FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
AND
THE PATENT RULES, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
"Methods for improving physical performance and capsicum compositions used therein"
OMNIACTIVE HEALTH TECHNOLOGIES LIMITED
An Indian Company, registered under the Indian Companies Act, 1956 having its registered
office located at OmniActive Health Technologies Limited, T-8b, 5th Floor, Phoenix House,
A wing, Phoenix Mills Compound, 462, Senapati Bapat Marg, Lower Parel,
Mumbai - 400013 Maharashtra, India,
The following specification particularly describes the invention and the manner in which it is to be performed.

Methods for improving physical performance and capsicum compositions used therein
Field
The invention relates to method for improving physical performance and endurance, the method comprising administering capsicum composition to a subject. More particularly the methods are comprised of use of effective amount of capsicum composition alone and or in combination with other nutrients for improvement in performance of physical activities such as exercise, improvement in endurance, fatigue suppression and post-exercise recovery from muscle fatigue and/or muscle soreness. The composition as described herein is comprised of capsicum extract as such or formulated in form of an extended and sustained release stable, free flowing, solid beadlet or powder composition formulated using pharmaceutically and/or nutraceutically acceptable excipient. The methods described herein are comprised of capsicum compositions which are administered to the subject undergoing physical activity to deliver daily dose of capsaicinoids in effective amounts. The methods are further comprised of administering capsicum compositions alone or in combination with other nutrients, muscle enhancers, stimulants, essential amino acids and/or anabolic ingredients for improving physical performance and endurance during activities such as exercise, sports and other strenuous indoor or outdoor physical activities. The methods are comprised of administering capsicum compositions to subjects in effective amounts wherein these reduce blood lipids and oxidative stress. The invention also relates to method for enhancing physical endurance and exhaustion time, by administering effective amount of capsicum composition to physically active subjects, wherein body antioxidants are increased and muscle lactates are decreased, thus resulting into recovery from muscle fatigue arising due to such indoor and/or outdoor physical activities.
Background
Indoor and outdoor physical activities such as sports and exercise are the main foundations of health and well-being. Exercise is an essential way which can stimulate our vitality, strength, and natural healing mechanisms of body. This stimulation also confers stamina required for carrying out strenuous physical activities from routine life such as fast walking, staircase climbing, long driving or weight lifting. Physical fitness and stamina can be enhanced through indoor and outdoor exercise activities such as swimming, cycling, walking, skipping, trekking and so on, or

by going to gym regularly for work-out. Although nowadays people have started realizing importance of regular exercise activities, our culture seems to have love-hate relationship with exercise and sports. On one hand, spending on sporting events and sporting products are at its highest level; on the other hand, rates of obesity and metabolic diseases has been steadily increasing for decades. Athletes are encouraged and supported in every possible way - as long as they perform and sport activities are pursued more for generating the talent rather than healthcare and encouragement. This cultural message seems to give the wrong impression to our youth - who either excel in sports or may quit physical activity altogether.
Stress of performance is so high that they need to always perform better to win and there is always a need of enhancing endurance for success. This gives rise to use of performance enhancing drugs. Many professional athletes are reported to use even banned drugs, which is illegal and also comes with slew of severe side effects. Thus it becomes important to look for safer options such as natural products or nutraceuticals for improving performance and endurance of the sports person.
Plants which provide us most nutrients and phytochemicals having nutritional or medicinal value are becoming popular for this purpose. From an athlete's perspective, the vitamin and mineral content of fruits and vegetables has an important role in maintaining health and well-being and optimizing exercise performance during periods of heavy training. These vitamins and minerals also have a functional role in recovery following strenuous exercise. These nutrients cannot be synthesized by the body so it's essential that athletes consume a diet rich in desired nutrients to support daily training and recovery from training.
Herbal dietary supplements are used to a large extent to fulfill this purpose. For example, Herbold and others [Traditional and nontraditional supplement use by collegiate female varsity athletes. Herbold NH, Visconti BK, Frates S, Bandini L, Int J Sport Nutr Exerc Metab. 2004 Oct; 14(5):586-93] reported that 17 percent of female collegiate athletes used herbal/botanical supplements. Herbal dietary supplements are marketed to physically active individuals for a variety of reasons, including increasing energy, inducing weight loss, promoting muscle growth, or inducing other physiological or metabolic responses that may enhance exercise performance. Some other dietary supplements are used to increase mental alertness, stimulate fat-burning

metabolism, and help enhance physical performance. Some sports drinks and sports bars contain herbals as well.
The overwhelming number and increased availability of sports supplements presents an ongoing challenge for the practitioner and the athlete to keep up-to-date about the validity of the claims and scientific evidence. Although use of nutritional products that enhance performance is highly prevalent, the fact remains that very few improve performance and some may cause concern because of false claims. Hence it is important to go for right choice of nutritional supplement that helps for improving performance with minimum side effects and also helps to improve endurance.
Although herbal sources such as Aswagandha, curcumin, ginseng, gingko, Echinacea, Rhodiola are being used and evaluated for improving exercise and sports performance, there is need for the compositions which also improve endurance and exhaustion time for these activities for sustained performance. Research is also ongoing on capsicum which is mainly reported for its weight management effect. Capsicum is a pepper that contains active capsaicinoids, which has property of warming and improving circulation to all parts of body, thus easing joint pain of arthritis, muscle spasms and cluster headaches. It is included in many cuisines and is a great aid for digestion and is believed to regulate heart and blood pressure and even improve athletic performance. There are some references in prior art which relate to use of capsicum for improving performance in physical activities like swimming in animal models.
PCT patent application WO2006060505 relates to compositions comprising combination of one or more vanilloid receptor agonists like capsaicin and methylxanthine compound in a nutritional supplement. The disclosed compositions are synergistically effective to enhance cognitive performance and boost energy, increase alertness, mental concentration, mental focus and wakefulness.
U.S. patent 4592912 discloses topical dosage form containing aqueous extract of capsicum from Capsicum frutescens along with slippery elm and myrrh gum for treatment of muscular aches and pains.The composition is applied topically to an individual's body in thin layer form for the relief of or for the prevention of muscular aches, pains, cramps and muscular spasms.

Patent application US20140343156 relates to a method for treatment or prevention of muscle cramp resulting from exercise, nocturnal cramp or menstrual cramp by orally administering to the subject solid or liquid capsaicin formulation comprising of at least one excipient.
Oh TW et al. (J Nutr Sci Vitaminol (Tokyo). 2003 Apr;49(2): 107-11) describe the influences of various doses of capsaicin on endurance capacity in rat models. The experiments were carried out by attaching weights to rat tails and they were allowed to swim for specific time period to check endurance, after administering different doses of capsaicin before starting swimming activity. It was observed that swimming endurance was improved with higher capsaicin dose which might be induced through the sparing of muscle glycogen and the rise of non-esterified fatty acids following the increase of circulating catecholamine.
Haramizu Set al. (Biosci. Biotechnol. Biochem. 70 (4), 774-781, 2006) disclose effect of capsiate on the swimming capacity of mice in an adjustable-current water pool. The results suggest that the oral administration of capsiate enhanced fat oxidation and spared carbohydrate utilization, and consequently increased the endurance swimming capacity of the mice via stimulation of their vanilloid receptors.
Patent application US 20150297546 relates to a method of promoting blood flow, comprising a step of administering citrulline or a salt thereof and capsaicin or capsaicinoids for improvement of athletic performance exhibited in relation to peripheral vasodilatation, suppression of fat accumulation, improvement of skin quality, or prophylaxis of ischemic disease.
US20160213673 discloses a method of enhancing the endurance of a mammal comprising administering a composition comprising dihydrocapsiate, caffeine and arginine to enhance the endurance of said mammal, said enhanced endurance being measured by a decrease in the rating of perceived exertion (RPE) during physical exertion, such as during running, swimming, weight lifting and/or walking, as compared to the RPE of said mammal prior to being administered the composition.

Summary
Prior art references report about evaluation of capsaicin in experimental animals at various doses to study their effect on enhanced physical activities, cognitive performance or for treatment of ailments such as muscle cramp. The references show that the active has effect on central nervous system hormones or receptors. The reported studies generally employ Swim test model study which is used as behavior test.
Instant invention reports evaluation of capsicum formulation in exercising subjects; which results in enhanced physical performance, endurance and also takes care of muscle soreness. It is also observed that the effect of increased physical performance and endurance is significantly enhanced in subjects administered with effective amount of capsicum composition and also undergoing physical activity as compared to the effect observed in subjects not undergoing any physical activity. This evaluation of effect of capsicum composition in exercising subjects is nowhere reported in prior art.
Present invention relates to method for improving physical performance and endurance, the method comprising administering effective amount of capsicum composition to a subject undergoing physical activity. The capsicum composition may be in the form of capsicum extract comprising capsaicinoids; or the extract may be formulated in the form of solid, free flowing solid dosage form, which is easy to administer. According to this method when capsicum composition is administered in effective amounts to subject undergoing exercise activity, improvement in performance as well as endurance is observed. The method also results in improvement in fatigue suppression during endurance exercise and post-exercise recovery from muscle fatigue and/or muscle soreness.
The composition as described herein is comprised of capsicum extract as such or extract formulated in the form of extended and sustained release stable, free flowing, solid composition using at least one food grade or pharmaceutically acceptable excipient. The excipient may be selected from, but not restricted to hydrophilic carrier, antioxidant, stabilizer, diluents alone or the mixture thereof. The compositions may be further comprised of compounds such as capsaicinoids and/or non-capsaicinoids.
Capsicum composition may be administered in the form of capsicum extract as such or formulated as capsicum beadlets, in daily doses so as to provide at least 0.01 mg/kg body weight

to 200 mg/kg body weight of capsaicinoids to the subject. The composition may be further administered in daily dose to provide about 10 mg/kg body weight to 100 mg/kg body weight/ of capsaicinoids to the subject for enhanced stamina and exercise endurance.
The method as per the present invention evaluates effect of capsicum composition through invito) cell line study on various sports nutrition biomarkers such as mitochondrial oxygen consumption, mitochondrial mass, IGF-1 and Cortisol. The method as described herein further evaluates effect of capsicum composition by administering effective amounts to subjects undergoing physical activity, as in-vivo animal models and to human volunteers to understand effect of capsaicinoids from capsicum composition on various plasma and muscle antioxidants, lipid profile, protein levels and actual effect on time to exhaustion and run time. The method as described herein makes use of capsicum compositions to enhance exercise performance and endurance through effective utilization of lipids such as cholesterol and triglycerides by increasing Phosphorylated AMP activated protein kinase (pAMPK) and Nuclear erythroid derived factor -like 2 (Nrf2). Capsicum composition also reduces the lactate amount in muscles, enhances running performance, increases heme-oxygenase (HO-1) and decreases interleukin (IL-10) and thus enhances exhaustion time as well as running performance in exercising subjects.
The composition may be administered to exercising subjects either in the form of capsicum extract as such or the extract formulated in the form of free flowing solid formulations prepared as extended and sustained release beadlet or powder using nutraceutically or pharmaceutically acceptable excipients. Capsicum extract is prepared from various varieties of paprika selected from the group of, but not limited to, varieties such as for example Teja and Namdhari. More particularly, the composition herein may be comprised of the capsicum extract obtained from varieties of Capsicum annum such as Teja and Namdhari.
Capsicum extract as described in instant invention is prepared by an industrially viable process which is comprised of employing non-polar, semi-polar, polar solvents or combinations thereof in suitable ratios. The composition is prepared by using a combination of polar and non-polar solvents in a suitable ratio for an extraction cycle, followed by purification of the extract by using polar solvent(s) to obtain the extract. The composition including the extract is safe for

human consumption and is comprised of biologically active chemical constituents including capsaicinoids and further may be comprised of non-capsaicinoid compounds.
The composition may be administered alone or in combination with other nutrients, muscle enhancers, stimulants, essential amino acids and/or anabolic ingredients for improving exercise performance and endurance during indoor and outdoor physical activities such as exercise, sports and other physical strenuous activities in normal routine.
The method described herein is comprised of administering effective amounts of capsicum compositions to subjects who are undergoing some physical activity such as exercise, wherein it lowers down oxidative stress significantly. The invention relates to method for enhancing exercise endurance and exhaustion time, by administering effective amount of capsicum composition to exercising subjects, wherein antioxidant amounts in body are increased and lactates are decreased, thus resulting into recovery from muscle fatigue during exercise and/or post exercise. Capsicum compositions are safe for oral administration and are prepared using food grade excipients and reagents and employing conventional equipments, thus it has industrial applicability.
Objectives
The present invention provides a method for administering capsicum composition and its evaluation in exercising subjects through in-vitro tests and in-vivo trials to demonstrate use for increasing performance time and enhancing endurance capacity during indoor and outdoor physical activities such as exercise, sports .and other strenuous routine activities.
As per one objective the present invention provides capsicum composition for significantly overcoming the exhaustive exercise-induced oxidative stress and muscle injury, and can be administered to subjects in need thereof. Such subjects include, for example animals, including mammalian subjects and may be administered to exercising human subjects. According to one more important objective, the present invention provides the method for improving physical performance and endurance by administering effective amount of capsicum

composition to exercising subject, wherein effective utilization of lipids such as cholesterol and triglyceride is carried out by increasing pAMPK and Nrf2.
As per yet one more objective, the invention provides method for administering capsicum composition which reduces the lactate amount in muscles, increases heme-oxygenase (HO-1) and decreases interleukin (IL-10), thus enhancing running performance and exhaustion time in exercising subject and reducing muscle soreness as after effects of prolonged exercise.
According to one more objective, the invention provides method for administering capsicum composition which enhances the level and activity of muscle building proteins such as IGF-1. The compositions described herein also enhance content of mitochondrial mass and enhance mitochondrial biogenesis, thus resulting into increasing endurance and stamina in exercising subjects.
According to one important embodiment, the invention also provides methods of administering capsicum compositions in the form of capsicum extract as such or extract formulated in the form of solid free flowing extended and sustained release formulation such as beadlets, tablets or capsules using at least one nutraceutical and/or pharmaceutically acceptable excipient. Capsicum extract may be comprised of compounds such as capsaicinoids and is prepared by solvent extraction method.
In an embodiment, a capsicum composition is comprised of a capsicum extract prepared for example from various varieties of paprika, which is further comprised of chemical constituents including capsaicinoids and further may be comprised in combination with non-capsaicinoids.
In an embodiment, a capsicum extract for the capsicum composition is prepared from various varieties of paprika selected from the group of, but not limited to, varieties such as for example Teja and Namdhari. More particularly, the composition herein may be comprised of the capsicum extract obtained from varieties of Capsicum annum such as Teja and Namdhari. In an embodiment, an industrially viable process is provided for preparation of a capsicum composition by employing non-polar, semi-polar, polar solvents or combinations thereof in

suitable ratios. In an embodiment, a capsicum composition is prepared using a combination of polar and non-polar solvents in a suitable ratio for an extraction cycle, followed by purification of the extract by using polar solvent(s) to obtain the extract. The composition including the extract is safe for human consumption and is comprised of biologically active chemical constituents including capsaicinoids and further may be comprised of non-capsaicinoids.
As per one objective, the invention provides capsicum composition comprised of capsicum extract alone and/or formulated with at least one more excipient selected from the group of, but not limited to carrier, diluents, antioxidant, stabilizer and the mixture thereof to prepare convenient and stable dosage forms.
Another objective of the present invention is to provide method for administering capsicum composition comprising capsaicinoids in the form of extract as such or formulated into a stable, free flowing, solid composition to provide extended and sustained release of the active ingredient, to the exercising subject in effective amount.
Yet another objective of the present invention is to provide a method for administering effective amount of stable, free flowing, solid composition of capsicum comprising capsaicinoids, which is manufactured using extrusion spheronization or beadlet technology.
One more important objective of the present invention is to provide a method for improving exercise performance and endurance, wherein capsicum composition is administered in effective daily dose of about 0.01 mg/kg body weight to 200 mg/kg body weight of capsaicinoids to an exercising subject. The compositions may also be administered preferably as a daily dose of about 10 mg/kg body weight to 100 mg/kg body weight of capsaicinoids to the exercising subject.
As per one more objective of the present invention, the method of improving exercise performance and endurance is comprised of reducing oxidative stress and increasing oxidants in the subjects by administering effective amount of capsicum composition, thus enhancing effect of exercise in subjects.

As per one more important objective of the invention, capsicum compositions also enhance endurance of exercising subject and enhance recovery from muscle fatigue and muscle soreness by decreasing amount of lactate and muscle oxidative stress, and increasing muscle antioxidant. The compositions are safe for human administration and are prepared by industrially convenient process and employed as per the method of present invention for enhancing performance and endurance in subjects undergoing physical indoor and outdoor activities.
Detailed Description of Figures
Figure 1 depicts effect of capsicum composition on mitochondrial respiration
Figure 2 depicts effect of capsicum composition on mitochondrial mass in cell-line study
Figure 3 depicts effect of Capsicum composition on IGF-1 in cell-line study
Figure 4 depicts effect of capsicum composition on Cortisol release as sports nutrition biomarker
Figure 5 depicts evaluation of effect of capsicum composition in protein levels in all 4 groups
Figure 6 depicts effect of capsicum composition on relative gene expression
Figure 7 depicts effect of capsicum composition on exercise duration and time to exhaustion
Detailed Description
Accordingly the present invention provides a method for improving exercise performance and endurance by administering capsicum composition in effective amount to exercising subjects.
It is to be appreciated that the term 'capsicum composition' can be interpreted to be within the scope of the compositions which are comprised of cpasium extract as such or the extract formulated in solid dosage form using food grade or pharmaceutically acceptable excipients. The compositions are comprised of compounds such as capsaicinoids and may be further also comprised of non-capsaicinoids. Capsaicinoids may be selected from the group of, but not limited to, the compounds such as capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homocapsaicin, dihydrohomocapsaicin, 6",7"-dihydro-5',5'"-dicapsaicin, 5,5'-dicapsaicin. Non-

capsaicinoid compounds may be selected from flavonoids and saponins. Capsicum compositions comprising capsaicinoids can be used as such in the form of extract or formulated as extended and sustained release stable, free flowing, solid composition suitable for formulating into tablets, capsules, blended powders, Heaps, ointments, pastes, lotions, liniments, mouthwashes, gargles, consumable dry syrups, liquid syrups, health drinks, diet drinks, fruit juices, soft drinks and the like. Capsicum composition may be prepared by solvent extraction to get capsicum extract comprising of capsaicionoids. Capsicum extract may be administered as such as per the scope of this invention or may be formulated in the form of solid dosage form, convenient to administer to exercising subjects as per methods described herein. The formulation may be prepared as extended and sustained release beadlets or spray dried powder using the methods known to person skilled in the art.
It is to be appreciated that the term 'effective amount' can be interpreted to be within the scope of amount of capsaicinoids comprised in capsicum composition, which is administered to exercising subjects, such that it is useful to bring out the desired effect and also avoids any adverse effect, over the time duration which is recommended for administration of the composition to the subjects. As per the methods described herein, the dose is delivered in the range of about 0.01 mg/kg body weight to about 200 mg/kg body weight of capsaicinoids, preferably about 10 mg/kg body weight/day to 100 mg/kg body weight/day of capsaicinoids to the subjects undergoing physical indoor and/or outdoor activities. The effective amount may vary depending upon the age and body weight of the subject or depending upon the type of activity the subject is undergoing such as sports. In such cases capsicum compositions may be administered with other nutrients such as proteins, essential amino acids or muscle stimulants, which may effectively lower down the daily dose of capsicum composition.
The present invention provides a method for improving physical performance and endurance, wherein capsicum composition is administered in the form of effective daily dose of amount of capsaicinoids, administered to a subject undergoing indoor or outdoor physical activities.
It is also to be appreciated that the term 'exercising subject or the subject undergoing physical activity' as used herein can be interpreted to be within the scope of present invention to mean that it is the practical or experimental condition for evaluating effect of capsicum composition in terms of exercise performance and endurance, wherein the composition is administered to the

subjects who are undergoing exercise at the time of evaluation. It is also the condition which is advised as per the methods described herein, to achieve the intended result from administration of capsicum compositions in effective dose. Thus the group of subjects, who are administered the capsicum composition are also subjected to specific type and duration of exercise. The effect of capsicum composition and exercise in combination is evaluated according to the method described herein. The term can be also interpreted as the recommended condition for the subjects who are administered with capsicum composition, so that the desired effect is obtained. As per the present invention, the subjects who are doing physical indoor and/or outdoor activities such as sports, exercise or strenuous other activities will be benefited more due to administration of capsicum compositions of the invention. The performance duration, endurance and stamina of such physically active subjects is enhanced because of administration of effective amount of capsicum composition comprising capsaicinoids. However the compositions described herein can be also administered to the subjects at rest and can be asked to have their daily activities to get desired benefit or to increase stamina required for some physical strenuous activities. In its still wider meaning, the term 'exercising subject' also means that the subject is carrying out some type of physical indoor and/or indoor activity such as sports, exercise and other strenuous activities selected from the group of, but not limited to aerobic exercises, anaerobic exercises, fitness exercises, trekking, jogging, staircase climbing, jumping, walking and the like or the combinations thereof.
Capsicum compositions as described herein may be administered alone or in combination with other nutrients, health supplements, muscle enhancers, stimulants, essential amino acids and/or anabolic ingredients for improving the performance and endurance during indoor and/or outdoor activities such as exercise, sports or others as per the scope of present invention.
Capsicum compositions herein are obtained from natural resources by human intervention and are safe for administration.
As per main embodiment, present invention relates to method for improving exercise performance and endurance, the method comprising administering effective amount of capsaicinoids from capsicum composition to an exercising subject. According to this method when capsicum composition is administered to deliver effective amount of capsaicinoids to subject undergoing indoor or outdoor physical activity such as exercise or sports, improvement

in performance as well as endurance is observed. The method also results in improvement in fatigue suppression during endurance exercise and post-exercise recovery from muscle fatigue and/or muscle soreness.
As per one more embodiment of the present invention, the composition as described herein may be comprised of capsicum extract alone or formulated as extended and sustained release stable, free flowing, solid composition of capsicum extract comprised of capsaicinoids and/or analogs, employing at least one food grade excipient.
In an embodiment, a capsicum composition is comprised of a capsicum extract as such prepared for example from various varieties of paprika, which is further comprised of chemical constituents including capsaicinoids and further may be comprised of other compounds such as non-capsaicinoids.
In an embodiment, a capsicum extract is prepared from various varieties of paprika selected from the group of, but not limited to, varieties such as for example Teja and Namdhari. More particularly, the composition herein may be comprised of the capsicum extract obtained from varieties of Capsicum annum such as Teja and Namdhari. In an embodiment, an industrially viable process is provided for preparation of a capsicum composition by employing non-polar, semi-polar, polar solvents or combinations thereof in suitable ratios. In an embodiment, a capsicum composition is prepared using a combination of polar and non-polar solvents in a suitable ratio for an extraction cycle, followed by purification of the extract by using polar solvent(s) to obtain the extract. The composition including the extract is safe for human consumption and is comprised of biologically active chemical constituents including capsaicinoids and further may be comprised of compounds such as non-capsaicinoids.
The methods described herein are comprised of administering effective amount of capsicum composition in the form of capsicum extract as such or the extract formulated using at least one pharmaceutically and/or nutraceutically acceptable excipient to get stable dosage form, convenient for administration. The excipeint may be selected from the group of, but not limited to carrier, antioxidant, stabilizer, diluents, coating polymer, solvent alone or the mixture thereof. Capsicum compositions as described herein are comprised of compounds such as capsaicinoids

and non-capsaicinoids. The capsaicinoid compounds present in capsicum compositions may be selected from, but not limited to, the compounds such as capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homocapsaicin, dihydrohomocapsaicin, 6",7"-dihydro-5',5'"-dicapsaicin, 5,5'-dicapsaicin.
According to one more embodiment, capsicum composition as described herein, is comprised of either capsicum extract alone containing pungent and oily capsaicinoids or the extract is formulated using at least one food grade excipient to entrap the extract at high shear pressure. Due to the high shear pressure extract containing capsaicinoids is entrapped in a carrier which remarkably delays or extends the release of the active ingredient thus reducing the pungency and irritation characteristic of the active ingredient, which would otherwise release in gastric region. The pungency can be further reduced or masked by coating the polymer entrapped substance with excipient such as a polymer that can form an effective barrier between pungent active and the outside environment and thus further sustains the release of the active substance and makes the present formulation palatable and safe for human consumption.
Thus extended and sustained release capsicum composition comprises of a spheroidal nutrient core containing the active substance and at least one more excipient; and a protective polymeric enteric coat; wherein the said coating facilitates gradual and uniform release of high dosage of the said active substance to reduce irritation and minimize abdominal pain and gastric discomfort associated with its release.
The oily and pungent capsaicinoid used in capsicum composition is selected from a group consisting of capsicum extract; capsicum oleoresin; capsaicin crystals, preferably capsicum extract. It may be used either alone or is present in the range of 0.1-90% of the total weight of capsicum composition, formulated using at least one food grade excipient.
The carrier used is selected from microcrystalline cellulose, Avicel® PH 101, Avicel' PH 102, Avicel® PH 103, Avicel® PH 105, Avicel® PH 112, Avicel® PH 113, Avicel® PH300, Avicel® PH212, Avicel®PH 301, Avicel®PH 302, colloidal grades Carboxymethyl cellulose Sodium and other cellulose containing polymers and their derivatives or mixtures thereof.

The sugar used is selected from the derivatives of sugar such as Mannitol, sucrose, xylitol, sorbitol, Maltitol, Lactitol, Isomalt or mixtures thereof.
The surfactants used are selected from polysorbate, sodium lauryl sulfate, sorbitan monooleate, other surfactants of the same class or mixtures thereof.
The polymers used for preventive coating and/or binders are selected from Methyl Cellulose, Agar, Sodium Alginate, Hydroxy Propyl Methyl Cellulose, Hydroxy Propyl Cellulose, Microcrystalline Cellulose, Polyvinyl Pyrrolidone, Starch, Gum Arabic, Xanthan Gum, Polyethylene Glycols, preferably, Microcrystalline Cellulose, Hydroxy Propyl Cellulose, Methyl Cellulose, Hydroxy Propyl Methyl Cellulose, etc, more preferably, Hydroxy Propyl Methyl Cellulose, Methacrylates, Phthalate methyl acrylate-methacrylic acid copolymers, cellulose acetate succinate, polyvinyl acetate phthalate, Marcoat containing polymers and there derivatives or mixtures thereof.
In another preferred embodiment the solvent employed may be selected from acetone, hexane, ethyl acetate, Isopropyl alcohol, ethanol, dichloromethane, methanol and the like or the combination thereof. The solvent may be selected, more preferably from acetone, ethanol, dichloromethane, Isopropyl alcohol, and more preferably Dichloromethane and Isopropyl alcohol.
Free flowing, stable and solid capsicum composition, as described herein is prepared by method known to a person skilled in the art such as extrusion spheronization or by spray drying method.
According to one embodiment of the invention, the method as described herein evaluates effect of capsicum composition by administering effective amounts of capsaicinoids to exercising subjects, for improving exercise performance and endurance.
Capsicum composition may be administered to the subject in the form of extract as such or a solid oral dosage formulation so as to provide daily dose of at least 0.01 mg/kg body weight to 200 mg/kg body weight of capsaicinoids, preferably daily dose of about 10 mg/kg body weight to 100 mg/kg body weight of capsaicinoids from this composition.

As per one more embodiment of the present invention, the method for evaluating effect of capsicum composition is comprised of in-vitro cell-line study to understand effect on sports nutrition biomarkers, mitochondrial oxygen consumption, mitochondrial mass, IGF (Insulin like growth factor) and Cortisol release. Capsicum extract may be used in such in-vitro study and the effects are monitored.
Mitochondria represent the principal energy source in cells, converting nutrients to energy via cellular respiration. The function and content of mitochondria increase with physical training and decrease with physical inactivity. An alteration in the rate of oxygen consumption can serve as a useful indicator of mitochondrial dysfunction. By measuring oxygen consumption, a direct and specific assessment of the functioning of the electron transport chain (the key element of oxidative phosphorylation and cellular metabolism) may be obtained. Mitochondrial abundance (mass) can also be used as an indicator of mitochondrial biogenesis.
As a direct result of aerobic exercise, elevated oxygen consumption contributes to an increase in the circulation of glucocorticoids, such as Cortisol. During exercise training, Cortisol causes rapid mobilization of fat, protein, and carbohydrates, providing the body with resources to manage an imbalance in homeostasis. However, Cortisol is catabolic, decreasing muscle growth hormones, such as insulin-like growth factor (IGF)-l. Conversely, IGF-1 is anabolic, promoting protein synthesis and is thus considered as important biomarker for fitness and exercise training.
As per one more embodiment, the methods described herein evaluate effect of capsicum composition through in-vivo study in animal models and human volunteers through plasma, muscle protein analysis and checking effect on physical performance, endurance, exhaustion time and actual run time. Capsicum composition in the form of capsicum extract or beadlets may be administered in such study.
The compositions as described herein are studied in experimental animal models to investigate effect of administration on changes in serum parameters, antioxidant status of muscles in rats after exhaustive exercise. The effects can also be investigated on exercise performance, exercise

time of exhaustion and changes in cardio-metabolic health markers such as HO-1 and SIRT1 pathways in the skeletal muscles of exercise-trained and sedentary rats.
The methods as described herein promote exercise performance and endurance through effective utilization of lipids such as cholesterol and triglycerides. The method as described herein also increases phosphorylated AMP activated protein kinase (pAMPK) and Nuclear erythroid derived factor -like 2 (Nrf2), thus reducing inflammatory process and improving exercise performance. The method also reduces lactate amount in muscles, enhances running performance, increases heme-oxygenase (HO-1) and decreases interleukin (IL-10) and thus enhances exhaustion time as well as running performance in exercising subject.
Exercise results into increased oxidative stress and capsaicinoids from capsicum compositions help to reduce oxidative stress and enhance antioxidant and anti-inflammatory effects. Activation of AMPK promotes glucose uptake, fatty acid oxidation, mitochondrial biogenesis, and insulin sensitivity, AMPK is activated by low energy status (increased AMP/ADP: ATP) such as during exercise, and regulates metabolic process and energy homeostasis by switching off ATP consuming pathways (fatty acid and cholesterol synthesis) and switching on ATP generating processes (glucose uptake and fatty acid oxidation).
As per one embodiment of the present invention, method described herein lowers down cholesterol and triglyceride levels and exhibits increased antioxidant capacity. As per one more embodiment, the invention relates to method for enhancing exercise endurance and exhaustion time, by administering effective amount of capsicum composition to exercising subjects, which enhances antioxidant amounts in body and lactates are decreased, thus resulting into recovery from muscle fatigue during exercise and/or post exercise.
The method described herein is comprised of administering effective amount of capsaicinoids from capsicum compositions to subjects who are undergoing physical activity, wherein it also lowers down oxidative stress significantly. Capsicum compositions as described herein are stable and safe for oral administration and are prepared using conventional equipments.

The details of the present invention are described in the Examples given below which are provided to illustrate the invention and therefore should not be construed to limit the scope of the present invention.
Examples
Example 1: In -vitro cell line study for effect of capsicum compositions on sports nutrition biomarkers
Preparation of C2C12 cell line
C2C12 cells (ATCC® CRL-1772) were seeded in 24- or 96-well culture plates as undifferentiated myoblasts and grown to 100% confluency in ATCC-formulated Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% heat-inactivated fetal bovine serum (FBS). Upon reaching confluency, cells were induced to differentiate from myoblasts into multinucleated, fused myotubes, which exhibit similar characteristics to mature muscle cells. Cell culture conditions were maintained at 37°C in a humidified atmosphere of 5% C02/95% air. After 5 days of differentiation, cells were ready for incubation with capsicum composition as test inputs and without the composition as controls.
The effect of Capsicum composition (also abbreviated as Cap or capsimax in graphs and figures) was assessed using the following assays:
Cell viability measurement: In order to determine appropriate dosages of capsaicinoids from capsicum composition for endurance/stamina related assays, differentiated C2C12 myotubes were treated with a range of capsaicinoids concentrations. Cell viability was assessed by MTT (3-(4, 5-desethyithiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide) assay, a common measurement of the in vitro cytotoxicity of capsicum composition (called as test inputs in this study). Conversion of MTT reagent (yellow colour) to formazan (purple colour) by living cells provides an indication of mitochondrial activity, which is directly related to cell viability. C2C12 cells were seeded in 96-well culture plates at a density of 2 x 104 cells/mL and induced to differentiate. After a 24-hour pre-treatment with a range of select test input concentrations, used medium was removed, replaced with MTT labeling reagent (5 mg/mL in phosphate buffered

saline), and incubated for 4 hours. The purple coloured formazan crystals formed in the intact cells were then dissolved overnight with MTT solubilisation solution (10% SDS in 0.01 M HC1). After solubilisation of the formazan crystals, absorbance was measured at 570 nm with a microplate reader. Data obtained from this cytotoxicity testing allowed for dose range optimization of capsicum composition for further testing.
A. Effect of capsicum composition on Mitochondrial oxygen consumption
Extracellular oxygen consumption in differentiated C2C12 cells was measured by assessing phosphorescence of a porphyrin-based, water soluble, oxygen sensitive probe (MitoXpress®-Xtra-HS, Luxcel Biosciences). Probe fluorescence is quenched by molecular oxygen (O2), resulting in lower probe signal. As cellular respiration reduces the concentration of O2, probe signal increases. The rate of this increase is related to the rate of cellular oxygen consumption. C2C12 cells were seeded in 96-well culture plates at a density of 2 x 104 cells/mL, induced to differentiate, and incubated with MitoXpress probe (1 uM), in the presence or absence of select test inputs. High sensitivity mineral oil was added (100 uL/well) to increase assay sensitivity by minimizing interference from ambient O2. Probe fluorescence was measured (excitation 380 nm, emission 645 nm) using a fluorescence plate reader.
B. Effect of capsicum composition on Mitochondrial mass
The effect of treatment with capsicum compositions on mitochondrial mass was assessed by measuring changes in fluorescent intensity in differentiated C2C12 cells. The nonyl acridine orange (NAO) probe binds to cardiolipin in all mitochondria, regardless of their energetic state, providing a measure of mitochondrial mass and an indication of mitochondrial biogenesis. C2C12 cells were seeded in 96-well culture plates at a density of 2 x 104 cells/mL, induced to differentiate, and pre-treated with capsicum composition or used as controls. Following treatment, media was replaced with NAO probe (100 ng/mL) and incubated for 30 mins at 37°C in a humidified atmosphere of 5% C02/95% air! Probe fluorescence was measured (excitation 380 nm, emission 645 nm) using a fluorescence plate reader. Fluorescent intensity relative to untreated control was then calculated. To standardize probe fluorescence to protein content of the cells, total protein content (in u.g) was assessed by bicinchoninic acid (BCA) using bovine serum albumin as standard.

C. Effect of capsicum composition on Insulin-like growth factor-1 (IGF-1)
To evaluate the effect of capsicum composition treatment on IGF-1 concentrations in differentiated C2C12 cells, the mouse IGF-1 enzyme-linked immunosorbent assay (ELISA) kit (Sigma) was utilized. The kit provides a quantitative measurement of mouse IGF-1 in cell culture supernatants by employing an antibody specific coated 96-well plate. Standards and test samples were added to the coated plate and any IGF-1 present in the sample gets bound to the immobilized antibody. After washing away any unbound antibody, HRP-conjugated streptavidin was added to the wells. The wells were washed again, followed by addition of a colorimetric reagent. Colour was developed in proportion to the amount of bound IGF-1. The colour intensity was read at wavelength 450 with a microplate reader. Blank-corrected unknown sample protein concentrations were then extrapolated from a known standard curve.
D. Effect of capsicum composition on Cortisol release in H295R Cell line
H295R cells (ATCC® CRL-2128) were seeded in 24-well culture plates and grown to confluence in ATCC-formulated Dulbecco's Modified Eagle's Medium (DMEM). Cell culture conditions were maintained at 37°C in a humidified atmosphere of 5% C02/95% air. Cells were incubated in the presence or absence of a capsicum composition and controls.
To evaluate the effect of capsicum composition on Cortisol concentrations in H295R cells, the DetectX® (Arbor Assays) immunoassay was utilized. A Cortisol standard was provided to generate a standard curve for the assay and all samples were read off the standard curve. Standards or samples (capsicum composition) were pipetted into a clear microtiter plate coated with an antibody. A Cortisol-peroxidase conjugate was added to the standards and samples in the wells. The binding reaction was initiated by the addition of a monoclonal antibody to Cortisol in each well. After one hour incubation, the plate was washed and substrate was added. The substrate was reacted with the bound cortisol-peroxidase conjugate. After a short incubation, the reaction was stopped and the intensity of the generated color was detected in a microtiter plate reader capable of measuring 450 nm wavelength. The concentration of Cortisol in the samples was then calculated by extrapolating from the standard curve.

Results:
A. Evaluation of mitochondrial respiration (oxygen consumption) as sports nutrition biomarker
Table 1: Effect of capsicum composition on mitochondrial respiration

Mitochondrial respiration Fluorescent Intensity
Product Concentration (ug/mL) n=l n=2 n=3 AVG SD SEM Relative to control
control N/A 28.8 30 29.9 29.6 0.6 0.4 99.9
Capsicum composition 10 38.5 38.5 38.5 38.5 0 0.0 130.2
Capsicum compositions increased mitochondrial oxygen consumption (respiration) significantly as compared to control.
Table 2: Effect of Capsicum composition on mitochondrial mass in C2C12 cells

Mitochondrial Mass Fluorescent Intensity
Product Concentration (ug/mL) n=l n=2 n=3 AVG SD SEM Relative
to control
control N/A 13673.0 13705.3 13769.3 13175.9 49.0 28.3 100
Capsicum composition 10 16271.7 16468.0 19181.7 17307.1 1626.4 939.0 126.2
Table 2 indicates that capsicum compositions enhanced mitochondrial mass in cell-line study as compared to control cells.
Table 3: Effect of Capsicum composition on IGF-1 in cell-line study

IGF-1 n=l n=2 n=3
Product Concentration (ug/mL) Concentration (pg/ml) AVG SD SEM Relative to control
control N/A 36.3 34.7 31.9 34.3 2.22 1.28 100
Capsicum composition 10 42.5 43.2 36.2 40.6 3.82 2.20 118.5

Table 3 indicates that IGF-1 concentrations increased significantly when the cells were treated with capsicum compositions.
Table 4: Effect of capsicum composition on Cortisol release in cell-line study

Cortisol n=l n=2 n=3
Product Concentration (ug/mL) Concentration (pg/ml) AVG SD SEM Relative
to control
control N/A 868.0 693.3 1200.9 920.7 257.9 148.9 100.0
cAMP (negative control) ImM 1446.1 1042.2 2183.3 1557.2 578.6 334.1 169.1
Capsicum composition 10 1073.7 827.3 1659.8 1186.9 427.7 246.9 76.2
Capsicum compositions reduced Cortisol release relative to control as indicated by cell-line study and thus enhance sport performance.
Table 5: Effect of capsicum composition on sports nutrition biomarkers in cell-line study

Product Mitochondri
al Mass Mitochondri
al Respiration IGF-1 Cortisol
Control 100 100.1 100 100
cAMP (control) 169.1
Capsicum composition 126.2 130.2 118.5 76.2
Improvements in endurance and stamina are related to both the content and function of the mitochondrion. Mitochondrial mass can be used as an indicator of mitochondrial biogenesis. Similarly, oxygen consumption rate, a direct measurement of the functioning of the electron transport chain, is indicative of cellular metabolism. The cell-line study indicates that capsicum composition enhanced mitochondrial mass as well as mitochondrial oxygen consumption (respiration) significantly as compared to control.
Mitochondrial efficiency enhancement also results in increased glucocorticoids such as Cortisol which is catabolic and can lead to decreases in protein synthesis and muscle growth hormones, such as IGF-1. In the sports nutrition market, controlling the deleterious catabolic effects of

Cortisol and enhancing the levels and activity of muscle building proteins such as IGF-1 is desired effect. Capsicum compositions showed good effect in all 4 assays related to endurance/stamina and thus represents a potentially beneficial natural supplement for this segment of the sports nutrition market.
Example 2: In-vivo study for evaluation of capsicum composition
Animals and exercise protocol: 8-10 male Wistar rats per treatment arm (age: 8 week, weight: 180 ± 20 g) were housed in a controlled environment and were provided with rat chow and water ad libitum. All experiments were conducted under the National Institutes of Health's Guidelines for the Care and Use of Laboratory Animals and approved by the Ethics'Committee of the Veterinary Control Institute. Following a 7-day acclimatization period, rats of both the control and exercise groups were sub-divided into groups by matched body weight. Animals were randomly divided into the following groups:

Group I - Control (No exercise or capsicum Group III - only Exercise (No capsicum
composition) composition)
Group II- Control + capsicum composition Group IV: Exercise + capsicum composition
(100 mg/kg body weight/day capsaicinoids) 100 mg/kg body weight/day capsaicinoids )
Capsicum compositions were administered to group II and IV animals daily as an oral supplement for 8 weeks to deliver specific dose of capsaicinoids.
The exercise protocols were performed on a motor-driven rodent treadmill equipped with an electric shock grid on the rear barrier to provide exercise motivation to the animals. All exercise tests were performed during the same time period of the day to minimize diurnal effects. The animals in the chronic exercise groups were habituated by treadmill exercise over a 5-d period such as: 1st day 10 m/min, 10 min; 2nd day 20 m/min; 10 min, 3rd day 25 m/min, 10 min; 4th day 25 m/min, 20 min and 5th day 25 m/min, 30 min. Thereafter, the animals were exercised at 25 m/min, 45 min/d, 5 d per week for 8 weeks (Liu et al. 2000.) To minimise diurnal effects, all animals were exercised at the same time.

Sample collection
The rats were killed 24 h after the last exercise in the chronic exercise group by cardiac puncture. To minimize diurnal effects, all animals were killed at the same hours. Plasma samples were stored at -80°C until the time of analysis. Muscle samples (100 mg) were collected and frozen at -80°C for further analyses.
Laboratory analyses
Plasma was used for the determination of glucose, lipid profile, Cortisol , serotonin, testosterone, creatine kinase activity (CK), aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) activity, urea, creatinine) with an automatic analyser (Olympus). The serum and muscle malondialdehyde (MDA) levels were measured by HPLC (Shimadzu). The total superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured using a commercially available assay kit (Cayman Chemical, Ann Arbor, MI, USA) according to the manufacturer's instructions. Inflammatory cytokines (TNFa, IL6 and IL10), C-reactive protein (CRP) were analyzed by ELISA. All proteins (AMP-activated protein kinase, SIRT1, mitochondrial transcription factor A, NF-kB, I-kB, Nrf2, HO-1) for pathways were analyzed by Western blot methods in muscle samples.
Histological analysis
Samples of skeletal muscle (vastus lateralis) were collected from each rat in each experimental condition and fixed with a solution of 2% glutaraldehyde in phosphate buffer at 4°C for 2 h. Samples were then washed several times in phosphate buffer and postfixed with 1% Os04 (Osmium tetroxide) in phosphate buffer for 1 h at room temperature. After being washed in phosphate buffer, samples were dehydrated in a graded series of ethanol and embedded in Epon 812 resin (Fluka, Sigma-Aldrich). From each sample, sections of 500 nm were obtained with ultramicrotome and subsequently stained with a solution of 1% toluidine blue buffered with borate. They were finally observed under light microscopy, and images were recorded by software.

Statistical Analyses
Data are given as mean ± SEM. Sample size will be calculated based on a power of 85% and a p value of 0.05. Given that assumption, a sample size of seven per treatment will be calculated. Data analysis will be done between control vs exercise vs control + capsicum composition vs exercise + effect of capsicum composition. The data were analyzed using the procedure of SAS (SAS Institute: SAS User's Guide: Statistics). The treatments were compared between control vs exercise vs control + capsicum vs exercise + product capsicum using ANOVA and student's unpaired t test; P < 0.05 was considered statistically significant.
Results:
Table 6: Effect of capsicum composiiton on distance run avearage per day and run to exhaustion

Capsicum compositions when administered to exercising subjects increased distance run average per day and run to exhaustion as compared to the subjects not administered with capsicum composition.
Table 7: Effect of capsicum composition on lipid profile in exercising subjects

Item Groups SEM ..p..

Control CAPs Exercise Exercise + CAPs

Glucose. mg/dL 101.57 99.14 91.43 93.86 5.14 0.512
T-C. mg/dL 75.14a 70.57b 74.00a 47.86c 0.70 0.0001

TG. mg/dL
103.713 100.14ab 84.29b 60.57c 3.62 0.0001
T-C: Total Cholesterol; TG: Triglycerides Data are means the standard error Different superscripts (a-d) indicate group mean differences (p < 0.05). of the mean (SEM).
Capsicum compositions decreased total cholesterol and triglycerides, when administered to exercising subjects.
Table 8: Effect of capsicum composition on lactates and muscle antioxidant activity

Item Groups SEM „P„

Control CAPs Exercise Exercise + CAPs

Lactate mg/dL 9.66a 8.77b 7.47c 5.43d 0.17 0.0001
Muscle MDA (nmol/mg protein) 78.84a 60.50b 74.16a 44.79c 2.07 0.0001
Muscle SOD (U/mg protein) 0.22d 0.43b 0.34c 0.56a 0.01 0.0001
Muscle GPx (U/mg protein) 143.29c 172.57b 155.71bc 203.863 5.13 0.0001
MDA: Malondialdehyde; SOD: supe are means the standard error of the group mean differences (p < 0.05). :roxide dismi mean (SEM) ltase; GPx: . Different s Glutathione uperscripts 1 peroxidase. Data ^a-d) indicate
When Capsicum compositions were administered to exercising subjects, this resulted in decreased muscle lactate and muscle malonaldehyde, which indicates decreased oxidative stress. On the other hand SOD and GPx values increased in exercising subjects with capsicum compositions (Group IV), which suggested increased muscle antioxidant activity.
It was observed that oxidative stress marker such as NFkB and Interleukin-10 (IL-10) was decreased in group II and IV.
Protein levels of phosphorylated AMP-activated protein kinase (pAMPK), Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase-1 (HOI) were increased in Group IV. There were no significant differences in any of the end points in Group I and II.

The results suggested that dietary capsaicinoids enhance running performance and decreased oxidative stress. These results suggest that administeration of capsicum compositions to the exercising subjects may enhance the effect of exercise by effective utilization of lipids by increasing pAMPK and Nrf2. Group IV significantly increased running performance and exhaustion time. In Group IV, significant decrease in triglycerides and cholesterol was observed compared with other treatments. A significant decrease in lactate, muscle oxidative stress and increase in muscle antioxidant activity were observed in Group IV. No significant changes in liver and kidney functions were observed in any of the treated groups.
Example 3: Human umbilical endothelial cells line model to study nitric oxide effects by Capsicum composition
Human Umbilical Vein Endothelial Cells (HUVEC) were purchased from Clonetics (Cambrex, Inc., Walkersville, MD, USA) as a frozen stock (passage 3), defrosted and cultured in endothelial basal medium 2 growth media plus bullet kit (Cambrex, Inc.) containing 2% fetal calf serum, antibiotics and growth factor supplements at 37C and 5% C02. The cells were passaged three times to provide a pool of cells to be used for experiments. Experiments were performed in six-well plates (Corning, Inc., Corning, NY, USA) when the cells were 80% confluent, at which stage the endothelial basal medium 2 growth media (2 % fetal calf serum, with growth factors) was replaced with endothelial basal medium 2 control media (08 % fetal calf serum, no growth factors) and incubated for 24 h (37C, 5% C02). Treatments were prepared in endothelial basal medium 2 containing 0.8 % fetal calf serum and antibiotics but no other supplements. Capsicum composition was dissolved in water at three concentrations, as shown. Eighteen hours after treatment RNA was extracted. Real-time PCR was performed on selected list of genes using standard protocols.

Name Concentration (ug/mL)
Untreated (DMSO only) Control 0
Capsimax beadlets 6.25
Capsimax beadlets 12.5
Capsimax beadlets 25
Rosiglitazone 10

It was observed that Capsicum compositions upregulated eNOS at higher concentration and down regulated ET1 in human umbilical endothelial cells. This indicates effect of exercise on decreasing reactive oxygen species, thus reducing oxidative stress in system, as beneficial effect of administration of capsicum compositions in exercising subjects.
Example 4: Evaluation of capsicum composition as sports nutrition in human volunteers
Capsicum formulation was administered to 152 normal to overweight females and males having BMI ranging from 18.3 to 30.0. Daily dosage of 2 mg capsaicionids from 2% capsimax beadlets was administered for 7 days. Heart rate, general health status and life style factors including exercise intensity were recorded at baseline and after 7 days. Effect of capsicum composition was evaluated and recorded in terms of duration of exercise and time to exhaustion at the end of 7 days.
At the end of 7 days it was observed that duration of exercise and time to exhaustion was significantly increased in individuals administered with capsicum composition. Subjects work out intensity also increased after capsicum supplementation.

Claims:
1. A method for improving physical performance, comprising administering to a subject undergoing physical activity, a capsicum composition comprising capsaicinoids in effective amounts, wherein said composition significantly enhances endurance capacity and resistance to fatigue.
2. The method of improving exercise performance as claimed in claim 1, wherein the subject desiring this improvement is selected from a mammal, selected from a group of, but not limited to an animal or human being who is subjected to indoor and/or outdoor activities such as exercise, sports and other physical strenuous activities either alone or in the combination thereof.
3. The method as claimed in claim 1, wherein the capsicum composition is comprised of capsicum extract comprised of capsaicinoids as such or the extract formulated with at least one pharmaceutically and/or nutraceutically acceptable excipient.
4. The method as claimed in claim 1, wherein the capsicum composition significantly enhances endurance capacity by virtue of enhancing mitochondrial biogenesis through increased mitochondrial oxygen consumption and mitochondrial biomass, when administered in an effective amount to the subject undergoing physical activity.
5. The method as claimed in claim 1, wherein the capsicum composition enhances resistance to fatigue by enhancing oxidative capacity of the muscles through reduction in muscle soreness and enhancing post-exercise recovery from muscle fatigue, when administered in an effective amount to the subject undergoing physical activity.
6. The method as claimed in claim 1, wherein the capsicum composition enhances physical endurance, by increasing levels of IGF-1 and decreasing release of Cortisol, when administered in an effective amount to the subject undergoing physical activity.
7. The method as claimed in claim 5, wherein the capsicum composition significantly reduces oxidative muscle stress by decreasing levels of muscle lactates and improving '

levels of antioxidant enzymes such as muscle malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx),when administered in an effective amount to the subject undergoing physical activity.
8. The method as claimed in claim 6, wherein the capsicum composition enhances effect of exercise by effective utilization of lipids through increase in levels of pAMPK (phosphorylated AMP-activated protein) and Nrf2 (Nuclear factor [erythroid-derived 2]-like 2), when administered in an effective amount to the subject undergoing physical activity.
9. The method as claimed in claim 6, wherein the capsicum composition enhances exercise performance by increasing distance run average per day and run time to exhaustion, when administered in an effective amount to exercising subject.
10. The method as claimed in claim 1 for improving physical performance, wherein the capsicum composition is administered as daily dose of about 0.01 mg/kg body weight to 200 mg/kg body weight of capsaicinoids to the subject undergoing physical activity.