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Physiological effects of caffeine, epigallocatechin-3-gallate, and exercise in overweight and obese women Abbie E. Smith, Christopher M. Lockwood, Jordan R. Moon, Kristina L. Kendall, David H. Fukuda, Sarah E. Tobkin, Joel T. Cramer, and Jeffrey R. Stout

Abstract: The aim of this study was to evaluate the combined effects of a 10-week exercise program with ingestion of caffeine and epigallocatechin-3-gallate (EGCG) on body composition, cardiovascular fitness, and strength in overweight and obese women. In a double-blind, placebo-controlled approach, overweight and obese women (n = 27) were randomly assigned to treatment groups with exercise (an active-supplementing group with exercise (EX-Act) and a placebo group with exercise (EX-PL)) or without exercise (an active-supplementing group without exercise (NEX-Act) and a placebo group without exercise (NEX-PL)). All participants consumed 1 drink per day for 10 weeks; EX-Act and EX-PL participated in a concurrent endurance and resistance training program. Changes in body composition were assessed using a 4compartment model. Changes in muscle mass (MM) were evaluated using a DXA-derived appendicular lean–soft tissue equation. There was a significant time  treatment interaction for MM (p = 0.026) and total cholesterol (TC) (p = 0.047), and a significant time  training interaction for peak oxygen consumption (p = 0.046) and upper-body and lower-body strength (p < 0.05). Significant differences between the EX groups and NEX groups for percentage change in MM and peak oxygen consumption, and upper-body and lower-body strength, were revealed. Clinical markers for hepatic and renal function revealed no adverse effects. TC significantly decreased for the active-supplementing groups (EX-Act, NEX-Act). The current study suggests that implementing a caffeine–EGCG-containing drink prior to exercise may improve MM, fitness, and lipid profiles in overweight women. Key words: green tea, body composition, obesity, cardiovascular health, caffeine, women. Re´sume´ : Cette e´tude se propose d’analyser les effets combine´s d’un programme d’exercices de 10 semaines et de la consommation de cafe´ine additionne´e d’e´pigallocate´chine-3-gallate (EGCG) sur la composition corporelle, la condition physique cardiovasculaire et la force chez des femmes pre´sentant un surplus de poids et des femmes obe`ses. Selon un devis expe´rimental a` double insu, des femmes pre´sentant un surpoids et des femmes obe`ses (n = 27) sont assigne´es ale´atoirement dans 4 groupes : un groupe avec supple´mentation et exercice (EX-Act), un groupe placebo, soit sans supple´mentation, mais avec exercice (EX-PL), un groupe avec supple´mentation, mais sans exercice (NEX-Act) et un autre groupe placebo, soit sans supple´mentation ni exercice (NEX-PL). Toutes les participantes consomment une boisson par jour durant 10 semaines; les groupes EX-Act et EX-PL participent a` un programme combine´ d’endurance et de force. Les variations de composition corporelle sont e´value´es en fonction d’un mode`le a` quatre compartiments. Les variations de la masse musculaire (MM) sont de´termine´es au moyen d’une e´quation de´terminant la masse maigre des tissus mous appendiculaires obtenue par DXA. On observe une interaction significative traitement  temps en ce qui concerne la MM (p = 0,026) et la concentration totale de choleste´rol (TC) (p = 0,047); on observe aussi une interaction significative traitement  temps en ce qui concerne le consommation d’oxygene de pointe (p = 0,046) et la force du haut et du bas du corps (p < 0,05). En outre, on observe des diffe´rences significatives entre les groupes EX et NEX en ce qui concerne les variations en pourcentage de la MM, du le consommation d’oxygene de pointe et de la force du haut et du bas du corps. Les marqueurs cliniques des fonctions he´patique et re´nale ne re´ve`lent aucun effet inde´sirable. La TC diminue significativement dans les groupes recevant des supple´ments (EX-Act, NEX-Act). Cette e´tude indique que boire un breuvage contenant de la cafe´ine et du EGCG avant l’exercice dans un programme d’entraıˆnement physique contribue a` l’ame´lioration de la masse musculaire, de la condition physique et du bilan lipidique chez des femmes pre´sentant un surpoids et des femmes obe`ses. Mots-cle´s : the´ vert, composition corporelle, obe´site´, sante´ cardiovasculaire, cafe´ine, femme. Received 25 May 2010. Accepted 29 June 2010. Published on the NRC Research Press Web site at apnm.nrc.ca on 28 September 2010. A.E. Smith, C.M. Lockwood, K.L. Kendall, D.H. Fukuda, J.T. Cramer,1 and J.R. Stout.2,3 Department of Health and Exercise Science, University of Oklahoma, 1401 Asp Avenue, Norman, OK 73019, USA. J.R. Moon. Department of Sports Fitness and Health, United States Sports Academy, One Academy Drive, Daphne, AL 36526, USA. S.E. Tobkin. College of Medicine, University of Oklahoma Health Science Center, Oklahoma City, OK 73126, USA. 1Present

address: Biophysics Laboratory, University of Oklahoma, Norman, Oklahoma. address: Metabolic and Body Composition Laboratory, University of Oklahoma, Norman, Oklahoma. 3 Corresponding author (e-mail: [email protected]). 2Present

Appl. Physiol. Nutr. Metab. 35: 607–616 (2010)

doi:10.1139/H10-056

Published by NRC Research Press

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[Traduit par la Re´daction]

_______________________________________________________________________________________ Introduction It is estimated that 64.1% of American women are overweight or obese (body mass index = 25 kgm–2), which represents an approximately 7% increase since 2000 (Flegal et al. 2010). Numerous comorbidities have been linked with obesity, including diabetes, hypertension, hypercholesterolemia, and cardiovascular disease (Flegal et al. 2007). Obesity is the result of a positive energy balance and contributes to more than 300 000 deaths per year, with a concomitant strain of US$75 billon in health care costs in the United States (Finkelstein et al. 2004; Flegal et al. 2007). In addition, the prevention and treatment of obesity has expanded to include nutritional and dietary ingredients as potential methods of mimicking the thermogenic action of sympathoadrenal catecholamines (Landsberg et al. 1984; Dulloo 1998). Recent research has been particularly focused on the use of plant compounds (i.e., caffeine, green tea, ephedrine, and capsaicin), with a principal aim of reducing energy intake and (or) increasing energy expenditure (Dulloo 1998; Hackman et al. 2006; Diepvens et al. 2007). The stimulatory effect of caffeine in vivo is widely accepted (Acheson et al. 1980; Jung et al. 1981; Bracco et al. 1995; Beck et al. 2008) and is attributed to the reduced degradation of intracellular cyclic AMP (cAMP) or, possibly, to the catecholaminergic stimulation of adipocytes (Jung et al. 1981; Dulloo et al. 1994; Bracco et al. 1995). Furthermore, caffeine consumption has been shown to influence appetite and reduce food intake, consequently acting as a practical method of altering energy expenditure and intake. Although chronic caffeine consumption has failed to elicit weight loss, it has been shown to facilitate thermogenesis and to upregulate lipolysis (Dulloo et al. 1989; Bracco et al. 1995; Acheson et al. 2004). Applied research has demonstrated that the effectiveness of caffeine is magnified when combined with other thermogenic agents and with energy restriction. Green tea is a widely consumed beverage that contains substantial amounts of catechins (30%–42%). The catechins epicatechin, epicatechin-3-gallate, epigallocatechin, and epigallocatechin-3-gallate (EGCG) are the primary components of green tea leaves. The EGCG catechin is the most abundant and has received the bulk of the attention as the most pharmacologically active ingredient (Kovacs et al. 2004). Rich in flavonoids, tea catechins such as EGCG have been shown to inhibit catechol-O-methyltransferase, an enzyme that degrades catecholamines, in particular, norepinephrine (Borchardt and Huber 1975). As an integral part of the sympathetic nervous system (SNS) and the control of thermogenesis and fat oxidation, norepinephrine — stimulated by the presence of catechins — has been proposed as a compound that increases thermogenesis and fat metabolism (Dulloo et al. 1999). Activating the SNS in this manner has also been shown to suppress hunger, enhance satiety, and stimulate energy expenditure (Astrup et al. 1991). EGCG has also been shown to inhibit the intestinal absorption of dietary lipids by reducing the emulsification and solubilization of lipids (Raederstorff et al. 2003; Klaus et al.

2005; Koo and Noh 2007) and may also reduce the sodiumdependent glucose transporter activity, possibly reducing dietary glucose uptake (Yoko et al. 2000). Furthermore, EGCG has been shown to have a hypocholesterolemic effect, suppressing the intestinal absorption of cholesterol (Muramatsu et al. 1986; Ikeda et al. 1992). In addition to the catechin constituents of the tea leaf, a portion (3%–5%) is composed of caffeine. Current research suggests that it is the EGCG catechin that stimulates brown fat tissue thermogenesis, resulting in a greater thermogenic advantage than caffeine alone. Ingesting a combination of caffeine (50– 200 mgday–1) and EGCG (90–1200 mgday–1) has been shown to increase 24-h energy expenditure by up to 8% (328–750 kJ) compared with a placebo or caffeine alone (Dulloo et al. 1999). It has been proposed that there is a potentiated synergistic effect on body composition and energy expenditure when combining ingredients that enhance SNS activity (Belza et al. 2007). In addition, it has been reported that a formula similar to that in the current study, combining caffeine and EGCG, significantly increased resting energy expenditure (REE) by approximately 10% and caused an increase in serum free fatty acids (FFA) in response to acute oral ingestion, compared with a placebo (Dalbo et al. 2008). In addition, Roberts et al. (2008) reported a decrease in percentage of body fat (%FAT; 0.80%FAT) and increased serum FFA, with no significant differences in blood lipids or other metabolic safety indices, after 28 days of chronic ingestion in a healthy population (Roberts et al. 2008). Dalbo et al. (2008) found that, compared with placebo, the caffeine–EGCG combination significantly increased postingestion REE (kcalday–1) by approximately 10% after 120 min, with no change seen at 180 min (Dalbo et al. 2008). Several other studies demonstrated the effectiveness of these ingredients as weight loss agents when implemented with a hypocaloric diet (Hackman et al. 2006; Diepvens et al. 2007). When combined with exercise, consuming these ingredients prior to exercise may safely improve body composition and fitness in healthy men (Lockwood et al. 2009). Although caffeine and EGCG formulas have been effective in increasing fat oxidation and energy expenditure in healthy individuals, the effects in an overweight population with moderate exercise and an ad libitum diet have not been examined. Therefore, the purpose of this study was to evaluate the combined effects of a 10-week exercise program and chronic ingestion of a drink containing caffeine and EGCG on body composition, cardiovascular fitness, strength, and safety in overweight and obese women.

Materials and methods Subjects Twenty-seven sedentary ( 0.05) among groups were found for caloric intake or carbohydrate, fat, or protein consumption. As expected, there was a significant time  group interaction observed for caffeine. Post-hoc analyses demonstrated significant differences (p < 0.05) between the active supplementing groups (EX-Act, NEX-Act) and the placebo groups (EX-PL, NEX-PL) at both week 5 (mean ± SD, Act = 357.2 ± 237.5 mg; PL = 61.2 ± 64.9) and week 10 (Act = 283.0 ± 76.9 mg; PL = 95.8 ± 1008.5), respectively. No differences were observed for the active supplementing groups. Published by NRC Research Press

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Table 2. Cardiovascular endurance training protocol for the 10-week exercise program, established using the guidelines from the American College of Sports Medicine (ACSM 2010). Week 1 2 3 4 5 6 7 8 9 10

Duration (min) 15–20 20–25 25–30 25–30 25–30 25–30 25–30 30–35 30–35 30–35

% Heart rate reserve 40–50 40–50 50–60 50–60 60–70 60–70 60–70 60–70 60–70 60–70

Table 3. Changes in body composition from pretraining (PRE) to post-training (POST).

Fat mass, kg EX-Act EX-PL NEX-Act NEX-PL %FAT, % EX-Act EX-PL NEX-Act NEX-PL Fat-free mass, kg EX-Act EX-PL NEX-Act NEX-PL Muscle mass, kg EX-Act EX-PL NEX-Act NEX-PL

PRE

POST

31.12±4.31 28.34±6.25 25.93±6.12 28.70±4.30

30.25±4.12 28.17±6.14 26.17±6.50 27.53±4.81

39.59±2.78 38.49±3.40 37.56±2.56 36.22±1.52

37.98±3.14 37.62±3.48 37.39±2.80 35.24±1.62

47.47±6.08 44.72±4.81 42.69±7.09 50.55±7.60

49.45±6.41* 46.03±3.95* 43.20±6.40 50.56±8.69

20.93±3.29 20.72±2.20 19.68±3.91 24.24±4.57

22.32±3.22* 21.74±1.89* 19.84±3.69 23.95±4.80

Note: Data are presented as means ± SD. EX-Act, exercising active-supplementing group; EX-PL, exercising placebo group; NEX-Act, nonexercising activesupplementing group; NEX-PL, nonexercising placebo group; %FAT, pecentage body fat. *Significant main effect for time (p < 0.05).

Body composition A significant time  treatment interaction (p = 0.026) was observed for MM only (Table 3). Although there were no significant differences between treatment groups (Act vs. PL) for increases in MM, 100% of the subjects in the Act (i.e., EX-Act and NEX-Act) groups increased MM from pretesting to post-testing, compared with 45% and 20% in the EX-PL and NEX-PL groups, respectively (Fig. 1). A significant time  training interaction (p < 0.01) also occurred for MM. When collapsing across groups, only the training groups (EX-Act and EX-PL) demonstrated significant increases in MM pre to post. FFM changes also demonstrated a significant time  training interaction (p = 0.039). Post-

hoc analyses revealed no significant differences among groups. Although not significant, 50% of the individuals in the EX-Act group and 43% in the EX-PL group demonstrated improvements in FFM greater than 2.11 kg (minimal difference (MD)), whereas 11% and 20% of the subjects in the NEX groups increased FFM (Fig. 1). %FAT or FM mean values did not demonstrate any significant (p > 0.05) changes from pretesting to post-testing. Notably, however, 50% of the individuals in the EX-Act group lost FM (MD = 1.64 kg), compared with 43% in the EX-PL, 11% in the NEX-Act, and 20% in the NEX-PL groups (Fig. 1). More interestingly, with respect to a loss in %FAT, individual responders demonstrated a 50% decrease in the EX-Act group (MD = 1.8%), 22% in the EX-PL group, 20% in the NEXPL group, and no response in the NEX-Act group (Fig. 1). Cardiovascular response There was a significant time  training interaction (p < _ 2 peak. Post-hoc analyses indicated no significant 0.05) for VO difference among training groups for improvements in _ 2 peak (Fig. 2A). Improvements in VT elicited a 2-way inVO teraction (p = 0.014). Both EX groups demonstrated a significantly greater increase in VT from pretraining to posttesting compared with the NEX groups, yet there was no significant difference between treatment groups (Fig. 2B). _ 2 peak was covaried for pretesting differTTE during the VO ences between groups, resulting in a significant interaction (p = 0.046). Bonferroni post-hoc comparisons yielded significantly greater improvements in the training groups compared with the nontraining groups (Fig. 2C). Resting heart rate and blood pressure demonstrated no significant change for any group (Table 4). Strength measurements A significant time  training interaction (p < 0.05) resulted for both 1RM bench press and 1RM incline leg press (Table 5). Upper-body and lower-body strength improved significantly for EX-Act (13.26% and 27.81%) and EX-PL (20.49% and 26.97%) but there were no changes in the NEX groups. No differences were observed between EX groups for either strength measurement. Blood lipids and safety Select blood safety analyses were completed to monitor hepatic and renal function. No significant changes were apparent for any blood or serum variables over time for any of the groups. Fasting lipid concentrations are presented in Table 6. There was a significant time  treatment interaction (p = 0.047) for TC. Bonferroni post-hoc analyses indicated a significant difference between the Act and PL groups. Follow-up dependent samples t tests resulted in a significant decrease (p < 0.05) for only the EX-Act group. LDL cholesterol resulted in a main effect for treatment (p = 0.05). When collapsing across training groups, only the active-supplementing groups (EX-Act and NEX-Act) demonstrated a significant decrease across time (p = 0.019). HDL values portrayed no interaction of main effects for any group. There was a main effect for treatment (p = 0.030) for triglycerides, with the EX-Act group increasing significantly from pretesting to post-testing. There were no significant Published by NRC Research Press

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Fig. 1. Individual data for all groups on percentage change for % body fat (%), fat mass (kg), muscle mass (kg), and fat-free mass (kg). EX-Act, exercising active-supplementing group; EX-PL, exercising placebo group; NEX-Act, nonexercising active-supplementing group; NEX-PL, nonexercising placebo group.

changes in other primary safety analyses, including glucose, hemoglobin, or hematocrit (Table 4).

Discussion The current study is the first to use a caffeine and EGCGcontaining formula administered prior to exercise as a method of impacting body composition and fitness in overweight and obese women. Recent data have suggested that acute (Dalbo et al. 2008) and chronic (Roberts et al. 2008) consumption of the same formula used in this study administered to nonobese individuals may augment lipolysis and lead to a decrease in %FAT and FM. In support, Lockwood et al. (2009) recently reported that administering the same beverage prior to exercise resulted in a significant decrease in FM and %FAT in men. In contrast, the current study did not result in a significant reduction in FM or %FAT for the EX-Act group, but did reveal a significant increase in total MM, which was greater than training only. In addition, the current study resulted in a significant decrease in TC and LDL only in the groups supplementing with the caffeine– EGCG drink (EX-Act and NEX-Act). The implementation of thermogenic supplements alone or supplements combined with exercise is arising as a practical method of reducing body weight and body fat. The effects of the current formula’s combined ingredients, caffeine (Acheson et al. 1980; Dulloo et al. 1989; Bracco et al. 1995), green tea extract (Hase et al. 2001; Diepvens et al. 2005), and guarana (Boozer et al. 2001), have been evaluated as possible thermogenic agents. However, the effect of these ingredients combined with exercise on body composition and lipid profiles in overweight and obese women has

yet to be identified. It is difficult to compare previous multiingredient supplements and single-ingredient doses directly, because most supplements contain slightly different doses and ingredients. It is widely accepted, however, that caffeine is an effective thermogenic agent because it inhibits the phosphodiesterase-induced degradation of intracellular cAMP and opposes the inhibitory effect of adenosine on norepinephrine release (Dulloo et al. 1994). Furthermore, green tea has been proven successful as a thermogenic agent because it increases energy expenditure and fat oxidation and improves body composition by inhibiting catechol O-methyl-transferase (Hase et al. 2001; Chantre and Lairon 2002; Diepvens et al. 2005). Body composition Caffeine alone has been shown to augment REE, lipolysis, and fat oxidation, and to reduce caloric intake (Costill et al. 1978; Acheson et al. 1980; Dulloo et al. 1989; Acheson et al. 2004). Furthermore, caffeine increases the prevalence of serum glycerol and FFA by stimulating the production of hormone-sensitive lipase as a result of an increase in catecholamines (Vannucci et al. 1989; Benowitz et al. 1995). Although caffeine is effective for acute increases in metabolism and lipid oxidation, chronic consumption has not demonstrated benefits in reducing body weight or body fat, possibly because of habituation (Westerterp-Plantenga et al. 2005). Supplementing obese individuals with caffeine alone demonstrates a blunted thermogenic and lipolytic response, compared with lean subjects (Jung et al. 1981; Bracco et al. 1995; Acheson et al. 2004). However, combining caffeine with other thermogenic agents, such as green tea, has been shown to be a more effective strategy for stimPublished by NRC Research Press

Smith et al. Fig. 2. Means ± SD from pretraining to post-training for (A) cardi_ 2 peak) (mLkg–1min-1), (B) ventilatory threshovascular fitness (VO -1 old (VT) (Lmin ), and (C) oxygen consumption time to exhaustion _ 2TTE). EX-Act, exercising active-supplementing group; (VO EX-PL, exercising placebo group; NEX-Act, nonexercising activesupplementing group; NEX-PL, nonexercising placebo group. *, Significance (p < 0.05).

613 Table 4. Change from preintervention to postintervention for safety measures, including resting heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DPB), glucose, hemoglobin (HGB), and hematocrit (HCT). Safety measure Rest HR SBP DBP Glucose HGB HCT

Change (%) EX-Act –5.80 1.10 –7.20 3.20 –0.15 –2.49

EX-PL 3.22 0.00 1.10 –1.12 1.25 –0.47

NEX-Act –3.80 –1.94 –6.09 –3.84 1.02 1.00

NEX-PL 3.99 2.57 –4.56 –5.91 2.54 2.51

Note: EX-Act, exercising active-supplementing group; EX-PL, exercising placebo group; NEX-Act, nonexercising active-supplementing group; NEX-PL, nonexercising placebo group.

2001). Although the formula in the current study contained these 3 supported ingredients, there was no significant loss in body weight or %FAT. Despite the conflicting results, participants in the current study maintained normal caloric intake (mean ± SD: 1789 ± 466 kcalday–1), whereas other studies implemented a hypocaloric approach (Boozer et al. 2001; Hase et al. 2001; Nagao et al. 2001; Tschida et al. 2002). General exercise recommendations prescribed by the ACSM within the current study demonstrated significant increases in MM and FFM, independent of energy drink consumption. The individual data give further support to a generalized exercise program, in combination with this supplement, to elicit more consistent improvements in MM and loss of FM (Fig. 2). Although the same beverage, in combination with exercise, did not demonstrate improvements in MM in healthy men (Lockwood et al. 2009), this study’s overweight and obese cohort may have strongly influenced the opposing results. In addition, the exercise program in the current study included less cardiovascular exercise, compared with previous studies (Lockwood et al. 2009).

ulating metabolism and fat oxidation and may be an effective tactic for promoting weight loss in obese individuals (Dulloo et al. 1999). Similar to the current study, 12 weeks of green tea consumption resulted in significant decreases in body weight (4.6%) and waist circumference (4.5%) in moderately obese individuals (Chantre and Lairon 2002). Additionally, Tschida et al. (2002) implemented a 12-week supplementation regime of green tea, demonstrating decreased body weight, visceral fat, and total fat in overweight men and women. More recent evidence also suggests that the addition of guarana to 8 weeks of exercise may be effective for weight loss and body fat reduction (Boozer et al.

Cardiovascular and strength adaptations Although it is reported consistently that caffeine is effective in improving prolonged, moderate-intensity exercise and that it improves TTE, the current study resulted in no appreciable benefits from the energy drink, with both the Ex-Act _ 2 peak, time to fatigue, and and Ex-PL groups increasing VO VT (Fig. 2B). Furthermore, the ergogenic benefit of caffeine on anaerobic and strength performance is limited, with the majority of evidence suggesting caffeine is not effective as an aid in increasing strength. In support of this evidence, both exercise groups demonstrated improvements in 1RM upper-body and lower-body strength, regardless of the treatment condition (Table 3), demonstrating the effectiveness of a moderate aerobic and resistance training program in improving cardiovascular fitness and strength in overweight and obese women. Blood lipid profile Despite the lack of significance of the current supplement on weight reduction, the blood panel results suggest strong support for its safety, demonstrating no deleterious effects Published by NRC Research Press

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Appl. Physiol. Nutr. Metab. Vol. 35, 2010 Table 5. Data for bench press and squat 1-repetition max. Bench press EX-Act EX-PL NEX-Act NEX-PL

PRE 81.67±18.07 67.78±7.95 70.71±14.56 80.00±7.91

Squat POST 92.5±16.96* 81.67±7.91* 72.14±14.96 78.00±10.95

PRE 251.67±78.34 238.89±66.23 245.00±71.12 323.00±41.47

POST 321.67±57.33* 303.33±46.37* 240.71±65.67 319.00±41.29

Note: Values are presented as means ± SD. There were no significant differences between training groups; both increased significantly from PRE to POST. EX-Act, exercising active-supplementing group; EX-PL, exercising placebo group; NEX-Act, nonexercising active-supplementing group; NEX-PL, nonexercising placebo group. *Significant time  training interaction (p < 0.05).

Table 6. Changes in clinical safety markers from PRE to POST.

Total cholesterol (mgdL–1) EX-Act EX-PL NEX-Act NEX-PL HDL (mgdL–1) EX-Act EX-PL NEX-Act NEX-PL LDL (mgdL–1) EX-Act EX-PL NEX-Act NEX-PL VLDL (mgdL–1) EX-Act EX-PL NEX-Act NEX-PL Triglycerides (mgdL–1) EX-Act EX-PL NEX-Act NEX-PL

PRE

POST

211.33±30.22 161.67±26.50 199.57±65.38 170.40±31.61

200.33±27.37* 165.56±26.69 173.14±41.59 170.20±31.23

52.33±9.04 54.11±8.96 55.29±6.97 51.80±15.83

52.83±7.17 54.89±10.45 51.86±8.40 57.20±20.56

137.50±30.85 92.56±22.69 125.57±61.15 101.20±30.04

120.33±24.31* 93.00±19.67 102.43±37.48* 95.40±31.00

21.50±5.13 15.00±5.20 18.71±6.26 17.40±5.68

27.17±7.25 17.67±4.64 18.86±7.80 17.60±7.20

108.00±24.80 74.44±26.17 94.14±31.21 86.40±29.10

135.83±35.49* 87.67±22.27 95.14±38.19 88.20±35.07

Note: Data are presented as means ± SD.EX-Act, exercising activesupplementing group; EX-PL, exercising placebo group; NEX-Act, nonexercising active-supplementing group; NEX-PL, nonexercising placebo group *Significant change over time (p < 0.05).

from chronic consumption on any of the clinical safety markers examining hepatic, renal, cardiovascular, and immune function (Table 4). In addition, TC was significantly decreased only in the Ex-Act group, whereas both Act groups (Ex-Act and NEX-Act) demonstrated a significant reduction in LDL values (12.5% and 18.4%, respectively) with no change in HDL. In support, recent studies (Hackman et al. 2006; Hsu et al. 2008) have reported decreases in TC and LDL with the use of green tea and caffeine in amounts similar to those used in the current study, although in differing combinations. Hsu et al. (2008) demonstrated decreases in LDL when supplementing obese women with green tea extract for only 12 weeks. In addition, Hackman et al.

(2006) showed comparable effects on TC, LDL, and triglyceride levels in obese women with a multinutrient thermogenic supplement containing caffeine. Moreover, Hase et al. (2001) demonstrated significant decreases in TC and FFA, with no change in plasma triglycerides. Furthermore, reductions in plasma insulin and glucose with the use of EGCG and the current drink have been reported previously, but no significant change was found in the current study (Table 3) (Hase et al. 2001; Nagao et al. 2001). Although the results of our study and others using a similar cohort of subjects demonstrate an improved blood lipid profile, the mechanism of EGCG and (or) caffeine on lowering plasma lipids remains to be determined. It has been suggested, however, that tea polyphenols in EGCG may suppress the biosynthesis of these specific lipids, inducing hypolipidemic and antiobesity effects. More research is needed to confirm our results and to determine the mechanism of action. Conclusions and practical applications In summary, these results suggest that the caffeine–EGCG supplement used in the current study, when used once daily in healthy overweight and obese women in combination with a moderate exercise program, may be beneficial in improving blood lipid profiles and increasing lean body mass without adverse effects. Interestingly, the changes observed occurred despite no dietary modifications. Although acute data (1–24 days of consumption) with the same ingredients have demonstrated an increase in energy expenditure and lipolysis (Dalbo et al. 2008; Roberts et al. 2008), the chronic data (12 weeks) reported in this study demonstrated no change in body fat. Despite no change in body fat, previous in vitro data suggest that green tea inhibits adipocyte proliferation and differentiation and can reduce carbohydrate and fat absorption by inhibiting various digestive enzymes. Furthermore, the combination of caffeine and green tea in men and women has resulted in significant increases in metabolism and fat oxidation (Dulloo et al. 1999). It is likely that the current study did not show a decrease in FM because subjects were not asked to follow a low-calorie diet. Previous studies have reported that consuming green tea with caffeine while on a low-calorie diet has accelerated fat loss more than being on a low-calorie diet only (Belza et al. 2007; Hsu et al. 2008). With the increased use of herbal products and the intensifying prevalence of obesity, additional long-term investigations combining a similar formula and exercise with caloric restriction are warranted for more promising changes in weight and FM. Published by NRC Research Press

Smith et al.

Acknowledgements We thank Celsius Inc. (Delray Beach, Fla.) for funding this study; and Ashley Walter, Jason DeFreitas, and Pablo Costa for their assistance in subject training. We declare no competing interests.

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