METABOLIC, CARDIOVASCULAR, AND PERCEPTUAL RESPONSES TO A THERMOGENIC NUTRITIONAL SUPPLEMENT AT REST, DURING EXERCISE, AND RECOVERY IN MEN HALEY C. BERGSTROM,1 TERRY J. HOUSH,1 DANIEL A. TRAYLOR,1 ROBERT W. LEWIS JR,1 KRISTEN C. COCHRANE,1 NATHANIEL D.M. JENKINS,1 RICHARD J. SCHMIDT,1 GLEN O. JOHNSON,1 DONA J. HOUSH,2 AND JOEL T. CRAMER1 1

Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska; and 2College of Dentistry, University of Nebraska Medical Center, Lincoln, Nebraska ABSTRACT

Bergstrom, HC, Housh, TJ, Traylor, DA, Lewis, Jr RW, Cochrane, KC, Jenkins, NDM, Schmidt, RJ, Johnson, GO, Housh, DJ, and Cramer, JT. Metabolic, cardiovascular, and perceptual responses to a thermogenic nutritional supplement at rest, during exercise, and recovery in men. J Strength Cond Res 28(8): 2154–2163, 2014—Twenty-one men (mean 6 SD; age = 23.5 6 2.6 years, BMI = 26.0 6 2.4 kg$m22) completed this randomized, double-blinded, placebo-controlled, crossover study to examine acute responses to a thermogenic nutritional supplement. Each testing session included: (a) 30 minutes resting, followed by placebo or thermogenic nutritional supplementation, (b) 50 minutes postsupplementation resting, (c) 60 minutes walking, and (d) 50 minutes postexercise recovery. Gas exchange variables and heart rate (HR) were recorded during each phase. Blood pressure was recorded during all phases except exercise. Ratings of perceived exertion (RPE) were recorded only during exercise. There were no significant differences for any of the measures between the supplement and placebo during the initial resting or postsupplementation phases. During exercise, energy expenditure (EE) (placebo = 18.98–19.06 k J$min21 and supplement = 19.44–19.82 kJ$min21) and V_ O2 (placebo = 11.27–11.35 ml$kg21$min21; supplement = 11.64–11.82 ml$kg21$min21) were greater for the supplement than placebo. There were no differences in respiratory exchange ratio (RER), HR, or RPE between the supplement and placebo during exercise. Postexercise, only V_ O2 (placebo = 3.53–3.63 ml$kg21$min21; supplement = 3.71–3.84 ml$kg21$min21) was greater for the supplement than placebo, but there were no differences in EE, RER, HR, Address correspondence to Haley C. Bergstrom, [email protected]. 28(8)/2154–2163 Journal of Strength and Conditioning Research Ó 2014 National Strength and Conditioning Association

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or blood pressure. These findings suggested that the specific blend of ingredients in the thermogenic nutritional supplement, when combined with exercise, increased the metabolic rate with minimal changes in cardiovascular function and no effect on RPE.

KEY WORDS physical activity, thermogenic aids, metabolic rate

INTRODUCTION

T

he use of thermogenic nutritional supplements is becoming increasingly popular. These supplements, marketed as “thermogenic aids,” have been shown to increase the metabolic rate (8,24,35,38,41). For example, several studies (8,24,31,35,38,41) have reported increases in resting energy expenditure (EE) (6–29%) and oxygen consumption (V_ O2) (15%) after supplementation with various thermogenic blends. There is, however, conflicting evidence regarding the effects of these supplements on the respiratory exchange ratio (RER) and substrate utilization. Specifically, previous studies have reported increases (31,35,38), decreases (24), or no change in RER (8) after supplementation with various thermogenic blends. In addition, recent studies (24,35,38) have reported that thermogenic supplementation was associated with small but significant changes in heart rate (HR), systolic blood pressure (SBP), and/or diastolic (DBP) blood pressure, whereas other studies (31,41) showed no effect on cardiovascular function. The increased metabolic rate and minimal cardiovascular changes associated with thermogenic supplementation have led previous investigators (8,24,35,38,41) to suggest that these supplements have the potential to help dieters to achieve a negative caloric balance, promote weight loss, and improve body composition. Thermogenic aids often contain a number of different ingredients, although caffeine is common to most blends (8,24,31,35,38,41). Caffeine supplementation alone has been

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Journal of Strength and Conditioning Research shown to result in significant increases in EE (14,17,20) and V_ O2 (17,20), with inconsistent effects on the RER (20). Although the exact mechanism by which caffeine exerts these metabolic effects has not been fully elucidated, increased catecholamine levels and actions at betaadrenergic receptors that increase sympathetic nervous system activity are often cited as potential mechanisms (8,35,41). For example, it has been suggested (4) that caffeine signals the release of catecholamines, which act on betaadrenergic receptors to increase lipolysis and consequently free fatty acid concentrations. In addition, it has been shown (13) that caffeine inhibits the phosphodiesterase enzyme that is responsible for cyclic adenosine-mono-phosphate (cAMP) degradation. As a result, cAMP actions on hormonesensitive lipase are prolonged, leading to greater rates of lipolysis and potential increases in lipid oxidation (12). It has been suggested (5) that the effects of caffeine may be potentiated when combined in a blend with other thermogenic ingredients. For example, capsaicin has been shown to increase concentrations of catecholamines that stimulate the mobilization of energy substrates through glycogenolysis and lipolysis (39). In addition, piperine (15,27), ginger (16,29), niacin (10,23), and cinnamon (43) have all been shown to have thermogenic properties. Ginger and cinnamon supplementation may result in acute (#3 hours) and longer-term (12 weeks) decreases in arterial blood pressure (2,19,36). Furthermore, recent studies have suggested that the longer-term supplementation with Boswellia serrata extract (33), and Mucuna pruriens (21) has the potential to decrease inflammation, total serum cholesterol, and/or aid in glycemic control. Thus, theoretically, various ingredients contained in thermogenic blends may work synergistically to increase the metabolic rate with potential acute and longer-term changes in cardiovascular function. Although caffeine and caffeine-containing blends have been shown to have thermogenic effects at rest (8,24,35,38,41), the effects of these supplements on the metabolic rate, cardiovascular function, and perception of effort (ratings of perceived exertion [RPE]) during and after lowintensity exercise are still unclear. For example, a caffeine-

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containing blend had no effect on EE, RER, or RPE during low-intensity walking, but small increases (3–4%) in V_ O2 and transient increases in HR were reported (35). In addition, a different thermogenic blend had no effect on EE, V_ O2, RER, or HR during submaximal exercise (31). Only 1 previous study (35) has examined metabolic and cardiovascular responses to a thermogenic blend after low-intensity exercise. Thus, there is conflicting evidence regarding the potential for thermogenic blends to increase the metabolic rate or alter substrate utilization during low-intensity exercise. In addition, there are limited data regarding the potential metabolic and cardiovascular effects of supplementation with a thermogenic blend during recovery from low-intensity exercise. Furthermore, no previous studies have examined the physiological responses to a blend containing caffeine, capsaicin, Piper longum, ginger, niacin, B. serrata extract, cinnamon, and M. pruriens. Therefore, the purpose of this study was to examine the acute metabolic (EE, V_ O2, and RER), cardiovascular (HR, SBP, and DBP), and perceptual (RPE) responses to a thermogenic nutritional supplement at rest, during low-intensity exercise, and recovery from exercise in men.

METHODS Experimental Approach to the Problem

This study used a randomized, double-blinded, placebocontrolled, crossover design. The subjects visited the laboratory on 3 separate occasions. The first visit was a screening and familiarization session. During the familiarization session, the subjects were screened for their exercise Problem and health status, height, and weight were recorded, and the subjects selected their preferred walking speed between 3.2 and 4.8 km$h21. The subjects returned to the laboratory within 1 week after the familiarization session for the first experimental trial. Six to 8 days later, the subjects completed the second experimental trial. Both experimental trials were performed at the same time of day. For each of the experimental trials, the subjects arrived after a 12-hour overnight fast, between 6 and 8 AM, and the report time was kept constant for the crossover visit. On arrival, the subjects rested supine for 30 minutes in a reclining chair. The laboratory was quiet with the lights dimmed during all resting measurements. The physiological measures were recorded after the 30-minute resting period during the experimental trial. Each experimental trial consisted of 4 phases (Figure 1): (a) 30 minutes of presupplementation resting measures, Figure 1. A description of the experimental design. Each experimental session took approximately 4 hours. Phase 1 = presupplmentation, phase 2 = postsupplementation, phase 3 = exercise, and phase 4 = postexercise. followed by ingestion of the placebo or thermogenic VOLUME 28 | NUMBER 8 | AUGUST 2014 |

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Responses to a Thermogenic Blend nutritional supplement (Table 1); (b) 50 minutes of postsupplementation resting; (c) 60 minutes of treadmill (Vision Fitness, Lake Mills, WI, USA) walking at the self-selected, predetermined speed (mean 6 SD = 3.8 6 0.4 km$h21), which remained constant for both experimental trials; and (d) 50 minutes of postexercise recovery. A priori planned compar_ O2, and isons were performed to compare the metabolic (EE, V RER), cardiovascular (HR, SBP, and DBP), and perceptual (RPE) responses to the placebo and supplement at each time point (28). Subjects

Twenty-one recreationally active men (mean 6 SD; age = 23.5 6 2.6, range = 21–30 years; height = 181.3 6 6.1, range = 168–191 cm; weight = 85.5 6 10.5 kg, range = 71–115 kg; body mass index, 26.0 6 2.4, 22–32 kg$m22) volunteered for this study. The subjects’ physical activities included walking or jogging (n = 10), cycling (n = 8), resistance training (n = 11), and recreational sports (n = 2). Specifically, the subjects participated in 1.7 6 1.5 hours (range = 0–3.5 hours) of physical activity per week, but none of the subjects were competitive athletes. In addition, none of the subjects reported or exhibited (a) a history of medical or surgical events that might have significantly affected the study outcome, including cardiovascular disease or metabolic, renal, hepatic, or musculoskeletal disorders; (b) use of any medication that might have significantly affected the study outcome; (c) use of nutritional supplements (e.g., creatine, protein drinks, amino acids, or vitamins) in the 6 weeks before beginning the study; or (d) participation in another clinical trial or ingestion of another investigational product within 30 days before screening and enrollment. This study was approved by the University Institutional Review Board for Human Subjects, and each subject completed a health history questionnaire and signed a written informed consent document before testing. Physiological Measurements

After the initial 30-minute resting period, the subjects were fitted with an HR monitor (Polar Electro Inc., Lake Success,

NY, USA), and HR was recorded during each of the 4 testing phases and reported as 10-minute mean values (35). In addition, EE, V_ O2, and carbon dioxide production rate (V_ CO2) were measured continuously during the resting and exercise conditions using a calibrated TrueMax 2400 metabolic cart (Parvo Medics, Sandy, UT, USA). The gas analyzers were calibrated with room air and gases of known concentration before all testing sessions. The temperature was kept between 22 and 248 C, and humidity was maintained at ;40%. The gas and flow calibration were less than or equal to 2% before each test. For all indirect calorimetry measures, the subjects were fitted with a nose clip and breathed through a 2-way valve (2700 breathing valve; Hans Rudolph Inc., Kansas City, MO, USA). During the resting phases, the subjects were instructed to remain supine and awake, while not talking or fidgeting. Energy expenditure (in kJ$min21) was derived from the RER data by using the Weir (40) conversion for non-protein RER. The O2, CO2, and EE parameters were recorded breath-by-breath and expressed as 10-minute mean values (35). The subject’s arterial blood pressure (i.e., SBP and DBP) was measured every 15 minutes during the resting conditions using a stethoscope (Save Rite Medical, Omron Marshall Nurse Stethoscope, Brooklyn, NY, USA) and an aneroid sphygmomanometer (MDF Instruments Direct, Inc., Agoura Hills, CA, USA) according to the procedures described by Housh et al. (25). Specifically, on arrival to the laboratory, the subjects rested for 30 minutes in a semireclined position. After the initial resting period, a blood pressure measurement was taken. The blood pressure cuff was placed on the subject’s upper arm, with the arm at the level of the heart. The brachial artery was palpated on the anterior aspect of the elbow and the middle of the cuff bladder was placed at this location, 2–3 cm above the antecubital fossa. The bell of the stethoscope was placed over the brachial artery with light pressure. The cuff was inflated to 30 mm Hg greater than the estimated systolic value to ensure the artery was completely occluded. The cuff was then deflated at a rate of 2–3 mm Hg per second until

TABLE 1. Supplement and placebo contents for 1 dose. Ingredients

Quantity (mg) Relative dose (mg$kg21)

Supplement Caffeine anhydrous 200 2.4 6 0.3 Capsicum seed extract (providing 2 mg capsaicinoids) 100 1.2 6 0.1 P. longum fruit extract 2 0.02 6 0.003 Boswellia serrata extract (providing 150 mg boswellic acid) 250 3.0 6 0.3 Ginger root extract (providing 25 mg gingerols) 500 5.9 6 0.7 Cinnamon bark extract (providing 15 mg polyphenols) 100 1.2 6 0.1 Niacin 20 0.2 6 0.3 M. pruriens seed extract (providing 100 mg L-Dopa) 500 5.9 6 0.7 Placebo Microcrystalline cellulose Matched in size and appearance

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Figure 2. The effect of the supplement and placebo on energy expenditure (kJ$min21) during (A) presupplementation, (B) postsupplementation, (C) exercise, and (D) postexercise. Values are mean 6 SD. *significant difference (p # 0.05) between the supplement and placebo.

pulsatile blood flow occurred. The SBP was determined (within 2 mm Hg) as the pressure where the first Korotkoff sounds were detected. The cuff was continuously deflated at 2–3 mm Hg per second, and DBP was determined when the Korotkoff sounds disappeared. The DBP measure was confirmed by continuing to deflate the cuff for another 10–20 mm Hg to confirm the absence of sounds. The test-retest reliability data from the tester for SBP and DBP indicated that for repeated blood pressures taken 30 minutes apart from the intraclass correlation coefficients (R) were 0.98 and 0.87 for SBP and DBP, respectively, with a standard error of the measurement that ranged from 1 to 2 mm Hg. Ratings of perceived exertion were also recorded every 15 minutes during the exercise trials using the Borg RPE Scale (6). The dependent variables in this study were chosen to determine if the thermogenic supplement had effects on the specific metabolic

variables (EE, V_ O2, and RER), cardiovascular function (HR, SBP, and DBP), and RPE during postsupplementation rest, exercise, and recovery from exercise. Supplementation

The subjects received either the placebo or the thermogenic supplement in a randomized order for the 2 experimental trials. The subjects received the dosage recommended by the manufacturer (General Nutrition, Inc., Pittsburgh, PA, USA). One dose of the nutritional supplement capsules included 200 mg of caffeine, 100 mg of capsicum extract, 2 mg of P. longum, 250 mg of B. serrata extract, 500 mg of dried ginger root, 100 mg of cinnamon bark, 20 mg of niacin, 500 mg of M. pruriens. To maintain the double-blind nature of the experiment, the placebo capsules were matched in size and appearance and contained microcrystalline cellulose (Table 1). In addition,

Figure 3. The effect of the supplement and placebo on oxygen consumption (V_ O2) (mL$kg21$min21) during (A) presupplementation, (B) postsupplementation, (C) exercise, and (D) postexercise. Values are mean 6 SD. *significant difference (p # 0.05) between the supplement and placebo.

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Responses to a Thermogenic Blend

Figure 4. The effect of the supplement and placebo on the respiratory exchange ratio (RER) during (A) presupplementation, (B) postsupplementation, (C) exercise, and (D) postexercise. Values are mean 6 SD.

third-party random laboratory testing (Nutra Manufacturing Inc., Greenville, SC, USA) was performed to confirm that the ingredients in the supplement and placebo capsules were 65% of the manufacturer claims. There were no adverse events reported. Two subjects did report side effects after supplementation. Specifically, 1 subject reported nausea and a headache during the walking portion of the test, and 1 subject reported a tingling sensation in his arms and legs. These side effects were not severe enough to cause the subject to withdraw from the study and all of the symptoms were resolved within the 4-hour testing period. Statistical Analyses

Separate 2-way analysis of variances (ANOVAs) (condition 3 time) were used to analyze the EE, V_ O2, RER, HR, SBP, DBP, and RPE data. The EE, V_ O2, RER, and HR data were

analyzed for the presupplementation, postsupplementation, exercise, and postexercise phases using separate 2 (supplement and placebo) 3 19 (measurement times) ANOVAs with a Greenhouse-Geisser correction. The SBP and DBP data were analyzed for the presupplementation, postsupplementation, and postexercise phases (2 3 12 ANOVAs), and the RPE data were analyzed for the exercise phase only (2 3 5 ANOVAs). The a priori planned comparisons of the mean differences between the supplement and placebo were examined using paired samples t-tests at an alpha level of p # 0.05. The a priori planned comparisons were also examined using Bonferroni corrected paired samples t-tests (p # 0.05/19 for EE, V_ O2, RER, and HR; p # 0.05/12 for SBP and DBP; p # 0.05/5 for RPE). All statistical analyses were performed using SPSS software (version 19.0; IMB SPSS Inc., Chicago, IL, USA).

Figure 5. The effect of the supplement and placebo on heart rate (b$min21) during (A) presupplementation, (B) postsupplementation, (C) exercise, and (D) postexercise. Values are mean 6 SD.

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a significant condition 3 time interaction (F = 7.345; p , 0.001; partial h2 = 0.269) for V_ O2. During the presupplementation and postsupplementation phases, there were no significant differences in V_ O2 between the supplement and placebo. During exercise, however, the V_ O2 was significantly greater for the supplement than the placebo at the Bonferroni corrected alpha (0.05/19 comparisons; p # 0.00263) at 20 (p = 0.000517), 30 (p = Figure 6. The effect of the supplement and placebo on systolic blood pressure (mm Hg) during (A) 0.00205), 40 (p = 0.00219), 50 presupplementation, (B) postsupplementation, and (C) postexercise. Values are mean 6 SD. (p = 0.00016), and 60 (p = 0.00009) minutes. In addition, the postexercise resting V_ O2 was significantly greater for the supplement than the RESULTS placebo at 20 (p = 0.00118) minutes (Figure 3). Energy Expenditure The results of the 2-way repeated measures ANOVA with a Greenhouse-Geisser correction indicated that there was a significant condition 3 time interaction (F = 3.23; p = 0.019; partial h2 = 0.139) for EE. There were no differences in EE between the supplement and placebo during the presupplementation, postsupplementation resting, or postexercise recovery phases. During the exercise phase, however, EE was significantly greater at the Bonferroni corrected alpha (0.05/19 comparisons; p # 0.00263) for the supplement than the placebo at 20 (p = 0.00116), 40 (p = 0.00189), 50 (p = 0.00027), and 60 (p = 0.00011) minutes (Figure 2). Oxygen Consumption Rate

The results of the 2-way repeated measures ANOVA with a Greenhouse-Geisser correction indicated that there was

Respiratory Exchange Ratio

The results of the 2-way repeated measures ANOVA with a Greenhouse-Geisser correction indicated that there was indicated a significant condition 3 time interaction (F = 2.758; p = 0.021; partial h2 = 0.121) for RER. There were no significant differences in RER between the supplement and placebo during the presupplementation, postsupplementation, exercise, or postexercise recovery phases (Figure 4). Heart Rate

The results of the 2-way repeated measures ANOVA with a Greenhouse-Geisser correction indicated that there was no significant condition 3 time interaction (F = 1.865; p = 0.122; partial h2 = 0.085) for HR. There were no significant differences in HR between the supplement and placebo during the presupplementation, postsupplementation, exercise, or postexercise recovery phases (Figure 5). Systolic Blood Pressure

Figure 7. The effect of the supplement and placebo on diastolic blood pressure (mm Hg) during (A) presupplementation, (B) postsupplementation, and (C) postexercise. Values are mean 6 SD.

The results of the 2-way repeated measures ANOVA with a Greenhouse-Geisser correction indicated that there was no condition 3 time interaction (F = 0.976; p = 0.434; partial h2 = 0.047) for SBP. In addition, during the resting and recovery phases, there were no significant differences in SBP between the supplement and placebo (Figure 6). VOLUME 28 | NUMBER 8 | AUGUST 2014 |

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Responses to a Thermogenic Blend _ O2 valwere within the range of V ues reported (3.5–3.7 ml$kg21$min21) at rest (7,17). In addition, the RER values in this study for the supplement and placebo (0.77 6 0.05 and 0.79 6 0.05, respectively) were not significantly different and were consistent with resting RER values previously reported (0.76–0.81) (31,34). Furthermore, the HR (supplement = 58 6 7.9 b$min21; placebo = 58 6 7.4 b$min21), SBP (supplement = 115 6 8 mm Hg; placebo = 116 6 8 mm Hg), and DBP (supplement = 72 6 5 mm Hg; placebo = 71 6 6 mm Hg) preFigure 8. The effect of the supplement and placebo on rating of perceived exertion (RPE) during exercise. Values are mean 6 SD. supplementation resting values were not different for the supplement and placebo and were simDiastolic Blood Pressure ilar to the HR (58 6 3 b$min21), SBP (110 6 3 mm Hg), and The results of the 2-way repeated measures ANOVA DBP (75 6 2 mm Hg), values were reported at rest (24,31). with a Greenhouse-Geisser correction indicated that there During the 50-minute postsupplementation resting phase, was no significant condition 3 time interaction (F = 0.874; there were no significant differences between the supplep = 0.499; partial h2 = 0.042) for DBP. In addition, during ment and placebo for any of the metabolic or cardiovascular the resting and recovery, there were no significant measures. Although no previous studies have examined the differences in DBP between the supplement and placebo physiological responses to the specific blend of thermogenic (Figure 7). ingredients (caffeine, capsaicin, P. longum, ginger, niacin, B. serrata extract, cinnamon, and M. pruriens) used in this study, Ratings of Perceived Exertion a number of studies (8,24,35,38,41) have examined the effects The results of the 2-way repeated measures ANOVA with of caffeine and various caffeine-containing thermogenic a Greenhouse-Geisser correction indicated there was no blends on resting EE, V_ O2, RER, HR, SBP, and DBP. In condition 3 time interaction (F = 0.677; p = 0.547; partial contrast to the current findings, significant increases in resth2 = 0.033) for RPE during the exercise phase and there ing EE (6–29%) and V_ O2 (4–15%) have been reported after were no significant differences in RPE between the supplesupplementation with thermogenic ingredients. In addition, ment and placebo at any time period. some studies have reported that thermogenic supplements resulted in increases (24,38) or decreases (24,38) in RER. DISCUSSION Furthermore, several studies (24,35,41) have shown that various thermogenic blends alter hemodynamic function, reThe purpose of the present study was to examine the acute _ O2, RER, HR, SBP, DBP, and RPE) flected by increases or decreases in HR and blood pressure. physiological effects (EE, V It is possible that, in this study, the lack of effect of the of supplementation with a thermogenic nutritional blend at rest, thermogenic blend on any of the metabolic or cardiovascular during low-intensity exercise, and recovery from exercise in measures during the initial 50 minutes of postsupplementamen. There were no significant differences between the supple_ O2, RER) or tion resting was related to the length of measurement at rest, ment and placebo for any of the metabolic (EE, V the relative dose of caffeine, or the specific blend of cardiovascular (HR, SBP, DBP) measures taken for 30 minutes thermogenic ingredients. Specifically, most studies before supplementation. In addition, the resting values for EE, _ O2, RER, HR, SBP, and DBP in this study were similar to (8,24,38,41) have examined the metabolic and cardiovascular V responses to various caffeine-containing blends over 3 or those typically reported after a 12-hour overnight fast more hours of rest. In this study, however, resting measure(7,12,17,24,31,34). Specifically, the mean (6SD) presupplemenments were only taken for 50 minutes after supplementation. tation EE for the supplement (6.10 6 0.92 kJ$min21) was not It has been shown (18) that caffeine concentration peaks in different from the placebo (6.13 6 0.79 kJ$min21) and was the blood between 15 and 120 minutes. Thus, the metabolic similar to the resting EE values (5.39–5.95 kJ$min21) previously _ O2 values for the supplement (3.6 6 0.36 and cardiovascular changes associated with caffeine may not reported (17,31). The V fully manifest for several hours after ingestion. For example, ml$kg21$min21) and the placebo (3.6 6 0.26 ml$kg21$min21)

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Journal of Strength and Conditioning Research Hoffman et al. (24) reported that the greatest increase in EE appeared 2 and 3 hours after supplementation with a caffeine-containing thermogenic blend, and no change in HR or RER was observed until hour 2. Although no significant changes in EE, V_ O2, RER, HR, SBP, or DBP were reported during the resting phase of this study, it is possible that responses typically observed after thermogenic supplementation would have been observed if the resting measures were continued for 2 or more hours. Previous studies have found that the effects of caffeine are dose dependent (3,9), and the magnitude of responses differ with various combinations of thermogenic ingredients (24,35,38). For example, a relative dose of 4.1 mg$kg21 of caffeine contained in a thermogenic blend (caffeine, green tea extract, G. cambogia, and niacin) resulted in significant increases in EE (12.1%), V_ O2 (15.1%), RER (2.3%), and SBP (1.3%), while at a lower relative dose of caffeine (2.1 mg$kg21) not contained in a thermogenic blend, there was no significant change in EE and significant decreases in V_ O2 (5.6%), RER (6.2%), as well as SBP (2.9%) (38). Differences in the magnitude of the metabolic responses have also been observed with blends containing the same relative dose (2.4 mg$kg21) of caffeine. Specifically, a thermogenic blend containing caffeine and epigallocatechin gallate resulted in a 10.5% increase in EE (8), while only a 6% increase in EE was reported after supplementation with a blend containing caffeine, capsaicin, bioperine, and niacin (35). In the present study, a mean relative dose of 2.4 6 0.3 mg$kg21 combined with capsaicin, P. longum, ginger, niacin, B. serrata extract, cinnamon, and M. pruriens did not result in any significant metabolic or cardiovascular changes at rest. These findings suggested that thermogenic blends that contain a relatively lower dose (2.4 mg$kg21) of caffeine may have less effect on metabolic and cardiovascular responses at rest than those that contain a relatively greater dose (4.1 mg$kg21). It is also possible, however, that the combination of ingredients used in the present study (Table 1) were less effective at rest than the combination of ingredients used in other thermogenic blends (e.g., caffeine, green tea extract, G. cambogia, and niacin). In this study, a caffeine-containing thermogenic blend (caffeine, capsaicin, P. longum, ginger, niacin, B. serrata extract, cinnamon, and M. pruriens), at a relative dose of 2.4 6 0.3 mg$kg21 resulted in EE and V_ O2 (Figure 3) values that were 3–4% greater for the supplement than the placebo, with no change in HR during 60 minutes of walking (3.2–4.8 km$hr21) . It has been shown (17) that caffeine supplementation, at a relative dose of 5 mg$kg21, increased the metabolic rate (EE and V_ O2) and blood pressure but did not change HR or RER during low-intensity (30% V_ O2max) exercise. During walking, caffeine supplementation at a lower relative dose (;3 mg$kg21), however, did not result in significant metabolic (V_ O2 or RER) changes, although blood pressure was increased and HR decreased (37). It has been suggested (35) that a relatively lower dose (2–4 mg$kg21) of

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caffeine combined with other thermogenic ingredients may work synergistically to increase the metabolic rate, with limited cardiovascular effects. The metabolic and cardiovascular responses to various thermogenic blends, however, have been shown to differ depending on the specific blend of ingredients (31,35). For example, Ryan et al. (35) reported that during 60 minutes of walking there were no changes in EE or RER, significant increases in V_ O2, and a transient increase in HR after supplementation with 1.9–4.1 mg$kg21 of caffeine contained in a blend (caffeine, capsaicin, niacin, and bioperine). Different combinations of thermogenic ingredients that contained a lower relative dose of caffeine (2 mg$kg21) have been shown to have less of an effect on metabolic and cardiovascular responses. Specifically, supplementation with various thermogenic blends (e.g., caffeine, taurine, guarana, yerba mate, etc.) containing approximately 2 mg$kg21 of caffeine did not have any significant effect on EE, V_ O2, HR, or RER during treadmill exercise at 50% V_ O2max (31). Thus, the current findings suggested that the specific blend of thermogenic ingredients used in this study was more effective for increasing the metabolic rate during exercise than those previously reported (31), despite using a similar (2.4 mg$kg21 vs. 2 mg$kg21) relative dose of caffeine. In addition, these findings indicated that, during exercise, the specific combination of thermogenic ingredients used in this study may work synergistically to increase the metabolic rate with fewer cardiovascular changes at a lower relative dose of caffeine (2.4 6 0.3 mg$kg21) than caffeine alone (5 mg$kg21) (17). Increases in the metabolic rate after thermogenic supplementation have been attributed to caffeine’s role as an adenosine receptor antagonist and/or b-adrenergic receptor agonist (1,20). Specifically, caffeine’s effects on b-adrenergic receptors prolong the actions of cAMP and increase lipolysis resulting in an increase in the metabolic rate and a potential shift in substrate utilization (1). In addition, it has been suggested (5) that the actions of caffeine may be enhanced when combined with other thermogenic ingredients such as capsaicin. Thus, in this study, the greater EE and V_ O2 values for the supplement than the placebo during exercise were likely related to the synergistic effects of caffeine and other thermogenic ingredients on b-adrenergic receptors. Previous studies (11,26,30,32) have suggested that caffeine ingestion may decrease the perception of effort during exercise. For example, caffeine has been shown to alter the central drive (26), have an analgesia effect (30,32), and/or improve cardiorespiratory dynamics (11). These effects have been reported during heavy to supramaximal exercise. In this study, however, the caffeine-containing thermogenic blend had no effect on RPE during low-intensity walking exercise (Figure 8). These findings were similar to those of Ryan et al. (35) who reported that thermogenic supplementation did not change the perception of effort during exercise. Thus, caffeine-containing thermogenic blends may have no effect on RPE during low-intensity exercise. VOLUME 28 | NUMBER 8 | AUGUST 2014 |

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Responses to a Thermogenic Blend In contrast to the findings of Ryan et al. (35), the caffeinecontaining thermogenic blend used in this study resulted no significant change in EE during recovery from exercise (Figure 2). Although EE was 10–11% greater, V_ O2 was 5–6% greater, and RER was 4–6% lower for the supplement than placebo, these difference were not significant using a Bonferroni correction for the type 1 error rate. In addition, in this study, the supplement had no effect on HR (Figure 5), SBP (Figure 6), or DBP (Figure 7) during recovery from lowintensity walking. Previous studies (22,35) have shown that both HR and blood pressure were increased after supplementation with caffeine or caffeine-containing thermogenic blends. For example, Ryan et al. (35) reported significant increases in HR, SBP, and DBP after supplementation with a caffeine-containing thermogenic blend (caffeine, capsaicin, niacin, bioperine) during postexercise recovery. In addition, it has been suggested (22) that the increased blood pressure and HR responses after caffeine supplementation (3.3 mg$kg21) in men were because of increased vascular resistance mediated through caffeine’s actions as an adenosine receptor antagonist that blocked the vasodilation actions of adenosine. It is possible that the differences in cardiovascular responses in this study and those that have examined a different thermogenic blend (35) or caffeine alone (22) were related to differences in the specific blend of thermogenic ingredients or the relative amount of caffeine. Although the thermogenic blend used in this study and that of Ryan et al. (35) contained some similar ingredients (caffeine, capsaicin, niacin, and P. longum), the addition of ginger, which has been shown to have a depressor effect on arterial blood pressure, to the blend used in this study may have had potential cardiovascular effects (19,36,43). Thus, it is possible that HR, SBP, and DBP did not change in this study as a result of the interaction between caffeine, which can increase blood pressure, and ginger, which has the potential to decrease blood pressure. It is also possible that the lack of any significant changes in EE, RER, blood pressure changes, or HR during postexercise recovery were related to the relatively lower mean dose of caffeine (2.4 6 0.3 mg$kg21) when compared with caffeine supplementation alone (3.3 mg$kg21) (22). It has been shown (1,22) that higher doses of caffeine (3.3–5.7 mg$kg21) are associated with greater metabolic and cardiovascular changes than lower doses (1.4–2.9 mg$kg21). Future studies should examine the metabolic and cardiovascular responses to various thermogenic blends during recovery from exercise to determine if these blends have the potential to increase the metabolic rate and minimize the changes in blood pressure and HR responses typically associated with caffeine ingestion. In conclusion, a thermogenic blend containing caffeine, capsaicin, piperine, ginger, niacin, Platycodi grandiflorus, cinnamon, and M. pruriens resulted in no metabolic (EE, V_ O2, and RER) or cardiovascular (HR, SBP, and DBP) changes during the 50-minute postsupplementation resting or postexercise recovery phase. During exercise, however, the thermogenic blend resulted in a greater metabolic rate and may

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have the potential to increase EE. Furthermore, there were no significant changes in HR, SBP, DBP, or RPE. These findings suggested that the specific blend of ingredients in the thermogenic nutritional supplement, when combined with exercise, increased the metabolic rate with no changes in cardiovascular function and no effect on the perception of effort in aerobically untrained younger men (19–29 years).

PRACTICAL APPLICATIONS Thermogenic blends are marketed as weight loss and/or weight management supplements. It has been suggested (5,42) that the various ingredients contained in these blends work synergistically to increase the metabolic rate, increase lipid oxidation, and alter cardiovascular function. Thus, it is possible that thermogenic supplements, used in conjunction with exercise, may increase weight loss and improve body composition. Few studies (31,35), however, have examined effects of various thermogenic blends during low-intensity exercise. It is important to examine the efficacy of the purported metabolic and cardiovascular responses to these supplements during various activities of daily living (e.g., at rest, during exercise, and recovery from exercise). The present findings suggested that, when taken with sufficient time (;50 minutes) before exercise, a thermogenic blend containing caffeine, capsaicin, P. longum, ginger, niacin, B. serrata extract, cinnamon, and M. pruriens has the potential to increase the metabolic rate without significant changes in the perception of effort or cardiovascular function. Therefore, it is possible that the thermogenic supplement used in this study would help athletes and nonathletes to achieve a negative caloric balance, increase weight loss, and improve body composition when combined with long duration, lowintensity exercise.

ACKNOWLEDGMENTS This study was funded by a research Grant from General Nutrition Corporation. The results of this study do not constitute endorsement of the product by the authors or the National Strength and Conditioning Association.

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Metabolic, cardiovascular, and perceptual responses to a thermogenic nutritional supplement at rest, during exercise, and recovery in men.

Twenty-one men (mean ± SD; age = 23.5 ± 2.6 years, BMI = 26.0 ± 2.4 kg-1·m-2) completed this randomized, double-blinded, placebo-controlled, crossover...
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