US 20160213673A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0213673 A1 BARTOS et al. (43) Pub. Date: Jul. 28, 2016 (54) ENDURANCE FORMULATION AND USE Publication Classification (71) Applicant: GLANBLA NUTRITIONALS (51) Int. Cl. (IRELAND) LIMITED, KILKENNY A613 L/522 (2006.01) (IE) A63L/98 (2006.01) A2.3L 2/52 (2006.01) (72) Inventors: Jeremy D. BARTOS, San Marcos, CA A63L/216 (2006.01) (US); Elaine DRUMMOND, Carlsbad, (52) U.S. Cl. CA (US) CPC ............. A6 IK3I/522 (2013.01); A61 K3I/216 (2013.01); A61 K3I/198 (2013.01); A23L I/3051 (2013.01); A23L 2/52 (2013.01); A23L (21) Appl. No.: 15/003,130 I/302 (2013.01); A23L 1/304 (2013.01); A23L I/30 (2013.01); A23 V 2002/00 (2013.01) 22) Filed: Jan. 21, 2016 (57) ABSTRACT (22) Filed: al. Al The present disclosure provides compositions and formula tions containing dihydrocapsiate, caffeine and arginine as Related U.S. Application Data well as methods of making and using the compositions and formulations. The compositions and formulations of the (60) Provisional application No. 62/108.207, filed on Jan. present disclosure increase human endurance during times of 27, 2015. physical activity. US 2016/0213673 A1 Jul. 28, 2016 ENDURANCE FORMULATION AND USE 0010 Capsinoids such as dihydrocapsiate exert similar 0001. The present application claims benefit of U.S. Pro thermogenic and lipolytic effects as the red pepper compound visional Patent Application No. 62/108.207, filed Jan. 27. capsaicin but without noxious sensations of pungency or 2015, the entire contents of which is incorporated herein by "hotness.” In addition, dihydrocapsiate does not cause reference. increases in blood pressure and heart rate like those attributed 0002 The present disclosure provides compositions and to capsaicin ingestion. The thermogenic and lipolytic effects formulations containing dihydrocapsiate, caffeine and argin of dihydrocapsiate (and all other capsaicins and capsinoids) ine as well as methods of making and using the compositions are mediated through the Transient Receptor Potential Vanil and formulations. The compositions and formulations of the loid 1 (TRPV1) receptors throughout the gastrointestinal present disclosure increase human endurance during times of tract, which in turn are linked with the sympathetic nervous physical activity. system (SNS). When activated, they increase SNS activity 0003. The compositions and formulations of the present which results in the downstream activation of uncoupling disclosure are believed to increase or enhance endurance proteins UCP-1, UCP-2, and UCP-3. when ingested by sparing glycogen stores, increasing aerobic 0011. Of particular importance for endurance is UCP-2 activity over anaerobic activity during times of physical activ and UCP-3, the latter of which is expressed in the skeletal ity and thereby reducing metabolite buildup that would nor muscle of all mammals and plays a role in the transport of free mally lead to exhaustion and limitations on endurance by a fatty acids. UCP-2 is primarily expressed in adipocytes and person not ingesting a composition or formulation of the plays a key role in lipolysis, which is the release of free fatty present disclosure. acids from their storage in adipocytes. This release is trig 0004 Compositions and formulations of the present dis gered as the body is searching for a fuel store to induce closure enhance endurance when ingested before or during, thermogenesis brought on by the TRPV-1 receptor activation or before and during physical exertion. Increasing endurance, (for example, in shivering). or the amount of time the body can work out, for example 0012 Free fatty acids can be utilized as a fuel source in running longer distances or for longer time, increasing num endurance training as well, and since UCP-3 is expressed in ber of reps of workout, etc., is an increasingly important focus skeletal muscle and helps transport free fatty acids, it is rea of sports nutrition. sonable to believe that it will help increase free fatty acid 0005. A focus of the presently disclosure technology is uptake by the muscles. enhancing endurance by increasing the sparing of glycogen 0013. In one animal study (“Upregulation of uncoupling stores, forcing aerobic activity as compared to anaerobic, proteins by oral administration of capsiate, a nonpungent increasing vasodilation, and reducing the build-up of metabo capsaicin analog J Appl Physiol. 2003 December; 95(6): lites that can lead to the feeling of exhaustion during and after 2408-15), UCP3 mRNA expression in skeletal muscle physical activity. occurred within minutes of capsinoid ingestion and persisted 0006. The combination of dihydrocapsiate, caffeine and for 2 hours. A separate animal study ("Capsiate, a Nonpun arginine provided in compositions and formulations of the gent Capsaicin Analog, Increases Endurance Swimming present disclosure provide a unique combination designed to Capacity of Mice by Stimulation of Vanilloid Receptors' enhance endurance via one or more of these mechanisms. Biosci Biotechnol Biochem. 2006 April; 70(4):774-81) dem 0007 Two of the main mechanisms for ATP synthesis are onstrated that mice taking capsiate were able to Swim signifi aerobic respiration (glycolysis, citric acid cycle, oxidative cantly longer than mice who hadn't taken capsiate. In addi phosphorylation, etc.) and anaerobic respiration (glycolysis tion, after 30 min of Swimming, the residual glycogen in the only). Aerobic respiration pathways occur in an oxygen-rich gastrocnemius muscle was higher, the serum free fatty acid state, have a more efficient output of ATP (36-38 ATP/glu concentration tended to be higher, and the serum lactic acid cose), and are typically associated with endurance exercise. concentration was significantly lower in the capsiate-admin Anaerobic respiration occurs in an oxygen poor environment, istered mice. has less efficient output of ATP (2 ATP/glucose), and is typi 0014. This suggests that the capsiate increased the release cally associated with intense exercise (weightlifting, sprint of free fatty acids, which UCP-3 brought to the muscle to use ing, etc.). Anaerobic respiration is also much quicker than as fuel, sparing glycogen stores for later and thus lengthening aerobic respiration (because it is only going through the gly the Swimming time. This allows for increased aerobic exer colysis), and is only utilized by muscle cells. cise and delayed anaerobic exercise. This mechanism of 0008. In theory, if the body can endure longer periods of action was Subsequently proved in the same experiment when anaerobic respiration than aerobic respiration, or if it can researchers demonstrated significantly higher oxygen con utilize free fatty acids as fuel instead of glucose, it will help Sumption (aerobic) and fat oxidation (using fat as fuel) with extend the short-term, high intensity activities associated reduced carbohydrate oxidation (glycogen sparing) follow with weight training. Once glycogen stores are used up, ing capsiate administration. fatigue will also set in. Glycogen sparing is maximized with 0015 While these studies were performed using capsiate the use of non-carbohydrates as a source of energy during and not dihydrocapsiate, a previous study (Assessment of the exercise so that the depletion of muscle glycogen is delayed. biological similarity of three capsaicin analogs (Capsinoids) Glycogen is spared because the body burns fats for energy, found in non-pungent chili pepper (CH-19 Sweet) fruits' making a greater contribution to an athlete’s efforts during the Biosci Biotechnol Biochem 2010; 74(2):274-8; and “Activa initial stages of a race. This leaves more glycogen for the later tion of transient receptor potential A1 by a non-pungent cap stages of racing or exercise, for example, and muscle fatigue saicin-like compound, capsiate; Br J Pharmacol' 2012 will be delayed. March; 165(5): 1476-86) have shown that capsiate and dihy 0009 Increasing vasodilation will also increase the rate of drocapsiate have similar rates of TRVP-1 activation, Suggest oxygen and glucose to the muscles, lengthening the time of ing that dihydrocapsiate will have a similar effect on endur aerobic respiration and further sparing glycogen stores. aCC. US 2016/0213673 A1 Jul. 28, 2016 0016 Respiratory quotient (RQ) is a simple measurement jugates with molecules Such as resveratrol, and in the form of of the ratio of carbon dioxide eliminated to oxygen con Arginine Silicate Inositol (ASI). Arginine is necessary for the Sumed. This is particularly helpful when calculating an synthesis of creatine in the body. Creatine is thought to build organism's basal metabolic rate from carbon dioxide produc lean muscle mass and assist with short high intensity bursts tion, which is easily measured when the organism exhales. (weightlifting, sprinting, etc.) Creatine has also been shown Based on the respiratory quotient one can determine if the to induce glycogensparing in animal studies. Finally, creatine organism’s primary energy source is carbohydrates (RQ is known to assist with water retention, and studies in con around 1) Such as Sugar or if it is primarily from fats (RQ junction with glycerol Supplementation have demonstrated a around 0.7). A mixed diet offat and carbohydrate results in an measurable effect on hyperhydration and endurance (“The average value between 0.7 and 1 and therefore the lower the effects of creatine and glycerol hyperhydration on running RQ the more likely the source of energy is from fats. Com economy in well trained