CranLoad Sport. Novel formula for high intensity sports performance and endothelial function*

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CranLoad Sport Novel formula for high intensity sports performance and endothelial function* *These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

CranLoad Sport CranLoad CranLoad Sport features CranLoad, a novel fruit blend developed as part of an extensive research program with the Institute of Nutraceuticals and Functional Foods (INAF) and Laval University in Quebec, Canada. CranLoad delivers a unique cranberry and grape seed blend that has been the subject of two pilot trials involving high-profile, elite athletes. Cranberries and grapes are particularly generous sources of proanthocyanidins and polyphenols. In addition to being powerful antioxidants, these compounds offer specific vascular support mechanisms that are associated with enhanced endothelial function, (1-3) making them of critical interest, particularly to sports nutritionists. As training intensity is known to be directly correlated to blood flow and impeded by accumulation of muscle lactate, nutrients that facilitate and upregulate blood flow could be utilized as a means to enhance high-intensity sports performance.* Green Tea Caffeine and MCTs CranLoad is combined with caffeine naturally derived from green tea and medium chain triglycerides (MCTs) in a liquid-filled Caplique Capsule for broadspectrum sports performance support. Caffeine promotes energy and mental focus and has also been associated with a positive dose-response effect on athletic performance. (4 7) Furthermore, green tea consumption has been shown to support metabolic capacity through the utilization of fatty acids for energy and has been shown to favorably affect oxidative markers during training. (8,9) MCTs provide easily-absorbed lipid fuel substrates for working muscle. (10) * 2 TO ORDER CALL 800-753-2277 Secure online ordering and information at www.pureencapsulations.com

Clinical Research Study 1: A pilot trial on the effects of CranLoad in elite athletes The effects of a CranLoad containing beverage were investigated in a pilot trial of elite athletes. The results indicated an increase in flow-mediated dilation (FMD). FMD reflects blood vessel dilation mediated by nitric oxide synthase (NOS), an enzyme that generates the endogenous vasodilator, nitric oxide (Figure 1). Figure 1. CranLoad supports nitric oxide synthase (NOS) activity in the vascular endothelium. NOS generates nitric oxide, which increases blood flow to muscles during exercise.* FMD, assessed by brachial artery diameter, is therefore indicative of blood flow to muscles and lactate clearance and recovery. Specifically, the pilot study indicated a statistically significant increase in FMD as a percentage over baseline within 30 minutes for the subjects (Figure 2). Moreover, FMD remained elevated over baseline for 2 hours.* Increased FMD with CranLoad Figure 2. Flow-mediated dilation (FMD) variation from baseline after intake of the polyphenol-rich drink and placebo; *P<0.05 versus baseline and placebo at specified time points. The insert presents the area under the curve (AUC) of the change in FMD over time above baseline (time 0) values. The Y axis is in % min.* *These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease. 3

The peak increase in brachial artery diameter following consumption of the CranLoad beverage was 2.8% at 60 minutes. A similar physiological effect has been demonstrated with arginine in which supplemental arginine at doses ranging from 3-21 g increased FMD on average 1.98%. (11) Most studies investigating the physiological effects of arginine have been conducted in populations dealing with coronary artery disease (CAD). While a comparative study was not performed between CranLoad and arginine, this pilot study indicates that these nutrients appear to produce similar effects on blood flow.* Study 2: A double-blind, placebo-controlled pilot trial on the effects of CranLoad in high-profile athletes In a double-blind, placebo-controlled pilot study, the effects of pre-exercise CranLoad administration was investigated in high-profile athletes. The athletes performed a 3 km stationary cycling time trial after consuming either CranLoad or a placebo. Results of the pilot study show a significant decrease in blood lactate in those athletes consuming CranLoad compared to placebo (Figure 3). This study supports the concept that CranLoad enhances blood flow, as determined in Study 1, and is associated with enhanced lactate clearance during high-intensity exercise. This outcome suggests a capacity for enhanced recovery.* CranLoad Placebo % diff P Lactate (mmol/l) Post warm up 1.7 ± 0.5 2.4 ± 1.2-30.1% 0.01 Post 3 km TT, 0 min 12.1 ± 1.4 13.1 ± 2.1-7.9% 0.03 Post 3 km TT, 2.5 min 14.1 ± 0.8 14.8 ± 0.9-4.8% 0.06 Post 3 km TT, 5 min 13.7 ± 0.7 14.1 ± 0.7-2.5% 0.06 Figure 3. Effects of CranLoad on blood lactate pre- and post-exercise. Data from the pilot study reveals a 30% reduction in blood lactate following warm up, and reduced lactate is maintained throughout exercise.* 4 TO ORDER CALL 800-753-2277 Secure online ordering and information at www.pureencapsulations.com

Athlete Survey A blinded survey was conducted in Olympic-level athletes who trained with CranLoad during the 2009-2010 season: 10 out of 11 athletes who trained with CranLoad experienced enhanced recovery and would recommend CranLoad to other athletes. * *These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease. 5

CranLoad Sport liquid-filled capsule *Novel fruit blend, green tea caffeine and medium chain triglycerides for optimal athletic performance CranLoad : A novel, proprietary cranberry and grape seed blend In a pilot trial involving elite athletes, CranLoad provided statistically significant support for healthy flow-mediated dilation (FMD) at rest, an effect similar to arginine administration.* In another pilot trial, CranLoad helped maintain healthy blood lactate levels in high-profile athletes, suggesting the potential for enhanced recovery.* Caffeine: Derived from green tea Provides support for energy and mental focus.* Supports metabolic capacity and provides antioxidant protection for working muscles.* Medium Chain Triglycerides (MCT): Provides easily-absorbed lipid fuel substrates for working muscle.* 3 Caplique Capsules contain v 00 CranLoad proprietary blend... 765 mg providing cranberry (Vaccinium macrocarpon) extract (fruit) and grape (Vitis vinifera) seed extract Green Tea extract (Camellia sinensis) (leaves)... 250 mg standardized to contain 20% caffeine... 50 mg other ingredients: rice maltodextrin, magnesium hydroxide, medium chain triglycerides, vegetable capsule 3 Caplique Capsules daily, 30-60 minutes before a workout. CranLoad is a trademark used by Pure Encapsulations under license. Caplique Capsule is a registered trademark used by Pure Encapsulations under license. Each Caplique Capsule is preserved with a nitrogen bubble, which may give the appearance of the capsule not being full. Contents may appear cloudy or thick and may settle or separate. Quantity Order Code CranLoad Sport 90 CLS9 6 TO ORDER CALL 800-753-2277 Secure online ordering and information at www.pureencapsulations.com

References 1. Caton PW et al. Regulation of vascular endothelial function by procyanidin-rich foods and beverages. J Agric Food Chem. 2010 Apr 14;58(7):4008-13. 2. Ariga T. The antioxidative function, preventive action on disease and utilization of proanthocyanidins. Biofactors. 2004;21(1-4):197-201. 3. Feng Z, Wei RB, Hong Q, Cui SY, Chen XM. Grape seed extract enhances enos expression and NO production through regulating calcium-mediated AKT phosphorylation in H2O2-treated endothelium. Cell Biol Int. 2010 Oct 1;34(10):1055-61. 4. Burke LM. Caffeine and sports performance. Appl Physiol Nutr Metab. 2008;33:1319-34. 5. Tarnopolsky M, Cupido C. Caffeine potentiates low frequency skeletal muscle force in habitual and nonhabitual caffeine consumers. J Appl Physiol. 2000 Nov;89(5):1719-24. 6. Gliottoni RC, Meyers JR, Arngrimsson SA, Broglio SP, Motl RW. Effect of caffeine on quadriceps muscle pain during acute cycling exercise in low versus high caffeine consumers. Int J Sport Nutr Exerc Metab. 2009 Apr;19(2):150-61. 7. Hadjicharalambous M, Georgiades E, Kilduff LP, Turner AP, Tsofliou F, Pitsiladis YP. Influence of caffeine on perception of effort, metabolism and exercise performance following a high-fat meal. J Sports Sci. 2006 Aug;24(8):875-87. 8. Nosaka N, Suzuki Y, Nagatoishi A, Kasai M, Wu J, Taguchi M. Effect of ingestion of medium-chain triacylglycerols on moderate- and high-intensity exercise in recreational athletes. J Nutr Sci Vitaminol (Tokyo). 2009 Apr;55(2):120-5. 9. Ricardo Schütz G, Comin L, Hecht KC, da Silva EL. Consumption of green tea favorably affects oxidative stress markers in weight-trained men. Panza VS, Wazlawik E, Nutrition. 2008 May;24(5):433-42. 10. Murase T, Haramizu S, Shimotoyodome A, Tokimitsu I, Hase T. Green tea extract improves running endurance in mice by stimulating lipid utilization during exercise. Am J Physiol Regul Integr Comp Physiol. 2006 Jun;290(6):R1550-6. 11. Bai Y, Sun L, Yang T, Sun K, Chen J, Hui R. Increase in fasting vascular endothelial function after shortterm oral L-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2009 Jan;89(1):77-84. *These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease. 7

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