submaximal running time to exhaustion at least 80% of the maximal heart rate, a maximal rate of oxygen consumption and anerobic threshold.

17. The method of claim 1, wherein dihydroberberine in the composition is served as an antioxidant to defend red blood cells against oxidative stress damage, by scavenging reactive oxygen species generated during exercise to increase the deformability and the survival of red blood cells.

18. The method of claim 17, wherein the antioxidant capacity of red blood cells and/or plasma is assessed based on at least one of the following: level of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), reactive oxygen species (ROS), 2,3-diphosphoglycerate (2,3-DPG), total antioxidant capacity (T-AOC), AMPK and the free oxygen radicals.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0027] For a more complete understanding of this disclosure and its features, reference is now made to the following description, taken in conjunction with the accompanying drawings, in which:

[0028] FIG. 1 shows the distance run by mice of each group during test. Data are present by mean ±SD from 10 mice. The star (*)indicates the group with statistical significance (p<0.05).

[0029] FIG. 2 shows the highest speed run by mice of each group.

[0030] FIG. 3 shows the total time run by mice of each group.

[0031] FIG. 4 shows SOD level in the plasma among different groups. Values are mean.

[0032] FIG. 5 shows CAT level in the plasma among different groups.

[0033] FIG. 6 shows MDA level in the plasma among different groups.

[0034] FIG. 7 shows ROS level in the red blood cells among different groups.

[0035] FIG. 8 shows 2,3-DPG level in the red blood cells among different groups.

[0036] FIG. 9 shows T-AOC level in the red blood cells among different groups.

[0037] FIG. 10 shows the AMPK level in the red blood cells among different groups.

DETAILED DESCRIPTION OF THE INVENTION

[0038] The embodiments and configurations described herein are neither complete nor exhaustive. As will be appreciated, other embodiments of the invention are possible utilizing, alone or in combination, one or more of the features set forth above or described in detail below.

[0039] Embodiments of the present invention generally include an ingestible composition comprising dihydroberberine (DHB). Embodiments of the present invention also include methods of administration of such compositions to a mammalian subject, preferably a human, to improve the exercise performance and endurance, and/or reduce muscle fatigue, finally to enhance the benefits of exercise, including, but not limited to, losing weight, lowering a blood glucose, reducing a body fat percentage, reducing a weight, decreasing a blood triglyceride level, decreasing a blood total cholesterol level, decreasing a blood very low-density lipoprotein level, increasing a muscular glycogen storage capacity, increasing a hepatic glycogen storage capacity, reducing a mass of retroperitoneal fat, increasing a mass of a muscle and/or combinations thereof. The compositions and methods exhibit advantageous efficiency and health benefits compared to placebo or a mixture of vitamin C and E.

[0040] One advantage of the present invention is that it can be utilized alone, and/or it can be utilized in combination with, and thereby improve the exercise performance and endurance, and reduce muscle fatigue in a subject.

[0041] In some embodiments, suitable dosage amounts for the compositions and methods of the invention range from about 1 to about 200 mg/kg/day, e.g., from about 1 to about 150 mg/kg/day, from about 5 to about 150 mg/kg/day, from about 10 to about 150 mg/kg/day, from about 20 to about 150 mg/kg/day, from about 20 to about 120 mg/kg/day, from about 50 to about 150 mg/kg/day, from about 50 to about 100 mg/kg/day, or from about 50 to about 80 mg/kg/day.

[0042] In the methods of the treatment disclosed herein, the dosage may be varied during the course of supplementation. In some embodiments, two or more discrete dosage steps may be used, wherein a first dosage may be administered to the subject for a first period; and a second dosage, which may be higher or lower than the first dosage, may be administered to the subject for a second period. By way of non-limiting example, the first and second dosages may be between about land about 200 mg/kg/day, and each of the first and second periods may be at least about one day, or at least about two days, or at least about three days, or at least about four days, or at least about five days, or at least about six days, or at least about one week, or at least about two weeks, or at least about three weeks, or at least about one month, or at least about two months, or at least about three months, or at least about four months, or at least about five months, or at least about six months, or at least about seven months, or at least about eight months, or at least about nine months, or at least about ten months, or at least about eleven months, or at least about one year. In some embodiments, the dosage may also be continually ramped (i.e. gradually increased) or tapered (i.e. gradually decreased). The use of two or more distinct dosages, or of a ramped or tapered dosing regimen, may be beneficial where, by way of non-limiting example, it is desired to treat two or more diseases or conditions, simultaneously and/or sequentially, or where the severity of a disease or condition to be treated may vary over time.

[0043] Ingestible compositions of the present invention may be provided in any suitable form and physical manifestation. By way of non-limiting example, the ingestible composition can be administered to a subject as a bioceutical composition, a dietary supplement, a medicated feed, a nutraceutical composition, and a pharmaceutical composition. By way of further non-limiting example, the ingestible compositions may be provided in any suitable physical form for oral administration, such as aqueous solutions or suspensions (e.g. an infused beverage, such as an energy beverage or energy “shot”), capsules (which may or may not be chewable), drops, granules, liquids, powders, syrups, tablets (e.g. chewable, saliva-soluble, and/or swallowable tablets), functionalized foods (e.g. energy or nutrition bars, cookies, gums, candies, etc.), sublingual articles, and the like. In some embodiments, the composition may be provided in a form, e.g. a powder, that can be applied to a food (similar to a seasoning or condiment, etc.) or mixed with a beverage. Ingestible compositions of the present invention may thus comprise any suitable nutritionally acceptable additives, binders, and/or fillers, and may also comprise an active nutritional agent other than DHB.

[0044] Preferred dosages and treatment lengths for the methods of the present invention may vary according to the particular condition to be treated and/or the particular physiological objective to be achieved. By way of non-limiting example, administration of compositions containing DHB may be continued for an indefinite period of time, e.g. as a maintenance regimen, or for continual or continuous enhancement of exercise performance.

[0045] The invention is further described by reference to the following non-limiting examples.

Example 1: Effects of Dihydroberberine Supplementation on Exercise Performance and

[0046] Endurance Prior to the experiment, all mice were acclimatized on a treadmill by running at 15% incline and at 10 m/min for two days. After the 2-day acclimatization, 40 mice were randomly divided into four groups as followings (10 for each group): Control group (normal diet supplemented with distilled water), Dihydroberberine (high) group (normal diet supplemented with dihydroberberine 26 mg/kg daily), Dihydroberberine (medium) group: (normal diet supplemented with dihydroberberine 19.5 mg/kg daily), Dihydroberberine (low) group (normal diet supplemented with dihydroberberine 13 mg/kg daily).Each group was fed on a normal diet, other than that, three experimental groups were supplemented with dihydroberberine daily for two consecutive months, while the control group was only supplemented with distilled water at the same time. Exercise endurance of the mice was evaluated by treadmill running. At the beginning of the formal experiment, mice were placed on treadmill, running at 10 m/min for 20 minutes, and then the running speed was increased by 2 m/min every 2nd minutes. End point occurs if the mouse touched the shock grid of the treadmill three times or on the treadmill for 5 consecutive seconds without attempting to reengage the treadmill. At the end point, the running distance, highest running speed, total running time of the mice were recorded.sup.[7].

[0047] FIGS. 1-3 show the exercise performance and endurance of mice after supplemented with DHB for two consecutive months. By comparing with the control group, the results showed that mice groups supplemented with DHB have enhanced endurance and better performance in terms of the running distance, running time, and highest running speed.

Example 2: Effects of Dihydroberberine Supplementation on Improvement of Antioxidant Capacity of RBCs and Plasma

[0048] After the treadmill exhaustion test, blood samples were collected from the mice into heparin tubes. By centrifugation at 4500 rpm for 15 minutes, plasma was separated from the top layer of the whole blood and red blood cells were also separated from the lower layer of the blood. The levels of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA)in the plasma were determined using commercially available kits.

[0049] FIG. 4 shows SOD level in plasma among different groups. The results showed that SOD level in the groups supplemented with DHB is higher than the control group, especially in the group with high-dose of DHB, the SOD level in the plasma increased significantly (p<0.01).

[0050] FIG. 5 shows CAT level in plasma among different groups. The results showed that CAT level in plasma also increased with administration of DHB. Especially, in the middle dose group and the high dose group, the CAT level increased significantly (p<0.05).

[0051] FIG. 6 shows MDA level in plasma among different groups. The results showed that MDA level in plasma increased with administration of DHB. Especially in high-dose group, the MDA level in plasma increased significantly (p<0.001).

[0052] The reactive oxygen species (ROS), 2,3-diphosphoglycerate (2,3-DPG), and total antioxidant capacity (T-AOC) in red blood cells were also determined using commercially available kits.

[0053] FIGS. 7-9 show the levels of ROS, 2,3-DPG, and T-AOC in the red blood cell, respectively. Results showed that levels of ROS, 2,3-DPG, and T-AOC in the groups supplemented with DHB were all increased. Especially, in the high-dose group, the T-AOC level increased significantly (p<0.001).

[0054] T-AOC and CAT are antioxidant indicators. The level of T-AOC can reflect the total antioxidant capacity of the body, including clearance of free radicals and the mutual interactions between antioxidants. T-AOC level can also reflect the general health status and age-related chances. Therefore, T-AOC is one of the best indicators to measure the capacity of an antioxidant in the biological organism.sup.[8]. Research showed that 2,3-DPG in red blood cells increases in response to anemia/hypoxia and causes a shift of the oxygen dissociation curve, allowing a more effective oxygen delivery. Hence, the increase of 2,3-DPG can indirectly indicate that DHB can promote the oxygen carrying capacity of red blood cells. Furthermore, 2,3-DPG modulates the effects of hydrogen ions and carbon dioxide upon hemoglobin O.sub.2 affinity.sup.[10].

[0055] Acute exercise leads to AMPK activation through ROS, the activation of AMPK is deleterious to mature erythrocytes.sup.[11-12]. FIG. 10 shows AMPK level in red blood cells among different groups. The results showed that the level of AMPK in the group supplemented with high dose of DHB decreased slightly, indicating that DHB can maintain the homeostasis of AMPK in red blood cell, thereby protecting red blood cells from eryptosis.

Example 3. Statistical Analysis

[0056] T-test was used to determine statistical significance for the experiments, and a P value of less than 0.05 was considered significant. Values are expressed as mean±SEM or mean±SD (Prism 6; GraphPad Software).

REFERENCES

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[0058] While specific embodiments and applications of the present invention have been illustrated and described, it is to be understood that the invention is not limited to the precise configuration and components described herein. Various modifications, changes, and variations which will be apparent to those skilled in the art may be made in the arrangement, operation, and details of the methods and systems of the present invention disclosed herein without departing from the spirit and scope of the invention. The examples and illustrations above are not intended to limit the scope of this invention. Any combination of compounds, methods, and applications of this invention, along with any obvious their extension or analogs, are within the scope of this invention. It is important, therefore, that the claims be regarded as including any such equivalent construction insofar as they do not depart from the spirit and scope of the present invention.

[0059] The advantages of the present invention will be apparent from the disclosure contained herein.

[0060] All publications or patent applications referred to above are incorporated herein by reference in their entireties. All the features disclosed in this specification (including any accompanying claims, abstract and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example of a generic series of equivalent or similar features.