Journal of the International Society of Sports Nutrition BioMed Central Research article Open Access The acute effects of the thermogenic supplement Meltdown on energy expenditure, fat oxidation, and hemodynamic responses in young, healthy males Jean Jitomir1, Erika Nassar1, Julie Culbertson3, Jen Moreillon1, Thomas Buford1, Geoffrey Hudson1, Matt Cooke1, Richard Kreider3 and Darryn S Willoughby*1,2 Address: 1Department of Health, Human Performance, and Recreation, Baylor University, Box 97313, Waco, TX 76798, USA, 2Institute for Biomedical Science, Baylor University, Waco, TX 87898, USA and 3Department of Health and Kinesiology, Texas A&M University, College Station, TX 78743, USA Email: Jean Jitomir - [email protected]; Erika Nassar - [email protected]; Julie Culbertson - [email protected]; Jen Moreillon - [email protected]; Thomas Buford - [email protected]; Geoffrey Hudson - [email protected]; Matt Cooke - [email protected]; Richard Kreider - [email protected]; Darryn S Willoughby* - [email protected] * Corresponding author Published: 16 December 2008 Received: 5 November 2008 Accepted: 16 December 2008 Journal of the International Society of Sports Nutrition 2008, 5:23 doi:10.1186/1550-2783-5-23 This article is available from: http://www.jissn.com/content/5/1/23 © 2008 Jitomir et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract The purpose of this study was to evaluate the effects of a thermogenic supplement, Meltdown, on energy expenditure, fat oxidation, and hemodynamics before and after maximal treadmill exercise. In a double-blind, randomized, placebo-controlled, cross-over design, 12 male participants underwent two testing sessions after consuming either the Meltdown or placebo supplement. While in a fasted state, participants rested for one hour, orally ingested either Meltdown or placebo and rested for another hour, performed a maximal treadmill exercise test, and then rested for another hour. Throughout the testing protocol, resting energy expenditure (REE) and respiratory exchange ratio (RER) were assessed. In addition, heart rate (HR) and blood pressure (BP) were assessed before and after exercise. Meltdown increased REE significantly more than placebo at 45 min (1.44 ± 0.25 vs. 1.28 ± 0.23 kcal/min; p = 0.003), 60 min (1.49 ± 0.28 vs. 1.30 ± 0.22 kcal/min; p = 0.025), and 120 min (1.51 ± 0.26 vs. 1.33 ± 0.27 kcals/min; p = 0.014) post-ingestion. Meltdown significantly decreased RER at 30 min (0.84 ± 0.03 vs. 0.91 ± 0.04; p = 0.022) and 45 min post- ingestion (0.82 ± 0.04 vs. 0.89 ± 0.05; p = 0.042), and immediately post-exercise (0.83 ± 0.05 vs. 0.90 ± 0.07; p = 0.009). Furthermore, over the course of the evaluation period, area under the curve assessment demonstrated that REE was significantly increased with Meltdown compared to placebo (992.5 ± 133.1 vs. 895.1 ± 296.1 kcals; p = 0.043), while RER was significantly less than placebo (5.55 ± 0.61 vs. 5.89 ± 0.44; p = 0.002) following ingestion. HR and BP were not significantly affected prior to exercise with either supplement (p > 0.05) and the exercise-induced increases for HR and BP decreased into recovery and were not different between supplements (p > 0.05). These data suggest that Meltdown enhances REE and fat oxidation more than placebo for several hours after ingestion in fully rested and post-exercise states without any adverse hemodynamic responses associated with maximal exercise. Page 1 of 7 (page number not for citation purposes) Journal of the International Society of Sports Nutrition 2008, 5:23 http://www.jissn.com/content/5/1/23 Background response depends upon on the receptor subtype to which Despite a restructured food guide pyramid, ambitious the hormone binds [7]. Healthy People 2010 guidelines, and an explosion of weight loss products, there is an absence of systemic obes- Adrenergic analogues utilized in a thermogenic supple- ity relief. In fact, obesity is a growing concern and the ment are likely to enhance the activation of the SNS. For problem may be accelerating. According to the CDC and instance, the compound synephrine, which structurally results from the Behavioral Risk Factor Surveillance Sys- resembles ephedrine, is primarily a sympathomimetic α1- tem (BRFSS) survey, obesity rates grew from 19.8% in AR agonist [8]. Typically, activation of the α1-AR mainly 2000 to 23.9% in 2005, which is an increase of about results in smooth muscle contraction, which causes vaso- 0.82% per year; obesity grew from 23.9% in 2005 to constriction in blood vessels of the skin, GI tract, kidney 25.6% in 2007, representing a 0.9% yearly increase [1]. and brain. Furthermore, one study revealed that syne- The ramifications of the escalating obesity epidemic phrine also has moderate non-selective β3-AR agonist include an increased incidence of chronic disease and activity in several cell lines [9]. As previously revealed by annual health care expenditure, as well as lost productiv- Weyer et al. [10], supplementation with a selective β3-AR ity [2]. agonist, specifically CL 316,243, stimulates lipolysis in healthy men. Therefore, if synephrine is a sufficiently Consumers often ingest diet products to bolster weight potent β3-AR agonist, the compound may promote fat loss efforts. Formerly, ephedrine and ephedra were inte- and weight loss in humans through enhanced lipolysis in gral components in weight loss supplements. Since the adipose tissue. most substantial effect of ephedrine use is enhanced sym- pathetic nervous system (SNS) activity via increased nore- Caffeine is also a popular addition to thermogenic com- pinephrine (NE) release from the nerve terminal, the drug pounds, and two of the effects of caffeine are particularly has an impact on all adrenergic receptors (AR). Moreover, relevant. Specifically, caffeine serves as an antagonist to the ephedrine compound also has β-AR agonist and α-AR adenosine in the neurons, via competitive inhibition, antagonist activity in circulation [3]. Previous investiga- which stimulates the SNS [11]. Therefore, NE, dopamine tions indicate that supplemental weight loss products and GABA secretion are increased in the brain, which containing a combination of ephedra (ma huang) or ephe- prompts a greater release of catecholamines into the sys- drine and caffeine increase resting energy expenditure temic circulation. Furthermore, since caffeine is also a (REE) and loss of fat mass [4-6]. Therefore, prudent sup- known non-selective inhibitor of the enzyme cAMP-phos- plementation with ephedra-containing products, in com- phodiesterase (PDE), which converts cAMP to its inactive, bination with a sensible diet and exercise plan, has the non-cyclic form, the compound amplifies the signal of potential to accelerate weight loss. cAMP through inhibition of PDE [12]. By promoting high concentrations of cAMP, caffeine intensifies and prolongs On April 12, 2004, however, ephedra-containing products the effects of E and NE, as well as other stimulatory AR were condemned by the FDA in response to safety con- agonists, such as synephrine and octopamine. The ther- cerns; therefore, manufacturers of nutrition supplements mogenic additive phenylethylamine also inhibits the sought to formulate alternative thermogenic weight loss reuptake of NE from the synaptic cleft [13]. Finally, products with comparable effectiveness. As such, supple- yohimbine acts as a α2-AR antagonist [14]. Since α2-AR ments containing caffeine and β-agonist compounds sim- exist on the adrenal medulla as a negative feedback system ilar to ephedra began to appear on the market. Therefore, for catecholamine release, a α2-AR antagonist may be of the Citrus aurantium-derived alkaloids synephrine and benefit in a weight loss supplement as a permissive pro- octapamine have gained popularity. Meltdown is a ther- moter of NE and E release and signaling [15]. Finally, mogenic product that combines synephrine, caffeine, hordenine, like ephedrine, may have non-specific effects phenylethylamine, yohimbine, hordenine and other on AR by stimulating the release of NE [16], though compounds to stimulate the β-AR, thereby activating human data is lacking. cyclic AMP (cAMP), while also inhibiting the α-AR that illicit an inhibitory response. When these compounds are combined in supplement form, they may work synergistically to enhance weight Activation of the SNS neurons stimulates the release of loss. Initially, phenylethylamine, caffeine, and hordenine two primary catecholamine signaling molecules, epine- may stimulate the SNS in a non-specific manner. Once phrine (E) and NE. After NE acts as an SNS stimulatory SNS stimulation is initiated, N and NE circulate in higher neurotransmitter (NT) in the brain, the adrenal medulla is than normal amounts, which activate AR throughout the prompted to release NE into blood. E or NE binding to an body. Simultaneously, the inhibitory effects of the α2-AR AR will produce a range of responses, the nature of the are blocked by yohimbine. Furthermore, stimulatory SNS responses are enhanced by synephrine, which promotes Page 2 of 7 (page number not for citation purposes) Journal of the International Society of Sports Nutrition 2008, 5:23 http://www.jissn.com/content/5/1/23 the activity of Gs and subsequent cAMP signaling